Which of the following terms is used to identify a chemical that causes cancer?

GUIDANCE FOR HAZARD DETERMINATION

FOR COMPLIANCE WITH THE
OSHA HAZARD COMMUNICATION STANDARD
(29 CFR 1910.1200)

U.S. Department of Labor
Occupational Safety and Health Administration

Edwin G. Foulke, Jr.
Assistant Secretary of Labor for
Occupational Safety and Health

This guidance is not a standard or regulation, and it creates no new legal obligations. It is advisory in nature, informational in content, and is intended to assist employers in providing a safe and healthful workplace. Pursuant to the Occupational Safety and Health Act, employers must comply with safety and health standards promulgated by OSHA or by a state with an OSHA-approved state plan. In addition, pursuant to Section 5(a)(1), the General Duty Clause of the Act, employers must provide their employees with a workplace free from recognized hazards likely to cause death or serious physical harm. Employers can be cited for violating the General Duty Clause if there is a recognized hazard and they do not take reasonable steps to prevent or abate the hazard. However, failure to implement any specific recommendations in this guidance is not, in itself, a violation of the General Duty Clause. Citations can only be based on standards, regulations, and the General Duty Clause.

TABLE OF CONTENTS

OVERVIEW

1. INTRODUCTION
   What is Hazard Determination?
   Who Must Conduct Hazard Determinations?
   What Resources are Needed to Conduct a Hazard Determination?
   How Should This Guidance Document be Used?

2. THE HAZARD DETERMINATION PROCESS
   What is the HCS Definition of a "Chemical"?
   How Will I Know if My Chemical is "Hazardous"?
   Is Hazard Determination the Same for Mixtures as for Individual Elements and Compounds?
   What is Involved in Conducting a Hazard Determination?

3. SELECTION OF CHEMICALS

4. DATA COLLECTION
   Physical and Chemical Properties
   Health Effects

5. DATA ANALYSIS
   Physical Hazards
   Fire Hazards
   Explosive Hazards
   Reactive Hazards
   Health Hazards
   Systemic Effects
   Target Organ Effects

6. DOCUMENTATION
   Chemical Inventory
   Description of Procedures Used for Hazard Determination
   Specific Data Retrieved for Each Chemical

APPENDICES

1. Glossary of Terms and Definitions
2. Information Sources to Assist with Hazard Determination
3. Materials Regulated by OSHA as Toxic and Hazardous Substances
4. OSHA Designated Carcinogens

OVERVIEW

This document is designed to help manufacturers and importers of chemicals identify chemical hazards so that employees and downstream users can be informed about these hazards as required by the Occupational Safety and Health Administration's (OSHA) Hazard Communication standard. This guidance may also be useful to employers who decide to conduct hazard determinations in order to assure the accuracy and completeness of information provided to them by suppliers. Hazard determination is the critically important first stage in the process of establishing an effective hazard communication program. The process of hazard determination consists of four basic steps. These are:

• Selection of chemicals to evaluate;
• Collection of data;
• Analysis of the collected data; and
• Documentation of the hazard determination process and the results obtained.

This document provides guidance as to the processes involved and identifies considerations in the conduct of hazard determinations. Since much of the discussion is of a technical nature, a Glossary of Terms and Definitions is included as Appendix A. Material contained in this publication is in the public domain and may be reproduced, fully or partially, without permission. Source credit is requested but not required.

I. INTRODUCTION

OSHA's Hazard Communication standard (HCS) is designed to protect against chemical source illnesses and injuries by ensuring that employers and employees are provided with sufficient information to anticipate, recognize, evaluate and control chemical hazards and take appropriate protective measures. This information is provided through material safety data sheets (MSDSs), labels, and employee training. In order for MSDSs, labels, and training to be effective, the hazard information they convey must be complete and accurate. Thus, it is critically important to obtain comprehensive and correct information about the hazards associated with particular chemicals.

What is Hazard Determination?

Hazard determination is the process of evaluating available scientific evidence in order to determine if a chemical is hazardous pursuant to the HCS. This evaluation identifies both physical hazards (e.g. , flammability or reactivity) and health hazards (e.g. , carcinogenicity or sensitization). The hazard determination provides the basis for the hazard information that is provided in MSDSs, labels, and employee training.

Hazard determination does not involve an estimation of risk. The difference between the terms hazard and risk is often poorly understood. Hazard refers to an inherent property of a substance that is capable of causing an adverse effect. Risk, on the other hand, refers to the probability that an adverse effect will occur with specific exposure conditions. Thus, a substance will present the same hazard in all situations due to its innate chemical or physical properties and its actions on cells and tissues. However, considerable differences may exist in the risk posed by a substance, depending on how the substance is contained or handled, personal protective measures used, and other conditions that result in or limit exposure. This document addresses only the hazard determination process, and will not discuss risk assessment, which is not performed under the OSHA HCS.

Who Must Conduct Hazard Determinations?

Only chemical manufacturers and importers are required to perform hazard determinations on the chemicals they produce or import. Under the HCS, an employer that manufactures, processes, formulates, or repackages a hazardous chemical is considered a "chemical manufacturer. " Distributors and employers may also choose to conduct hazard determinations if they are concerned about the adequacy of hazard information for the chemicals they use in their business or distribute to others.

Regardless of who performs the hazard determination, the procedures used must be described in writing and made available, upon request, to employees and their designated representatives, as well as to OSHA and National Institute for Occupational Safety and Health (NIOSH) officials.

What Resources are Needed to Conduct a Hazard Determination?

Two primary resources are required for hazard determination. First is the complete, accurate, up-to-date literature and data concerning the chemical in question. Second is the ability to properly understand and interpret the information retrieved in order to identify and document hazards. Manufacturers and importers of hazardous chemicals are responsible for ensuring that hazard information provided to their employees and downstream users is complete and accurate. To achieve this, the person(s) assigned to conduct hazard determinations must have the ability to conduct complete and effective literature and data retrieval. They should also be able to effectively interpret the literature and data in order to determine the nature and extent of physical and health hazards. A lack of qualified employees does not exempt a manufacturer or importer from compliance with the HCS.

How Should This Guidance Document be Used?

The hazard determination requirements of the HCS are performance oriented. That is, chemical manufacturers, importers, and employers evaluating chemicals are not required to follow any specific procedures for determining hazards, but they must be able to demonstrate that they have adequately ascertained and reported the hazards of the chemicals produced or imported in accordance with the criteria set forth in the HCS.

This guidance document will not provide detailed methods that must be followed. However, a basic framework for hazard determination is provided, along with a description of a process that can be used to comply with the requirements of the HCS. The interpretation of information relating to the physical and health hazards associated with a chemical can be a highly technical undertaking, and should be conducted by trained staff such as toxicologists, industrial hygienists, and safety professionals. This document will not replace the need for such professional expertise in certain situations. It is intended to serve only as useful guidance as to the basic considerations and operational aspects involved in the conduct of hazard determinations.

II. THE HAZARD DETERMINATION PROCESS

What is the HCS Definition of a "Chemical"?

The definition of a chemical in the HCS is much broader than that which is commonly used. The HCS definition of chemical is "any element, chemical compound, or mixture of elements and/or compounds. " Thus, virtually any product is a "chemical. " These various types of chemicals are as follows:

• Element - the simplest form of matter. There are currently 109 known elements in the periodic table. Examples of elements are aluminum, carbon, chlorine, hydrogen, mercury and oxygen.
• Chemical compound - a substance consisting of two or more elements combined or bonded together so that its constituent elements are always present in the same proportions.
• Mixture - any combination of two or more chemicals if the combination is not, in whole or in part, the result of a chemical reaction.

Although virtually all materials are considered chemicals under this definition, the HCS identifies certain categories of chemicals that are not covered by the standard. These categories are:

• Any hazardous waste as defined by the Solid Waste Disposal Act when subject to regulations issued under that Act by the Environmental Protection Agency;
• Any hazardous substanceas defined by the Comprehensive Environmental Response, Compensation and Liability Act when the hazardous substance is the focus of remedial or removal action being conducted under that Act in accordance with Environmental Protection Agency regulations;
• Tobacco or tobacco products;
• Wood or wood products, including lumber which will not be processed, where the chemical manufacturer or importer can establish that the only hazard they pose to employees is the potential for flammability or combustibility (wood or wood products which have been treated with a hazardous chemical covered by this standard, and wood which may be subsequently sawed or cut, generating dust, are not exempted);
• Articles, defined as a manufactured item other than a fluid or particle: (i) which is formed to a specific shape or design during manufacture; (ii) which has end use function(s) dependent in whole or in part upon its shape or design during end use; and (iii) which under normal conditions of use does not release more than very small quantities, e.g. , minute or trace amounts of a hazardous chemical, and does not pose a physical hazard or health risk to employees.
• Food or alcoholic beverages which are sold, used, or prepared in a retail establishment (such as a grocery store, restaurant, or drinking place), and foods intended for personal consumption by employees while in the workplace;
• Any drug, as that term is defined in the Federal Food, Drug, and Cosmetic Act, when it is in solid, final form for direct administration to the patient (e.g. , tablets or pills); drugs which are packaged by the chemical manufacturer for sale to consumers in a retail establishment (e.g. , over-the-counter drugs); and drugs intended for personal consumption by employees while in the workplace (e.g. , first-aid supplies);
• Cosmetics which are packaged for sale to consumers in a retail establishment, and cosmetics intended for personal consumption by employees while in the workplace;
• Any consumer product or hazardous substance, as those terms are defined in the Consumer Product Safety Act and Federal Hazardous Substances Act, respectively, where the employer can show that it is used in the workplace for the purpose intended by the chemical manufacturer or importer of the product, and the use results in a duration and frequency of exposure which is not greater than the range of exposures that could reasonably be experienced by consumers when used for the purpose intended;
• Nuisance particulates where the chemical manufacturer or importer can establish that they do not pose any physical or health hazard covered under this section;
• Ionizing and nonionizing radiation; and
• Biological hazards.

How Will I Know if My Chemical is "Hazardous"?

Under the HCS, any chemical that presents a physical hazard or a health hazard is considered a hazardous chemical. The HCS definitions for physical and health hazards are:

• Physical hazard means a chemical for which there is scientifically valid evidence that it is a combustible liquid, a compressed gas, explosive, flammable, an organic peroxide, an oxidizer, pyrophoric, unstable (reactive) or water-reactive.
• Health hazard means a chemical for which there is statistically significant evidence based on at least one study conducted in accordance with established scientific principles that acute or chronic health effects may occur in exposed employees. The term "health hazard" includes chemicals which are carcinogens, toxic or highly toxic agents, reproductive toxins, irritants, corrosives, sensitizers, hepatotoxins, nephrotoxins, neurotoxins, agents which act on the hematopoietic system, and agents which damage the lungs, skin, eyes, or mucous membranes.

These different types of hazards identified in the HCS are presented in Table 1.

Table 1. HCS Listed Hazard Categories

For a hazard determination to be complete, one must consider all possible hazards, and document any hazards that are identified. While the hazards listed in the HCS represent the majority of potential workplace hazards, the list is not all-inclusive, especially for health hazards. Table 2 is a list of important health hazards that should be evaluated in addition to those specifically listed by the HCS. In conducting the hazard determination, one should be cognizant of all types of physical and health hazards.

Table 2. Other Important Health Hazards

Certain chemicals are specifically designated as hazardous by the HCS. The HCS listing of hazardous chemicals has been referred to as the "floor" to which other hazardous chemicals should be added. The HCS base list of these per se hazardous chemicals is provided in the following references:

• OSHA Toxic and Hazardous Substances, 29 CFR part 1910, Subpart Z (see Appendix C);
• Threshold Limit Values for Chemical Substances and Physical Agents (American Conference of Governmental Industrial Hygienists, latest edition); or
• Carcinogens or potential carcinogens according to one or more of the following sources:
  • 29 CFR part 1910, Subpart Z, Toxic and Hazardous Substances (OSHA) (see Appendix D);
  • National Toxicology Program Annual Report on Carcinogens, latest edition.

The definition for hazardous chemical in the standard is thus very broad, and it is not likely that many chemicals will be considered non-hazardous if they have been adequately tested. However, the standard does not require the testing of chemicals - only the collection and analysis of currently available data. Testing should be considered if hazardous properties are suspected.

Is Hazard Determination the Same for Mixtures as for Individual Elements and Compounds?

Generally speaking, the chemical and physical properties and hazards of pure elements and chemical compounds are precise and constant. For example, benzene has explicit boiling and flashpoints of 176ºF and 12ºF (at sea level), respectively. In contrast, the properties of the complex mixture, Stoddard Solvent, can vary considerably depending on the manufacturer and lot received, with ranges for boiling and flashpoints of 309-396ºF and 102-110ºF, respectively.

The process for evaluating mixtures may require additional steps along with those indicated for single chemical agents. The HCS has designated specific requirements for mixtures. These requirements depend upon the availability of test data as indicated below:

• If a mixture has been tested as a whole, the results should be used to determine whether the mixture is hazardous.
• If a mixture has not been tested as a whole for health hazards, the mixture shall be assumed to present the same hazards as components which comprise 1.0 percent (1%) or more of the mixture. An exception pertains to carcinogens. In this case, the mixture shall be assumed to present a carcinogenic hazard if it contains a carcinogenic component which comprises 0.1 percent (0.1%) or more of the mixture.
• If a mixture has not been tested as a whole to determine whether the mixture is a physical hazard, the chemical manufacturer or importer may use whatever scientifically valid data are available to evaluate the physical hazards of the mixture.
• If there is evidence that a component is present at less than one percent (< 0.1% for carcinogens) and could be released into the workplace environment in concentrations that would exceed an OSHA permissible exposure limit (PEL) or American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV), or present a health risk in those concentrations, the mixture is assumed to present the same hazard.

What is Involved in Conducting a Hazard Determination?

All possible physical or health hazards that might be associated with a chemical's use must be considered. The hazard determination process consists of four main steps:

• Selection of chemicals to evaluate;
• Collection of data;
• Analysis of the collected data; and
• Documentation of the hazard determination process and the results obtained.

Written procedures generally describe the process followed; they do not have to address, individually, each chemical evaluated. If no hazards are found, the manufacturer, importer, or employer is not required to take further action pertaining to the evaluated chemical. Even if no hazards are found, however, documentation of the steps taken to evaluate the chemical (and any retrieved data) may be useful for future reference.

For most of the chemicals specifically designated as hazardous in the HCS, the available information has been compiled in readily available and reliable sources (see Appendix B). If a chemical is not specifically designated as hazardous, you must collect and evaluate the data and determine if the chemical is hazardous. The hazard determination for these chemicals may be more involved since reliable data compilations may not exist. The determination in this case requires a more exhaustive search for information.

In some cases, a chemical may present a single hazard. In other cases, several hazards may be associated with exposure to a chemical. Hazards can range from mild to severe. For example, an identified health hazard for acetic acid, as normally used in industry, is irritation and corrosion (sensory and respiratory). In contrast, exposure to lead may involve a multitude of health hazards, including neurotoxicity, blood effects, cardiovascular and kidney damage, and birth defects.

The hazard evaluation is a process that relies heavily on the professional judgment of the evaluator, particularly in the area of chronic hazards. The performance-orientation of the HCS does not diminish the duty of the chemical manufacturer, importer or employer to conduct a thorough evaluation, examining all relevant data and producing a scientifically defensible evaluation

III. SELECTION OF CHEMICALS

The ultimate goal in the hazard determination process is to know and document the hazards of all covered chemicals you manufacture or import. In order to achieve this you must first determine which chemicals require a hazard determination. The logical way to do this is to first prepare an inventory of all chemicals manufactured or imported. Items exempted from coverage under the HCS may be excluded from the inventory. For chemicals obtained from suppliers, you may rely upon the MSDSs and labels provided by the chemical manufacturer or importer. However, you may choose to conduct hazard determinations for those chemicals if you are concerned about the adequacy of the hazard information you have received.

