HAZARD COMMUNICATION

Hazard Classification Guidance

for Manufacturers, Importers, and Employers

OSHA 3844-02 2016
Occupational Safety and Health Act of 1970

“To assure safe and healthful working conditions for 

working men and women; by authorizing enforcement 

of the standards developed under the Act; by assisting 

and encouraging the States in their efforts to assure 

safe and healthful working conditions; by providing for 

research, information, education, and training in the field 

of occupational safety and health.”

This guidance document is not a standard or regulation, and it creates no new legal obligations. It contains 

recommendations as well as descriptions of mandatory safety and health standards. The recommendations 

are advisory in nature, informational in content, and are intended to assist employers in providing a safe 

and healthful workplace. The Occupational Safety and Health Act requires employers to comply with 

safety and health standards and regulations promulgated by OSHA or by a state with an OSHA-approved 

state plan. In addition, the Act’s General Duty Clause, Section 5(a)(1), requires employers to provide their 

employees with a workplace free from recognized hazards likely to cause death or serious physical harm.

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in OSHA standards, and the Occupational Safety and Health 

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HAZARD COMMUNICATION

Hazard Classification Guidance

for Manufacturers, Importers, 

and Employers

Occupational Safety and Health Administration

U.S. Department of Labor

OSHA 3844-02 2016

i 

TABLE OF CONTENTS

OVERVIEW ................................................................................................................................... 1

I. INTRODUCTION ................................................................................................................. 3

II. THE HAZARD CLASSIFICATION PROCESS .................................................................. 6

III. IDENTIFYING HAZARDOUS CHEMICALS .................................................................. 14

IV. DATA COLLECTION ........................................................................................................ 15

V. DATA ANALYSIS.............................................................................................................. 19

VI. RECORDING THE RATIONALE BEHIND THE RESULTS OBTAINED ..................... 28

VII. CLASSIFICATION OF HEALTH HAZARDS .................................................................. 32

VII.1 Acute Toxicity ............................................................................................................ 32

VII.2 Skin Corrosion/Irritation ............................................................................................. 63

VII.3 Serious Eye Damage/Eye Irritation ............................................................................ 86

VII.4 Respiratory or Skin Sensitization.............................................................................. 115

VII.5 Germ Cell Mutagenicity ........................................................................................... 135

VII.6 Carcinogenicity ......................................................................................................... 149

VII.7 Reproductive Toxicity .............................................................................................. 170

VII.8 Specific Target Organ Toxicity – Single Exposure .................................................. 189

VII.9 Specific Target Organ Toxicity – Repeated or Prolonged Exposure ........................ 210

VII.10 Aspiration Hazard ..................................................................................................... 227

VII.11 Simple Asphyxiants .................................................................................................. 237

VIII. CLASSIFICATION OF PHYSICAL HAZARDS ............................................................ 239

VIII.1 Explosives ................................................................................................................. 240

VIII.2 Flammable Gases ...................................................................................................... 258

VIII.3 Flammable Aerosols ................................................................................................. 266

VIII.4 Oxidizing Gases ........................................................................................................ 279

VIII.5 Gases under Pressure ................................................................................................ 286

VIII.6 Flammable Liquids ................................................................................................... 294

VIII.7 Flammable Solids...................................................................................................... 301

VIII.8 Self-Reactive Chemicals ........................................................................................... 307

VIII.9 Pyrophoric Chemicals ............................................................................................... 322

VIII.10 Self-Heating Chemicals ............................................................................................ 332

VIII.11 Chemicals Which, in Contact with Water, Emit Flammable Gases ......................... 339

VIII.12 Oxidizing Liquids and Solids.................................................................................... 346

VIII.13 Organic Peroxides ..................................................................................................... 358

VIII.14 Corrosive to Metals ................................................................................................... 372

VIII.15 Combustible Dust...................................................................................................... 380

IX. HAZARDS NOT OTHERWISE CLASSIFIED................................................................ 385
ii

APPENDIX A. Glossary of Terms and Definitions .................................................................. 386

APPENDIX B. Information Sources to Assist with Hazard Classification ............................... 397

APPENDIX C. List of Substances Deemed Toxic or Hazardous by an Authoritative Process ....406

APPENDIX D. OSHA-Designated Carcinogens ....................................................................... 419

Workers’ Rights .......................................................................................................................... 420

OSHA Assistance, Services and Programs ................................................................................. 420

NIOSH Health Hazard Evaluation Program ............................................................................... 423

OSHA Regional Offices ............................................................................................................. 423

How to Contact OSHA ............................................................................................................... 424
1 

OVERVIEW

In March 2012, the Occupational Safety and Health Administration (OSHA) revised its Hazard 

Communication Standard to align it with the United Nations Globally Harmonized System of 

Classification and Labelling of Chemicals (GHS), Revision 3. The revision to the Hazard 

Communication Standard (HCS) built on the existing standard, by requiring chemical 

manufacturers and importers to follow specific criteria when evaluating the hazardous chemicals 

and when communicating the hazards through labels and safety data sheets (SDSs).

This document is designed to help manufacturers and importers of chemicals not only identify 

chemical hazards, but also to classify these hazards so that workers and downstream users can be 

informed about and better understand these hazards as required by OSHA’s Hazard 

Communication Standard. This guidance may also be useful to employers who decide to 

conduct hazard classifications to assure the accuracy and completeness of information provided 

to them by suppliers. 

Understanding the hazards is the critically important first stage in the process of establishing an 

effective hazard communication program. The process of hazard classification consists of four 

basic steps.

 Selection of chemicals to evaluate; 

 Collection of data; 

 Analysis of the collected data; and 

 Records of the rationale behind the results obtained. 

This document provides guidance on the processes involved and identifies considerations in the 

conduct of hazard classifications. Guidance on the allocation of the hazard communication label 

elements is provided in an OSHA Brief on Labels and Pictograms, located on the Hazard 

Communication webpage, at www.osha.gov/hazcom. 

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.

How this Document is Organized 

This guidance is organized into several chapters. Chapter I introduces the guidance. Chapter II

provides an overview of the hazard classification process. Chapter III discusses how to identify 

the chemicals to be classified. Chapter IV explains the process of data collection. Chapter V

describes the process and information needed for data analysis. Chapter VI discusses the 

information that may be useful to note in recording the rationale used to develop the 

classification of the various hazards. Chapters VII, VIII, and IX present the guidance to classify 

health hazards, physical hazards, and hazards not otherwise classified covered by the Hazard 

Communication Standard, respectively. 
2 

In addition, several appendices are provided at the end of this document:

 A glossary of terms and definitions is included in Appendix A, since much of the 

discussion in this document is of a technical nature. 

 A list of sources is provided in Appendix B. This list is by no means exhaustive, but it 

contains many useful resources. 

 Appendix C contains a list of chemicals for which OSHA has adopted permissible 

exposure limits. This is a helpful starting point for identifying chemicals that are toxic or 

hazardous The HCS does not contain a “floor” (list) of chemicals pre-determined to be 

hazardous under the standard (except for chemicals OSHA has already determined to be 

carcinogens); however, there are lists of hazardous chemicals compiled by authoritative 

sources that classifiers may find useful to consult. The chemicals listed in Appendix C 

are an example of one such list. Classifiers should also consult the American Conference 

of Governmental Industrial Hygienists’ (ACGIH’s) list of Threshold Limit Values 

(TLVs) and the items identified as carcinogens by the International Agency for Research 

on Cancer (IARC) Monographs on the Evaluation of Carcinogenic Risks to Humans, or 

the Report on Carcinogens from the National Toxicology Program (NTP). These lists are 

updated periodically, and users should check to determine whether there has been an 

update. 

 A list of OSHA-designated carcinogens is provided in Appendix D. Please see Chapter 

VII.6, Carcinogenicity, for guidance on classification of these chemicals. 
3 

I. INTRODUCTION

OSHA's Hazard Communication Standard (HCS) is designed to protect against chemical-source 

injuries and illnesses by ensuring that employers and workers are provided with sufficient 

information to anticipate, recognize, evaluate, and control chemical hazards and take appropriate 

protective measures. This information is provided through safety data sheets (SDSs), labels, and 

employee training. In order for SDSs, 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 Classification? 

Hazard classification is the process of evaluating the full range of available scientific evidence to 

determine if a chemical is hazardous, as well as to identify the level of severity of the hazardous 

effect. When complete, the evaluation identifies the hazard class(es) and associated hazard 

category of the chemical. 

The HCS defines hazard class as the nature of a physical or health hazard, e.g., flammable solid, 

carcinogen, and acute toxicity. Hazard category means the division of criteria within each 

hazard class, e.g., acute toxicity and flammable liquids each include four hazard categories 

numbered from category 1 through category 4. These categories compare hazard severity within 

a hazard class and should not be taken as a comparison of hazard categories more generally. 

That is, a chemical identified as a category 2 in the acute toxicity hazard class is not necessarily 

less toxic than a chemical assigned a category 1 of another hazard class. The hierarchy of the 

categories is only specific to the hazard class. The hazard classification process provides the 

basis for the hazard information that is provided in SDSs, labels, and worker training. 

The hazard classification process, as provided in the Hazard Communication Standard, has 

several steps, including: 

 Identifying the chemical;

 Identifying the relevant data regarding the hazards of a chemical;

 Reviewing the relevant data to ascertain the hazards associated with the chemical;

 Determining whether the chemical will be classified as hazardous according to the 

definition of hazardous chemical in the standard; and 

 Determining the degree of the hazard, where appropriate, by comparing the data with 

the criteria for health and physical hazards.

The HCS provides specific criteria for hazard classification to ensure that chemical 

manufacturers, importers, and other classification experts come to similar conclusions regarding 

the hazards of chemicals. The resulting classification is then used to determine appropriate 

hazard warnings. This method not only provides employers and workers with more consistent 

classification of hazards, but the hazard information on SDSs and labels is in a form that is more 
4 

consistent and presented in a way that facilitates the understanding of the hazards of chemicals. 

This hazard information can then be used when evaluating the workplace conditions to determine 

the hazards in the workplace, as well as to respond to exposure incidents. 

The information and criteria provided in Appendix A to 29 CFR 1910.1200 are used to classify 

the health hazards posed by hazardous chemicals. Similarly, the information and criteria 

provided in Appendix B to 29 CFR 1910.1200 are used to classify the physical hazards posed by 

hazardous chemicals. 

Hazard classification 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 chemical 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 chemical, depending on how the chemical is contained or handled, personal 

protective measures used, and other conditions that result in or limit exposure. This document 

addresses only the hazard classification process, and will not discuss risk assessment, which is 

not performed under the HCS.

Who Must Conduct Hazard Classifications? 

Only chemical manufacturers and importers are required to perform hazard classifications on the 

chemicals they produce or import. Under the HCS, an employer that manufactures, processes, 

formulates, blends, mixes, repackages, or otherwise changes the composition of a hazardous 

chemical is considered a "chemical manufacturer." Distributors and employers may also choose 

to conduct hazard classifications if they are concerned about the adequacy of the hazard 

information received for the chemicals they use in their business or distribute to others.

What Resources are Needed to Conduct a Hazard Classification? 

Three primary resources are required for hazard classification. First is the complete, accurate, 

most up-to-date literature and data concerning the hazardous chemical in question (discussed 

below in Chapter V, Data Analysis). Second, is the ability to properly understand and interpret 

the information retrieved in order to identify and document hazards. Third, is the specific 

criteria for each health and physical hazard class and category defined in the Hazard 

Communication Standard. As mentioned above, Appendix A to 29 CFR 1910.1200 provides the 

classification criteria for health hazards, and Appendix B to 29 CFR 1910.1200 provides the 

classification criteria for physical hazards. 

Manufacturers and importers of hazardous chemicals are responsible for ensuring that hazard 

information provided to their workers and downstream users is complete and accurate. To 

achieve this, the person(s) assigned to conduct hazard classifications must have the ability to 

Risk is often expressed 

as the simple equation: 

Hazard X Exposure = Risk.
5 

conduct complete and effective literature research 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 workers does not exempt a manufacturer or importer 

from compliance with the HCS.

How to Use This Guidance Document 

The hazard classification requirements of the HCS are specification-oriented. That is, chemical 

manufacturers, importers, and employers evaluating chemicals are required to follow specific 

criteria for evaluating and classifying hazards, and they must be able to demonstrate that they 

have accurately reported the hazards of the chemicals produced or imported in accordance with 

the criteria set forth in the HCS.

This document provides a detailed description of the criteria used to classify a hazardous 

chemical and guidance on how to apply them. In addition, a basic framework for hazard 

classification is provided, along with a description of the process that can be used to comply with 

the requirements of the HCS. An example using a mock chemical is also provided to illustrate 

the classification process of the given hazard. 

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. It is intended to serve only as useful guidance on the basic 

considerations and operational aspects involved in the conduct of hazard classifications.

Once hazard classification is complete, classifiers must select the appropriate label elements for 

the hazards identified. Appendix C to 29 CFR 1910.1200, Allocation of Label Elements, 

identifies the proper pictogram, signal word, hazard and precautionary statements for each 

hazard class and category in the HCS. 

This document does not address detailed labeling requirements or SDSs. OSHA has developed 

QuickCardsTM and OSHA Briefs on labels, pictograms, and SDSs, as well as other guidance. 

These materials can be found on the HCS website at: www.osha.gov/hazcom.
6 

II. THE HAZARD CLASSIFICATION PROCESS

Introduction 

The purpose of the Hazard Communication Standard is to ensure that the hazards of all 

chemicals produced or imported are classified, and that the information on the hazardous 

chemicals is transmitted to employers and workers. The standard covers only hazardous 

chemicals. During the classification process, the chemical manufacturer or importer must 

determine if the chemical being evaluated is hazardous or not. With the alignment of the HCS to 

the GHS, the hazard information will be consistent in format and content, making it easier for 

employers and workers to understand and use. This section of the guidance clarifies what is 

considered a hazardous chemical.

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 in 

everyday speech. The HCS definition of chemical is “any substance, or mixture of substances.”

Thus, virtually any product is a “chemical.” These various types of chemicals are defined as 

follows:

 Substance - chemical elements and their compounds in the natural state or obtained by 

any production process, including any additive necessary to preserve the stability of the 

product and any impurities deriving from the process used, but excluding any solvent 

which may be separated without affecting the stability of the substance or changing its 

composition.

 Element - the simplest form of matter. There are currently 118 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 - a combination or a solution composed of two or more substances in which they 

do not react. 

Although virtually all products 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, as amended by the 

Resource Conservation and Recovery Act of 1976 (42 U.S.C. 6901 et seq.), as amended, 

when subject to regulations issued under that Act by the Environmental Protection Agency;

 Any hazardous substance as defined by the Comprehensive Environmental Response, 

Compensation and Liability Act (42 U.S.C. 9601 et seq.) when the hazardous substance 

is the focus of remedial or removal action being conducted under that Act in 

accordance with Environmental Protection Agency regulations;
7 

 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 (21 

U.S.C. 301 et seq.), 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 (15 U.S.C. 2051 et seq.) and the Federal Hazardous 

Substances Act (15 U.S.C. 1261 et seq.), 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. 