If a chemical inventory is not already in place, a good start would be to review purchase orders and receipts to create an initial inventory. Next, the workplace should be inspected to identify any additional chemicals present. It would be ideal to note the location and quantity of each chemical found. Chemical inventories are often maintained as computer files for ease and efficiency in keeping them current. With knowledge of the chemicals in your possession, hazard determinations can now be performed for chemicals in the inventory. The chemical inventory or survey can also be used to decide which chemicals to dispose of as well as to identify potentially unsafe storage areas and techniques. Some chemicals should not be stored near each other due to incompatibilities and potential reactions.

IV. DATA COLLECTION

The second step in the hazard determination process is data collection. There are two main questions to be answered: 1) what type of data should be searched for and collected; and 2) how do I go about finding sources that might contain the desired data? You should recognize that the hazard determination process involves the identification of all of the hazards associated with a chemical, not just some of them. This process must be completed even though some data elements may be difficult to locate. Any hazard that exists for the chemical must be identified and communicated to downstream employers and employees.

To complete the hazard identification, information is needed in three categories:

• chemical identity;
• chemical and physical properties; and
• health effects.

There are numerous sources that could be searched for this information. A list of commonly used data sources is provided in Appendix B, although other sources exist and new sources continue to appear online and in print. For new or less commonly used chemicals, there may not be much data available from any of these sources. While the HCS does not require testing, you may choose to test chemicals to determine chemical and physical properties and identify hazards. Testing may be particularly useful for new chemicals, since it may no longer be assumed that the new chemical has the same intrinsic hazards as its components.

In the sections that follow, a discussion of data needs for the three categories of information is provided. Also, a few recommended key references for the various types of data are listed. You should recognize that complete and reliable data must be entered on MSDSs and labels in order to meet HCS requirements. Before the search for hazard data can begin, however, you must identify the exact chemical composition of the chemical(s) or products manufactured or imported. For mixtures or products, this chemical search includes the name of each chemical in the mixture, including active ingredients, inactive ingredients, and impurities.

The specific chemical identity of all chemicals on your Chemical Inventory should be carefully and completely compiled. The specific chemical identity should include:

• the chemical name along with common name and synonyms;
• the Chemical Abstracts Services (CAS) Registry Number (if available); and
• any other information that reveals the precise chemical designation and composition of the substance.

Correct identification of chemicals is critical for data retrieval. Use the precise chemical name and CAS number when searching for information. A problem with the use of common names or abbreviations is that they may be used for more than one molecular entity. For example, TCE is sometimes used as an acronym for tetrachloroethylene, although it more frequently refers to trichloroethylene. To avoid confusion, literature is often indexed using the CAS number or the primary chemical name. An example of the type of chemical identification data that is needed is presented for Perclene®, a widely used industrial solvent. Perclean® is a trade name for perchloroethylene or Perc (common name), or more specifically tetrachloroethylene (CAS Number 127-18-4). Thus, the most effective search of computerized databases is conducted using tetrachloroethylene and/or CAS Number 127-18-4. Several databases exist that can be searched for the CAS number or chemical name if one only has a trade or common name(s) or abbreviation(s). CAS numbers are assigned by the Chemical Abstract Service of the American Chemical Society.

The percent composition should be available in-house for all chemicals and products manufactured or imported. The chemical composition information should be based on an analysis of the final or technical product. A technical grade product is not usually a pure substance and often contains other chemicals such as stabilizers, solvents, carriers, "inert" ingredients, or impurities. For the hazard evaluation process, these other chemicals must also be listed if they are more than 1.0% of the composition for non-carcinogenic substances or 0.1% of the product if the substance is a carcinogen.

Thus, the initial step is to collect as much data as possible pertaining to the physical and chemical properties and toxicity data for chemicals on your chemical inventory.

Key sources of information related to chemical identification are:

• Company records;
• MSDSs and product safety bulletins from manufacturers or suppliers;
• OSHA Chemical Sampling Information pages;
• The Merck Index;
• ChemID; and
• Trade associations.

Physical and Chemical Properties

The physical properties of a substance can be directly related, in many cases, to the probability of the substance representing a physical hazard. However, the fact that a substance has a certain physical property cannot necessarily be used to predict a physical hazard. For example, all volatile substances are not necessarily explosive. Some solids can also be explosive (e.g. , TNT or grain dust particles). Nevertheless, knowing the physical properties has great value in predicting whether a substance may pose a physical hazard.

Key sources of information related to physical and chemical properties include:

• Fire Protection Guide to Hazardous Materials;
• Department of Transportation 2000 Emergency Response Guidebook;
• Hazardous Substances Data Bank (HSDB);
• Product safety bulletins from manufacturers or suppliers;
• The Merck Index;
• NIOSH Pocket Guide to Chemical Hazards;
• CRC Handbook of Chemistry and Physics;
• Bretherick's Handbook of Reactive Chemicals Hazards; and
• Trade associations.

Health Effects

All potential health hazards must be determined - not just those identified by OSHA

The HCS includes a list of 14 potential health hazards, as well as the criteria for determining when a chemical represents a health hazard (see Section 3). In many cases, a chemical may pose more than one type of health hazard. If your company is manufacturing a new chemical you may be required to submit premanufacturing health effects data to the Environmental Protection Agency (EPA) to comply with the Toxic Substances Control Act (TSCA). Data submitted to EPA by other companies may be available to you by contacting the EPA. This data should be used to assist with hazard determination and the preparation of MSDSs and labels. For chemicals that have not been studied in-house or via company-sponsored toxicology studies, the company should seek toxicity data from the literature, government, or private sources. Some recommended reference sources are listed below.

• Company-sponsored research;
• MSDSs and product safety bulletins from manufacturers, suppliers, or Internet sites;
• Hazardous Substances Data Bank (HSDB);
• Registry of Toxic Effects of Chemical Substances (RTECS®);
• NIOSH Pocket Guide to Chemical Hazards;
• OSHA Chemical Sampling Information pages;
• IARC Monographs on the Evaluation of Carcinogenic Risks to Humans;
• NTP Annual Report on Carcinogens;
• TLVs and BEIs (ACGIH);
• Hawley's Condensed Chemical Dictionary, latest edition;
• Sax's Dangerous Properties of Industrial Materials, latest edition;
• Published literature; and
• Trade associations.

V. DATA ANALYSIS

The third step in the hazard determination process is data analysis. This step is the most demanding in terms of technical expertise. The HCS requires that chemical manufacturers and importers conduct a hazard determination to determine whether physical or health hazards exist. In some cases, especially for physical hazards, a definition in the HCS establishes the criteria to be followed. For example, if a liquid has a flashpoint below 100ºF, it is by definition a "flammable liquid". This type of procedure is a simple data analysis. You can look up the flashpoint in a standard reference and accept it at face value. In the event that your company is manufacturing or importing a chemical for which there is no information on the flashpoint, you may choose to determine the flashpoint by laboratory testing, but testing is not required by the HCS.

As a rule, the HCS attempts to minimize the burden of literature search and review while satisfying the need to provide information required to protect employees who are exposed to hazardous chemicals. For this reason, a suggested approach is to go to the most likely sources first to obtain the needed data, and then proceed to additional sources, if necessary.

For health hazards, explicit criteria are provided in the HCS for some health hazards. For example, criteria are given for classifying a chemical as highly toxic or toxic based on acute effects, and for designating a chemical as a carcinogen. For other health hazards, a simple generic requirement is provided for the determination of a specific health hazard. The HCS states that "evidence that is statistically significant and which is based on at least one positive study conducted in accordance with established scientific principles is considered to be sufficient to establish a hazardous effect if the results of the study meet the [HCS] definitions of health hazards. "

Let us examine this requirement further. There are three key criteria that must be met, namely "statistically significant", "positive study", and "established scientific principles". Thus, the evaluation of study results requires some knowledge of statistics, commonly accepted scientific test methodology, and the definitions of health hazards.

Statistical significance is a mathematical determination of the confidence in the outcome of a test. The usual criterion for establishing statistical significance is the p-value (probability value). A statistically significant difference in results is generally indicated by p<0.05, meaning there is less than a 5% probability that the toxic effects observed were due to chance and were not caused by the chemical. Another way of looking at it is that there is a 95% probability that the effect is real, i.e. , the effect seen was the result of the chemical exposure.

The other major measure of statistical significance is the 95% confidence level for a specific data point. Most reports of toxicity testing will include some information on the confidence in the data. For example, for a study with a stated confidence level of 95%, an LD50 with a listed value of 9.5 ± 1.2 indicates that if the same study were to be repeated many times, the LD50 would be expected to be within the range of 8.3 - 10.7 on 95 out of every 100 times.

Most toxicity and epidemiology reports will provide an analysis of the data and conclude whether the results were positive or negative, or will describe the adverse effects observed at specific dose levels. Positive results mean that the exposed humans or animals were more likely to develop toxic effects than the non-exposed population.

Hazard evaluation relies on professional judgment, particularly in the area of chronic hazards. The performance-orientation of the HCS does not diminish the duty of the chemical manufacturer, importer or employer to conduct a thorough evaluation, examining all relevant data and producing a scientifically defensible determination.

In the remainder of this section, an overview is presented of the HCS designated hazards and their definitions. In addition, a brief discussion is presented to further explain the specific hazard as well as procedures that can be used to analyze the data. Because this document can only present a limited discussion of the various hazards, you are encouraged to consult references that go into greater detail (see Appendix B of this document).

Physical Hazards

A chemical is a physical hazard if it:

• is likely to burn or support fire;
• may explode or release high pressures that can inflict bodily injury; or
• can spontaneously react on its own, or when exposed to water.

Fire Hazards

Combustible and Flammable Liquids

The ability of a chemical to either burn or support burning is a potentially disastrous physical hazard. The two primary measures of the ease with which a liquid will burn are the flashpoint and autoignition temperature. The flashpoint is the lowest temperature at which a liquid will emit sufficient vapors to form an ignitable mixture with air. In contrast, autoignition is the characteristic of a material in which it will spontaneously burn without the aid of an ignition source, such as a spark or flame. Many agents will burn when ignited whereas there are only a few that will spontaneously erupt into flames. While no single measure of flammability is sufficient for all purposes, the most commonly found measure in the literature is the flashpoint. For this reason, HCS uses flashpoint in classifying the fire hazard of a chemical.

Flammable liquids and combustible liquids are discussed together since flashpoint is the criterion for classification of both. The only difference between a "flammable" and "combustible" liquid is the relative ease (temperature) with which the substance burns or supports burning. The data analysis and hazard categorization are clear. For a pure chemical compound, the assignment to combustible or flammable liquid categories is quite simple:

• if the flashpoint is between 100ºF - 200ºF (37.8ºC - 93.3ºC), it is a combustible liquid;
• if the flashpoint is below 100ºF (38ºC), it is a flammable liquid.

The HCS definition for combustible liquid is "any liquid having a flashpoint at or above 100ºF (37.8ºC), but below 200ºF (93.3ºC), except any mixture having components with flashpoints of 200ºF (93.3ºC) or higher, the total volume of which makes up 99 percent or more of the total volume of the mixture. "

The HCS definition for flammable liquid is "any liquid having a flashpoint below 100ºF (37.8ºC), except any mixture having components with flashpoints of 100ºF (37.8ºC) or higher, the total of which make up 99 percent or more of the total volume of the mixture. "

You see that the HCS has made exceptions for chemical mixtures. A mixture will not be categorized as a combustible liquid so long as less than 1% of the total volume of components have flashpoints between 100º and 200ºF. For example, if Chemical A has a flashpoint of 180ºF and represents 0.5% of the mixture and all other chemicals have flashpoints above 200ºF, then the mixture is not considered a combustible liquid. Similarly, a mixture will not be categorized as a flammable liquid if it is composed of at least 99% (by volume) of components with flashpoints above 100ºF (38ºC). Many mixtures will contain more than 1% of a flammable liquid and the mixture will have a flashpoint above 100ºF. Where data indicating the flashpoint of a chemical are not available, you may choose to test the chemical to determine the flashpoint.

The HCS specifies that the testing should be conducted by one of the following methods:

(a) Tagliabue Closed Tester (see American National Standard Method of Test for Flash Point by Tag Closed Tester, Z11.24 1979 [ASTM D 56-79]).

(b) Pensky-Martens Closed Tester (see American National Standard Method of Test for Flash Point by Pensky-Martens Closed Tester, Z11.7-1979 ASTM D 93-79]).

(c) Setaflash Closed Tester (see American National Standard Method of Test for Flash Point by Setaflash Closed Tester [ASTM D 3278-78]).

If data are available that were derived from another testing method, a description of the method should be provided along with the results of the testing.

When a substance flashes, the resulting flame will spread through the vapor from the ignition source to the nearby surface of the liquid. From a practical viewpoint, a flammable liquid is potentially more hazardous than a combustible liquid. A flammable liquid presents a fire hazard if present in an open container near an ignition source in an environment in which the temperature is near or below normal room temperature. Examples of flammable liquids (with flashpoint temperatures) are: acetone (0ºF), ethyl ether (-49ºF), ethyl alcohol (55ºF), and gasoline (-45ºF). For a combustible liquid to present a fire hazard it must be above normal room temperature. Examples of combustible liquids are kerosene (100º-162ºF) and Stoddard solvent (102º-110ºF).

The lower flammability limit (LFL) is the minimal concentration of vapor below which combustion will not occur even in the presence of an external ignition source, whereas the upper flammability limit (UFL) is the maximum vapor concentration above which combustion cannot take place. To understand the concept, that at a certain concentration combustion will occur whereas it will not if the concentration is too low or too high, consider the carburetor of an automobile. The carburetor must be correctly adjusted so that the gasoline/air mixture is not too lean or too rich, or the gasoline/air vapor mixture will not burn in the automobile engine. Gasoline has an LFL of 1.4% and an UFL of 7.6%.

Flammable Aerosol

The HCS definition for flammable aerosol is "an aerosol that, when tested by the method described in 16 CFR 1500.45, yields a flame projection exceeding 18 inches at full valve opening, or a flashback (a flame extending back to the valve) at any degree of valve opening. "

The analysis as to whether the chemical is a flammable aerosol is more difficult and usually must be based upon laboratory testing of the aerosol as emitted from a pressurized container. In practice, most aerosols are mixtures, usually in air, and are primarily propellant formulations of droplets, particles, gases, and/or vapors. Their flammability is highly dependent on the nature of the propellant formulation. Therefore, data obtained from a literature search that does not pertain to the exact mixture of ingredients in the product may not be relevant when determining the flammability of the product. In the event that you choose to test a chemical product to determine if it is a flammable aerosol, the method described in 16 CFR 1500.45 should be used. A positive test is obtained if a flame is projected at least 18 inches at full valve opening, or if there is a flashback (i.e. , a flame extends back to the valve) at any degree of valve opening.

Flammable Gas

The HCS definition for flammable gas is "a gas that, at ambient temperatures and pressures, forms a flammable mixture with air at a concentration of less than thirteen (13) percent by volume; or forms a range of flammable mixtures with air wider than twelve (12) percent by volume. "

Thus, a gas can be categorized as flammable if the gas:

• burns in air at a concentration of less than 13%; or
• has an LFL of 13% or more with a concentration range for burning in air greater than 12%. The range is the difference between the LFL and the UFL.

Methane and butane are examples of flammable gases that burn at less than 13% concentration in air. Acetone is an example of a flammable liquid that volatilizes but does not represent a flammable gas. This is true because the LFL is 16% and the UFL is 25%, which is a range of only 9% (the definition requires a range of greater than 12%). On the other hand, ammonia is categorized as flammable since it has a LFL of 15% and an UFL of 28%, a range of 13%.

Flammable Solid

The HCS definition of a flammable solid is "a solid, other than a blasting agent or explosive as defined in [29 CFR] 1910.109(a), that is liable to cause fire through friction, absorption of moisture, spontaneous chemical change, or retained heat from manufacturing or processing, or which can be ignited readily and when ignited burns so vigorously and persistently as to create a serious hazard. A chemical shall be considered a flammable solid if, when tested by the method described in 16 CFR 1500.44, it ignites and burns with a self-sustained flame at a rate greater than one tenth of an inch per second along its major axis. "

The analysis as to whether a solid chemical will burn with such intensity to be classified as a flammable solid usually must be based upon the results of laboratory testing. If you choose to test a chemical to determine if it is a flammable solid, such testing should be conducted by the method described in 16 CFR 1500.44. A flammable solid can be ignited readily and then will burn so vigorously as to create a serious fire hazard. Blasting agents or explosives may be solids that burn but with an intensity so great that they are classified as explosives. An example of a flammable solid that can be ignited by friction is the chemical formulation on the head of matches. Some metal powders (such as magnesium) can react with moisture and burn and are thus classified as flammable solids.

Oxidizer

The HCS classifies a chemical as an oxidizer if it is a "chemical other than a blasting agent or explosive as defined in [29 CFR] 1910.109(a), that initiates or promotes combustion in other materials, thereby causing fire either of itself or through the release of oxygen or other gases. "

An oxidizing agent is a chemical or substance that brings about an oxidation reaction. The agent may provide the oxygen to the substance being oxidized (in which case the agent has to be oxygen or contain oxygen), or it may receive electrons being transferred from the substance undergoing oxidation (e.g. , chlorine is a good oxidizing agent for electron-transfer purposes, even though it contains no oxygen).

Oxidation materials can initiate or greatly accelerate the burning of fuels. The most common oxidizer is atmospheric oxygen. Oxygen-containing chemicals (e.g. , hydrogen peroxide and nitrous oxide) and halogens (e.g. , bromine, chlorine, and fluorine) can also be strong oxidizers. Some chemicals may be oxidizers with such an extremely fast burning potential that they are classified as explosives or blasting agents rather than oxidizers. Often the fact that a chemical possesses oxidizing potential can be determined by an examination of its chemical structure. For example, oxidizing substances usually include recognizable functional chemical groups, e.g. , perchlorate (ClO4-), chlorate (ClO3-), chlorite (ClO2-), hypochlorite (ClO-), peroxide (-O-O-), nitrate (NO3-), nitrite (NO2-), dichromate (Cr2O7), persulfate (S2O8), and permanganate (MnO4).

While the potential for oxidizing can often be inferred by chemical structure, absolute certainty can only be properly established in the laboratory since oxidation involves not only the oxidizing potential of the oxidizer, but also the chemical formulation of the fuel with which it comes in contact. Oxidizers are classified by comparison with the oxidizing properties of a standard test chemical, ammonium persulfate, applied to dry, conditioned sawdust. A solid that promotes combustion of the conditioned sawdust at a greater rate than ammonium persulfate is classified as an oxidizer.

Pyrophoric Hazards

The HCS definition for a pyrophoric chemical is "a chemical that will ignite spontaneously in air at a temperature of 130º F (54.4ºC) or below. " Fortunately, there are only a few chemicals that have the ability to catch fire without an ignition source when exposed to air. Many of these are elements (e.g. , lithium, powdered aluminum, magnesium) or organometallic compounds (such as lithium hydride, diethyl zinc and arsine). Moisture in the air often increases the probability of spontaneous ignition of pyrophoric materials.

Explosive Hazards

Compressed Gas

The HCS definition for Compressed Gas is:

(i) "a gas or mixture of gases having, in a container, an absolute pressure exceeding 40 psi at 70ºF (21.1ºC): or

(ii) a gas or mixture of gases having, in a container, an absolute pressure exceeding 104 psi at 130ºF (54.4ºC) regardless of the pressure at 70ºF (21.1ºC); or

(iii) a liquid having a vapor pressure exceeding 40 psi at 100ºF (37.8ºC) as determined by ASTM D-323-72. "

All compressed gases are potentially hazardous since they are under great pressure in a container. Accidental rupture of the container and the rapid release of the pressurized gas can result in injury to persons and damage to objects in the vicinity. Not only can the gas be released with great force, but the force of the release may propel the container for a long distance. In addition to the mechanical hazard from the pressure or propelled container, other hazards may exist from the released gas. The hazard from some compressed gases may be strictly mechanical (e.g. , compressed air), others may possess other types of hazards, such as being flammable (e.g. , methane and propane) or toxic (e.g. , ammonia and chlorine).

Explosive

The HCS definition for explosive is "a chemical that causes a sudden, almost instantaneous release of pressure, gas, and heat when subjected to sudden shock, pressure, or high temperature. "

Explosives are unstable materials and are of two types. One type consists of material capable of supersonic reactions (detonation), for example, nitroglycerine and TNT. The other type consists of materials (usually mixtures) that burn rapidly but at a subsonic rate. Examples of this type are gunpowder, rocket propellants, and pyrotechnic mixtures (fireworks). The difference between fire and explosion is the rate at which high temperature gases are produced and the physical containment of the burning gases. When high temperature gases build up extremely fast, there can be such a sudden release of energy from the gases that a shock wave or explosion is created. Confining the build-up of high pressure gases in a drum or vessel, which prevents venting of the gases, may promote an increase in the pressure within the restricted volume until an explosion occurs. Such is the principle behind some munitions, which confine high pressure gases until the pressure exceeds the strength of the casing.

Most explosives have a chemical structure that contains both oxidizing and fuel functional groups. Examples of functional groups contained in explosives are: azides, dizonium, and styphnate. While the presence of such functional groups suggests explosive potential, it is usually necessary to confirm this hazard via experimental studies.

Reactive Hazards

These reactive materials can cause damage to the human body by the release of gases that will burn, explode, or produce high pressure that can inflict injury to a person nearby. In some cases, the reactive materials may release substances that are considerably more toxic than themselves. HCS has defined three types of reactive hazards: organic peroxides, unstable (reactive) materials, and water-reactive materials. However, in addition to these three categories there are other types of reactive hazards that should be determined, especially those involving other organic heteroatomic bonds that may be unstable and chemicals that might be involved in slow decomposition processes that give rise to reactive materials or increased pressure in containment vessels.

While there are classes of chemicals that in themselves may be reactive, there are also stable chemicals which are not reactive but when combined may interact, resulting in an explosive reaction. Good sources for information about chemical interactions are Bretherick (1999), Sax (Lewis, 2004), and the U.S. Chemical Safety and Hazard Investigation Board (2002). Mixing incompatible materials may result in the formation of unstable/reactive materials; therefore, the literature search should document incompatible materials. In addition to discrete chemicals, it should be realized that certain dusts might be combustible and explosive, such as that produced by bakeries, sawmills, and in grain handling.

Organic Peroxide

The HCS definition for organic peroxide is "an organic compound that contains the bivalent -O-O structure and which may be considered a structural derivative of hydrogen peroxide where one or both of the hydrogen atoms has been replaced by an organic radical. "

The peroxide functional group (-O-O) is relatively unstable and most organic peroxides will spontaneously decompose at a slow rate. Some organic peroxides, however, are capable of very violent reactions with detonation at environmental temperatures, causing fires and explosions. Several organic peroxides are used in the plastics industry to initiate polymerization and serve as cross-linking agents. Recognizing an organic peroxide is quite simple - the presence of the peroxide group (-O-O) in its chemical structure. However, the characterization of the severity of the hazard is usually based upon fairly extensive laboratory testing. Examples of organic peroxides are benzoyl peroxide and allyl hydroperoxide.

Note: In addition to simple peroxide groups, other heteroatomic bonds may also be reactive, in particular -N-O- and -N-N- bonds, such as hydroxylamine, hydrazine, and their derivatives.

Unstable (Reactive) Material

The HCS definition for an unstable (reactive) material is a "chemical which in the pure state, or as produced or transported, will vigorously polymerize, decompose, condense, or will become self-reactive under conditions of shocks, pressure or temperature. "

The main difference between an unstable material and an explosive is the rate of the reaction. While the rate of reaction for unstable materials is less than that in the case of explosives, the unstable materials can still present a serious hazard due to the generation of high temperatures and pressures. In some cases, the reaction may be rapid enough to approach explosive potential.

Polymerization is a reaction in which small molecules (usually monomers) react with each other to form larger molecules (polymers). In the chemical process, a large amount of heat may be released. This raises the temperature of the monomer mixture that further accelerates the polymerization process until the reaction runs away or explodes.

Decomposition reactions can occur with many chemicals and mixtures. In this process, complex molecules dissociate to form simpler substances. This process may require input of heat or there may be a release of heat during the chemical reaction. The most hazardous reactions are those in which heat is released. If the reactions take place within a vessel, the high temperature may increase the vessel pressure to the point that it ruptures or explodes. Examples of unstable materials are acrylonitrile and butadiene.

It should be noted, however, that slower reactions such as slow decomposition processes may also create serious hazards. A number of such reactions have been observed by the U.S. Chemical Safety and Hazard Investigation Board (2002). Analyses of such reactions should be reviewed by those preparing MSDSs to gain an understanding of how such reactions can occur. The CSB and CCPS reports provide several examples of slow, oxygen-generating chemical reactions that may gradually produce a highly dangerous fuel-oxygen atmosphere, such as in a waste tank. Another example of a slow chemical reaction is with slow, endothelmic polymer decomposition reactions resulting in pressure build-up within enclosed tanks. The potential for decomposition reactions that might lead to production of an explosive substance should also be considered.

Water-Reactive Material

The HCS definition for water-reactive material is a "chemical that reacts with water to release a gas that is either flammable or presents a health hazard. "

Many chemicals fall in this category. For example, sodium and potassium, when exposed to water, will react and release hydrogen, presenting an explosive hazard. Carbides (e.g. , calcium carbide) can generate acetylene, a flammable gas, when exposed to water. In other cases, the gases released may be highly toxic, as in the case of cyanide that can be released when an inorganic salt containing cyanide (e.g. , potassium cyanide) comes in contact with water.

Health Hazards

To define with precision every possible health effect that can occur in the workplace as the result of chemical exposure is an unrealistic goal. There can be a variety of toxic effects on different organs, which may depend upon dose level, frequency, duration, and route of exposure. This does not negate the need for employees to be informed of such effects and be protected from them. The HCS provides a list of the most common health hazards. However, it should be stressed that the list does not include all health hazards.

Some of the health hazard definitions provide for an extremely precise testing procedure (e.g. , test species or weight range). This is because those test protocols had been codified in previous government regulations. However, other test methods have been developed and are acceptable for hazard determination. In view of this, Appendix A of the HCS indicates that if there are available scientific data that involve other animal species or test methods, they must also be evaluated to determine their applicability.

Assigning chemicals to discrete health hazard categories is not precise, and several schemes have been proposed. Separation into acute and chronic health hazards is used by the American National Standards Institute (ANSI) in its labeling standard (ANSI Z129.1) and its guidance for preparation of MSDSs (Z400.1-2004). The main difference between acute and chronic is related to duration of exposure and to the rapidity of onset after exposure.

In some exposure situations, the effects may occur rapidly after a single or short-term exposure (acute effects); in other cases, the damage may accumulate after multiple exposures or over a long exposure period, or arise long after earlier exposures (chronic effects). Examples of chronic effects are cancer and cirrhosis of the liver. A chemical may have the ability to cause both acute and chronic effects. For example, ethyl alcohol can cause death when consumed in large amounts at one time, birth defects when consumed for only a few days by a pregnant woman, and cirrhosis of the liver if consumed for several years. OSHA has listed a number of health hazards, some general or systemic (whole-body) effects, and others that are specific to certain organs (known as target organs).

Following is a brief description of the HCS identified health hazards. In many cases, the determination is based on data obtained from standard experiments with laboratory animals. Reliable human data are preferred to animal data. However, in many cases, reliable human data are not available, and animal data must be used. The search strategy previously discussed should attempt to obtain human data, animal data, and cell and tissue studies, as well as data on the mechanisms by which a chemical causes toxicity.

Systemic Effects

Carcinogens

Under the HCS, "a chemical is considered to be a carcinogen if:

(a) It has been evaluated by the International Agency for Research on Cancer (IARC), and found to be a carcinogen or potential carcinogen; or

(b) It is listed as a carcinogen or potential carcinogen in the Annual Report on Carcinogens published by the National Toxicology Program (NTP) (latest edition); or,

(c) It is regulated by OSHA as a carcinogen. "

A chemical classified by IARC in Group 1 (i.e. , the agent is carcinogenic to humans), Group 2A (i.e. , the agent is probably carcinogenic to humans) or Group 2B (i.e. , the agent is possibly carcinogenic to humans) or identified by NTP as being "known to be carcinogenic" or "reasonably anticipated to be carcinogenic" is considered a carcinogen under the HCS. In addition to the determinations of these organizations, all available scientific data on carcinogenicity must be considered. As with other health hazards, the results of any studies which are designed and conducted according to established scientific principles, and which report statistically significant conclusions regarding the carcinogenicity of a chemical, are sufficient for determining that the chemical is a carcinogen under the HCS. Some examples of workplace carcinogens are asbestos, benzene, hexavalent chromium, and vinyl chloride.

The simple definition of a carcinogen is "a substance that has the potential to cause cancer. " The terminology used to describe cancer may be confusing. Cancer is a type of tumor. A tumor (also known as a neoplasm) is simply an uncontrolled growth of cells. Tumors may be benign or malignant. Benign tumors grow only at the site of origin, and do not invade adjacent tissues or go to distant sites in the body (known as "metastasis"). Except for those that develop deep in vital organs (such as the brain), benign tumors can be successfully treated (usually by surgical removal) and the potential for causing death is low. Malignant tumors are cancers and can grow outside their original site in an organ, invade surrounding tissue, or metastasize to distant organs where they can start new growths of the cancerous tissue. Malignant tumors (cancer) are difficult to treat and frequently cause death of the patient.

Cancers vary greatly in type and behavior in the body. Some cancers grow slowly and rarely metastasize. Others are highly invasive and metastasize rapidly. Cancers are usually named for the specific cell type or organ of origination. For example, squamous cell carcinoma of the lung is a cancer that arose from a squamous cell in the lung. A hepatocellular carcinoma is a cancer arising from a liver cell (hepatocyte). Sometimes the name given to a cancer also reflects its nature. For example, chronic lymphocytic leukemia is a cancer involving lymphocytes (a type of blood cell) in which the leukemia is chronic or long-lasting in nature. OSHA, NTP, and IARC report the specific types of cancer caused by chemicals that they list.

Toxic Agents

The HCS classifies chemical agents as toxic or highly toxic based on the number of deaths that occur following brief (acute) exposure of rodents. The difference in the two categories is strictly the dose at which the toxicity (death) occurs. Exposure is by the three major workplace exposure routes, mouth (oral), skin (dermal), or breathing (inhalation). The analysis is based on the LD50 (median lethal dose by oral or dermal exposure) and LC50 (median lethal inhalation concentration for a one-hour exposure. The LD50 and LC50 represent the dose or concentration, respectively, at which 50% of the test animals (and supposedly humans) will be expected to die.