The HCS also does not require labeling for certain chemicals, but hazard classification is still 

needed for these chemicals to provide the required safety data sheet. The chemicals include:

 Any pesticide as such term is defined in the Federal Insecticide, Fungicide, and 

Rodenticide Act (7 U.S.C. 136 et seq.), when subject to the labeling requirements of that 

Act and labeling regulations issued under that Act by the Environmental Protection 

Agency; 
8 

 Any chemical substance or mixture as such terms are defined in the Toxic Substances 

Control Act (15 U.S.C. 2601 et seq.), when subject to the labeling requirements of that Act 

and labeling regulations issued under that Act by the Environmental Protection Agency; 

 Any food, food additive, color additive, drug, cosmetic, or medical or veterinary device 

or product, including materials intended for use as ingredients in such products (e.g. 

flavors and fragrances), as such terms are defined in the Federal Food, Drug, and 

Cosmetic Act (21 U.S.C. 301 et seq.) or the Virus-Serum-Toxin Act of 1913 (21 U.S.C. 

151 et seq.), and regulations issued under those Acts, when they are subject to the 

labeling requirements under those Acts by either the Food and Drug Administration or 

the Department of Agriculture; 

 Any distilled spirits (alcoholic beverages), wine, or malt beverage intended for 

nonindustrial use, as such terms are defined in the Federal Alcohol Administration Act

(27 U.S.C. 201 et seq.) and regulations issued under that Act, when subject to the labeling 

requirements of that Act and labeling regulations issued under that Act by the Bureau of 

Alcohol, Tobacco, Firearms and Explosives; 

 Any consumer product or hazardous substance as those terms are defined in the 

Consumer Product Safety Act (15 U.S.C. 2051 et seq.) and the Federal Hazardous 

Substances Act (15 U.S.C. 1261 et seq.) respectively, when subject to a consumer product 

safety standard or labeling requirement of those Acts, or regulations issued under those 

Acts by the Consumer Product Safety Commission; and, 

 Agricultural or vegetable seed treated with pesticides and labeled in accordance with the 

Federal Seed Act (7 U.S.C. 1551 et seq.) and the labeling regulations issued under that 

Act by the Department of Agriculture.

How to Determine if a Chemical is “Hazardous” 

Under the HCS, any chemical that is classified as a physical hazard, a health hazard, a simple 

asphyxiant, combustible dust, pyrophoric gas, or hazard not otherwise classified is considered a 

hazardous chemical. The HCS definitions for physical hazard and health hazard are:

 Physical hazard means a chemical that is classified as posing one of the following 

hazardous effects: explosive; flammable (gases, aerosols, liquids, or solids); oxidizer 

(liquid, solid or gas); self-reactive; pyrophoric (liquid or solid); self-heating; organic 

peroxide; corrosive to metal; gas under pressure; or in contact with water emits flammable 

gas. The criteria for determining whether a chemical is classified as a physical hazard are 

detailed in Appendix B to 29 CFR 1910.1200 – Physical Hazard Criteria.

 Health hazard means a chemical that is classified as posing one of the following 

hazardous effects: acute toxicity (any route of exposure); skin corrosion or irritation; 

serious eye damage or eye irritation; respiratory or skin sensitization; germ cell 

mutagenicity; carcinogenicity; reproductive toxicity; specific target organ toxicity 

(single or repeated exposure); or aspiration hazard. The criteria for determining 

whether a chemical is classified as a health hazard are detailed in Appendix A to 

29 CFR 1910.1200 – Health Hazard Criteria. 
9 

The definitions for each of the specific physical and health hazards identified above are the same 

as those found in the GHS, Rev. 3. To maintain the coverage of those hazards that were included 

in the 1994 Hazard Communication Standard, OSHA included hazard communication elements 

for the following hazards that are not found in GHS Rev. 3: combustible dusts, pyrophoric gases, 

and simple asphyxiants. OSHA has also created “hazards not otherwise classified”, a hazard 

class to capture hazards for which criteria have not yet been created. 

Each of these hazards are included in this guidance document. Guidance on classification of 

simple asphyxiants is presented in Chapter VII, Classification of Health Hazards. Guidance on 

classification of pyrophoric gases and combustible dusts is presented in Chapter VIII, 

Classification of Physical Hazards. Guidance on classification of hazards not otherwise 

classified is presented in Chapter IX, Classification of Hazards not Otherwise Classified.

Table II.1 lists the different health hazard classes and categories identified in the HCS. 

Similarly, Table II.2 lists the different physical hazard classes and categories found in the HCS. 

Those hazard classes listed in italicized font in these two tables are the hazard classes not 

identified in GHS Rev.3, but are included in the HCS to maintain workplace coverage. 

Explanations of the classification process for each of these hazard classes and their associated 

hazard categories are presented in Chapters VII and VIII of this document, respectively. 

Table II.1. Health Hazard Classes and Categories. 

Hazard Class Hazard Category

Acute Toxicity 1 2 3 4

Skin Corrosion/Irritation 1A 1B 1C 2

Serious Eye Damage/

Eye Irritation

1 2A 2B

Respiratory or Skin 

Sensitization

1A 1B

Germ Cell Mutagenicity 1A 1B 2

Carcinogenicity 1A 1B 2

Reproductive Toxicity 1A 1B 2 Lactation

STOT –

Single Exposure 1 2 3

STOT –

Repeated Exposure 1 2

Aspiration 1

Simple Asphyxiants Single Category
10

Table II.2. Physical Hazard Classes and Categories. 

Hazard Class Hazard Category

Explosives Unstable

Explosives Div 1.1 Div 1.2 Div 1.3 Div 1.4 Div 1.5 Div 1.6

Flammable Gases 1 2

Flammable Aerosols 1 2

Oxidizing Gases 1

Gases under Pressure

Compressed Gases

Liquefied Gases

Refrigerated 

Liquefied Gases

Dissolved Gases

1

Flammable Liquids 1 2 3 4

Flammable Solids 1 2

Self-Reactive 

Chemicals

Type A Type B Type C Type D Type E Type F Type G

Pyrophoric Liquids 1

Pyrophoric Solid 1

Pyrophoric Gases Single 

category

Self-heating 

Chemicals

1 2

Chemicals, which in 

contact with water, 

emit flammable gases

1 2 3

Oxidizing Liquids 1 2 3

Oxidizing Solids 1 2 3

Organic Peroxides Type A Type B Type C Type D Type E Type F Type G

Corrosive to Metals 1

Combustible Dusts Single 

category

For a hazard classification process to be complete, one must consider all possible hazards, and 

should document any hazards that are identified. In conducting the hazard classification, one 

should be cognizant of all types of physical and health hazards to properly identify the nature and 

severity of the chemical’s hazards. 
11

OSHA regulates a number of chemicals as toxic and hazardous substances, which are contained 

in Subpart Z of 29 CFR 1910. The classifier must refer to the regulations of these substances for 

specific hazard classification requirements. For example, the Lead standard requires that at least 

the hazards of reproductive/developmental toxicity, central nervous system effects, kidney 

effects, blood effects, and acute toxicity effects be addressed in classification (See 29 CFR 

1910.1025(m)(ii)). In addition, there are certain lists that can help the classifier identify 

chemicals that have been deemed hazardous by nationally and internationally recognized 

organizations, such as the American Conference of Governmental Industrial Hygienists 

(ACGIH) Threshold Limit Values (TLVs), National Institute for Occupational Safety and Health 

(NIOSH) Recommended Exposure Limits (RELs), National Toxicology Program (NTP) Report 

on Carcinogens (RoC), and International Agency for Research on Cancer (IARC). Appendix C

of this document contains a list of those materials regulated by OSHA as toxic and hazardous 

substances. Appendix D of this document contains a list of OSHA-designated carcinogens. 

The classifier must evaluate all the evidence and data available for the given chemical and use 

the specific criteria spelled out for each health and physical hazard to classify the chemical in 

appropriate hazard classes and categories. In some cases, available data provides enough 

information to classify a chemical. In other cases, classification is determined on the basis of the 

total weight of evidence using expert judgment. This means that all available information 

bearing on the classification of the hazard must be considered together. In the case of health 

hazards, for example, this includes the results of valid in vitro tests, relevant animal data, and 

human experience, such as epidemiological and clinical studies, and well-documented case 

reports and observations.

If OSHA has designated a chemical as a carcinogen, then the chemical must be classified as a 

carcinogen. There are also organizations that evaluate chemicals for carcinogenicity. These 

organizations, such as the International Agency for Research on Cancer (IARC) and the National 

Toxicology Program (NTP), publish lists of hazardous chemicals that they have determined, with 

varying degrees of certainty, to be carcinogens. OSHA has provided a crosswalk table to aid 

classifiers in translating the classification from NTP or IARC into the HCS classification scheme 

in Chapter VII.6 of this document. The discussion on carcinogens in this guidance provides 

more detail on the classification of carcinogens. 

The definition for hazardous chemical in the standard is thus very broad. The standard does not 

require the testing of chemicals - only the collection and analysis of currently available data. 

Nevertheless, if no data is available or it is questionable, testing should be considered when 

hazardous properties are suspected.
12

Is Hazard Classification the Same for Mixtures as for 

Individual Chemicals? 

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 176 °F and 12 °F (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 309-396 °F and 102-110 °F, respectively.

The process for evaluating mixtures may require steps in addition to those required for single 

chemical agents. The HCS has designated specific classification requirements for mixtures, 

which depend upon the availability of test data. Please see Chapter V, Data Analysis, for a 

detailed discussion on classification of mixtures. In addition, the chapters for the individual 

hazard classes discuss the specifics necessary for classification of mixtures. 

What is Involved in Conducting a Hazard Classification? 

All possible physical or health hazards that might be associated with a chemical’s use must be 

considered. The hazard classification process consists of four main steps:

 Selection of chemicals to evaluate; 

 Collection of data; 

 Analysis of the collected data using the criteria provided in the HCS; and 

 Documentation of the hazard classification process and the results obtained1. 

The Hazard Communication Standard provides the specific criteria upon which the hazard 

classification for a given chemical is based, ensuring that all those evaluating data and 

performing hazard classification are following the same process, resulting in similar 

classification conclusions. If no hazards are found, the manufacturer, importer, or employer is 

not required to take further action pertaining to the evaluated chemical. Documentation of the 

results of the analysis used in the classification process may be useful for future reference. 

For many chemicals, hazard information has been compiled in readily available and reliable 

sources (see Appendix B of this document). The specific classification criteria for each health or 

physical hazard class identified in the HCS enables manufacturers, importers, and others 

performing hazard classification to collect and evaluate the available data to determine if the 

chemical is hazardous and identify the associated level of severity. 

In some cases, a chemical may present a single hazard. In other cases, several hazards may be 

associated with exposure to a chemical. The severity of the hazardous effect can range from 

mild to severe. In the HCS, for example, identified health hazards for acetic acid, as normally 

 

1

 Note that documentation of the hazard classification process and the results obtained is not required by the HCS; 

however OSHA recommends it. See Chapter VI, Recording the Rationale Behind the Results Obtained, of this 

document. 
13

used in industry, are skin irritation/corrosion and respiratory sensitization. In contrast, exposure 

to lead may involve a multitude of hazards, including reproductive/developmental toxicity, 

central nervous system effects, kidney effects, and acute toxicity effects.

Hazard evaluation is a process that relies heavily on the professional judgment of the evaluator, 

particularly in the area of chronic health hazards. The specification approach of the HCS requires 

the chemical manufacturer, importer or employer to conduct a thorough evaluation, examining the 

full range of available data and producing a scientifically defensible evaluation of the chemical 

hazards.
14

III. IDENTIFYING HAZARDOUS CHEMICALS

The ultimate goal in the hazard classification 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 classification. The logical way to do this is to first prepare an 

inventory of all the chemicals you manufacture or import, as well as a list of the ingredients in 

the mixtures produced. To create the list of ingredients from the mixtures produced, consider 

information found in the chemical formula, on order receipts, batch sheets, and so on. 

While a single SDS must be created for the mixtures produced, you may rely upon the 

information provided on the SDSs and labels for ingredients obtained from the chemical 

manufacturer or importer, unless you have reason to believe the information is incorrect.

However, you may choose to conduct a hazard classification for those ingredients if there is 

concern about the adequacy of the hazard information received.

All employers are required to have a list of hazardous chemicals known to be present in the 

workplace under 29 CFR 1910.1200(e)(1)(i). 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, 

take time to inspect the workplace 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, you can use this information to perform hazard 

classifications for chemicals that you manufacture or import. 

On a related safety note, 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.
15

IV. DATA COLLECTION

The second step in the hazard classification 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 classification process involves the identification of all of the hazards associated 

with a chemical, not just some of them. OSHA expects classifiers to use reasonable efforts in 

their search for available data for all hazard classes (see Chapter V, Data Analysis), for a 

discussion on the use of available data). Specific types of data used for classification of a given 

hazard are discussed in the individual hazard chapters of this document. Any hazard that exists 

for the chemical must be identified and communicated to downstream employers and workers. 

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

 chemical identity; 

 physical and chemical 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 of this document, 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. 

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. 

Complete and reliable data must be entered on SDSs and labels to meet the HCS requirements. 

Before the search for hazard data can begin, the exact chemical composition of the chemical(s) 

or products manufactured or imported must be identified. This chemical search includes the 

name of each chemical (whether it is a substance or a mixture), including active ingredients, 

inactive ingredients, impurities, and stabilizing additives.

Chemical Identity 

The specific chemical identity of all chemicals on your chemical inventory should be carefully 

and completely compiled. The specific chemical identity includes:

 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, such as impurities and stabilizers.
16

Correct identification of chemicals is critical for data retrieval. Use the precise chemical name, 

where available, and Chemical Abstract Service (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. To avoid confusion, literature is often indexed using the CAS number or the 

primary chemical name. For example, TCE is commonly used as an acronym for trichloroethylene 

(CAS 79-01-6), but sometimes this same acronym is used to 

refer to tetrachloroethylene (CAS 127-18-4). 

Additionally, the use of trade names could cause difficulty in 

finding information. An example of the type of chemical 

identification data that is needed is presented for Perclene®, a 

widely used industrial solvent. Perclene® is a trade name for perchloroethylene or Perc 

(common name), or more specifically tetrachloroethylene (CAS Number 127-18-4). Several 

databases exist that can only be searched using the CAS number or chemical name. Thus, the 

most effective search of computerized databases is conducted using both the precise chemical 

name (tetrachloroethylene) and the CAS number (CAS Number 127-18-4). Searches using the 

trade or common name(s) or abbreviation(s) may not return information for that chemical. 

The percent composition (or exact percentage) should be available in-house for all chemicals 

manufactured or imported. The chemical composition information may be based on an analysis

of the final or technical grade product or product formulation. 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 purposes of hazard classification, these other 

chemicals must also be considered since they may have their own unique hazards and may 

contribute to the hazards of the chemical.

Thus, one of the initial steps 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; 

 SDSs and product safety bulletins from manufacturers or suppliers; 

 OSHA Chemical Sampling Information pages; 

 The Merck Index; 

 ChemID; and 

 Trade associations. 

CAS numbers are assigned 

by the Chemical Abstract 

Service of the American 

Chemical Society.
17

Physical and Chemical Properties 

The physical and chemical properties of a hazardous chemical are the empirical data of the 

substance or mixture. That is, this data has been gathered from observation or by tests performed 

on the chemical. For many hazardous chemicals, this data has been compiled and is readily 

available. 

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

 Fire Protection Guide to Hazardous Materials; 

 Department of Transportation Emergency Response Guidebook, most recent version 

(phmsa.dot.gov/hazmat/library/erg); 

 OSHA’s Occupational Chemical Database (www.osha.gov/chemicaldata);

 Hazardous Substances Data Bank (HSDB) (toxnet.nlm.nih.gov);

 Product safety bulletins from manufacturers or suppliers; 

 National Institute for Occupational Safety and Health (NIOSH) documents 

(www.cdc.gov/niosh/topics/chemical.html);

 NIOSH Pocket Guide to Chemical Hazards (www.cdc.gov/niosh/npg); 

 International Chemical Safety Cards (www.cdc.gov/niosh/ipcs); 

 OECD eChemPortal (www.oecd.org/env/ehs/riskassessment/echemportalglobalportaltoinformationonchemicalsubstances.htm);

 The Merck Index; 

 CRC Handbook of Chemistry and Physics; 

 Sax's Dangerous Properties of Industrial Materials, latest edition; 

 Bretherick's Handbook of Reactive Chemicals Hazards, latest edition; and

 Trade associations.

The HCS includes classification criteria for 17 physical hazard classes (see Table II.2) and are 

discussed in detail in Chapter VIII. These physical hazard classes should not be confused with 

the physical and chemical properties of a chemical. 

Health Effects 

The HCS includes the classification criteria for 11 health hazard classes (see Table II.1) and are 

discussed in detail in Chapter VII. 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 

pre-manufacturing health effects data to the U.S. 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 EPA. This data may be used to assist with 

hazard classification and the preparation of SDSs and labels. The company also should seek 

toxicity data from the literature, government, or private sources. Some recommended reference 

sources are listed below. 
18

 Company-sponsored research, if available; 

 SDSs and product safety bulletins from manufacturers, suppliers, or Internet sites; 

 OSHA’s Occupational Chemical Database (www.osha.gov/chemicaldata);

 Hazardous Substances Data Bank (HSDB) (toxnet.nlm.nih.gov);

 National Institute of Occupational Safety and Health (NIOSH) documents 

(www.cdc.gov/niosh/topics/chemical.html);

 NIOSH Pocket Guide to Chemical Hazards (www.cdc.gov/niosh/npg); 

 Center for Disease Control’s (CDC) Agency for Toxic Substances and Disease Registry 

(ATSDR), www.atsdr.cdc.gov/toxprofiles/index.asp

 International Chemical Safety Cards (www.cdc.gov/niosh/ipcs); 

 NIOSH Registry of Toxic Effects of Chemical Substances (RTECS®)

(www.cdc.gov/niosh/rtecs/RTECSaccess.html); 

 OSHA Chemical Sampling Information pages; 

 IARC Monographs on the Evaluation of Carcinogenic Risks to Humans

(monographs.iarc.fr); 

 NTP Annual Report on Carcinogens (ntp.niehs.nih.gov/pubhealth/roc ); 

 TLVs and BEIs (ACGIH) (www.acgih.org/tlv-bei-guidelines/policies-procedurespresentations/overview); 

 OECD eChemPortal (www.oecd.org/env/ehs/riskassessment/echemportalglobalportaltoinformationonchemicalsubstances.htm);

 Hawley's Condensed Chemical Dictionary, latest edition; 

 Sax's Dangerous Properties of Industrial Materials, latest edition; 

 Published literature; and 

 Trade associations. 
19

V. DATA ANALYSIS

The third step in the hazard classification 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 classification to determine whether physical hazards or health 

hazards exist. 

For both health and physical hazards, explicit classification criteria are provided in the HCS. For 

example, criteria are given for classifying a chemical as a flammable liquid, an organic peroxide, 

and for designating a chemical as acutely toxic or a carcinogen. 

In some cases, the HCS establishes the criteria to be followed. For example, if a liquid has a 

flashpoint of less than or equal to 93°C (199.4°F), it is by definition a “flammable liquid.” To 

determine into what category of flammable liquid the chemical is classified, you also will need to 

identify its initial boiling point. This involves a simple data analysis. You can rely on the 

flashpoint and boiling point listed in a standard reference. In the event that your company is 

manufacturing or importing a chemical for which there is no information on the flashpoint and 

boiling point, you may choose to determine the flashpoint by laboratory testing. See Use of 

available data, test methods and test data quality below for a more detailed discussion.

The following discusses the general considerations for analyzing data to complete the 

classification process as defined in the Hazard Communication Standard. 

Hazard Classification 

In the Hazard Communication Standard, the term “hazard classification” is used to indicate that 

only the intrinsic hazardous properties of chemicals are considered. Hazard classification 

incorporates three steps: 

a) Identification of relevant data regarding the hazards of a chemical; 

b) Subsequent review of those data to ascertain the hazards associated with the 

chemical; 

c) Determination of whether the chemical should be classified as hazardous and the 

degree of hazard, where applicable. 

For many hazard classes, the criteria are semi-quantitative or qualitative and expert judgment is 

required to interpret the data for classification purposes.
20

Use of available data, test methods and test data quality 

The criteria for determining health hazards are test-method neutral. That is, they do not specify 

particular test methods, as long as the methods are scientifically validated. The term 

“scientifically validated” refers to the process by which the reliability and the relevance of a 

procedure are established for a particular purpose. Any test that determines hazardous 

properties, which is conducted according to recognized scientific principles, can be used for 

purposes of a hazard determination for health hazards. Test conditions need to be standardized 

so that the results are reproducible for a given chemical, and the standardized test yields “valid” 

data for defining the hazard class of concern. OSHA allows the use of existing test data for 

classifying chemicals, although expert judgment also may be needed for classification purposes. 

The effect of a chemical on biological systems is influenced by the physical and chemical 

properties of the substance and/or ingredients of the mixture and the way in which ingredient 

substances are biologically available. A chemical need not be classified when it can be shown 

by conclusive experimental data from scientifically validated test methods that the chemical is 

not biologically available. 

For classification purposes, epidemiological data and experience on the effects of chemicals on 

humans (e.g., occupational data, data from accident databases) must be considered in the 

evaluation of the chemical’s human health hazards.2

 

Testing is not required by the HCS. Therefore, if existing data is not available, you have the 

option to state this on the safety data sheet. However, if you decide to test the chemical, use the 

test methods specified in the appropriate health or physical hazard appendices to the HCS to 

gather the data (see the Classification Procedure and Guidance section for each health hazard 

class and for each physical hazard class of this guidance, and Appendix A and Appendix B to 29 

CFR 1910.1200). Appropriate test methods for each physical hazard class are identified in the 

standard and discussed in each physical hazard section of this guidance. 

Classification based on weight of evidence (WoE) 

For some hazard classes, classification results directly when the data satisfy the criteria. This is 

the case for most physical hazard classes. For others, classification of a chemical may be 

determined on the basis of the total weight of evidence using expert judgment. Under the GHS, 

weight of evidence (WoE) means that all available information bearing on the classification of a 

hazard is considered together, including the results of valid in vitro tests, relevant animal data, 

and human experience, such as epidemiological and clinical studies and well-documented case 

reports and observations. There are several reasons to utilize a WoE approach. First, WoE 

makes use of all available information. This is important especially when there is conflicting 

information between studies. Second, less reliable studies can be pooled to draw a conclusion on 

the relevant endpoint. Finally, WoE allows for use of different but adequate information that is 

available (e.g., data on other species, or routes of exposure). 

 

2

 As human experience can also provide information on the hazards of a chemical, occupational data and data from 

accident databases are examples of where you can get such information. 
21

OSHA has provided general criteria on how to perform an analysis based on weight of evidence 

in Appendix A.0.3 to 29 CFR 1910.1200, as well as specific criteria in the individual health 

chapters where weight of evidence is used (skin corrosion/irritation, serious eye damage/eye 

irritation, respirator or skin sensitization, germ cell mutagenicity, carcinogenicity, reproductive 

toxicity, specific target organ toxicity - single exposure (STOT-SE), and STOT-repeated or 

prolonged exposure). See Appendices A.2-A.9 to 29 CFR 1910.1200.

When performing a WoE assessment to determine the classification of a chemical, the classifier 

must determine which data or study results have the most utility and validity to support the 

resulting hazard classification of the chemical. These considerations include four basic elements: 

data adequacy, data reliability, data relevance, and quantity of evidence. It is also necessary to 

understand how to apply this information to the data in order to make hazard classification 

decisions. Information on chemicals related to the material being classified must also be 

considered, as appropriate, along with site of action and mechanism or mode of action study 

results. In addition, both positive and negative results must be considered together in a single 

weight-of-evidence determination. 

Most toxicity and epidemiology reports provide an analysis of the data and conclude whether the 

results were positive or negative, or 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. 

Positive effects which are consistent with the criteria for classification, whether seen in humans 

or animals, normally justify classification. Where evidence is available from both humans and 

animals and there is a conflict between the findings, the quality and reliability of the evidence 

from both sources must be evaluated in order to resolve the question of classification. Reliable, 

good quality human data generally has precedence over other data. However, even welldesigned and conducted epidemiological studies may lack a sufficient number of subjects to 

detect relatively rare but still significant effects, or to assess potentially confounding factors. 

Therefore, positive results from well-conducted animal studies are not necessarily negated by the 

lack of positive human experience, but require an assessment of the robustness, quality and 

statistical power of both the human and animal data. 

Route of exposure, mechanistic information, and metabolism studies are used in determining the 

relevance of a health effect in humans. When such information raises doubt about relevance in 

humans, a lower classification may be warranted. When there is scientific evidence 

demonstrating that the mechanism or mode of action is not relevant to humans, the data may not 

justify classification. 

Both positive and negative results are considered together in the weight of evidence 

determination. However, a single positive study performed according to established scientific 

principles and with statistically and biologically significant positive results may justify 

classification. 
22

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, a study with a stated confidence level of 95% and an LD50

3 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. 

Hazard evaluation relies on professional judgment, particularly in the area of chronic hazards. 

The specific and detailed 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 classification.

Considerations for the classification of mixtures 

Classification of mixtures is based on the following sequence for most hazard classes:

1. If the mixture has been tested as a whole and test data are available for the complete 

mixture, these results are used to classify the mixture. 

2. If a mixture has not been tested as a whole or test data are not available for the 

complete mixture, the bridging principles designated in each health hazard chapter of 

Appendix A of the Hazard Communication Standard are used to classify the mixture. 

3. If test data are not available for the mixture itself, and the available information is 

not sufficient to allow application of the above-mentioned bridging principles, then the 

method(s) described in each chapter for estimating the hazards based on the information 

known will be applied to classify the mixture (e.g., application of cut-off values/ 

concentration limits).

An exception to the above order of precedence is made for Carcinogenicity, Germ Cell 

Mutagenicity, and Reproductive Toxicity (CMR). For these three hazard classes, mixtures are 

classified based upon information on the ingredient substances, unless on a case-by-case basis, 

justification can be provided for classifying based upon the mixture as a whole. Mixture rules 

for these three hazard classes are presented in Chapters VII.5, VII.6, and VII.7 of this document. 

See also chapters A.5, A.6, and A.7 in the Hazard Communication Standard for further 

information.

 

3 LD50 (Lethal Dose 50) is the amount of a chemical, given all at once, which causes the death of 50% (one half) of a 

group of test animals. 
23

Bridging principles for the classification of mixtures where test data 

are not available for the complete mixture 

Where the mixture itself has not been tested to determine its toxicity, but there are sufficient data on 

both the individual ingredients and similar tested mixtures to adequately characterize the 

hazards of the mixture, the following bridging principles are used, subject to any specific provisions 

for mixtures for each hazard class. These principles ensure that the classification process uses the 

available data to the greatest extent possible in characterizing the hazards of the mixture. 

Dilution 

For mixtures classified in accordance with all the health hazard classes of the HCS (see 

Appendices A.1 through A.10 to 29 CFR 1910.1200), if a tested mixture is diluted with a diluent 

that has an equivalent or lower toxicity classification than the least toxic original ingredient, and 

which is not expected to affect the toxicity of other ingredients, then: 

(a) The new diluted mixture is classified as equivalent to the original tested mixture; or 

(b) For classification of acute toxicity, the additivity formula must be applied (see 

A.1.3.6 in Appendix A to 29 CFR 1910.1200). 

Batching

The toxicity of a tested production batch of a mixture can be assumed to be substantially 

equivalent to that of another untested production batch of the same mixture, when produced by 

or under the control of the same chemical manufacturer, unless there is reason to believe there 

is significant variation such that the toxicity of the untested batch has changed. If the latter 

occurs, a new classification is necessary. The batching approach is used for mixtures classified 

in accordance with all the health hazard classes of the HCS (see Appendices A.1 through A.10 to 

29 CFR 1910.1200).

Concentration of mixtures 

The concentration of ingredients may be used to classify mixtures for the following hazard 

classes: acute toxicity, skin corrosion/irritation, serious eye damage/eye irritation, specific target 

organ toxicity - single exposure (STOT-SE), STOT-repeated or prolonged exposure, or 

aspiration (see Appendices A.1, A.2, A.3, A.8, A.9, or A.10 to 29 CFR 1910.1200). In these 

cases, if a tested mixture is classified in Category 1, and the concentration of the ingredients of 

the tested mixture that are in Category 1 is increased, the resulting untested mixture is classified 

in Category 1. 

Interpolation within one toxicity category 

For three mixtures (A, B and C) with identical ingredients, where mixtures A and B have been 

tested and are in the same toxicity category, and where untested mixture C has the same 

toxicologically active ingredients as mixtures A and B but has concentrations of toxicologically 

active ingredients intermediate to the concentrations in mixtures A and B, then mixture C is 

assumed to be in the same toxicity category as A and B. This approach to interpolating data 
24

within one toxicity category is used for mixtures classified in accordance with the classification 

criteria for the following hazard classes in the HCS: acute toxicity, skin corrosion/irritation, 

serious eye damage/eye irritation, specific target organ toxicity - single exposure (STOT-SE), 

STOT-repeated or prolonged exposure, or aspiration (see Appendices A.1, A.2, A.3, A.8, A.9, or 

A.10 to 29 CFR 1910.1200).

Substantially similar mixtures

For mixtures classified in accordance with all health hazard categories of the HCS (see 

Appendices A.1 through A.10 to 29 CFR 1910.1200), given the following set of conditions: 

(a) Where there are two mixtures: 

 (i) A + B; 

 (ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) And data on toxicity for A and C are available and substantially equivalent; i.e.,

they are in the same hazard category and are not expected to affect the toxicity of 

B; then 

If mixture (i) or (ii) is already classified based on test data, the other mixture can be assigned the 

same hazard category. 

Aerosols 

For mixtures classified in accordance with the classification criteria for acute toxicity, skin 

corrosion/irritation, serious eye damage/eye irritation, respiratory or skin sensitization, specific 

target organ toxicity - single exposure (STOT-SE), or STOT-repeated or prolonged exposure 

(see Appendices A.1, A.2, A.3, A.4, A.8, or A.9 to 29 CFR 1910.1200), an aerosol form of a 

mixture is classified in the same hazard category as the tested, non-aerosolized form of the 

mixture, provided the added propellant does not affect the toxicity of the mixture when spraying. 