Under the HCS, a toxic chemical is "a chemical falling within any of the following categories:

(a) A chemical that has a median lethal dose (LD50) of more than 50 milligrams per kilogram but not more than 500 milligrams per kilogram of body weight when administered orally to albino rats weighing between 200 and 300 grams each.

(b) A chemical that has a median lethal dose (LD50) of more than 200 milligrams per kilogram but not more than 1,000 milligrams per kilogram of body weight when administered by continuous contact for 24 hours (or less if death occurs within 24 hours) with the bare skin of albino rabbits weighing between two and three kilograms each.

(c) A chemical that has a median lethal concentration (LC50) in air of more than 200 parts per million but not more than 2,000 parts per million by volume of gas or vapor, or more than two milligrams per liter but not more than 20 milligrams per liter of mist, fume, or dust, when administered by continuous inhalation for one hour (or less if death occurs within 1 hour) to albino rats weighing between 200 and 300 grams each. "

The following table illustrates how a chemical can be classified as a Highly Toxic or Toxic, depending on the results of the appropriate animal tests.

Remember the HCS instructions pertaining to whether a study is scientifically acceptable for hazard determination. While only one positive study is required, it must be:

• conducted in accordance with established scientific principles; and
• the results must be statistically significant.

As can be seen, the acute toxicity for a toxic agent is considerably less than with the highly toxic agents. For example, the break point for oral exposures is 50 mg/kg. Below 50 mg/kg, the chemical is highly toxic whereas if the LD50 is above 50 mg/kg, it is only toxic. Examples of highly toxic chemicals are parathion (with an oral rat LD50 of 2 mg/kg and a dermal LD50 of 22 mg/kg) and methyl isocyanate (with an inhalation one-hour LC50 in rats of 45 ppm). Examples of toxic chemicals are chloroform (with an LD50 of 140 mg/kg), acrylonitrile (with a 24-hour dermal LD50 between 200 and 2000 mg/kg), and ammonia (with an inhalation one-hour LC50 in rats between 200 ppm and 2000 ppm). Agents having an oral LD50 greater than 500 mg/kg are not classified as toxic. This does not mean that they do not represent a health hazard (e.g. , the chemical could present a chronic hazard, such as cancer or hepatotoxicity), but only that they are not classified as toxic under the HCS.

While these criteria are based on laboratory animals that are quite different than humans, the relative response between animals and humans is generally comparable on a per body weight basis. Thus, expressing the effect in terms of kilogram of body weight provides a satisfactory basis for determining potential human effects based on animal research results. Translating a 50 mg/kg LD50 to an understandable situation in humans, if a group of 150-pound humans ingested about one-half teaspoon of such a chemical, approximately 50% would be expected to die.

The HCS provides criteria for classifying chemicals as highly toxic and toxic based on experiments that used 200-300 gram albino rats or 2-3 kilogram albino rabbits. However, current testing procedures accept other species and do not prescribe exact weights. Although specific criteria are provided, the HCS also indicates that information pertaining to other species and test methods is also relevant. In determining hazards, you need to search for and analyze all data pertaining to toxicity and make judgments as to whether the tests were conducted using appropriate and accepted methodology. If the studies are acceptable, the data should be used as appropriate to determine whether the chemical is highly toxic, toxic, or belongs to another health hazard category (e.g. , hepatotoxicity or irritant).

Irritant

Under the HCS, an irritant is "A chemical, which is not corrosive, but which causes a reversible inflammatory effecton living tissue by chemical action at the site of contact. A chemical is a skin irritant if, when tested on the intact skin of albino rabbits by the methods of 16 CFR 1500.41 for four hours exposure or by other appropriate techniques, it results in an empirical score of five or more. A chemical is an eye irritant if so determined under the procedure listed in 16 CFR 1500.42 or other appropriate techniques. "

The difference between an irritant and a corrosive is the ability of the body to repair the tissue reaction. With irritants the inflammatory reaction can be reversed whereas with corrosive damage it is permanent or irreparable. The site of irritation is often the skin or eye but can also be any mucous membrane or other tissue that the chemical comes in contact with. This could include the mouth or throat if the irritant is swallowed, and the nose or lungs if the irritant is inhaled. If an immunologic mechanism (allergy) is responsible for the tissue reaction, the material will be classified as a sensitizer rather than an irritant. Examples of irritants are acetic acid, ammonia, and isopropyl alcohol. The standard toxicology test for inflammation consists of the application of a substance to the shaved skin of white rabbits. White rabbits have been widely used as the irritation is easy to detect and the results have been shown to be highly predictive of potential skin effects in humans. Data obtained with other strains or species can also be used in the determination of irritation potential.

Corrosive

The HCS definition for corrosive is "A chemical that causes visible destruction of, or irreversible alterations in, living tissue by chemical action at the site of contact. For example, a chemical is considered to be corrosive if, when tested on the intact skin of albino rabbits by the method described by the U.S. Department of Transportation in appendix A to 49 CFR part 173, it destroys or changes irreversibly the structure of the tissue at the site of contact following an exposure period of four hours. This term shall not refer to action on inanimate surfaces. "

Corrosion is manifested by ulcers, cell death, and scar formation. The site of a corrosive effect can be any place on the body that the chemical contacts. This is often the skin or eye but can also be any mucous membrane (such as the mouth or esophagus if swallowed and the nose and trachea if inhaled).

Generally speaking, corrosive materials have a very low pH (acids) or a very high pH (bases). Strong bases are usually more corrosive than acids. Examples of corrosive materials are sodium hydroxide (lye) and sulfuric acid.

The standard toxicology test for corrosivity uses white rabbits with the material applied to the shaved (but not damaged) skin. Experience has shown that results obtained with white rabbits are highly predictive of potential skin effects in humans. Corrosion determined using other species and procedures must also be considered in the decision as to classification as a corrosive.

Sensitizer

The HCS definition for sensitizer is "A chemical that causes a substantial proportion of exposed people or animals to develop an allergic reaction in normal tissue after repeated exposure to the chemical. "

A sensitizer (allergen) causes little or no reaction in man or test animals on first exposure. The problem arises on subsequent exposures when a marked immunological response occurs. The response is not necessarily limited to the contact site as it may be a generalized body condition. Skin sensitization is common in industry. Respiratory sensitization and generalized hyperallergy to a few chemicals has also been known to occur. Well-known examples of sensitizers are toluene diisocyanate, nickel compounds, and poison ivy.

Target Organ Effects

Hepatotoxin

The HCS definition for hepatotoxins is "chemicals which produce liver damage". Signs of hepatotoxicity may include jaundice and liver enlargement. Hepatotoxicity includes not only the liver but also the gallbladder and bile duct. The liver is particularly susceptible to foreign chemicals because of its large blood supply and the major role it plays in metabolism. These factors can result in exposure to high doses of a toxicant and the production and immediate exposure to potentially toxic metabolites.

The primary forms of hepatotoxicity are: chemical hepatitis (inflammation of the liver), fatty liver or steatosis (lipid accumulation in hepatocytes), hepatic necrosis (death of the hepatocytes), cholestasis (stoppage of bile flow and backup of bile salts in the liver), cirrhosis (chronic fibrosis, often due to alcohol), hypersensitivity (immune reaction resulting in hepatic necrosis) and hepatic cancer (cancer of the liver). Examples of hepatotoxins are arsenic, carbon tetrachloride, ethyl alcohol, halothane, and vinyl chloride.

Nephrotoxin

The HCS definition for nephrotoxins is "chemicals which produce kidney damage". Signs often include edema and proteinuria. The kidney is highly susceptible to toxicants for two reasons. There is a very high volume of blood flow through the kidney, and the kidney can filter large amounts of toxins that can concentrate in the kidney tubules. The kidney eliminates body wastes, maintains body levels of electrolytes and fluids, and produces special enzymes and hormones that regulate blood pressure, pH, calcium, and the production of red blood cells. Thus, the effects of nephrotoxicity are systemic in nature, such as hypertension, body fluid and electrolyte imbalance, and anemia. The primary forms of nephrotoxicity are nephritis (inflammation of the kidneys), glomerulonephritis (damage to the glomerulus portion of the nephron), and acute or chronic renal failure.

Examples of nephrotoxins are heavy metals (e.g. , chromium, lead, mercury, and uranium) and halogenated hydrocarbons (e.g. , carbon tetrachloride and chloroform). While some toxins cause acute effects, many exert their toxicity by long-term exposure at lower levels.

Neurotoxins

The HCS definition for neurotoxins is "chemicals which produce their primary toxic effects on the nervous system. " The nervous system directs many of the body's activities so that changes in the nervous system may be apparent throughout the body. Electrical impulses move through the body via neurons (nerve fibers). Toxins can damage cells of the central nervous system (brain and spinal cord) or the peripheral nervous system (nerves outside the central nervous system).

The primary types of neurotoxicity are: neuronopathies (neuron injury), axonopathies (axon injury), demyelination (loss of axon insulation), and interference with neurotransmission. Signs and symptoms of neurotoxicity include narcoses, behavioral changes, and decreases in motor function. Examples of neurotoxins are carbon disulfide, ethylene oxide, hexane, lead, and mercury.

Blood/Hematopoietic Toxin

Blood/hematopoietic toxins are also referred to as hemotoxins or hematotoxins. The HCS defines these chemicals as "Agents which act on the blood or hematopoietic system: Decrease hemoglobin function; deprive the body tissues of oxygen. "

While one might consider the blood and hematopoietic system as independent tissues, they are intimately related. The hematopoietic system gives rise to the blood elements (cells and platelets). Toxins can act at various points in the hematopoietic/blood system. Some affect the circulating blood elements, interfering with their function. Others damage the hematopoietic system and may prevent it from producing the blood elements.

The formed elements (cells and platelets) in the circulating blood are usually not directly affected by toxins. An exception are the red blood cells (erythrocytes). Several toxic agents can bind with the hemoglobin of the red blood cells and interfere with transport of oxygen to body tissues (hypoxia). Examples of chemicals that bind with hemoglobin and cause hypoxia, by interfering with the oxygen transporting capability of the blood, are carbon monoxide, sodium nitrite, and hydrogen sulfide. Cyanides also cause hypoxia by interfering with the tissue cell's ability to utilize oxygen.

The more common form of hemotoxicity results from chemicals acting directly on the hematopoietic tissues (blood-forming tissue). The primary effect is a decrease in formation of specific blood cells so that the number in the circulating blood is reduced, impairing their ability to function normally. For example, phenothiazine and anticonvulsant drugs can damage the bone marrow cells that give rise to the granuloctyes and decreased ability to fight infections. Aspirin and nitroglycerin can be toxic to megakaryocytes that produce blood platelets. The decrease in platelets impairs blood-clotting capability. Other toxins, e.g. , arsenic, benzene, and chlordane, can cause a decrease in the formation of all blood elements, a condition known as aplastic anemia. Cancer of the hematopoietic tissues (primarily acute myelogenous leukemia) also occurs due to exposure to some industrial chemicals and drugs,for example, benzene, chloramphenicol, and phenylbutazone.

Respiratory Toxin

The HCS definition for agents which damage the lung is "chemicals which irritate or damage pulmonary tissue. " These are commonly known as respiratory toxins. The primary function of the respiratory system is to deliver oxygen to the bloodstream and remove carbon dioxide from the blood. Thus, damage to the respiratory tissues interferes with blood/gas exchange that may cause serious malfunction of all tissues of the body, especially the brain and heart. Respiratory toxicity can occur in the upper respiratory system (nose, pharynx, larynx, and trachea) or in the lower respiratory system (bronchi, bronchioles, and lung alveoli). The primary types of respiratory toxicity are pulmonary irritation, asthma/bronchitis, reactive airway disease, emphysema, allergic alveolitis, fibrotic lung disease, pneumoconiosis, and lung cancer. Some exert their toxicity quickly (acute effects, such as pulmonary irritation) while others act over a long period to time (chronic effects, such as pulmonary fibrosis). Examples of respiratory toxins are asbestos, formaldehyde, ozone, nitrogen dioxide, and silica.

Reproductive Toxin

The HCS definition for reproductive toxins is "chemicals which affect the reproductive capabilities including chromosomal damage (mutations) and effects on fetuses (teratogenesis). " This definition is comprehensive and incorporates toxic effects on all elements of the process of reproduction, including damage to the germ cells of both males and females (sperm and ova).

Thus, a wide variety of effects can occur, including sterility, decreased libido, impotence, interrupted pregnancy (abortion, fetal death, or premature delivery), birth defects in the offspring, altered sex ratio and multiple births, chromosome abnormalities, childhood morbidity, and childhood cancer. Both male and female reproductive effects should be determined. Examples of reproductive toxins are lead and 1,2-Dibromo-3-chloropropane (DBCP). Reproductive toxicity can involve toxicant damage to either the male or female reproductive system. Those substances that can cause birth defects are referred to as teratogens.

The term developmental toxicity refers to adverse effects observed in the embryo, fetus or newborn. In testing, these reproductive effects are usually considered separately from those effects on an adult animal's capacity to successfully mate (fertility) and deliver and nurture offspring (perinatal and postnatal development and maternal function). Developmental toxicity can result from toxicant exposure to either parent before conception or to the mother and her developing embryo-fetus. The three basic types of developmental toxicity are: Embryolethality which is the failure to conceive, spontaneous abortion or stillbirth; embryotoxicity which is the growth retardation or delayed growth of specific organ systems, and teratogenicity which pertains to irreversible conditions that leave permanent birth defects in live offspring (e.g. , cleft palate, missing limbs).

Chemicals can cause developmental toxicity by two mechanisms. They can act directly on cells of the embryo causing cell death or cell damage that leads to abnormal organ development. A chemical might also induce a mutation in a parent's germ cell that is transmitted to the fertilized ovum. Some mutated fertilized ova develop into abnormal embryos.

Genetic toxicity has also been included in the HCS definition of reproductive toxins. Genetic effects result from damage to DNA and altered genetic expression. This process is known as mutagenesis. The genetic change is referred to as a mutation and the agent causing the change as a mutagen. There are three types of genetic change: Gene mutation is a change in DNA sequence within a gene. Chromosome aberrations are changes in the chromosome structure. Aneuploidy/polyploidy is an increase or decrease in the number of chromosomes

If the mutation occurs in a germ cell (sperm and ova) the effect can be heritable. There is no effect on the exposed person, rather the effect is passed on to future generations. If the mutation occurs in a somatic cell (all body cells except sperm and ova), it can cause altered cell growth (e.g. , cancer) or cell death (e.g. , teratogenesis) in the exposed person.

Cutaneous Hazard

The HCS definition for cutaneous hazards is "chemicals which affect the dermal layer of the body. " This overlaps to a certain extent with the previously described hazards, irritant and corrosive. However, here we are concerned only with effects of toxins on the skin. A variety of skin conditions can arise from exposure to toxic substances. Contact dermatitis or inflammation of the skin can be of two types, irritant dermatitis and allergic contact dermatitis. The basic inflammatory reaction is the same but the cause and progress of the dermatitis differs. With irritant dermatitis the effect is immediate without prior exposure, whereas the allergic dermatitis requires previous exposure with the development of allergy or sensitization. Contact dermatitis is common in industry and usually consists of redness (erythema), thickening and firmness of skin (induration), flaking (scaling), and blisters (vesiculation). Normally, the contact dermatitis is reversible if the irritant or allergen is removed.

In contrast, chemical burns can sometimes occur in which immediate necrosis, ulceration, and sloughing of the skin occurs. This injury may be permanent and can leave deep wounds that scar or require transplanted skin to repair the damaged area. Some chemicals can cause irritation by defatting of the skin; for example, commonly used ketones or chlorinated compounds, such as the solvents trichloroethylene, methylene chloride, and gasoline.

Cutaneous hazards may cause skin reactions that are neither irritation or allergic reactions. Oils and halogenated aromatic hydrocarbons can cause acne, mercury and lead can cause increased pigmentation of the skin, hydroquinone can cause decreased pigmentation, and skin cancer can be induced by workplace exposure to arsenic.

Eye Hazard

The HCS definition for eye hazards is "chemicals which affect the eye or visual capacity. " The primary toxic effects from direct exposure of chemicals to the eye are conjunctivitis or corneal damage. Conjunctivitis is inflammation of the conjunctiva, the delicate membrane that lines the eyelids and covers the eyeballs. The cornea is the transparent front surface of the eyeball.

Chemicals that accidentally splash onto the face can directly contact either of these eye structures. Acids and strong alkalis (such as lye) may cause severe corneal corrosion and may result in permanent blindness. Organic solvents (such as acetone) and detergents can cause temporary clouding of vision, primarily due to dissolving of fats from the cornea.

Some chemicals can cause toxic effects to the eye even if they do not directly contact the eye. Chemicals that are inhaled or ingested may move to the eye through the blood circulation and produce eye damage. 2-4-Dinitrophenol (a wood preservative) can cause cataracts after ingestion. The ingestion of thallium salts (found in some pesticides) and methanol (wood alcohol) has been associated with blindness due to damage to the optic nerve. Retina damage has been associated with exposures to arsenicals and carbon disulfide.

While animal ocular tests are routinely conducted during the safety testing of new chemicals, detection of damage to the optic nerve and retina are difficult to detect. Unfortunately, this information results from case reports of humans exposed to toxic substances. Irritation and corrosion may be predicted on the basis of the pH of the chemical substance. However, pH has little value in predicting other types of ocular toxicity.

Other Types of Target Organ Hazards

As previously indicated, the HCS does not identify all possible target organ effects due to exposure to toxic agents. Certain chemicals may target one or more specific organs not listed in the HCS. Based on the chemistry of the toxin and how it is metabolized and distributed in the body, virtually any organ or organ system may potentially be at risk. Therefore, data found in the literature search pertaining to other organs must also be evaluated and documented. Of the other important health hazards listed in Table 2, effects on the cardiovascular system and immune system are most likely to be reported for industrial chemicals.

Cardiovascular toxicity has been reported for several industrial chemicals. The effects on the heart are primarily interference with cardiac nerve transmissions or damage to the heart musculature (cardiomyopathy). Either type of effect can prevent the heart from contracting (beating) normally so that the blood is not adequately circulated through the body, resulting in multiple organ damage and dysfunction. Some chemicals can also affect the circulatory vessels (veins, arteries and capillaries). Examples of cardiovascular toxins are ethanol and cobalt (cardiomyopathy); arsenic (arteriosclerosis and vascular lesions); toluene and halogenated alkanes (arrhythmias); and mercury (aortic lesions).

Toxicity to the immune system can lead to several different effects, depending on which cells are damaged, and whether the toxic effects are due to impairment of the immune system (immunosuppression) or the effects are caused by an altered or enhanced immune system (e.g. , allergy/hypersensitivity and autoimmunity). A wide variety of industrial chemicals are known to be immunotoxins, including toluene diisocyanate, formaldehyde, silicone, benzene, heavy metals, halogenated aromatic hydrocarbons, and insecticides.

VI. DOCUMENTATION

The fourth and final step in the hazard determination process is very important. All the other steps will be wasted if you do not document your findings carefully. If a chemical is found to be hazardous, it is recommended that the findings be documented in order to assist in preparing labels and MSDSs, and to maintain a record for future reference and updating. In addition, the HCS requires data documentation of the hazard determination as follows:

Chemical manufacturers, importers, or employers evaluating chemicals shall describe in writing the procedures they use to determine the hazards of the chemical they evaluate. The written procedures are to be made available, upon request, to employees, their designated representatives, the Assistant Secretary and the Director [OSHA and NIOSH officials]. The written description may be incorporated into the written hazard communication program required under paragraph (e) of this section [the HCS].

To meet the HCS requirements, it is recommended that a structured approach to data retrieval and compilation be adopted. This structured approach applies to preparation of MSDSs and labels.

Compilations of four types of data are considered essential:

• Initial chemical inventory;
• Description of procedures used for hazard determination;
• Specific data retrieved for each chemical; and
• Hazardous chemicals list.

Chemical Inventory

The chemical inventory should consist of all chemicals that are produced, imported, or used by the company. The chemical inventory should be complete and contain, at a minimum, the following:

• chemical name;
• CAS Number;
• common name;
• synonyms;
• product/mixture name (if applicable); and
• percentage of ingredients in product/mixture (if applicable).

It is recommended that this chemical inventory be computerized for future sorting, additions, deletions, and status reports.

Description of Procedures Used for Hazard Determination

As indicated previously, the procedures used to determine hazards of chemicals are to be written down and made available upon request to employees as well as to OSHA and NIOSH officials. This written description of procedures should be incorporated into the company's written hazard communication program.

The procedures used for the following hazard determination steps should be described in detail:

• Development of chemical inventory;
• Search strategy and sources used to obtain data on chemicals for which hazard determinations are conducted;
• References retrieved and used to identify each specific physical or health hazard;
• Summary for each retrieved reference that contained relevant data (retrieved computer abstracts can be used);
• Summary of important data that were used for hazard determination; and
• Identification of hazards.

Specific Data Retrieved for Each Chemical

It is recommended that data be organized so as to facilitate the preparation of MSDSs and labels. Listing all the hazard categories and the relevant data obtained for each hazard will also facilitate the gathering of data and document the effectiveness and completeness of the hazard determination process. When data are not located for a specific type of hazard or when a specific hazard would not occur due to the chemical or physical form of the chemical, this should be indicated.

The retrieved data should be listed in the basic format of the MSDS in order to facilitate preparation of MSDSs and labels, as well as to allow for future updating as the need arises. It is highly recommended that the data be computerized and archived in a secure location for future use. A commonly used title for hazard data compilations for specific chemicals is hazards profile. A suggested organization for the documentation is provided in Table 3.

Table 3. LIST OF DATA RECOMMENDED FOR INCLUSION IN THE HAZARDS PROFILE FOR A CHEMICAL

(Reference source should be included for each item, where appropriate. In the event that no information on an item is known or it is not applicable, this should be so indicated. )

COMPANY INFORMATION

• Company Name
• Name of Responsible Company Official
• Date Prepared

HAZARDOUS INGREDIENTS/IDENTITY INFORMATION

• Chemical Name
• CAS Number
• Common Name
• Synonyms
• Product/Mixture Name (If Applicable)
• Percentage of Ingredients in Product/Mixture (If Applicable)

PHYSICAL/CHEMICAL CHARACTERISTICS

• Boiling Point
• Freezing Point
• Vapor Pressure (mm Hg. )
• Vapor Density (air = 1)
• Specific Gravity (H2O = 1)
• Melting Point
• Evaporation Rate (Butyl Acetate = 1)
• Solubility in Water
• Appearance and Odor

FLAMMABILITY/EXPLOSIVITY DATA

• Autoignition Temperature
• Flammable Range
• Flashpoint (indicate method used)
• Lower Explosive Limit (LEL)
• Upper Explosive Limit (UEL)
• Extinguishing Media
• Special Fire Fighting Procedures
• Unusual Fire and Explosion Hazards
• Extinguishant

REACTIVITY DATA

• Stability - conditions to avoid
• Incompatibilities - materials to avoid
• Hazardous Decomposition or Byproducts
• Hazardous Polymerization - conditions to avoid

SUMMARY of Physical/Chemical Information

• Chemical/Product Identity Information
• List of Potentially Hazardous Properties
• Description of controls that should be employed

HEALTH HAZARD DATA

• Routes of Entry
• Odor Threshold
• Government Exposure Regulations and Guidance
  • OSHA PEL
  • ACGIH TLV
  • NIOSH IDLH
  • NIOSH REL
• Cancer Classifications:
  • OSHA
  • NTP
  • IARC

SUMMARY of Known or Suspected Health Effects

Systemic Effects

• Carcinogen
• Toxic
• Highly toxic
• Irritant
• Corrosive
• Sensitizer

Target Organ Effects

• Hepatotoxicity
• Nephrotoxicity
• Neurotoxicity
• Blood/hematopoietic toxicity
• Respiratory toxicity
• Reproductive effects
• Cutaneous hazard
• Eye hazard

Other Important Health Effects

• Cardiovascular toxicity
• Immune toxicity
• Others

APPENDIX A
GLOSSARY OF TERMS AND DEFINITIONS

The following glossary presents brief explanations of acronyms and common terms used in this document.

Absorbed Dose. The amount of a substance that actually enters into the body, usually expressed as milligrams of substance per kilogram of body weight (mg/kg).

ACGIH. The American Conference of Governmental Industrial Hygienists is an organization of government and academic professionals engaged in occupational safety and health programs. ACGIH establishes recommended occupational exposure limits for chemical substances and physical agents known as Threshold Limit Values; see TLV.

Acid. A compound that undergoes dissociation in water with the formation of hydrogen ions. Acids have pH values below 7 and will neutralize bases or alkaline media. Acids will react with bases to form salts. Acids have a sour taste and with a pH in the 0 to 2 range cause severe skin and eye burns.

Acute Dose. The amount of a substance administered or received over a very short period of time (minutes or hours), usually within 24 hours.

Acute Toxicity. The toxic effects resulting from a single dose or short exposure to a substance.

Alkali. (Also referred to as a base) - A compound that has the ability to neutralize an acid and form a salt. Alkali also forms a soluble soap with a fatty acid. Alkalis have pH values above 7 to 14. They are bitter in a water solution. Alkalis with pH values between 12 to14 are considered to be corrosive (caustic) and will cause severe damage to the skin, eyes and mucous membranes. Common strong alkalis are sodium and potassium hydroxide.

Allergic Reaction. An abnormal immunologic response in a person who has become hypersensitive to a specific substance. Some forms of dermatitis and asthma may be caused by allergic reactions to chemicals.

ANSI. The American National Standards Institute is a privately funded, voluntary membership organization that identifies industrial and public needs for national consensus standards and coordinates development of such standards.

ASTM. The American Society for Testing and Materials develops voluntary consensus standards for materials, products, systems, and services. ASTM is a resource for sampling and testing methods, information on health and safety aspects of materials, safe performance guidelines, and effects of physical agents, biological agents, and chemicals.

Autoignition Temperature. The lowest temperature at which a flammable gas or vapor-air mixture will spontaneously ignite without spark or flame. Vapors and gases will spontaneously ignite at a lower temperature in oxygen than in the air. The autoignition temperature may also be influenced by the presence of catalytic substances. Materials should not be heated to greater than 80% of the autoignition temperature.

Benign. Not recurrent or not tending to progress; not cancerous.

Boiling Point (BP). The temperature at which a liquid changes to a vapor state, at a given pressure; usually expressed in degrees of Fahrenheit or Centigrade at sea level pressure (760 mm Hg or one atmosphere). Flammable materials with low boiling points generally present special fire hazards.

CAS Number. A number assigned to a specific chemical by the Chemical Abstracts Service, an organization operated by the American Chemical Society. CAS Numbers are used internationally to identify specific chemicals or mixtures.

Carcinogenicity. The complex process whereby normal body cells are transformed to cancer cells.

cc. Cubic centimeter is a volume measurement in the metric system that is equal in capacity to one milliliter (ml). One quart is approximately 946 cubic centimeters.

CFR. Code of Federal Regulations. A collection of the regulations that have been promulgated under United States Law.

Chemical Name. The name given to a chemical in the nomenclature system developed by the International Union of Pure and Applied Chemistry (IUPAC) or the Chemical Abstracts Service (CAS) or a name which will clearly identify the chemical for hazard evaluation purposes.

Chronic Toxicity. Adverse effects resulting from repeated doses or exposures to a substance over a relatively prolonged period of time.

Decomposition. Breakdown of a material or substance into simpler substances by heat, chemical reaction, electrolysis, decay, or other processes

Dermal. Relating to the skin.

DNA. Deoxyribonucleic acid; the molecules in the nucleus of the cell that contain genetic information.

Dose. The amount of a substance received at one time. Dose is usually expressed as administered or absorbed dose (e.g. , milligrams material/kilogram of body weight).

DOT. U.S. Department of Transportation; the Federal agency that regulates transportation of chemicals and other hazardous and non-hazardous substances.

Epidemiology. The branch of science concerned with the study of human disease in specific populations, in order to develop information about the causes of disease and identify preventive measures.

Evaporation Rate. The ratio of the time required to evaporate a measured volume of a liquid to the time required to evaporate the same volume of a reference liquid (butyl acetate, ethyl ether) under ideal test conditions; The higher the ratio, the slower the evaporation rate. The evaporation rate can be useful in evaluating the health and fire hazards of a material.

Explosive Limits. The range of concentrations of a flammable gas or vapor (percent by volume in air) in which explosion can occur if an ignition source is present. Also see Flammable Limits, LEL, and UEL.

Flammable. A material which is easily ignited and burns with extreme rapidity. The two primary measures of this physical hazard are the flashpoint and the autoignition temperature. For specific information on the definition and test methods of flammable materials, refer to 29 CFR 1910.1200. Also see: Flammable Aerosol, Flammable Gas, Flammable Liquid, and Flammable Solid.

Flammable Aerosol. An aerosol that, when tested by the method described in 16 CFR 1500.45, yields a flame projection exceeding 18 inches at full valve opening, or a flashback (a flame extending back to the valve) at any degree of a valve opening.

Flashback. Occurs when flame from a torch burns back into the tip, the torch, or the hose. It is often accompanied by a hissing or squealing sound with a smoky or sharp-pointed flame.

Flashpoint. The minimum temperature at which a liquid gives off a vapor in sufficient concentration to form an ignitable mixture in air or oxygen. There are several flash point test methods, and flash points may vary for the same material depending on the method used, so the test method is indicated when the flash point is given. See 29 CFR 1910.1200(c) for further information.

Genetic. Pertaining to or carried by genes; hereditary.

Hazard. The inherent capacity of a substance to cause an adverse effect.

IARC. International Agency for Research on Cancer, a component of the World Health Organization, located in Lyon, France.

Ignitable. A solid, liquid or compressed gas which is capable of being set afire.

In Vitro. Outside a living organism (e.g. , in a test tube).

Inhalation. Breathing in of a substance in the form of a gas, vapor, fume, mist, or dust.

Latency Period. The time that elapses between exposure and the first manifestations of disease or illness.

LC50 - Lethal Concentration 50, Median Lethal Concentration. The calculated concentration of a material in air, which based on laboratory tests (respiratory route) is expected to kill 50% of a group of test animals when administered as a single exposure in a specific time period, usually 1 hour. The LC50 can be expressed in several manners:

• as parts of material per million parts of air by volume (ppm) for gases and vapors,
• as micrograms of material per liter of air (mg/l), or
• as milligrams of material per cubic meter of air (mg/m3) for dusts and mists, as well as for gases and vapors.

LD50 - Lethal Dose 50, Median Lethal Dose. The estimated single dose of material which, based on laboratory tests, is expected to kill 50% of a group of test animals. The material may be administered orally or applied to the skin. The LD50 dose is usually expressed as milligrams or grams of material per kilogram of animal body weight (mg/kg or g/kg).