Use of cut-off values/concentration limits 

When classifying an untested mixture based on the hazards of its ingredients, cut-off 

values/concentration limits4

for the classified ingredients of the mixture are used for several 

hazard classes. While the adopted cut-off values/concentration limits adequately identify the 

hazard for most mixtures, there may be some that contain hazardous ingredients at lower 

concentrations than the specified cut-off values/concentration limits that still pose an identifiable 

hazard. There may also be cases where the cut-off value/concentration limit is considerably 

lower than the established non-hazardous level for an ingredient. 

 

4

 For the purposes of the HCS, the terms “cut-off values” and “concentration limits” mean the same thing. 
25

If the chemical manufacturer, importer or other hazard classifier has information that the hazard 

of an ingredient will be evident (i.e., it presents a health risk) below the specified cut-off 

value/concentration limit, the mixture containing that ingredient must be classified accordingly. 

In exceptional cases, conclusive data may demonstrate that the hazard of an ingredient will not 

be evident (i.e., it does not present a health risk) when present at a level above the specified cutoff value/concentration limit(s). In these cases the mixture may be classified according to those 

data. The data must exclude the possibility that the ingredient will behave in the mixture in a 

manner that would increase the hazard over that of the pure substance. Furthermore, the mixture 

must not contain ingredients that would affect that determination. 

The HCS has established specific cut-off values for different health hazards. Table V.1 presents 

these cut-off values. When a substance in a specified hazard class is present in a mixture at or 

above the cut-off level, the mixture must be classified in that hazard class. 

Table V.1. Cut-off Values for Health Hazards 

Hazard class Label Cut-Off 

Values

SDS Cut-Off 

Values

Respiratory/Skin sensitization  0.1%  0.1%

Germ cell mutagenicity (Category 1)  0.1%  0.1%

Germ cell mutagenicity (Category 2)  1.0%  1.0%

Carcinogenicity  0.1%  0.1%

Reproductive toxicity  0.1%  0.1%

Specific target organ toxicity (single exposure)  1.0%  1.0%

Specific target organ toxicity (repeated exposure)  1.0%  1.0%

Specific target organ toxicity Category 3 ≥20% ≥20%

Synergistic or antagonistic effects 

When performing an assessment in accordance with the requirements of the Hazard 

Communication Standard, the evaluator must take into account all available information about 

the potential occurrence of synergistic effects among the ingredients of the mixture. Lowering 

the classification of a mixture to a less hazardous category on the basis of antagonistic effects 

may be done only if the determination is supported by sufficient data. 

Synergistic effects result when the overall effect of the ingredients is greater than the sum of any 

of the individual effects, while antagonistic effects result from the contrasting actions or negative 

effect from two (or more) ingredients, so that the overall effect is less than the sum of any of the 

individual effects. 
26

Hazard Classification of Petroleum Streams 

To classify the health hazards of petroleum streams, follow the guidance presented below in 

conjunction with the general guidance found in Appendix A.0.1-A.0.3 to 29 CFR 1910.1200, and 

the classification criteria provided for the health hazards presented in Appendix A to 29 CFR 

1910.1200. 

1. For hazard classes other than carcinogenicity, germ cell mutagenicity, and reproductive 

toxicity (“CMR”), classify a petroleum stream as follows:

a) Where test data are available for the petroleum stream, the classification of the stream 

will always be based on those data.

b) Where test data are not available for the stream itself, the classification may be based on 

a toxicologically appropriate read across from test results of a substantially similar 

stream. A substantially similar stream is one that has a similar starting material, 

production process, and range of physico-chemical properties (e.g., boiling point and 

carbon number) and similar constituent compositions.

c) If test data are not available either for the stream itself or a substantially similar stream, 

then apply the method(s) described in each chapter of Appendix A to 29 CFR 1910.1200 

for estimating the hazards based on the information known to classify the stream (i.e., 

application of cut-off values/concentration limits). 

2. For the CMR hazard classes:

a) When reliable and good quality data are available to classify a petroleum stream, based 

on testing of the stream or the toxicologically appropriate read-across to a substantially 

similar stream, a weight of evidence analysis supported by that data may be relied upon 

for classification regardless of whether a CMR constituent is present in the stream. A 

substantially similar stream is one that has a similar starting material, production process, 

and range of physico-chemical properties (e.g., boiling point and carbon number) and 

similar constituent compositions.

b) To be reliable and good quality test data, the data must be from one or more tests that 

reflect appropriate study design and performance. The study or studies must appropriately 

take into account dose and other factors such as duration, observations, and analysis (e.g.,

statistical analysis, test sensitivity) so as to conclusively exclude the possibility that the 

lack of effect(s) is due to a poor study design, e.g., insufficient dose or number of 

subjects. A study (or studies) is conclusive in this sense if, when viewed in conjunction 

with all relevant information about the chemical, its results are consistent with the 

relevant information and allow a strong inference that the lack of effects is not due to a 

poor study design.

c) Where reliable and good quality data are not available on the stream or a substantially 

similar stream, then apply the method(s) described in each chapter of Appendix A of 29 

CFR 1910.1200 for estimating the hazards based on the information known to classify the 

stream (i.e., application of cut-off values/concentration limits).
27

Interface Between the HCS and U.S. Department of Transportation 

(DOT) labeling 

As mentioned earlier, the purpose of the HCS is to ensure that the hazards of all chemicals 

produced or imported are classified, and that information concerning the hazards is transmitted to 

employers and workers. This information is transmitted by means of a comprehensive hazard 

communication program, which includes container labeling and other forms of warning, safety 

data sheets, and worker training. 

With the alignment of the HCS to the GHS, one will find that there is generally a correlation 

between the DOT packing group and the HCS physical hazard class category. If the chemical 

being classified is the same chemical that has previously undergone classification to meet DOT’s 

Hazardous Materials Regulations, you may use this data to classify the physical hazards of the 

chemical to meet the requirements of OSHA’s Hazard Communication Standard. You may find 

the information contained in DOT’s Hazardous Materials Regulations is another useful 

reference, in particular the Hazardous Materials Table, located in 49 CFR 172.101. 

DOT labeling (referred to as placarding) applies to chemicals that are transported by means of 

rail car, aircraft, motor vehicle, and vessel. These placards must follow certain size and color 

requirements. The labels for the transport of dangerous goods are those prescribed by DOT’s 

Hazardous Materials Regulations (49 CFR Parts 100-185). The classification criteria and testing 

procedures found in the DOT Hazardous Materials Regulations are aligned with the UN 

Recommendations on the Transport of Dangerous Goods – Model Regulations. 
28

VI. RECORDING THE RATIONALE BEHIND THE 

RESULTS OBTAINED

The fourth and final step in the hazard classification process is also important. All the other 

steps will be wasted if findings are not recorded carefully. If a chemical is found to be 

hazardous, OSHA recommends that the findings and the rationale used to arrive at these findings 

be documented. 

The HCS no longer requires documentation of the procedures used to determine the hazards of a 

chemical since this is now provided through the classification procedures specified in 

Appendices A and B of the HCS, and all those performing hazard classification must follow the 

same process. However, OSHA still recommends the data, the rationale used, and other results 

gathered during the classification process be maintained for future reference and use.

To assist in this, OSHA recommends that a structured approach to data retrieval and compilation 

be adopted. This structured approach also applies to the preparation of SDSs and labels. If you 

decide to take such an approach, this section provides some guidelines you may wish to consider.

Compilations of three types of data are considered essential:

 Initial chemical inventory; 

 Specific data retrieved for each chemical; and 

 List of hazardous chemicals. 

Chemical Inventory 

The chemical inventory5should consist of all chemicals that are imported or produced by the 

company, and those chemicals that are ingredients used in a mixture produced by the company. 

Classifiers may find it helpful if the chemical inventory includes the following information for 

future reference:

 chemical name; 

 CAS Number; 

 common name; 

 synonyms; 

 product/mixture name (if applicable); and 

 percentage of ingredients in product/mixture (if applicable). 

 

5

 The chemical inventory is different than the list of hazardous chemicals required under paragraph (e) of the HCS 

(29 CFR 1910.1200). The chemicals listed on the chemical inventory would be required to appear on the list of 

hazardous chemicals required under paragraph (e) of the HCS if they are present in the workplace. 
29

As discussed in Chapter III, Identifying Hazardous Chemicals, it is recommended that this 

chemical inventory be computerized for future sorting, additions, deletions, and status reports. 

Specific Data Retrieved for Each Chemical 

OSHA recommends that the data retrieved be organized to facilitate the preparation of SDSs and 

labels. Listing all the hazard classes and categories, and the relevant data obtained for each 

hazard will also facilitate the gathering of data to document the effectiveness and completeness 

of the classification 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 data retrieved should be listed in the basic format of the SDS to facilitate preparation of 

SDSs and labels, as well as to allow for future updating as the need arises. As you would expect, 

OSHA recommends that the data be computerized and archived in a secure location for future 

use. A commonly used phrase for hazard data compilations for specific chemicals is hazards 

profile. A suggested organization for the documentation is provided in Table VI.1.

Table VI.1. 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.)

TYPE OF INFORMATION DATA

Company Information  Company Name, address, and 

telephone number 

 Name of Responsible Company Official 

 Date Prepared 

Hazards Identification  Hazard classification (list appropriate 

health and physical hazards, including the 

classification rationale)

Hazardous Ingredients/Identity Information  Chemical Name 

 Common Name and Synonyms 

 CAS Number or other unique identifiers

 Impurities and stabilizing additives 

 Product/Mixture Name (If Applicable) 

 Percentage of Ingredients in 

Product/Mixture (If Applicable) 

Description of Controls and 

Protective Measures

 First-aid measures

 Fire-fighting measures

 Accidental release measures

 Handling and storage

 Exposures control and personal protection
30

TYPE OF INFORMATION DATA

Physical/Chemical Characteristics  Appearance (physical state, color, etc.)

 Odor

 Odor threshold

 pH

 Melting point/freezing point

 Initial boiling point and boiling range

 Flash point

 Evaporation rate

 Flammability (solid, gas)

 Upper/lower flammability or 

explosive limits

 Vapor pressure

 Vapor density

 Relative density

 Solubility(ies)

 Partition coefficient: n-octanol/water

 Auto-ignition temperature

 Decomposition temperature

 Viscosity

Reactivity Data  Reactivity

 Chemical stability 

 Possibility of hazardous reactions

 Conditions to avoid (e.g., static discharge, 

shock, or vibration)

 Incompatible materials 

 Hazardous decomposition or byproducts 

Health Hazard Data  Description of the various toxicological 

(health) effects and the available data used 

to identify those effects, including:

 Information on the likely routes of 

exposure (inhalation, ingestion, skin 

and eye contact);

 Symptoms related to the physical, 

chemical and toxicological 

characteristics;

 Delayed and immediate effects and also 

chronic effects from short- and longterm exposure;

 Numerical measures of toxicity (such 

as acute toxicity estimates); and
31

TYPE OF INFORMATION DATA

 Whether the hazardous chemical is 

listed as a carcinogen or potential 

carcinogen by

o National Toxicology Program 

(NTP) Report on Carcinogens 

(latest edition), or

o International Agency for Research 

on Cancer (IARC) Monographs 

(latest edition), or OSHA.

Other Miscellaneous Information

List of Hazardous Chemicals 

The Hazard Communication Standard requires employers to maintain a list of hazardous 

chemicals present in the workplace as a part of the Written Hazard Communication Program 

(29 CFR 1910.1200(e)). The purpose of having a list of hazardous chemicals at your facility is 

to document those chemicals used or stored at the facility. Not only will the list facilitate the 

identification of the hazards presented by the hazardous chemicals at the facility or in a given 

work area, a complete list of chemicals also may help identify the information you already have 

on the chemicals or other ingredients used in production of the final product. Since safety data 

sheets are required for the chemicals you receive, this may be a good place to start the list. The 

hazards profile developed for each chemical (discussed above) also may be useful to determine 

which of the chemicals in the facility or work area are considered hazardous. 

If a chemical meets the definition of hazardous chemical, as defined by the Hazard 

Communication Standard, and the hazardous chemical is one that requires classification, then it 

must be included on the hazardous chemicals list. OSHA recommends that the list be 

alphabetized to ease retrieval, stored so that it may be accessed easily, and archived in a secure 

location for future use. 
32

VII. CLASSIFICATION OF HEALTH HAZARDS

Introduction 

Health hazards presented by chemicals can harm human health through a variety of routes. 

Workers can be exposed to hazards by inhaling vapors, mists, or dusts from the chemical; by 

ingesting the chemical; or by getting it on their skin. Symptoms from exposure can be acute or 

chronic. The hazards include those that affect eyes, skin, reproductivity, and specific target 

organs. In addition, some chemicals can be toxic, corrosive, or carcinogenic. 

Classification of health hazards is based on data found in available literature, as a result of a 

calculation, or through the use of other criteria specific to the health hazard itself. The Hazard 

Communication Standard does not require the testing of chemicals -- only the collection and 

analysis of currently available data. However, if you choose to test the substance or mixture, the 

test methods used must be scientifically validated. OSHA has provided scientifically validated test 

methods in the appropriate health hazard chapters to ensure proper classification under the HCS. 

Selection of Hazard Classes 

Once the chemical manufacturer, importer, or classifier has collected the data, that information is 

compared to the classification criteria for each hazard class. The decision logic included in this 

guidance for each health hazard can be used to identify the appropriate hazard class and category 

of the chemical. As mentioned throughout this guidance document, many hazardous chemicals 

have more than one physical hazard and/or health hazard. Each hazard must be presented on the 

label, 29 CFR 1910.1200(f)(2), and SDS, 29 CFR 1910.1200(g)(2) as specified in HCS Appendix 

C, Allocation of Label Elements, and HCS Appendix D, Minimum Information for an SDS. 

Classification examples:

In addition to the classification examples provided at the end of each chapter in this section, the 

United Nations Sub-Committee of Experts on the GHS has developed several classification 

examples and posted them as guidance on their website. The examples are at the following 

location: www.unece.org/trans/danger/publi/ghs/guidance.html.

VII.1 Acute Toxicity 

Introduction

The HCS 2012 classifies chemical agents as acutely toxic based on the number of deaths that occur 

following brief (acute) exposure of test animals. The difference in the 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 

four-hour exposure. The LD50 and LC50 represent the dose or concentration, respectively, at 

which 50 percent of the test animals (and, presumptively, humans) will be expected to die. 
33

While these criteria are based on laboratory animals that are quite different from humans, the 

relative response between animals and humans is generally comparable on a per body weight 

basis. Thus, the LD50 is expressed in terms of kilogram of body weight in order to determine 

potential human effects based on animal research results. For example, if a chemical has a 50 

mg/kg LD50, it would be expected to be lethal to approximately 50 percent of humans weighing 

150 pounds at a dose of 3.4 grams or approximately about three quarters of a teaspoon.6 On the 

other hand, the LC50 value is expressed as weight of test substance per standard volume of air 

(mg/1) for vapors, dust, and mists, or as volume parts per million (ppmV) for gases. 

Classification for acute toxicity can also be based on human evidence which shows lethality 

following human exposure. 

Definition and General Considerations 

Acute toxicity refers to those adverse effects occurring following oral or dermal administration of 

a single dose of a substance, or multiple doses given within 24 hours, or an inhalation exposure 

of 4 hours.