LEL or LFL - Lower Explosive Limit or Lower Flammable Limit. Lowest concentration of the substance in air (usually expressed in percent by volume) that will produce a flash or fire when an ignition source (heat, electric arc, or flame) is present. At concentrations lower than the LEL, propagation of a flame will not occur in the presence of an ignition source. Also see UEL.

m3. Cubic meter; a metric measure of volume, approximately 35.3 cubic feet or 1.3 cubic yards.

Malignant Tumor. A tumor that can invade surrounding tissues or metastasize to distant sites resulting in life-threatening consequences.

Melting Point. The temperature at which a solid substance changes to a liquid state.

Metabolism (biotransformation). The conversion of a chemical from one form to another within the body.

Metabolite. A chemical produced during metabolism.

mg/kg. Milligrams of substance per kilogram of body weight, commonly used as an expression of toxicological dose (e.g. , 15 mg/kg).

mg/m3. Milligrams per cubic meter; a unit for measuring concentrations of particulates or gases in the air (a weight per unit volume). For example, 20 mg/m3.

milligram (mg). The most commonly used unit of measure in medicine and toxicity consisting of one thousandth of a gram (1x10-3 g).

Mixture. Any combination of two or more substances, if the combination is not, in whole or part, the result of chemical reaction.

ml. Milliliter; a metric unit of volume. There are 1,000 milliliters in one liter. 1 teaspoon = 5 milliliters.

Mutagen. A substance or agent capable of altering the genetic material in a living cell (mutation).

NFPA. The National Fire Protection Association is an international membership organization which promotes fire protection and prevention and establishes safeguards against loss of life and property by fire.

NIOSH. The National Institute for Occupational Safety and Health is a part of the Centers for Disease Control and Prevention, U.S. Public Health Service, U.S. Department of Health and Human Services.

NTP. The National Toxicology Program is a component of the U.S. Public Health Service. The NTP publishes the Annual Report on Carcinogens.

Odor Threshold. The lowest concentration of a substance in air that can be detected by smell.

Oxidation. A change in a chemical characterized by the loss of electrons. In a literal sense, oxidation is a reaction in which a substance combines with oxygen.

PEL - Permissible Exposure Limit. A legally enforceable occupational exposure limit established by OSHA, usually measured as an eight-hour time-weighted average, but also may be expressed as a ceiling concentration exposure limit.

ppm. Parts per million; the proportion (by volume) of a gas or vapor per million parts of air; also the concentration of a chemical in a liquid or solid form.

Reactivity. A substance's susceptibility to undergo a chemical reaction or change that may result in dangerous side effects, such as an explosion, burning, and corrosive or toxic emissions.

Risk. The probability that an adverse effect will occur.

Solubility. The ability of a substance to be dissolved in a solvent. Solubility is expressed according to the solvent (e.g. , solubility in water, solubility in acetone, etc. ).

STEL. Short-Term Exposure Limit (ACGIH terminology); see TLV.

Synonym. Another name or names by which a material is known. Methyl alcohol, for example, is also known as methanol or wood alcohol.

Target Organ. An organ on which a substance exerts a toxic effect.

Teratogen. A substance that can cause malformations or alterations in the appearance or function of a developing embryo.

TLV - Threshold Limit Value. The occupational exposure limit published by the American Conference of Governmental Industrial Hygienists (ACGIH). ACGIH expresses Threshold Limit Values in four ways:

• TLV-TWA: The allowable Time-Weighted Average - A concentration for a normal 8-hour workday or 40-hour workweek.
• TLV-STEL: Short-Term Exposure Limit - A maximum concentration for a continuous 15-minute exposure period (maximum of four such periods per day, with at least 60 minutes between exposure periods, and provided the daily TLV-TWA is not exceeded).
• TLV-C - Ceiling limit - A concentration that should not be exceeded even instantaneously.
• TLV-Skin - The skin designation refers to the potential contribution to the overall exposure by the cutaneous route, including mucous membranes and the eye. Exposure can be either by airborne or direct contact with the substance. This designation indicates that appropriate measures should be taken to prevent skin absorption.

Toxic Substance. Any substance that can cause injury or illness, or which is suspected of being able to cause injury or illness under some conditions.

Toxicity. A relative property of a chemical agent that refers to a harmful effect on some biological mechanism and the conditions under which this effect occurs.

Toxicology. The study of the harmful interactions of chemicals on living organisms and biological systems.

Trade Name. The trademark name or commercial trade name for a material or product.

TWA. Time-Weighted Average; the concentration of a material to which a person is exposed, averaged over the total exposure time-generally the total workday (8 to12 hours); also see TLV.

UEL or UFL. Upper explosive limit or upper flammable limit; the highest concentration of a vapor or gas (highest percentage of the substance in air) that will produce a flash of fire when an ignition source (e.g. , heat, arc, or flame) is present. At higher concentrations, the mixture is too "rich" to burn; also see LEL.

Unstable. Tending toward decomposition or other unwanted chemical change during normal handling or storage.

Vapor density. The weight of a vapor or gas compared to the weight of an equal volume of air is an expression of the density of the vapor or gas. Materials lighter than air (e.g. , acetylene, methane, hydrogen) have vapor densities less than 1.0. Materials heavier than air (e.g. , propane, hydrogen sulfide, and ethane) have vapor densities greater than 1.0. All vapors and gases will mix with air, but the lighter materials will tend to rise and dissipate (unless confined). Heavier vapors and gases are likely to concentrate in low places along or under floors, in sumps, sewers, manholes, trenches, and ditches where they may create fire or health hazards.

Vapor pressure. Pressure exerted by a saturated vapor above its liquid in a closed container. Three facts are important to remember:

• Vapor pressure of a substance at 100º F will always be higher than the vapor pressure of the substance at 68º F (20º C),
• Vapor pressures reported on MSDS/s in millimeters of mercury (mmHg) are usually very low pressures; 760 mmHg is equivalent to 14.7 pound per square inch (psi).
• The lower the boiling point of a substance, the higher its vapor pressure.

Volatility. The tendency or ability of a liquid or solid material to form a gaseous form at ordinary temperatures. Liquids such as alcohol and gasoline, because of their tendency to evaporate rapidly, are called volatile liquids.

APPENDIX B
Information Sources to Assist with Hazard Determination

This compilation is not intended to be a complete listing of the many literature sources and computerized databases that include information on the physical/chemical and health hazards of chemical substances. Researchers should conduct their own literature search and use the most recent editions of the literature, even though a date is provided in this list for some books and documents.

Documents and Books:

I. Sources for Specific Chemical Data:

A Comprehensive Guide to the Hazardous Properties of Chemical Substances, 2nd Edition. Pradyot Patnaik. Wiley & Sons, New York. 1999.

A Guide to Hazardous Materials Management. Physical Characteristics, Federal Regulations, and Response Alternatives. Aileen Schumacher. Greenwood Press, Westport, CT. 1988.

A Guide to OSHA Regulations on Storing and Handling Flammable and Combustible Liquids. Matthew M. Carmel. 1991.

ATSDR's Toxicological Profiles 2004 on CD-ROM. U.S. Public Health Service, Atlanta, Georgia, USA. 2005.

Bretherick's Handbook of Reactive Chemicals Hazards: An Indexed Guide to Published Data, 6th Edition. L. Bretherick, P. L. Urben, and M. Pitt. Butterworth-Heinemann, Boston. 1999. Also on CD-ROM.

Canadian Centre for Occupational Health and Safety (CCOHS). CD-ROMs containing the complete text of more than 80,000 MSDSs on chemical products contributed by over 600 manufacturers and suppliers.

Chemical Hazards in the Workplace. Ronald M. Scott. Lewis Publishers, Inc. , Chelsea, Michigan. 1989.

Chemical Reaction Hazards, 2nd Edition. John Barton and Richard Rogers. Gulf Professional Publishing. 1997.

Chemical Safety Manual for Small Business. American Chemical Society, Washington, D.C.

Chemically Induced Birth Defects, 2nd Edition. James L. Schardein. Marcel Dekker, Inc. , New York. 1993.

Chemistry of Hazardous Materials. 4th Edition. Eugene Meyer. Prentice-Hall, Inc. , Englewood Cliffs, NJ. 2005.

Clinical Toxicology of Commercial Products. Gleason, Gosselin, and Hodge. The Williams and Wilkins Co. , Baltimore. 1984.

Cooper's Toxic Exposures Desk Reference with CD-ROM. Andre R. Cooper, Sr, editor. CRC Press/Lewis Publishers, Inc. , Boca Raton, Florida. 1996.

CRC Handbook of Chemistry and Physics, 83rd Edition. David R. Lide, editor. CRC Press, Boca Raton, Florida. 2003. Also on CD-ROM.

Dangerous Properties of Industrial and Consumer Chemicals. Nicholas P. Cheremisinoff. Marcel Dekker, Inc. , New York. 1994.

Dictionary of Chemical Names and Synonyms. Philip H. Howard and Michael Neal. ACGIH Publication 9422. ACGIH, Cincinnati. 1992.

Dictionary of Toxicology. Robert A. Lewis, editor. Lewis Publishers, Inc. , Boca Raton, Florida. 1998.

Documentation of the Threshold Limit Values and Biological Exposure Indices, 7th Edition. ACGIH, Cincinnati. 2005.

Emergency Responder Training Manual for the Hazardous Material Technician. Center for Labor Education and Research. Van Nostrand Reinhold Co. , New York. 1992.

Emergency Response to Chemical Spills. W. Brock Neely. Lewis Publishers, Inc. , Boca Raton, Florida. 1992.

Emergency Response Guidebook (2004): A Guidebook for First Responders During the Initial Phase of a Hazardous Materials/Dangerous Goods Incident. DOT, Washington, DC. 2004.

Emergency Toxicology. Peter Viccellio, editor. Lippincott-Raven. 1998.

Encyclopedia of Toxicology. Second Edition. Philip Wexler, editor-in-chief. Elsevier Academic Press, San Diego. 2005.

Environmental and Occupational Medicine, 3rd Edition. William N. Rom, editor. Little, Brown and Co. , Boston. 1998.

Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Three volumes. Elsevier Science Publishing Co. , New York. 1992.

Explosives Identification Guide. Mike Pickett and Delmar Learning. 1998.

Fire Protection Guide to Hazardous Materials, 13th Edition. National Fire Protection Association (NFPA), Quincy, MA, USA. 2001.

General and Applied Toxicology, 2nd edition. Bryan Ballantyne, Timothy Marrs and Tore Syverson, editors. McMillan References, Ltd. , London. 1999.

Guide to Occupational Exposure Values. ACGIH, Cincinnati. 2005.

Guidelines for Safe Storage and Handling of Reactive Materials. Center for Chemical Process Safety (CCPS). American Institute of Chemical Engineering. 1995. Guidelines for Chemical Reactivity Evaluation and Application to Process Design. Center for Chemical Process Safety (CCPS), American Institute of Chemical Engineering. 1995.

Hamilton and Hardy's Industrial Toxicology, 5th Edition. Raymond D. Harbison. Mosby, Inc. , St. Louis. 1998.

Handbook of Chemical Health and Safety. Robert Alaimo, editor. 2001.

Handbook of Hazard Communication and OSHA Requirements. George G. Lowry and Robert C. Lowry. Lewis Publishers, Inc. , Chelsea, Michigan. 1988.

Handbook of Hazardous Chemical Properties. Nicholas P. Cheremisinoff. Butterworth-Heinemann. 2000.

Handbook of Hazardous Materials. Morton Corn. Academic Press, San Diego. 1993.

Handbook of Highly Toxic Materials Handling and Management. Stanley S. Grossel and Daniel A. Crowl, editors. Marcel Dekker, Inc. , New York. 1994.

Handbook of Industrial Toxicology, 3rd Edition. E.R. Plunkett, editor. Chemical Publishing Co. , Inc. , New York. 1987.

Handbook of Organic Solvent Properties. Ian Smallwood. Butterworth-Heinemann. 1996.

Handbook of Physical Properties of Organic Chemicals. Phillip H. Howard and William M. Meylan, editors. Lewis Publishers, Inc. 1997.

Handbook of Toxic and Hazardous Chemicals and Carcinogens, 4th Edition. Marshall Sittig. Noyes Data Corp. , Park Ridge, New Jersey. 2001.

Handbook of Toxicology, 2nd Edition. Michael J. Derelanko and Mannfred A. Hollinger. CRC Press. 2002.

Hawley's Condensed Chemical Dictionary, 14th Edition. Richard J. Lewis, editor. Van Nostrand Reinhold, New York. 2001.

Hazardous and Toxic Materials: Safe Handling and Disposal, 2nd edition. Howard Fawcett. 1988.

Hazardous Chemicals Desk Reference, 5th Edition. Richard J. Lewis, Jr. , John Wiley & Sons/Van Nostrand Reinhold, New York. 2002.

Hazardous Chemicals Handbook, 2nd Edition. P. Carson and C. J. Mumford. Butterworth-Heinemann. 2002.

Hazardous Industrial Chemicals - Material Safety Data Sheets - Preparation. ANSI Z400.1 Standard American National Standards Institute, Washington D.C. 2004.

Hazardous Materials Behavior and Emergency Response Operations. Denis Zeimet and David Ballard. ASSE. 2000.

Hazardous Materials Chemistry, 2nd Edition. A. Bevelacqua. 2005.

Hazardous Materials Chemistry for Emergency Responders: 2nd Edition. Robert Burke. 2002.

Hazardous Materials Handbook. Richard P. Pohanish and Stanley A. Greene, John Wiley & Sons. 1996.

Hazardous Materials Response Handbook, 2nd Edition. National Fire Protection Association. Quincy, Massachusetts. 1992.

Hazardous Materials Toxicology: Clinical Principles of Environmental Health. John B. Sullivan and Gary R. Krieger. William and Wilkins, Baltimore. 1992.

Hazardous Substances Resource Guide. Richard P. Pohanish and Stanley A. Green, editors. Gale Research, Inc. , Detroit. 1993.

Health Protection from Chemicals in the Workplace. P. Lewis. Englewood Cliffs, Prentice Hall, New Jersey. 1993.

IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. International Agency for Research on Cancer, WHO, Lyon, France.

Improving Reactive Hazard Management. U.S. Chemical Safety and Hazard Investigation Board, Report No. 2001-01-H. 2002.

Industrial Organic Chemicals, 2nd edition. Harold A. Wittcoff, Bryan Reuben, and Jeffery Plotkin. 2004.

Kirk Othmer Encyclopedia of Chemical Technology, Fifth edition. 15 volumes. Wiley-Interscience. 2005.

Material Safety Data Sheets. The Writer's Desk Reference. Richard P. Molinelli, Michael J. Reale, and Ralph I. Freudenthal, editors. Hill and Garnett Publishing, Inc. , Boca Raton, Florida. 1992.

MERCK Index. Full text of the printed edition. Gives concise information on over 10,000 chemicals.

MSDS Pocket Dictionary, 3rd edition. Genium Publishing. 1998.

NIOSH Pocket Guide to Chemical Hazards. National Institute for Occupational Safety and Health, U.S. Public Health Service. NIOSH Pub. 2005-151. U.S. Government Printing Office, Washington, D.C. 2005. Available online at

NIOSH/OSHA Occupational Health Guidelines for Chemical Hazards. Original plus 4 supplements. NIOSH/OSHA. 1981-1995.

NTP's Annual Report on Carcinogens. National Toxicology Program, Research Triangle Park, NC.

Occupational Health and Safety, 2nd Edition. Joseph LaDou, editor. National Safety Council, Chicago, Illinois. 1993.

Occupational Health Guidelines for Chemical Hazards. NIOSH/OSHA. NIOSH Pub. No. 81-123. 1981.

Occupational Health Risk Assessment and Management. Blackwell Science, Ltd. , Oxford, England. 1999.

Occupational Medicine, 3rd Edition. Carl Zenz, O. Bruce Dickerson and Edward P. Horvath, Jr. , Mosby - Year Book, Inc. , St. Louis. 1994.

Occupational Toxicology, 2nd edition. Neill H. Stacey and Chris Winder, editors. Taylor & Francis, Inc. , Bristol, Pennsylvania. 2002.

OSHA Technical Manual, 5th edition. OSHA. 1999.

Patty's Hygiene and Toxicology, 5th Edition, 13 Volume Set. Eula Bingham, Barbara Cohrssen, and Charles H. Powell. John Wiley & Sons, New York. 2001.

Patty's Industrial Hygiene and Toxicology, 5th edition. Robert Harris. John Wiley & Sons, New York. 2000.

Patty's Toxicology Mini Set Volume Two and Three - Metals. Eula Bingham and Barbara Cohrssen, editors. John Wiley & Sons, New York. 2001.

Patty's Toxicology, 8 Volume + Index Set. Eula Bingham, Barbara Cohrssen, and Charles H. Powell. 2001.

Proctor and Hughes' Chemical Hazards of the Workplace, 5th Edition. Gloria J. Hathaway and Nick H. Proctor. Van Nostrand Reinhold, New York. 2004.

Product Safety Management and Engineering, 2nd Edition. Willie Hammer. ASSE.

Rapid Guide to Chemical Incompatibilities. Richard Pohanish and Stanley Greene. 1997.

Rapid Guide to Hazardous Chemicals in the Workplace, 3rd Edition. Richard J. Lewis, Sr. , Van Nostrand Reinhold. 1994.

Recognition of Health Hazards in Industry, 2nd Edition. William A. Burgess. John Wiley and Sons, New York. 1995.

Reproductively Active Chemicals; A Reference Guide. Richard J. Lewis. Van Nostrand Reinhold, New York. 1997.

Sax's Dangerous Properties of Industrial Materials, 11th edition. 3 volume set. Richard J. Lewis. Wiley-Interscience. 2004.

Sittig's Handbook of Toxic and Hazardous Chemicals and Carcinogens, 4th edition. 2 Volume Set. Richard P. Pohanish, editor. Noyes Publications. 2002.

Storage and Handling of Petroleum Liquids, 3rd edition.Hughes, John R. , Center for Chemical Process Safety (CCPS), American Institute of Chemical Engineering. John Wiley & Sons. 1988.

The Chemistry of Explosives. Jacqueline Akhavan, Springer Verlag. 1998.

The Comprehensive Handbook of Hazardous Materials. H.L.A. Sacarello. Lewis Publishers, Inc. , Boca Raton, Florida. 1994.

The Merck Index: An Encyclopedia of Chemicals, Drugs and Biologicals, 13th Edition. Maryadele J. O'Neil, Ann Smith, Patricia, E. Heckelman, John R. Obenchain, Jo Ann R. Gallipeau , and Mary Ann D'Arecca, editors. Merck Co. 2001.

TLVs and BEIs (2006). ACGIH, Cincinnati. 2006.

Toxicology Desk Reference. The Toxic Exposure and Medical Monitoring Index, 5th edition. Robert P. Ryan and Claude E. Terry, editors. Taylor & Francis. 1999.

Toxicology of Industrial Compounds. Hemut Thomas, Robert Hess and Felix Waechter. Taylor & Francis, London. 1996.

Wiley Guide to Chemical Incompatibilities, 2nd Edition. Richard P. Pohanish and Stanley A. Greene. John Wiley & Sons. 2003.

II. Useful References on Principles and Procedures:

A Textbook of Modern Toxicology, 2nd Edition. Ernest Hodgson and Patricia E. Levi. McGraw-Hill Professional. 1997.

Basic Concepts of Industrial Hygiene. Ronald M. Scott. 1997.

Basic Environmental Toxicology. Lorris G. Cockerham and Barbara S. Shane. CRC Press, Boca Raton, Florida. 1994.

Basic Toxicology: Fundamentals, Target Organs, and Risk Assessment, 3rd Edition. Frank C. Lu. Taylor and Francis, Washington DC. 1996.

Casarett and Doull's Toxicology: The Basic Science of Poisons, 6th Edition. Louis J. Casarett, Curtis D. Klaasen, and John Doull, editors. McGraw-Hill Professional, New York. 2001.

Chemical Hazard Communication Guidebook, 2nd Edition. Andrew B. Waldo. McGraw Hill Book Company, Highstown, New Jersey. 1993.

Comprehensive Review in Toxicology, 2nd Edition. Peter D. Bryson. Aspen Publishers, Rockville, Maryland. 1989.

Comprehensive Toxicology. I. Glenn Sipes, A. Jay Gaddolfi, and Charlene A. McQueen, Elsevier Science. 1997.

Dictionary of Toxicology, 2nd edition. Ernest Hodgson, Richard Mailman, and Robert Dow. McMillan References, Ltd. London. 1998.

Essentials of Environmental Toxicology. W. William Hughes. Taylor and Francis, Washington D.C. 1996.

Fundamentals of Industrial Hygiene. Barbara A. Plog and Patricia J. Quinlan, Natl Safety Council. 2001.

Handbook of Chemical Industry Labeling. Charles J. O'Connor and Sidney I. Lirtzman, editors. Noyes Publications, Park Ridge, New Jersey. 1984.

Hazard Communication Compliance Manual - A User's Guide to OSHA's Hazard Communication Standard. J.C. Silk and M.B. Kent, editors. Society for Chemical Hazard Communication. The Bureau of National Affairs, Inc. , Washington D.C. 1995.

Industrial Toxicology. Phillip L. Williams and James L. Burson. Van Nostrand Reinhold, New York. 1989.

Information Resources in Toxicology, 3rd edition. P.J. Hakkinen, Gerald Kennedy, Frederick Stoss, and Philip Wexler, editors. Academic Press. 1999.

International Directory of Testing Laboratories, 1997 Edition. ASTM, West Conshohocken, Pennsylvania. 1997.

Loomis's Essentials of Toxicology, 4th Edition. Ted A. Loomis. Academic Press, San Diego, California. 1996.

Principles and Methods of Toxicology, 3rd Edition. A. Wallace Hayes, editor. Raven Press, New York. 1994.

Principles of Toxicology: Environmental and Industrial Applications, 2nd Edition. Phillip L. Williams, Robert C. James and Stephen M. Roberts, editors. 2000.

The Occupational Environment: Its Evaluation and Control. Second Edition. Salvatore R. Dinardi, editor. AIHA. 2003.

Toxicology. Thomas J. Haley and William O. Berndt, editors. Hemisphere Publishing Corp. , New York. 1988.

Toxicology: A Primer on Toxicology Principles and Applications. Michael A. Kamrin. Lewis Publishers, Inc. , Boca Raton, Florida. 1988.

III. Comprehensive Bibliographic and Factual Databases

Chemical Hazard Response Information System (CHRIS). This online database developed by the U.S. Coast Guard contains physical and chemical properties and health hazards for over 1,000 chemical substances. U.S. Coast Guard. Department of Transportation.

Chemical Information Systems (CIS). CIS is a collection of 33 databases from various sources like EPA, NIOSH, NLM that contains references to literature including: toxicological and/or carcinogenic research data; information on handling hazardous materials; chemical/physical property information; regulations; safety and health effects information; and pharmaceutical data. It is operated by the National Information Services Corporation (NISC USA), Baltimore, Maryland.

CHEMTREC Hazard Information Transmission. Chemical profiles represent a synthesis of information from reference materials and MSDSs submitted by industry. The database is for use of groups which respond to chemical emergencies.

Immediately Dangerous to Life or Health (IDLHs). The "immediately dangerous to life or health air concentration values (IDLHs)" are used by NIOSH as respirator selection criteria. They were first developed in the mid-1970s, and reviewed and revised in 1994. Available via NIOSH.

International Chemical Safety Cards (ICSCs). ICSC cards summarize essential health and safety information on chemicals for their use at the "shop floor" level by employees and employers in factories, agriculture, construction and other work places. The ICSCs project is an undertaking of the International Programme on Chemical Safety (IPCS). The U.S. version of the ICSCs has been modified by the National Institute for Occupational Safety and Health (NIOSH) to include the following: Occupational Safety and Health Administration Permissible Exposure Limits (OSHA PELs); National Institute for Occupational Safety and Health Recommended Exposure Limits (NIOSH RELs); IDLHs, and links to the NIOSH Pocket Guide to Chemical Hazards. Available via NIOSH.

• NIOSH Pocket Guide to Chemical Hazards (NPG). The NPG is intended as a source of general industrial hygiene information on several hundred chemicals/classes for employees, employers, and occupational health professionals. Available via NIOSH.

  Occupational Safety and Health Guidelines for Chemical Hazards. Summarizes information on permissible exposure limits, chemical and physical properties, and health hazards. It provides recommendations for medical surveillance, respiratory protection, and personal protection and sanitation practices for specific chemicals that have Federal occupational safety and health regulations. Available via NIOSH.

  Registry of Toxic Effects of Chemical Substances (RTECS®). This is an extensive chemical database originally developed and published by NIOSH that serves as an important reference for the identification of health hazards literature. It is now maintained and marketed by MDL Information Systems.

  TSCATS. An index of unpublished health and safety studies and test data for over 2,700 chemicals submitted to EPA under the Toxic Substances Control Act (TSCA).

  NLM Databases:

  • CCRIS. Chemical Carcinogenesis Research Information System - carcinogenicity, mutagenicity, tumor promotion, and tumor inhibition data provided by the National Cancer Institute (NCI). Contains coverage of literature on cancer research and testing from 1963 to the present.
  • ChemIDplus. This is an online data file of the NLM that contains names, synonyms, CAS registry numbers, and a locator for other databases that contain information for thousands of chemicals.
  • CHEMID/SUPERLIST. This file maintained by the NLM serves as a locator for NLM databases containing information for over 180,000 compounds. It also lists chemicals regulated by other government agencies.
  • DART. A bibliographic database covering teratology and other aspects of developmental and reproductive toxicology. Serves as a continuation of ETIC, below.
  • DERMAL. Contains toxic effects, absorption, distribution, metabolism, and excretion data related to dermal absorption of 650+ chemicals.
  • DIRLINE. A database containing information about information resource centers, primarily health and biomedical organizations.
  • EMIC. A bibliographic database on chemical agents that have been tested for mutagenic activity.
  • ETIC. A bibliographic database on chemical agents that have been tested for mutagenic activity.
  • GENETOX. Peer-reviewed mutagenicity test data from the Environmental Protection Agency (EPA).
  • ITER. Integrated search of any or all of the following databases: Hazardous Substances Data Bank (HSDB), Integrated Risk Information System (IRIS), International Toxicity Estimates for Risk (ITER), Chemical Carcinogenesis Research Information (CCRIS), and Genetic Toxicology (GENE-TOX).
  • IRIS. Integrated Risk Information System - data from the Environmental Protection Agency (EPA) in support of human health risk assessment, focusing on hazard identification and dose-response assessment.
  • Haz-Map. Haz-Map is an occupational health database designed for health and safety professionals and for consumers seeking information about the health effects of exposure to chemicals and biologicals at work.
  • Household Products. This database links over 5,000 consumer brands to health effects from Material Safety Data Sheets (MSDS) provided by the manufacturers and allows scientists and consumers to research products based on chemical ingredients.
  • HSDB. Hazardous Substances Data Bank. This is peer-reviewed database which contains chemical and physical properties for over 4,200 chemicals. It is available from the NLM.
  • PubMed/MEDLINE. Indexes articles from 3,200+ biomedical journals published in the U.S. and abroad. It is a major source of biomedical literature with coverage from 1966 to the present. Produced by the NLM.
  • TERIS. Produced by the University of Washington and deals with the risks of prenatal exposure to hazardous substances.
  • Toxicology Tutorials. Three college-level tutorials covering the principles of toxicology, toxicokinetics, and cellular toxicology.
  • TOXLINE. Contains comprehensive bibliographic coverage of toxicology information in published literature.
  • TRI. Toxics Release Inventory, an annual report of the EPA that estimates releases of toxic chemicals to the environment.

IV. Internet Access Addresses for Information or Publications Related to Chemical Hazards and HazCom:

American Conference of Governmental Industrial Hygienists (ACGIH)
American Industrial Hygiene Association (AIHA)
American Society of Safety Engineers (ASSE)
Canadian Centre for Occupational Safety and Health
Center for Chemical Process Safety
Center for Environmental and Regulatory Services
Environmental Protection Agency (EPA)
MSDSOnline.com
MSDSSearch.com
National Institute for Occupational Safety and Health (NIOSH)
National Library of Medicine (NLM) Data Bases
Occupational Safety and Health Administration (OSHA)
OSHA Occupational Chemical Database
Society for Chemical Hazard Communication (SCHC)
TOXTUTOR
U. Kentucky MSDS Locator

Trade Associations:

American Chemistry Council (ACC). Arlington, VA.
American Petroleum Institute (API). Washington D.C.
Chemical Producers and Distributors Association. Alexandria, VA.
National Safety Council.
Synthetic Organic Chemical Manufacturers Association (SOCMA). Washington D.C.

APPENDIX C
Materials Regulated by OSHA as Toxic and Hazardous Substances

29 CFR 1910, Subpart Z - Toxic and Hazardous Substances. Occupational Safety and Health Administration. This list may be updated periodically, so the most current list should be consulted.