The Acute Toxicity Estimate (ATE) for the classification of a substance is derived using the 

LD50/LC50 where available. The ATE for the classification of a substance or ingredient in a 

mixture is derived using: 

(i) the LD50/LC50 where available. Otherwise, 

(ii) the appropriate conversion value from Table VII.1.6 that relates to the results of a range 

test, or 

(iii) the appropriate conversion value from Table VII.1.6 that relates to a classification 

category. 

Classification Criteria for Substances 

Substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, 

dermal or inhalation route according to the numeric cut-off criteria shown in Tables VII.1.1 

through VII.1.5. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or 

LC50 (inhalation) values or as acute toxicity estimates (ATE). 

Acute Oral Toxicity Categories and Classification Criteria 

There are four classification categories for acute oral toxicity. The category is assigned according 

to the HCS 2012 classification criteria for acute oral toxicity, as follows: 

 

6

150 lb. x 0.454 kg/lb.= 68.1 kg; 

 68.1 kg x 50mg/kg = 3405 mg; 

3.5 g ÷ 454 g/lb. = 7.5 x 10-3 lbs.; 

7.5 x 10-3lbs. = 0.12 oz.; 

0.12 oz. = 0.72 tsp. 
34

Table VII.1.1. Acute Oral Toxicity Categories and Classification Criteria 

Classification 

Criteria Category 1 Category 2 Category 3 Category 4

Oral LD50 ≤ 5

mg/kg 

bodyweight

>5 and ≤ 50 

mg/kg 

bodyweight 

>50 and ≤ 300 

mg/kg 

bodyweight 

>300 and ≤ 2000 

mg/kg bodyweight 

Acute Dermal Toxicity Categories and Classification Criteria 

There are four classification categories for acute dermal toxicity. The category is assigned 

according to the HCS 2012 classification criteria for acute dermal toxicity, as follows: 

Table VII.1.2. Acute Dermal Toxicity Categories and Classification Criteria 

Classification 

Criteria Category 1 Category 2 Category 3 Category 4

Dermal LD50 ≤ 50

mg/kg 

bodyweight

>50 and ≤ 200

mg/kg 

bodyweight 

>200 and ≤ 1000

mg/kg bodyweight 

>1000 and ≤ 2000

mg/kg bodyweight 

Acute Inhalation Toxicity Categories and Classification Criteria 

There are four classification categories for acute inhalation toxicity. The category is assigned 

according to the HCS 2012 classification criteria for acute inhalation toxicity. 

Values for inhalation toxicity are based on 4-hour tests in laboratory animals. When 

experimental values are taken from tests using a 1-hour exposure, to avoid the need to retest, 

they can be converted to a 4-hour equivalent as explained below. Units for inhalation toxicity are 

a function of the form of the inhaled material. Values for vapors, dusts, and mists are expressed 

in mg/l. Values for gases are expressed in ppmV. The equation for converting mg/L to ppm 

where ppm is parts per million and MW is molecular weight is: 

mg

L

⁄ =

ppm × MW

24,450

Gases 

Gas means a substance which (i) at 50 °C (122 °C)has a vapor pressure greater than 300 kPa; or 

(ii) is completely gaseous at 20 °C (68 °F) at a standard pressure of 101.3 kPa. 

Inhalation cut-off values are based on 4-hour testing exposures. Conversion of existing 

inhalation toxicity data which has been generated according to 1-hour exposure is achieved by 

dividing by a factor of 2 for gases. For gases, LC50 (4-hr.) is equivalent to LC50 (1-hr.) divided by 

a factor of 2. 
35

Table VII.1.3. Gases: Acute Inhalation Toxicity Categories and Classification Criteria 

Classification 

Criteria Category 1 Category 2 Category 3 Category 4

Inhalation 

LC50 (4-hr.)

≤ 100 

ppmV 

>100 and ≤ 500

ppmV 

>500 and ≤ 2500

ppmV 

>2500 and ≤ 20000

ppmV 

Vapors 

Vapor means the gaseous form of a substance or mixture released from its liquid or solid state. 

Inhalation cut-off values are based on 4-hour testing exposures. Conversion of existing 

inhalation toxicity data which has been generated according to 1-hour exposure is achieved by 

dividing by a factor of 2 for vapors. For vapors, LC50 (4-hr.) is equivalent to LC50 (1-hr.) divided 

by a factor of 2. 

For some substances, the test atmosphere will be a combination of liquid and gaseous phases. 

For other substances, the test atmosphere may be nearly all the gaseous phase. For those test 

atmospheres which are near the gaseous phase, classification should be based on the cutoff 

values for gases in units of ppmV (refer to table for gases, above). 

Table VII.1.4. Vapors: Acute Inhalation Toxicity Categories and Classification Criteria 

Classification 

Criteria Category 1 Category 2 Category 3 Category 4

Inhalation 

LC50 (4-hr.)

≤ 0.5

mg/L

>0.5 and ≤ 2.0

mg/L

>2.0 and ≤ 10.0

mg/L

>10.0 and ≤ 20.0

mg/L

Dusts and Mists 

Dust means solid particles of a substance or mixture suspended in a gas (usually air). Dust is 

generally formed by mechanical processes. 

Mist means liquid droplets of a substance or mixture suspended in a gas (usually air). Mist is 

generally formed by condensation of supersaturated vapors or by physical shearing of liquids.

Dusts and mists generally have sizes ranging from less than 1 to about 100 μm. 

Inhalation cut-off values are based on 4-hour testing exposures. Conversion of existing 

inhalation toxicity data which has been generated according to 1-hour exposure is achieved by 

dividing by a factor of 4 for dusts and mists. For dusts and mists, LC50 (4-hr.) is equivalent to 

LC50 (1-hr.) divided by a factor of 4. 
36

Table VII.1.5. Dusts and Mists: Acute Inhalation Toxicity Categories and 

Classification Criteria 

Classification 

Criteria Category 1 Category 2 Category 3 Category 4

Inhalation 

LC50 (4-hr.)

≤ 0.05

mg/L

>0.05 and ≤ 0.5

mg/L

>0.5 and ≤ 1.0

mg/L

>1.0 and ≤ 5.0

mg/L

Classification criteria for mixtures

For mixtures, it is necessary to obtain or derive information that allows the criteria to be applied 

to the mixture for the purpose of classification. The approach to classifying mixtures for acute 

toxicity is tiered, and is dependent upon the amount of information available for the mixture 

itself and for its ingredients. The flowchart below outlines the process to be followed: 

Figure VII.1.1. Tiered approach to classification of mixtures for acute toxicity 

Test data on the mixture as a whole

No Yes

Sufficient data available on 

similar mixtures to estimate 

classification hazards

Apply bridging principles in A.1.3.5 CLASSIFY

No

Available data for all 

ingredients

Apply formula in A.1.3.6.1 CLASSIFY

Other data available to 

estimate conversion 

values for classification

Apply formula in A.1.3.6.1 CLASSIFY

Convey hazards of the 

known ingredients

Apply formula in A.1.3.6.1 

(unknown ingredients ≤ 10%) or

Apply formula in A.1.3.6.2.4 

(unknown ingredients > 10%)

CLASSIFY

Yes

Yes

Yes

No

No

It should be noted that the classification criteria for acute toxicity includes a tiered scheme in 

which test data available on the complete mixture are considered as the first tier in the 

evaluation, followed by the applicable bridging principles, and lastly, use of additivity formulas. 

Tier 1

Tier 2

Tier 3
37

Tier 1: Classification of mixtures when data are available for the complete mixture 

When acute toxicity test data on the mixture as a whole is available, it must be used to classify 

the mixture using the same criteria as those specified for substances. If acute toxicity test data for 

the mixtures is not available, then the classifier can consider the application of the bridging 

principle criteria in Tier 2, if appropriate, or use the classification resulting from the application 

of criteria in Tier 3. 

Tier 2: Classification of mixtures when data are not available for the complete mixture – 

bridging principles 

Where the mixture itself has not been tested to determine its acute toxicity, but there are 

sufficient data on BOTH the individual ingredients AND similar tested mixtures to adequately 

characterize the hazards of the mixture, these data can be used in accordance with the bridging 

principles, below. 

All six bridging principles are applicable to the acute toxicity hazard class: 

 Dilution 

 Batching 

 Concentration of mixtures 

 Interpolation within one toxicity category 

 Substantially similar mixtures, and 

 Aerosols. 

The application of bridging principles ensures that the classification process uses the available 

data to the greatest extent possible in characterizing the potential acute toxicity hazard. 

Dilution 

If a tested mixture is diluted with a diluent that has an equivalent or lower toxicity 

classification than the least toxic original ingredient, and which is not expected to affect 

the toxicity of other ingredients, then the new diluted mixture may be classified as 

equivalent to the original tested mixture. Alternatively, the additivity formula explained 

below and in A.1.3.6.1 could be applied. 

Batching 

The toxicity of a tested production batch of a mixture can be assumed to be substantially 

equivalent to that of another untested production batch of the same commercial product, 

when produced by or under the control of the same manufacturer, unless there is reason 

to believe there is significant variation such that the toxicity of the untested batch has 

changed. If the latter occurs, a new classification is necessary. 
38

Concentration of mixtures 

If a tested mixture is classified in Category 1, and the concentration of the ingredients of 

the tested mixture that are in Category 1 is increased, the resulting untested mixture 

should be classified in Category 1 without additional testing. 

Interpolation within one toxicity category 

For three mixtures (A, B and C) with identical ingredients, where mixtures A and B have 

been tested and are in the same toxicity category, and where untested mixture C has the 

same toxicologically active ingredients as mixtures A and B but has concentrations of 

toxicologically active ingredients intermediate to the concentrations in mixtures A and B, 

then mixture C is assumed to be in the same toxicity category as A and B. 

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

 (ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) Data on toxicity for A and C are available and substantially equivalent, i.e., 

they are in the same hazard category and are not expected to affect the acute 

toxicity of B. 

If mixture (i) or (ii) is already classified by testing, then the other mixture can be 

classified in the same hazard category. 

Aerosols 

An aerosol form of a mixture may be classified in the same hazard category as the tested, 

non-aerosolized form of the mixture for oral and dermal toxicity provided the added 

propellant does not affect the toxicity of the mixture on spraying. Classification of 

aerosolized mixtures for inhalation toxicity should be considered separately. 

If appropriate data is not available to apply the above bridging principles, then the classifier 

applies the criteria in Tier 3. 

Tier 3: Classification of mixtures based on ingredients of the mixture (additivity formula) 

The basic approach to estimating a mixture’s acute toxicity in Tier 3 is to calculate an Acute 

Toxicity Estimate for the mixture (ATEmixture) which represents the expected LD50/LC50 of the 

mixture. This is accomplished by collecting the LD50/LC50 for each ingredient if it is known or a 

point estimate of an ingredient’s LD50/LC50 if either a classification or an acute toxicity range 

from a limit dose test is known. 
39

The rules for applying the additivity formula are dependent on whether acute toxicity 

information is available for all the ingredients of a mixture. This accommodation was made 

because the mathematics involved in applying the additivity formula implicitly assumes that any 

ingredient not included in the calculation has a dilution effect on the calculated ATEmixture. The 

two acute toxicity additivity formulas and rules for their use are discussed below. 

Data available for all ingredients 

Rules on when to include or ignore ingredients in the ATEmixture calculation are provided to 

ensure consistent application of the additivity formula.

Include: 

(a) Ingredients with a known acute toxicity, which fall into any of the acute toxicity 

categories, or have an oral or dermal LD50 greater than 2000 but less than or equal to 

5000 mg/kg body weight (or the equivalent dose for inhalation). This includes GHS 

Acute Toxicity Category 5 in the ATEmixture calculation.7

Ignore: 

(a) Ingredients with a known acute toxicity outside the level specified above can be 

ignored in the calculation. For example, an ingredient with an Oral LD50 (rat) of > 5,000 

mg/kg could be ignored. 

(b) Ingredients that are presumed not acutely toxic (e.g., water, sugar); 

Application of this rule requires expert judgment to determine if an ingredient 

meets the intent of the requirement. Ingredients that are not biologically available 

could be considered “presumed not acutely toxic”. 

 

7

 The criteria for GHS Category 5 are: 

(i) The chemical is classified in category 5 if reliable evidence is available that indicates (1) the oral/dermal LD50

is in the range of >2000 and ≤5000 mg/kg bodyweight and the LC50 is in the equivalent range of the oral and 

dermal LD50 (i.e., >2000 and ≤ 5000 mg/kg bodyweight) or (2) other animal studies or toxic effects in humans 

indicate a concern for human health of an acute nature. 

(ii) The chemical is classified in category 5, through extrapolation, estimation or measurement of data, if 

assignment to a more hazardous category is not warranted, and: 

- reliable information is available indicating significant toxic effects in humans; or 

- any mortality is observed when tested up to Category 4 values by the oral, inhalation, or dermal routes; or 

- where expert judgment confirms significant clinical signs of toxicity, when tested up to Category 4 values, 

except for diarrhea, piloerection or an ungroomed appearance; or 

- where expert judgment confirms reliable information indicating the potential for significant acute effects from 

other animal studies. 

The HCS does not require classification in this category.
40

(c) Ingredients for which the data available are from a limit dose test8(at the upper 

threshold for Category 4 for the appropriate route of exposure, e.g., oral LD50 = 2000) 

and do not show acute toxicity. 

The ATE of the mixture is determined by calculation from the LD50-LC50-ATE values for 

all relevant ingredients according to the following formulas for oral, dermal or inhalation 

toxicity. More information on relevant ingredients can be found below under “important 

considerations.” 

Formula 1A: 

 

n i

i

mix ATE

C

ATE

100

Where: 

Ci = concentration of ingredient I 

n ingredients and i is running from 1 to n 

ATEi = Acute Toxicity Estimate of ingredient i 

ATEmix= Acute Toxicity Estimate of mixture 

Formula 1B is a different way of expressing Formula 1A that may be easier to 

understand. The formula is essentially calculating the ATEmixture or LD50/LC50 of the 

mixture. C is the concentration of the ingredients expressed as a percentage. The math is 

addition, multiplication and division. 

Formula 1B: 

100 (%)

ATEmix

=

C1

LD50 (1)

+

C2

LD50(2)

+

C3

LD50(3)

+

C4

LD50(4)

+∙∙∙∙∙∙∙∙∙

Cetc

LD50(etc )

or

ATEmix =

100 (%)

C1

LD50 (1)

+

C2

LD50(2)

+

C3

LD50(3)

+

C4

LD50(4)

+∙∙∙∙∙∙∙∙∙

Cetc

LD50(etc )

Data are not available for one or more ingredients 

If the total concentration of the relevant ingredient(s) with unknown acute toxicity is  10%

then Formula 1A or 1B as shown above must be used. 

 

8

 Limit dose test – the preferred test when toxicity is expected to be low and lethality is unlikely at the limit dose. 

The limit dose must be adequate for assessment purposes, and it is usually 2000 mg/kg body-weight. 
41

However, if the total concentration of ingredient(s) with unknown toxicity is > 10% then the 

“corrected” additivity formula which adjusts for the total percentage of unknown ingredient(s) 

must be used. The “corrected” additivity formula corrects the left hand side of the ATE 

formula by subtracting the total percent of unknowns, if they exceed 10%, from 100. 

Formula 2A:

ATEi

Ci

ATEmix n



 

100  unknown C( if  10% )

Formula 2B is a different way of expressing Formula 2A that may be easier to 

understand. C is the concentration of the ingredients expressed as a percentage. The math 

is addition, multiplication and division. 

Formula 2B: 

100 % − ∑ Cunk if > 10% 

ATEmix

=

C1

LD50 (1)

+

C2

LD50(2)

+

C3

LD50(3)

+

C4

LD50(4)

+∙∙∙∙∙∙∙∙∙

Cetc

LD50(etc )

or

ATEmix =

100 % − ∑ Cunk if > 10% 

C1

LD50 (1)

+

C2

LD50(2)

+

C3

LD50(3)

+

C4

LD50(4)

+∙∙∙∙∙∙∙∙∙

Cetc

LD50(etc )

Important considerations 

An important consideration when applying the additivity formula is recognition that the 

additivity formula is applied to each route of exposure separately. In other words, ATEmixture is 

calculated for a specific route (e.g., oral, dermal, and inhalation) and the ingredient LD50/LC50

values and point estimates used in a calculation must correspond to the specific route (and 

physical state for inhalation) for which the ATEmixture is being calculated. 

Consistent application of the additivity formula 

In order to ensure consistent application of the additivity formula guidance is provided on: 

 When ingredients should be included in the ATE calculation, 

 When ingredients can be ignored in the ATE calculation, and 

 How to convert an acute toxicity range estimate from a limit dose test or hazard 

classification into a point estimate for use in the ATEmixture calculation. 
42

The following guidance needs to be considered when calculating the ATEmixture: 

 “Relevant Ingredient” Concept 

For the purpose of the ATEmixture calculation, only “relevant ingredients” need to be included 

when applying the additivity formula. The general rule is to only include ingredients at a 

concentration of  1% in the calculation. However, an ingredient could still be considered 

relevant and included in the calculation at a concentration of < 1% if the classifier suspects 

that the ingredient could be relevant for classifying the mixture. The relevant ingredient 

criteria particularly point out that consideration should be given to include Category 1 and 

Category 2 ingredients at concentrations <1%. In these cases, the classifier must use expert 

judgment to determine at what concentration below 1% Category 1 or 2 ingredients should be 

included in the calculation. Important points to consider when making the decision are: 

o The lower the LD50/LC50, the more significant its impact is on the calculation since 

the additivity formula is a proportional calculation which places a greater weight on 

more toxic ingredients in the calculation. The decision to exclude an ingredient could 

result in underestimating the acute toxicity of the mixture.

o As the total number of Category 1 and/or Category 2 ingredients increases in a 

mixture, a decision not to include them in the ATEmixture calculation with 

concentrations below 1% may result in underestimating the acute toxicity of the 

mixture since the additivity formula places greater weight on more toxic ingredients 

and the additivity effect of multiple ingredients would not be considered in the 

ATEmixture calculation. 

 Unknown acute toxicity 

In the event that an ingredient with unknown acute toxicity is used in a mixture at a 

concentration ≥ 1%, and the mixture has not been classified based on testing of the mixture 

as a whole, the mixture cannot be attributed a definitive acute toxicity estimate. In this 

situation, the mixture is classified based on the known ingredients only. A statement that “X 

percent of the mixture consists of ingredient(s) of unknown acute toxicity” is required on the 

label and safety data sheet in such cases. See 29 CFR 1910.1200 Appendix C, Allocation of 

Label Elements and Appendix D, Safety Data Sheets. 

The unknown acute toxicity statement is only required on the label and the SDS where the 

chemical mixture is already classified as acutely toxic for a particular route of exposure, and 

there are one or more other “relevant ingredients” (as defined above) of unknown acute toxicity 

for that particular route. 

Classifiers may present the unknown acute toxicity information on ingredients either as a single 

statement or as multiple statements, where routes are differentiated. If there is acute toxicity by 

more than one route of exposure and the classifier chooses to provide one statement, then the 

route with the highest total percentage unknown toxicity from one or more relevant ingredients 

will be used in the statement. 
43

The single statement on the label would read: 

Y% of the mixture consists of ingredients of unknown acute toxicity. 

Because it is possible to have ingredients with unknown toxicity for more than one route (e.g., 

oral, dermal, inhalation), differentiating the unknown toxicity statement by route is 

recommended. As such, classifiers may also communicate the information as: 

X% of the mixture consist of ingredient(s) of unknown acute oral toxicity 

X% of the mixture consists of ingredient(s) of unknown acute dermal toxicity 

X% of the mixture consists of ingredient(s) of unknown acute inhalation toxicity 

The GHS clarified the classification criteria with regard to the unknown toxicity statement in 

Revision 4 to indicate that the statement of unknown toxicity should be differentiated by route. 

The HCS adopted Revision 3 of the GHS and thus does not require the unknown toxicity 

statement to be differentiated by route. However, OSHA’s recommendation is that classifiers 

follow the guidance provided in Revision 4 of the GHS (see GHS Rev. 4 paragraphs 3.1.3.6.2.2 

and 3.1.4.2).

Example 1: 

Mixture A: Relevant routes of exposure are Oral and Dermal 

Ingredient Wt%

Ingredient with unknown Acute toxicity

Oral Route

Dermal 

Route

Inhalation 

Route

X 10 Yes

Y 30 Yes

Z 60 Yes Yes

Using the data for Mixture A above it would be appropriate to have: 

1. The statements on the SDS would read: 

70% of the mixture consists of ingredients of unknown acute inhalation toxicity 

60% of the mixture consists of an ingredient of unknown acute dermal toxicity 

30% of the mixture consists of an ingredient of unknown acute oral toxicity 

2. The single statement on the label would read: 

70% of the mixture consists of ingredients of unknown acute toxicity 
44

 Mixtures containing other mixtures 

When a mixture (i.e., Mixture A) is used as an ingredient of another mixture either an 

actual LD50/LC50 value or the calculated toxicity estimate (ATE) for Mixture A may be 

used in the ATEmixture calculation for the new mixture instead of using the LD50/LC50

values or point estimates for each ingredient of Mixture A.

 Conversion from experimentally obtained acute toxicity range values (or acute 

toxicity hazard categories) to acute toxicity point estimates for use in the formulas 

for the classification of mixtures 

The additivity formula requires a single numeric value for each ingredient included in the 

ATEmixture calculation. If an LD50/LC50 is available it should be used in the ATE 

Calculation. In those cases where the only known information about an ingredient is 

its hazard category, Table VII.1.6 can be used to look up the converted acute toxicity 

point estimate. 

Additionally, in those cases where a limit dose test was used to establish a LD50/LC50

range, the range may also be converted to a acute toxicity point estimate using Table 

VII.1.6. Limit dose data generated prior to the creation/adoption of the GHS acute 

toxicity substance criteria will not always match the ranges specified in Table VII.1.6 

since GHS criteria represent a change in ranges for many existing regulatory systems. In 

those cases where existing limit dose data do not exactly match the ranges in Table 

VII.1.6, expert judgment will be necessary to determine what point estimate to use in the 

ATEmixture calculation. 

As you can see below, the converted acute toxicity point estimate is conservative and 

where there is a lack of data it would tend to classify the mixture into a more hazardous 

subcategory. OSHA would expect a similar approach if using alternate ranges. 

Table VII.1.6. Conversion from experimentally obtained acute toxicity range values (or 

acute toxicity hazard categories) to acute toxicity point estimates for use in the formulas for 

the classification of mixtures 

Exposure routes Classification category or experimentally 

obtained acute toxicity range estimate

Converted acute toxicity 

point estimate

Oral

(mg/kg bodyweight)

0 < Category 1  5 0.5

5 < Category 2  50 5

50 < Category 3  300 100

300 < Category 4  2000 500

Dermal

(mg/kg bodyweight)

0 < Category 1  50 5

50 < Category 2  200 50

200 < Category 3  1000 300

1000 < Category 4  2000 1100
45

Exposure routes Classification category or experimentally 

obtained acute toxicity range estimate

Converted acute toxicity 

point estimate

Gases

(ppmV)

0 < Category 1  100 10

100 < Category 2  500 100

500 < Category 3  2500 700

2500 < Category 4  20000 4500

Vapours

(mg/l)

0 < Category 1  0.5 0.05

0.5 < Category 2  2.0 0.5

2.0 < Category 3  10.0 3

10.0 < Category 4  20.0 11

Dust/mist

(mg/l)

0 < Category 1  0.05 0.005

0.05 < Category 2  0.5 0.05

0.5 < Category 3  1.0 0.5

1.0 < Category 4  5.0 1.5

Note: Gas concentrations are expressed in parts per million per volume (ppmV) 

There is an example at the end of this chapter which illustrates the application of the type of 

expert judgment that can be used when considering how to use existing range data that do not 

match the ranges presented in Table VII.1.6. 

 Data are not available for one or more ingredients of the mixture 

In some cases an ingredient’s LD50-LC50-ATE is not available but other information is 

available that allows for a derived or estimated acute toxicity estimate. 

This approach generally requires substantial supplemental technical information which needs 

to be interpreted by highly trained and experienced experts. The types of information that 

may be considered to derive or estimate an ingredient ATE is provided below. 

(a) Route-to-route extrapolation between oral, dermal and inhalation acute toxicity 

estimates. Such an evaluation requires appropriate pharmacodynamic and 

pharmacokinetic data. 

(b) Evidence from human exposure that indicates toxic effects but does not provide lethal 

dose data. Human evidence can be used to derive an ATE. 

(c) Information from other types of toxicity tests/studies can sometimes be useful in 

deriving an acute toxicity classification. These studies will not usually provide an LD50-

LC50-ATE value that can be used directly for classification, but they may provide 

information to allow an estimate of acute toxicity. 
46

(d) Data from closely analogous substances using structure activity relationships (SAR) 

may be used to estimate an ATE. 

In cases where such information is not available, then the criteria provided in 29 CFR 

1910.1200 paragraph A.1.3.6.2.4 must be reviewed to determine if the modified additivity 

formula should be used for the ATEmixture calculation. 

Relevant routes of exposure 

The ATEmixture calculation is not automatically required for all routes of exposure. The 

calculation need be done for only one route of exposure as long as all the ingredients have actual 

LD50/LC50 values or a converted acute toxicity point estimate for use in that route’s ATEmixture

calculation. However, if there is relevant evidence suggesting acute toxicity by multiple routes of 

exposure then the ATEmixture should be calculated for all the appropriate routes of exposure. 

The use of expert judgment will be necessary to evaluate each ingredient’s acute toxicity 

information, across all routes of exposure, and determine if that data support calculating the 

ATEmixture across multiple routes of exposure. There is an example at the end of this chapter 

which illustrates the concept of evaluating the relevant substance data to determine which 

route(s) need to be calculated. 

An additional important point to consider when deciding which route(s) to calculate is an 

understanding of how the HCS is structured. The HCS applies to any chemical which is known 

to be present in the workplace in such a manner that employees may be exposed to hazards under 

normal conditions of use or in a foreseeable emergency. Consideration of a “foreseeable 

emergency” or “misuse” of chemicals may be needed in addition to considering the normal use 

of chemicals. It is possible that such considerations may influence the decision on which route(s) 

are needed for ATEmixture calculations. 

Classification Procedure and Guidance 

Test Data 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS only 

requires classifiers to collect and evaluate the best available existing evidence on the hazards of 

each chemical. For classification purposes, epidemiological data and experience on the effects of 

chemicals on humans (e.g., occupational data, data from accident databases) must be taken into 

account in the evaluation of human health hazards of a chemical. 

Data generated in accordance with recognized scientific principles are acceptable under HCS 

2012. If valid data on acute toxicity of a substance or mixture are available (LD50/LC50), these 

data must be used in the classification.

ATEi

Ci

ATEmix n



 

100  unknown C( if  10% )
47

Examples of scientifically validated test methods 

There are a number of test methods that use recognized scientific principles for investigation of 

acute toxicity: 

Acute Oral Toxicity: 

 OECD Test Guideline 401: Acute Oral Toxicity. This test method was deleted in 

December 2002 because of animal welfare concerns. Classical acute toxicity studies are 

based on lethality, e.g., LD50 values. 

 OECD Test Guideline 420: Acute Oral Toxicity – Fixed Dose Procedure provides a range 

estimate of the oral LD50. Contemporary test methods use clinical signs of nonlethal 

toxicity (evident toxicity).

 OECD Test Guideline 423: Acute Oral Toxicity – Acute Toxic Class Method provides a 

range estimate of the oral LD50.

 OECD Test Guideline 425: Acute Oral Toxicity – Up-and-Down-Procedure (UPD) 

provides a point-estimate of the LD50 value with confidence intervals. 

 USEPA OTS code: 798.1175; 

 USEPA OPP code: 81-1; 

 USEPA OPPTS code: 870.1100; 

 EEC Directive 92/32/EEC (B.1 bis & B.1 tris). 

Acute Dermal Toxicity: 

 OECD Test Guideline 402: Acute Dermal Toxicity. The preferred test species are rats, 

rabbits, or guinea pigs.

 USEPA OTS code: 798.1100; 

 USEPA OPP code: 81-2; 

 USEPA OPPTS code: 870.1200; 

 EEC Directive 92/32/EEC (B.3). 

Acute Inhalation Toxicity: 

 OECD Test Guideline 403: Acute Inhalation Toxicity. The test exposure period is usually 

4 hours. The preferred test species is the rat.

 USEPA OTS code: 798.1150; 

 USEPA OPP code: 81-3; 

 USEPA OPPTS code: 870.1300 & 870.1350; 

 EEC Directive 92/32/EEC (B.2). 

There are currently no internationally recognized in vitro tests for acute toxicity. 

See the above guidance on using Table VII.1.6 to convert a LD50/LC50 range from a limit dose 

test to an acute toxicity point estimate. Where an existing LD50/LC50 range does not exactly 

match the ranges in Table VII.1.6, expert judgment will be necessary to determine what point 

estimate to use in the ATEmixture calculation. 
48

Test species 

The preferred test species for evaluation of acute toxicity by the oral and inhalation routes is the 

rat, while the rat or rabbit are preferred for evaluation of acute dermal toxicity. Test data already 

generated for the classification of chemicals under existing systems should be accepted when 

reclassifying these chemicals under HCS 2012. When experimental data for acute toxicity are 

available in several animal species, scientific judgment should be used in selecting the most 

appropriate LD50 value from among scientifically validated tests. 

Although the HCS provides specific classification criteria, including the appropriate test methods 

and species to use for evaluation, 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 recognized scientific principles. If the studies are acceptable, the data should be 

used as appropriate to determine whether the chemical is acutely toxic, or belongs to another 

health hazard category (e.g., hepatotoxicity or irritant). 

The ATE is usually obtained from animal studies but in principle suitable human data can also be 

used if available. Where human data are available they should be used to estimate the ATE 

which can be used directly for classification as described above. 

Corrosivity 

In addition to classification for inhalation toxicity, if data are available that indicates that the 

mechanism of toxicity was corrosivity of the substance or mixture, the classifier should consider 

if the chemical is corrosive to the respiratory tract. Corrosion of the respiratory tract is defined as

destruction of the respiratory tract tissue after a single, limited period of exposure analogous to 

skin corrosion; this includes destruction of the mucosa. The corrosivity evaluation could be 

based on expert judgment using such evidence as: human and animal experience, existing (in 

vitro) data, pH values, information from similar substances or any other pertinent data. 