2,4,5-T
2,4-D (Dichlorophenoxyacetic acid)
Acetaldehyde
Acetic acid
Acetic anhydride
Acetone
Acetonitrile
Acetylene tetrabromide
Acetylsalicylic acid (Aspirin)
Acrolein
Acrylamide
Acrylic acid
Aldrin
Allyl alcohol
Allyl chloride
Allyl glycidyl ether
Allyl propyl disulfide
alpha-Alumina
Aluminum metal
Aluminum, alkyls
Aluminum, pyro powders
Aluminum, soluble salts
Aluminum, welding fumes
2-Aminopyridine
Amitrole
Ammonia
Ammonium chloride fume
Ammonium sulfamate
sec-Amyl acetate
n-Amyl acetate
Aniline and homologs
Anisidine (o-, p- isomers)
Antimony
Antimony compounds
ANTU (alpha-Naphthyl thiourea)
Arsenic
Arsine
Atrazine
Azinphos-methyl
Barium
Barium sulfate
Barium, soluble compounds
Benomyl
Benzene
Benzoyl peroxide
Benzyl chloride
Beryllium
Beryllium compounds, n.o.s.
Bismuth telluride (Se doped)
Bismuth telluride, undoped
Borates, tetra, sodium salts, anhydrous
Borates, tetra, sodium salts, decahydrate
Borates, tetra, sodium salts, pentahydrate
Boron oxide
Boron tribromide
Boron trifluoride
Bromacil
Bromine
Bromine pentafluoride
Bromoform
Butadiene (1,3-Butadiene)
Butane
2-Butanone (Methyl ethyl ketone)
2-Butoxyethanol
n-Butyl acetate
tert-Butyl acetate
sec-Butyl acetate
Butyl acrylate
tert-Butyl alcohol
sec-Butyl alcohol
n-Butyl alcohol
tert-Butyl chromate
n-Butyl glycidyl ether (BGE)
n-Butyl lactate
Butyl mercaptan
Butylamine (n-)
o-sec-Butylphenol
p-tert-Butyltoluene
Cadmium
Cadmium fume
Calcium carbonate
Calcium cyanamide
Calcium hydroxide
Calcium oxide
Calcium silicate
Calcium sulfate
Camphor, synthetic
Caprolactam
Captafol (Difolatan)
Captan
Carbaryl (Sevin)
Carbofuran (Furadan)
Carbon black
Carbon dioxide
Carbon disulfide
Carbon monoxide
Carbon tetrabromide
Carbon tetrachloride
Carbonyl fluoride
Catechol (pyrocatechol)
Cellulose
Cesium hydroxide
Chlordane
Chlorinated camphene
Chlorinated diphenyl oxide
Chlorine
Chlorine dioxide
Chlorine trifluoride
1-Chloro-1-nitropropane
2-Chloro-6-(trichloromethyl)pyridine
Chloroacetaldehyde
alpha-Chloroacetophenone (Phenacyl chloride)
Chloroacetyl chloride
Chlorobenzene
o-Chlorobenzylidene malonitrile
Chlorobromomethane
Chlorodifluoromethane
Chlorodiphenyl (42% chlorine) (PCB)
Chlorodiphenyl (54% chlorine) (PCB)
Chloroform (Trichloromethane)
Chloropentafluoroethane
Chloropicrin
Chloropicrin/methyl chloride
beta-Chloroprene
o-Chlorostyrene
o-Chlorotoluene
Chlorpyrifos
Chromates
Chromic acid
Chromium
Chromium (III) compounds, soluble
Chromium insoluble salts
Clopidol
Coal dust (greater than or equal to 5% SiO2), respirable quartz fraction
Coal tar pitch volatiles
Cobalt carbonyl
Cobalt hydrocarbonyl
Cobalt metal, dust and fume
Copper
Copper dusts and mists
Cotton dust (raw)
Crag herbicide (Sesone)
Cresol, all isomers
Crotonaldehyde
Crotonaldehyde, (E)-
Crufomate
Cumene
Cyanamide
Cyanides
Cyanogen
Cyanogen chloride
Cyclohexane
Cyclohexanol
Cyclohexanone
Cyclohexene
Cyclohexylamine
Cyclonite
Cyclopentadiene
Cyclopentane
Cyhexatin
Decaborane
Demeton (Systox)
Di-sec octyl phthalate (Di-2-ethylhexyl-phthalate)
2,6-Di-tert-butyl-p-cresol
Diacetone alcohol (4-Hydroxy-4-methyl-2-pentanone)
Diazinon
Diazomethane
Diborane
Dibutyl phosphate
Dibutyl phthalate
2-N-Dibutylaminoethanol
Dichloro diphenyl trichloroethane (DDT)
1,1-Dichloro-1-nitroethane
1,3-Dichloro-5,5-dimethyl hydantoin
Dichloroacetylene
o-Dichlorobenzene
p-Dichlorobenzene
Dichlorodifluoromethane
1,1-Dichloroethane
Dichloroethyl ether
1,2-Dichloroethylene
Dichlorofluoromethane
1,3-Dichloropropene
2,2-Dichloropropionic acid
1,2-Dichlorotetrafluoroethane
Dichlorvos (DDVP)
Dicrotophos
Dicyclopentadiene
Dicyclopentadienyl iron
Dieldrin
Diethanolamine
Diethyl ketone
Diethyl phthalate
Diethylamine
2-Diethylaminoethanol
Diethylene triamine
Difluorodibromomethane
Diglycidyl ether (DGE)
Diisobutylketone
Diisopropylamine
Dimethyl 1,2-dibromo-2,2-dichloroethyl phosphate
Dimethyl acetamide
Dimethyl aniline (N,N-dimethylaniline)
1,1-Dimethyl hydrazine
Dimethyl phthalate
Dimethyl sulfate
Dimethylamine
Dimethylformamide
Dinitolmide (3,5-Dinitro-o-toluamide)
Dinitro-o-cresol
Dinitrobenzene (alpha-)
Dinitrobenzene (meta-)
Dinitrobenzene (para-)
Dinitrobenzene, all isomers
Dinitrotoluene
Dioxane (Diethylene dioxide)
Dioxathion (Delnav)
Diphenyl (Biphenyl)
Diphenylamine
Dipropyl ketone
Dipropylene glycol, methyl ether
Diquat
Disulfiram
Disulfoton
Diuron
Divinyl benzene
Emery
Endosulfan
Endrin
Epichlorohydrin
EPN
Ethanolamine
Ethion
2-Ethoxyethanol
2-Ethoxyethyl acetate (Cellosolve acetate)
Ethyl acrylate
Ethyl alcohol (Ethanol)
Ethyl amyl ketone (5-Methyl-3-heptanone)
Ethyl benzene
Ethyl bromide
Ethyl butyl ketone (3-Heptanone)
Ethyl chloride
Ethyl ether
Ethyl formate
Ethyl mercaptan
Ethyl silicate
Ethylacetate
Ethylamine
Ethylene chlorohydrin
Ethylene diamine
Ethylene dibromide (1,2-Dibromoethane)
Ethylene dichloride
Ethylene glycol
Ethylene glycol, dinitrate
Ethylidene norbornene
N-Ethylmorpholine
Fenaminphos
Fensulfothion (Dasanit)
Fenthion
Ferbam
Ferrovanadium dust
Fluorides
Fluorine
Fluorotrichloromethane (Trichlorofluoromethane)
Fonofos
Formaldehyde
Formamide
Formic acid
Furfural
Furfuryl alcohol
Gasoline
Germanium tetrahydride
Glutaraldehyde
Glycerin mist
Glycidol
Grain dust (oat, wheat, barley)
Graphite, natural
Graphite, synthetic
Gypsum
Hafnium
Heptachlor
Heptane (n-Heptane)
Hexachlorobutadiene
Hexachlorocyclo-pentadiene
Hexachloroethane
Hexachloronaphthalene
Hexafluoroacetone
n-Hexane
Hexane isomers
2-Hexanone (Methyl n-butyl ketone)
Hexone (Methyl isobutyl ketone)
sec-Hexyl acetate
Hexylene glycol
Hydrazine
Hydrogen bromide
Hydrogen chloride
Hydrogen cyanide
Hydrogen fluoride
Hydrogen peroxide
Hydrogen selenide
Hydrogen sulfide
Hydrogenated terphenyls
Hydroquinone
2-Hydroxypropyl acrylate
Indene
Indium
Indium compounds, n.o.s.
Iodine
Iodoform
Iron oxide fume
Iron salts (soluble)
Iron, pentacarbonyl-
Isoamyl acetate
Isoamyl alcohol (primary and secondary)
Isobutyl acetate
Isobutyl alcohol
Isooctyl alcohol
Isophorone
Isophoronediisocyanate
2-Isopropoxyethanol
Isopropyl acetate
Isopropyl alcohol
Isopropyl ether
Isopropyl glycidyl ether (IGE)
Isopropylamine
N-Isopropylaniline
Kaolin
Ketene
L.P.G. (liquified petroleum gas)
Lindane
Lithium hydride
Magnesite
Magnesium oxide fume
Malathion
Maleic anhydride
Manganese
Manganese cyclopentadienyl tricarbonyl
Manganese fume
Manganese tetroxide
Mercury
Mercury (organo) alkyl compounds
Mesityl oxide
Methacrylic acid
Methomyl (Lannate)
Methoxychlor
4-Methoxyphenol
Methyl 2-cyanoacrylate
Methyl acetate
Methyl acetylene (Propyne)
Methyl acetylene - Propadiene mixture (MAPP)
Methyl acrylate
Methyl acrylonitrile
Methyl alcohol
Methyl bromide (Bromomethane)
Methyl cellosolve (2-methoxyethanol)
Methyl cellosolve acetate (2-Methoxyethyl acetate)
Methyl chloride
Methyl chloroform (1,1,1-Trichloroethane)
Methyl cyclopentadienyl manganese tricarbonyl
Methyl demeton
Methyl ethyl ketone peroxide (MEKP)
Methyl formate
Methyl hydrazine (Monomethyl hydrazine)
Methyl iodide
Methyl isoamyl ketone
Methyl isocyanate
Methyl isopropyl ketone
Methyl methacrylate
Methyl n-amyl ketone
Methyl parathion
Methyl silicate
alpha-Methyl styrene
Methylal (Dimethoxymethane)
Methylamine
Methylcyclohexane
Methylcyclohexanol
o-Methylcyclohexanone
Methylene bis (4-cyclohexylisocyanate)
Methylene bisphenol isocyanate (MDI)
Methylene chloride
4,4'-Methylenebis (2-chloroaniline) (MBOCA)
Methylisobutyl carbinol
Methylmercaptan
Metribuzin
Mica
Molybdenum
Molybdenum insoluble compounds
Molybdenum soluble compounds
Monocrotophos (Azodrin)
Monomethylaniline
Morpholine
Naphtha (coal tar)
Naphthalene
Nickel
Nickel carbonyl
Nickel insoluble compounds
Nickel soluble compounds
Nicotine
Nitric acid
Nitric oxide
p-Nitroaniline
Nitrobenzene
p-Nitrochlorobenzene
Nitroethane
Nitrogen dioxide
Nitrogen trifluoride
Nitroglycerin
Nitromethane
2-Nitropropane
1-Nitropropane
o-Nitrotoluene
m-Nitrotoluene
p-Nitrotoluene
Nonane
Octachloronaphthalene
Octane
Oil mist, mineral
Osmium tetroxide
Oxalic acid
Oxygen difluoride
Ozone
Paraffin wax fume
Paraquat
Paraquat
Paraquat methosulfate
Parathion
Particulates not otherwise regulated
Pentaborane
Pentachloronaphthalene
Pentachlorophenol
Pentaerythritol
Pentane
2-Pentanone (Methyl propyl ketone)
Perchloroethylene (Tetrachloroethylene)
Perchloryl fluoride
Perlite
Petroleum distillates (naphtha) (rubber solvent)
Phenol
Phenothiazine
Phenyl ether
Phenyl ether-Biphenyl mixture vapor
Phenyl glycidyl ether (PGE)
Phenyl mercaptan
p-Phenylene diamine
Phenylhydrazine
Phenylphosphine
Phorate
Phosdrin (Mevinphos)
Phosgene (Carbonyl chloride)
Phosphine
Phosphoric acid
Phosphorus (yellow)
Phosphorus oxychloride
Phosphorus pentachloride
Phosphorus pentasulfide
Phosphorus trichloride
Phthalic anhydride
m-Phthalodinitrile
Picloram
Picric acid
Pindone (2-pivalyl-1,3-indandione)
Piperazine dihydrochloride
Plaster of paris
Platinum
Platinum soluble salts
Portland cement
Potassium hydroxide
Propane
Propargyl alcohol
Propionic acid
Propoxur (Baygon)
n-Propyl acetate
n-Propyl alcohol
n-Propyl nitrate
Propylene dichloride
Propylene glycol dinitrate
Propylene glycol monomethyl ether
Propylene imine
Propylene oxide
Pyrethrum
Pyridine
Quinone
Resorcinol
Rhodium
Rhodium soluble compounds
Rhodium, insoluble compounds
Ronnel
Rosin core solder pyrolysis products, as formaldehyde
Rotenone
Rouge
Selenium
Selenium compounds
Selenium hexafluoride
Silica, amorphous, diatomaceous earth, containing less than1% crystalline silica
Silica, amorphous, precipitated and gel
Silica, crystalline, tridymite
Silica, fused
Silica-crystalline, cristobalite
Silica-crystalline, quartz
Silica-crystalline, tripoli
Silicon
Silicon carbide
Silicon tetrahydride
Silver soluble compounds
Silver, metal
Soapstone
Sodium azide
Sodium bisulfite
Sodium fluoroacetate
Sodium hydroxide
Sodium metabisulfite
Starch
Stibine
Stoddard solvent
Strychnine
Styrene
Subtilisins (proteolytic enzymes)
Sucrose
Sulfur dioxide
Sulfur hexafluoride
Sulfur monochloride
Sulfur pentafluoride
Sulfur tetrafluoride
Sulfuric acid
Sulfuryl fluoride
Sulprofos
Talc (containing no asbestos)
Tantalum metal
Tantalum, oxide dusts
TEDP (Sulfotep)
Tellurium
Tellurium compounds, n.o.s.
Tellurium hexafluoride
Temephos
TEPP
Terphenyls
1,1,2,2-Tetrachloro-1,2-difluoroethane
1,1,1,2-Tetrachloro-2,2-difluoroethane
1,1,2,2-Tetrachloroethane
Tetrachloronaphthalene
Tetraethyllead
Tetrahydrofuran
Tetramethyl lead
Tetramethyl succinonitrile
Tetranitromethane
Tetrasodium pyrophosphate
Tetryl (2,4,6-Trinitro-phenylmethylnitramine)
Thallium soluble compounds
Thallium soluble compounds
4,4'-Thiobis (6-tert-butyl-m-cresol)
Thioglycolic acid
Thionyl chloride
Thiram
Tin
Tin inorganic compounds
Tin organic compounds
Tin oxide
Titanium dioxide
Toluene
Toluene 2,4-diisocyanate (TDI)
p-Toluidine
o-Toluidine
m-Toluidine
Tributyl phosphate
1,1,2-Trichloro-1,2,2-trifluoroethane
Trichloroacetic acid
1,2,4-Trichlorobenzene
1,1,2-Trichloroethane
Trichloroethylene
Trichloromethanesulphenyl chloride
Trichloronaphthalene
1,2,3-Trichloropropane
Triethylamine
Trifluorobromomethane
Trimellitic anhydride
Trimethyl benzene
Trimethyl phosphite
Trimethylamine
2,4,6-Trinitrotoluene (TNT)
Triorthocresyl phosphate
Triphenyl amine
Triphenyl phosphate
Tungsten
Tungsten, insoluble compounds
Tungsten, soluble compounds
Turpentine
Uranium
Uranium insoluble compounds
Uranium soluble compounds
n-Valeraldehyde
Vanadium
Vegetable oil mist
Vinyl acetate
Vinyl bromide
Vinyl cyclohexene dioxide
Vinyl toluene
Vinylidene chloride (1,1-Dichloroethylene)
VM&P Naphtha
Warfarin
Welding fumes (total particulate)
Wood dust, all soft and hard woods, except western red cedar
Wood dust, western red cedar
m-Xylene-alpha, alpha'-diamine
Xylenes (o-, m-, p- isomers)
Xylidine
Yttrium
Zinc chloride fume
Zinc chromate
Zinc oxide
Zinc stearate
Zirconium
Zirconium compounds, n.o.s.

APPENDIX D
OSHA Designated Carcinogens

29 CFR 1910, Subpart Z - Toxic and Hazardous Substances. Occupational Safety and Health Administration.

Chemical Name
1,2-Dibromo-3-chloropropane
1,3-Butadiene
2-Acetylaminofluorene
3,3'-Dichlorobenzidine (and its salts)
4-Aminodiphenyl
4-Dimethylaminoazobenzene
4-Nitrobiphenyl
Acrylonitrile
alpha-Naphthylamine
Asbestos
Benzene
Benzidine
beta-Naphthylamine
beta-Propiolactone
bis-Chloromethyl ether
Cadmium
Chromium (VI) compounds
Coke oven emissions
Ethylene oxide
Ethyleneimine.
Formaldehyde
Inorganic arsenic
Methyl chloromethyl ether
Methylene chloride
Methylenedianiline
N-Nitrosodimethylamine
Vinyl chloride

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