If data are available that indicates acute inhalation toxicity with corrosion of the respiratory tract 

that leads to lethality, the chemical may be labeled ‘corrosive to the respiratory tract’. The 

corrosion pictogram (used for skin and eye corrosivity) may be added together with the hazard 

statement ‘corrosive to the respiratory tract’. 

If data are available that indicates acute inhalation toxicity with corrosion of the respiratory tract 

and the effect does not lead to lethality, then the hazard may be addressed in the Specific Target 

Organ Toxicity hazard classes as explained in Sections VII.8 and VII.9 of this document. 

Decision Logic 

Two decision logics for classifying acute toxicity are provided. The first decision logic is for 

substances and mixtures where there is test data for the mixture as a whole. The second decision 

logic is for classifying mixtures according to the bridging principles and classification based on 

ingredients of the mixture. The decision logics are provided as additional guidance. It is strongly 

recommended that the person responsible for classification study the criteria before and during 

use of the decision logic. 
49

These decision logics are essentially flow charts for classifying substances and mixtures 

regarding acute toxicity. They present questions in a sequence that walks you through the 

classification steps and criteria for classifying acute toxicity. Once you answer the questions 

provided, you will arrive at the appropriate classification. 

Decision logic #1 for acute toxicity 

(Cont’d on next page)

Substance: Are there data and/or information to evaluate acute toxicity?

Yes

No

No

Yes

Category 1

Danger 

Mixture: Does the mixture as a whole or its ingredients have 

data/information to evaluate acute toxicity?

Yes

No

Classification not 

possible 

According to the Category 2 criteria, does it have an:

(a) Oral LD50 >5 but  50 mg/kg bodyweight; or 

(b) Dermal LD50 >50 but  200 mg/kg bodyweight; or

(c) Inhalation (gas) LC50 >100 but < 500 ppm; or 

(d) Inhalation (vapor) LC50 > 0.5 but < 2.0 mg/l; or

(e) Inhalation (dust/mist) LC50 >0.05 but  0.5 mg/l?

Classification not 

possible 

According to the Category 1 criteria, does it have an: 

(a) Oral LD50  5 mg/kg bodyweight; or 

(b) Dermal LD50  50 mg/kg bodyweight; or 

(c) Inhalation (gas) LC50  100 ppm; or 

(d) Inhalation (vapor) LC50  0.5 mg/l ; or

(e) Inhalation (dust/mist) LC50  0.05 mg/l?

See decision logic #2 to 

calculate an ATE from 

ingredients

Mixture: Does the mixture as a whole have 

data/information to evaluate acute toxicity? No

Yes

Yes

Category 2

Danger 

No

ATE from next decision logic
50

(Cont’d on next page)

No

According to the Category 4 criteria in, does it have an:

(a) Oral LD50 >300 but ≤ 2000 mg/kg bodyweight; or

(b) Dermal LD50 >1000 but ≤ 2000 mg/kg bodyweight; or

(c) Inhalation (gas) LC50 >2500 but ≤ 20000 ppm; or

(d) Inhalation (vapor) LC50 >10 but ≤ 20 mg/l; or

(e) Inhalation (dust/mist) LC50 >1.0 but ≤ 5 mg/l? 

According to the Category 3 criteria, does it have an:

(a) Oral LD50 >50 but ≤ 300 mg/kg bodyweight; or

(b) Dermal LD50 > 200 but ≤ 1000 mg/kg bodyweight; or

(c) Inhalation (gas) LC50 >500 but ≤ 2500 ppm; or

(d) Inhalation (vapor) LC50 >2 but ≤ 10 mg/l; or

(e) Inhalation (dust/mist) LC50 >0.5 but ≤ 1.0 mg/l? 

No

Yes

Category 3

Danger 

Yes

Category 4

Warning 

Not classified 

No
51

Decision logic #2 for acute toxicity (see criteria in A.1.3.5 and A.1.3.6 of the HCS 

(29 CFR 1910.1200))

_____________________ 

1 In the event that an ingredient without any useable information is used in a mixture at a concentration  1%, the 

classification should be based on the ingredients with the known acute toxicity only, and additional statement(s) 

should identify the fact that x % of the mixture consists of ingredient(s) of unknown acute (oral/dermal/inhalation) 

toxicity. See the discussion above for additional guidance on presenting information about unknown toxicity. The 

additional statement(s) must be communicated on the label and in SDS Section 2. 

Is acute toxicity data available 

for all ingredients of mixture? 

See A.1.3.6.1 of HCS 2012 Yes

Is it possible to estimate missing 

ATE(s) of the ingredient(s), i.e., 

can conversion value(s) be 

derived?

Is the total concentration of the 

ingredient(s) with unknown 

acute toxicity > 10%?

No

No

Apply the acute toxicity estimate 

calculation to determine the ATE of

the mixture

where:

Ci = concentration of ingredient i

n = ingredients and i is running 

from 1 to n 

ATEi = Acute toxicity estimate 

of ingredient i. 

Yes

No1

Apply the acute toxicity estimate calculation 

(i.e., when the total concentration of ingredients 

with unknown acute toxicity is > 10%) 

Can bridging principles be applied?

No

 Yes

Classify in 

appropriate 

category

ATEmix

to decision 

logic #1

ATEmix

to decision 

logic #1

Yes1
52

Acute Toxicity Classification Examples 

The following examples are provided to demonstrate the acute toxicity calculation and 

classification process. 

Examples of a substance fulfilling the criteria for classification: 

Substance Example #1

Acute Toxicity - Corrosive Substance

Test Data 

HCS 2012

Classification Rationale

Toxicity data:

In a GLP-compliant acute toxicity 

study in rats the following results 

were observed:

At a test dose of 200 mg/kg bw: 

no mortality, only transient 

symptoms and no necropsy 

findings

At a test dose of 500 mg/kg: 

100% mortality, symptoms: poor 

general state; necropsy findings: 

hyperemia in stomach (due to 

local irritation/corrosivity), no 

other organs affected

Acute Toxicity 

Oral Category 4

Since at a dose of 200 mg/kg bw no 

mortality and only slight transient 

symptoms without necropsy findings 

were observed, and at 500 mg/kg bw 

the high amount/concentration of the 

corrosive substance caused serious 

effect only at the site of action and 

mortality, based on expert judgment 

it can be assumed that the likely 

LD50 is > 300 mg/kg bw. Therefore, 

the Acute Toxicity Estimate (ATE) 

value for classification purpose is 

between 300 and 500 mg/kg bw, 

corresponding to Category 4 

classification for acute toxicity.

Substance Example #2

Acute Toxicity Use of Human Data 

Test Data 

HCS 2012

Classification Rationale

Toxicity Data: 

Animal test data: LD50 (rat) > 

5,000 mg/kg bw (several values)

Human experience: lethal in 

relatively low dose range (ca. 

300-1,000 mg/kg)

Acute Toxicity

Oral Category 3

Valid human data from a large data 

base (case studies) have precedence 

over animal data; the rat in this case 

is not the appropriate test species. 
53

Substance Example #3

Acute Toxicity - Dermal

Test Data 

HCS 2012

Classification Rationale

Toxicity Data: 

Aromatic Amine

Animal test data: LD50 (rat) > 

2,000 mg/kg bw

Human experience: many lethal 

intoxications at relatively low 

doses after dermal exposure (dose 

range of 200 to 1000 mg/kg bw) 

Acute Toxicity 

Dermal Category 3

Human experience (valid) has 

precedence over experimental data; 

the rat is not an appropriate species 

for this substance class.

Substance Example #4

Acute Toxicity - Dermal

Test Data 

HCS 2012

Classification Rationale

Animal data:

A study to evaluate the acute 

dermal toxicity was performed in 

rabbits. The following test data 

results were reported:

- At the dose level of 50 mg/kg 

bw: no mortality was observed

- At 200 mg/kg bw: 100% 

mortality 

Therefore, LD50 was estimated to 

be between 50 mg/kg bw and 200

mg/kg bw

Acute Toxicity 

Dermal Category 2

Since the dermal LD50 is above 50 

mg/kg bw and less than 200 mg/kg 

bw, Category 2 classification is 

warranted.
54

Substance Example #5

Acute Toxicity – Inhalation/dust

Test Data 

HCS 2012

Classification Rationale

Toxicity Data:

The acute inhalation toxicity was 

studied in rats in a GLPcompliant study performed 

according to OECD test guideline 

403. The LC50 (1-hr.) = 3 mg/l.

Acute Toxicity 

Inhalation 

Category 3

The classification criteria for acute 

inhalation toxicity refer to a 4-hour

exposure time. Therefore to classify 

a substance, existing inhalation 

toxicity data generated from 1-hour 

exposure should be converted 

accordingly: LC50 values with 1hour

have to be converted by dividing by 

4.

The LC50 (4-hr.) = 0.75 mg/l which 

is Category 3.

Substance Example #6

Acute Toxicity – Inhalation/gas

Test Data 

HCS 2012

Classification Rationale

Animal data:

A GLP-compliant test for acute 

inhalation toxicity (gaseous form) 

was performed in accordance 

with OECD test guideline 403 in 

rats. The LC50 was 4500 ppm/4h.

Acute Toxicity 

Inhalation 

Category 4

LC50 = 4500 ppm is considered an 

Acute Toxicity Estimate (ATE) for 

classification purposes. According to 

the classification criteria for acute 

inhalation toxicity for gases, this 

value corresponds to Category 4. 
55

Substance Example #7

Acute Toxicity – Oral

Test Data 

HCS 2012

Classification Rationale

Oral LD50 : 300 mg/kg bw 

(observed in a GLP-compliant 

study in rats)

Acute Toxicity 

Oral Category 3

LD50 = 300 mg/kg bw is considered 

an Acute Toxicity Estimate (ATE) 

for classification purposes; 

according to the classification 

criteria for acute oral toxicity, 300

mg/kg bw is the upper value for 

Category 3. Therefore, it is assigned 

Category 3 Acute Oral Toxicity 

classification.

Examples of substances not fulfilling the criteria for classification: 

Substance Example #8

Acute Toxicity – Inhalation/Vapors

Test Data 

HCS 2012

Classification Rationale

Toxicity Data:

Three values for acute inhalation 

toxicity of TS10 (vapor form) in 

rats were described. Two studies 

were performed in accordance 

with OECD test guideline 403.

One study was determined not to 

be scientifically valid. The LC50

values were reported as follows: 

LC 50 (4-h): 19 mg/l (not 

scientifically valid)

LC 50 (4-h): 23 mg/l (TG 403)

LC 50 (4-h): 28 mg/l (TG 403)

HCS- No Acute 

Toxicity 

Classification

With 3 different available LC50 

values, a validity check proved that 

the 1st study with 19 mg/l is not 

scientifically valid in contrast to the 

two others; thus, with an ATE> 20 

mg/l the criteria for Category 4 are

not fulfilled.
56

Substance Example #9

Acute Toxicity – Oral

Test Data 

HCS 2012

Classification Rationale

Tested in rats in accordance with 

OECD Test Guideline 423. In a 

limit test at a value of 2000 mg/kg 

bw no mortality or signs of 

toxicity were observed.

No Acute Toxicity 

classification

There was no mortality nor signs of 

toxic effects at the outer limit of 

category 4. Therefore there is no 

acute toxicity classification.

Substance Example #10

Acute Toxicity – Oral

Test Data 

HCS 2012

Classification Rationale

Oral LD50 > 2,000 mg/kg (no 

further details available)

Further information from SDS: 

NOAEL (No Adverse Effect 

Level) in a 90 day oral study > 

3,000 mg/kg bw

No Acute Toxicity 

classification

Does not fulfill criteria for 

classification:

 Oral LD50 > 2,000 mg/kg

 At 3,000 mg/kg after daily 

administration (90 times) of 

3,000 mg/kg no adverse health 

effects (i.e., no toxicity) were 

observed.
57

Example of a mixture fulfilling the criteria for classification 

Mixture Example #1

Acute Toxicity – Dermal 

Data 

HCS 2012

Classification Rationale

Component data:

Component 1: 5%, Dermal LD50

= 40 mg/kg

Component 2: 44%, Dermal LD50

> 200 < 1,000

Component 3: 48%, Dermal LD50

= 90 mg/kg

Component 4: 3%, Acute Dermal 

Toxicity Category 4

Acute Toxicity 

Dermal Category 2

The LD50 data for Components 1 and 

3 are used in the ATEmixture

calculation since data are available.

For Components 1 and 2, apply the 

guidance in Note (b) to Table A.1.1:

 The Dermal LD50 > 200 < 1,000

range estimate for Component 2

is converted to the acute toxicity 

point estimate of 300 mg/kg 

using Table A.1.2. of the HCS. 

 The classification category for 

Component 4 is converted to the 

acute toxicity point estimate of 

1,100 using Table A.1.2.

 

mixture n ATEi

Ci

ATE

100

,1100

3

90

48

300

44

40

100 5



ATEmixture

Dermal ATEmixture = 123 mg/kg, 

Category 2
58

Mixture Example #2

Acute Toxicity – Oral 

Data 

HCS 2012

Classification Rationale

Component data:

Component 1: 16%, oral LD50 =

1,600 mg/kg

Component 2: 4%, oral LD50 > 

200 < 2,000

Component 3: 80%, oral LD50 =

3,450 mg/kg

Acute Oral 

Toxicity 

Category 4

Per A.1.3.6.1 (a) include ingredients 

with a known acute toxicity, which 

fall into any of the acute toxicity 

categories, or have an oral LD50 > 

2000 ≤5000 mg/kg body weight.

The LD50 data for Components 1 and 

3 are used in the ATEmixture

calculation since data are available.

For Component 2, apply the 

guidance in Note (b) to Table A.1.1: 

The use of expert judgment is needed 

to determine what value to use in the 

ATEmixture calculation for Component

2. The oral LD50 > 200 < 2,000 

range for Component 2 does not 

match up with the ranges provided in 

Table A.1.2. The lower end of the 

range falls within the Category 3 

range of 50 – 300 mg/kg and the 

converted acute toxicity point 

estimate for an Oral Category 3 

ingredient is 100. Given that the 

converted point estimate is lower 

than the experimentally determined 

value of > 200 mg/kg it does not 

make sense to use the converted 

point estimate. In this case, one 

should apply the known information, 

and 200 mg/kg should be used in the 

ATEmixture calculation.

 

mixture n ATEi

Ci

ATE

100

Oral ATEmixture = 1,880 mg/kg, 

Category 4

,3 450

80

200

4

,1 600

100 16



ATEmixture
59

Mixture Example #3

Acute Toxicity – Oral 

Data 

HCS 2012

Classification Rationale

Component data:

Component 1: 4%, oral LD50 = 125 

mg/kg

Component 2: 92%, No data 

available

Component 3: 3%, oral LD50 = 

1500 mg/kg

Component 4: 0.9%, No data 

available

Component 5: 0.1%, oral LD50 = 

10 mg/kg, Oral Category 2

Acute Oral Toxicity 

Category 3

Components 1 and 3 are included in 

the ATEmixture calculation because they 

have data that fall within an acute 

toxicity category.

The total concentration of relevant 

ingredients with unknown acute 

toxicity (i.e., Component 2) is 92%. 

Therefore, the ATEmixture equation that 

corrects for ingredients with unknown 

acute toxicity above 10% of the 

mixture must be used.

Component 2 does not have any 

useable information for the oral route 

ATEmixture calculation and is in the 

mixture at a concentration  1% so an 

additional statement is included on the 

label and SDS.

The “relevant ingredients” concept 

means that Component 4 could be 

excluded from both the ATEmixture

calculations. This same reasoning 

could also apply to Component 5, as it 

is below the “relevant ingredients” 

threshold; however, the use of expert 

judgment is necessary to make this 

decision for Component 5 as it is 

classified in Category 2. For this 

example, since the percentage of this 

ingredient is well below the 1% 

threshold (i.e., 0.1%) and the 

ingredient is classified in Category 2 

rather than Category 1, it may be 

excluded from the ATE calculation.

ATEmixture = 235 mg/kg, Category 3

“92% of the mixture consists of an 

ingredient of unknown acute oral 

toxicity.”

  





 

n i

i

mixture

unknown

ATE

C

ATE

100 C if 10%

1500

3

125

100 (92 4)





ATEmixture
60

Mixture Example #4

Acute Toxicity – Multiple Routes

Components Wt%

Acute toxicity test data

Oral Dermal

Inhalation

Vapors

Component 1 26 LD50: 2,737 

mg/kg

LD50: 6,480 mg/kg LC50: 11 mg/l

Component 2 23 LD50: 4,500 

mg/kg

LD50:> 6,000 mg/kg LC50: 19 mg/l

Component 3 11 LD50: > 

5,000 mg/kg

No data available No data 

available

Component 4 40 LD50: 400 

mg/kg

Dermal limit dose > 2,000 

mg/kg (No signs of toxicity)

LC50: 4 mg/l

Oral route 

 

mixture n ATEi

Ci

ATE

100

400

40

4,500

23

2,737

26

ATE

100

mixture



ATEmixture = 873 mg/kg, Acute Oral Toxicity Category 4

Inhalation route 

  





 

n i

i

mixture

unknown

ATE

C

ATE

100 C if 10%

4

40

19

23

11

26

ATE

100 (11)

mixture





ATEmixture = 6.6 mg/l, Acute inhalation toxicity Category 3 and “11% of the 

mixture consists of an ingredient of unknown acute inhalation toxicity” 
61

HCS 2012 Classification Rationale

Acute Oral Toxicity 

Category 4

Acute Inhalation Toxicity 

Category 3

Review of the component test data show there is relevant 

evidence to suggest acute toxicity via the oral and inhalation 

routes so the ATEmixture calculation was applied to the oral and 

inhalation routes

Oral route

 Data is available for all ingredients via the oral route

 Components 1 and 4 are included in the ATEmixture

calculation because they have data that fall within an acute 

toxicity category

 Component 2: per A.1.3.6.1(a) include ingredients with a 

known acute toxicity, which fall into any of the acute 

toxicity categories, or have an oral LD50 > 2000 ≤5000 

mg/kg body weight.

 Component 3 is excluded because it does not fall within 

acute toxicity categories 1-4 and its LD50 > 5000 mg/kg.

 Apply the guidance in Note (a) to Table A.1.1 for 

Components 1, 2 and 4 in the ATEmixture calculation since 

LD50 data is available.

Inhalation route

 The total concentration of ingredients with unknown 

inhalation acute toxicity (i.e., Component 3) is 11%.

Therefore, the ATEmixture equation that corrects for 

ingredients with unknown acute toxicity above 10% of 

the mixture must be used for the inhalation route.

 Components 1, 2 and 4 are included in the ATEmixture

calculation because they have data that fall within an 

acute toxicity category.

 Apply the guidance in Note (a) to Table A.1.1 for 

Components 1, 2 and 4 in the ATEmixture calculation since 

LD50 data is available.

 Component 3 does not have any useable information for 

the inhalation route ATEmixture calculation and is in the 

mixture at a concentration  1% so an additional 

statement is included.

Dermal route

None of the ingredient test data for the dermal route show a 

LD50 < 5000 mg/kg bodyweight and so a dermal ATEmixture

calculation was not performed. See A.1.3.6.1(a).
62

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.1 Acute Toxicity. 

29 CFR 1910.1200, Hazard Communication. Appendix C, Allocation of Label Elements. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

The Organization for Economic Co-operation and Development (OECD) Guidelines for the 

Testing of Chemicals. 

United States Environmental Protection Agency (EPA) Office of Prevention, Pesticides, and 

Toxic Substances (OPPTS) Health Effects Test Guidelines.
63

VII.2 Skin Corrosion/Irritation 

Introduction

Changes at the site of first contact (e.g., skin, eye) can be caused regardless of whether a 

chemical can become systemically available. These changes are considered local effects. 

Chemicals causing local effects after a single exposure can be further distinguished as irritant or 

corrosive chemicals, depending on the reversibility of the effects observed. 

Corrosive chemicals are those which can destroy living tissues with which they come into 

contact. In toxicology, the term ”corrosive” normally means causing visible destruction of the 

skin, eyes, or the lining of the respiratory tract or the gastrointestinal tract on contact. Corrosion 

is manifested by ulcers, cell death, and scar formation. 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. 

Irritant chemicals are non-corrosive chemicals which, through immediate contact with the 

tissue under consideration, may cause inflammation. Dermal irritation is a skin reaction resulting 

from a single or multiple exposures to a physical or chemical entity at the same site, 

characterized by the presence of inflammation. 

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 and irreparable. 

Appendix A.2 of the HCS addresses the classification of those chemicals which present a 

corrosion or irritation hazard to the skin. 

General Considerations 

Classification for skin corrosion/irritation should be conducted using a tiered weight-of-evidence 

approach. In the tiered approach, emphasis should be placed upon existing human data, followed 

by existing animal data, followed by in vitro data, and then other sources of information. 

Classification results directly when the data satisfy the criteria. However, in some cases, 

classification of a substance or a mixture is made on the basis of the weight of evidence within a 

tier. If no decision can be made about classification after following the tiered approach, then a 

total weight-of-evidence approach to classification should be used. In a total weight-of-evidence 

approach all available information bearing on the determination of skin corrosion/irritation is 

considered together, including the results of appropriate validated in vitro tests, relevant animal 

data, and human data, such as epidemiological and clinical studies and well-documented case 

reports and observations. 
64

Classification Criteria for Substances

There are two categories assigned for skin effects in the HCS. In addition, the category for skin 

corrosion is subdivided into three subcategories according to specific criteria outlined below. 

(a) Category 1 (skin corrosion) 

This category is further divided into three sub-categories (1A, 1B and 1C) 

(b) Category 2 (skin irritation) 

Classification criteria for substances using animal test data 

Skin Corrosion (Category 1) 

Skin corrosion is the production of irreversible damage to the skin; namely, visible necrosis 

through the epidermis and into the dermis, following the application of a test substance for up to 

4 hours. Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of 

observation at 14 days, by discoloration due to blanching of the skin, complete areas of alopecia, 

and scars. Histopathology should be considered to evaluate questionable lesions. 

A substance is classified as corrosive to skin when it produces destruction of skin tissue, namely, 

visible necrosis through the epidermis and into the dermis, in at least one tested animal after 

exposure for up to 4 hours. 

Table VII.2.1. Skin corrosion category and sub-categories 

Category Criteria

Category 1 Destruction of skin tissue, namely, visible necrosis through the 

epidermis and into the dermis, in at least one tested animal after 

exposure ≤ 4 hours

Sub-category 1A Corrosive responses in at least one animal following exposure ≤ 3 

minutes during an observation period ≤ 1 hour

Sub-category 1B Corrosive responses in at least one animal following exposure > 3 

minutes and ≤ 1 hour and observations ≤ 14 days

Sub-category 1C Corrosive responses in at least one animal after exposures > 1 hour and 

≤ 4 hours and observations ≤ 14 days

Skin Irritation (Category 2) 

Skin irritation is the production of reversible damage to the skin following the application of a 

test substance for up to 4 hours. 

Animal irritant responses within a test can be variable, as they are with corrosion. A separate 

irritant criterion accommodates cases where there is a significant irritant response but less than 

the mean score criterion for a positive test. For example, a test material might be designated as 
65

an irritant if at least 1 of 3 tested animals shows a very elevated mean score throughout the study, 

including lesions persisting at the end of an observation period (normally 14 days). Other 

responses could also fulfill this criterion. However, it should be ascertained that the responses are 

the result of chemical exposure. Addition of this criterion increases the sensitivity of the 

classification system. 

Reversibility of skin lesions is another consideration in evaluating irritant responses. When 

inflammation persists to the end of the observation period in two or more test animals, taking 

into consideration alopecia (limited area), hyperkeratosis, hyperplasia, and scaling, then a 

chemical should be considered to be an irritant. 

The classification criteria for skin irritation (Category 2) are presented in Table VII.2.2. The 

major criterion for the irritation category is that at least 2 of 3 tested animals have a mean score 

of  2.3 and  4.0. 

Table VII.2.2. Skin irritation categories a, b 

Categories Criteria

Irritation

(Category 2)

(1) Mean score of  2.3 and  4.0 for erythema/eschar or for edema in at 

least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after 

patch removal or, if reactions are delayed, from grades on 3 consecutive 

days after the onset of skin reactions; or

(2) Inflammation that persists to the end of the observation period 

(normally 14 days) in at least 2 animals, particularly taking into account 

alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

(3) In some cases where there is pronounced variability of response among 

animals, with very definite positive effects related to chemical exposure 

in a single animal but less than the criteria above. 

a

 Grading criteria correspond to those described in OECD Test Guideline 404. 

b Criteria for evaluation of a 4, 5 or 6-animal study are provided below under the heading “Guidance on evaluation 

of data from studies with more than three animals.”

Classification in a tiered approach 

A tiered approach to the evaluation of initial information should be considered, where applicable 

(Figure VII.2.1), recognizing that not all elements in the approach may be relevant. 

The tiered approach explains how to organize existing information on a substance and to make a 

weight-of-evidence decision about hazard assessment and hazard classification (ideally without 

conducting new animal tests). Although information might be gained from the evaluation of 

single parameters within a tier, consideration should be given to the totality of existing 

information and making an overall weight-of-evidence determination. This is especially true 

when there is information available on some but not all parameters. Emphasis should be placed 
66

upon existing human experience and data, followed by animal experience and data, followed by 

other sources of information, but case-by-case determinations are necessary. 

Existing human and animal data including information from single or repeated exposure is the 

first line of evaluation, as they give information directly relevant to effects on the skin. 

Acute dermal toxicity data must be considered for classification if available. If a substance is 

highly toxic by the dermal route, a skin corrosion/irritation study may not be practicable since 

the amount of test substance to be applied would considerably exceed the toxic dose and, 

consequently, would result in the death of the animals. When observations are made of skin 

corrosion/irritation in acute toxicity studies and are observed up through the limit dose, these 

data must be used for classification provided that the dilutions used and species tested are 

equivalent. Solid substances (powders) may become corrosive or irritant when moistened or in 

contact with moist skin or mucous membranes.

In vitro alternatives that have been validated and accepted must be used to make classification 

decisions. 

Likewise, pH extremes such as ≤ 2 and ≥ 11.5 may indicate skin effects, especially when 

associated with significant acid/alkaline reserve (buffering capacity). 9

 Generally, such substances 

are expected to produce significant effects on the skin. In the absence of any other information, a 

substance is considered corrosive (Skin Category 1) if it has a pH ≤ 2 or ≥ 11.5. However, if 

consideration of acid/alkaline reserve suggests the substance may not be corrosive despite the low 

or high pH value, this needs to be confirmed by other data, preferably by data from an appropriate 

validated in vitro test. 

In some cases sufficient information may be available from structurally related substances to 

make classification decisions. 

 

9

 For further information concerning acid/alkaline reserve, see (1) Young et al, 1988, “Classification as corrosive or 

irritant to skin of preparations containing acidic or alkaline substances, without test on animals,” Toxicology in Vitro

2, 19-26 and (2) Young and How, 1994, “Product classification as corrosive or irritant by measuring pH and acid / 

alkali reserve,” Alternative Methods in Toxicology vol. 10 - In Vitro Skin Toxicology: Irritation, Phototoxicity, 

Sensitization, 23-27. 
67

Figure VII.2.1: 

Tiered evaluation for skin corrosion and irritation

Step Parameter Finding Conclusion

1a: Existing human or animal 

skin corrosion/irritation data a

Skin corrosive Category 1 b

Not corrosive/No data

1b: Existing human or animal 

skin corrosion/irritation data a

Skin irritant Category 2 b

Not irritant/No data

1c: Existing human or animal 

skin corrosion/irritation data a

Not a skin corrosive or 

skin irritant

Not classified

No/Insufficient data

2: Other, existing skin data in 

animals c

Yes; other existing data 

showing that substance 

may cause skin corrosion 

or skin irritation

Category 1 bor 

Category 2 b

No/Insufficient data

3: Existing ex vivo/in vitro data d

Positive: Skin corrosive Category 1 b

Positive: Skin irritant Category 2 b

No/Insufficient data/Negative 

response

4: pH-Based assessment (with 

consideration of acid/alkaline 

reserve of the chemical) e

pH ≤ 2 or ≥ 11.5 with 

high acid/alkaline 

reserve or no data for 

acid/alkaline reserve

Category 1

Not pH extreme, no pH data or 

extreme pH with data showing 

low/no acid/alkaline reserve

5: Validated Structure Activity 

Relationship (SAR) methods

Skin corrosive Category 1 b

Skin irritant Category 2 b

No/Insufficient data
68

Tiered evaluation for skin corrosion and irritation

Step Parameter Finding Conclusion

6: Consideration of the total 

weight-of-evidence f

Skin corrosive Category 1b

Skin irritant Category 2 b

7: Not classified

a

 Existing human or animal data could be derived from single or repeated exposure(s), for example in occupational, 

consumer, transport, or emergency response scenarios; from ethically conducted human clinical studies; or from 

purposely generated data from animal studies conducted according to validated and internationally accepted test 

methods. Although human data from accident or poison center databases can provide evidence for classification, 

absence of incidents is not itself evidence for no classification. 

b

 Classify in the appropriate category/sub-category, as shown in Tables VII.2.1 and VII.2.2. 

c

 All existing animal data should be carefully reviewed to determine if sufficient skin corrosion/irritation evidence is 

available. In evaluating such data, however, the reviewer should bear in mind that the reporting of dermal lesions 

may be incomplete, testing and observations may be made on a species other than the rabbit, and species may differ 

in sensitivity in their responses. 

d

 Evidence from studies using scientifically validated protocols with isolated human/animal tissues or other, nontissue-based, though scientifically validated, protocols should be assessed. Examples of scientifically validated test 

methods for skin corrosion include OECD Test Guidelines 430 (Transcutaneous Electrical Resistance Test), 431 

(Human Skin Model Test), and 435 (Membrane Barrier Test Method). An example of a scientifically validated in 

vitro test method for skin irritation is OECD Test Guideline 439 (Reconstructed Human Epidermis Test Method). 

e

 Measurement of pH alone may be adequate, but assessment of acid or alkali reserve (buffering capacity) would be 

preferable. Presently, there is no scientifically validated and internationally accepted method for assessing this 

parameter. 

f

 All information that is available should be considered and an overall determination made on the total weight of 

evidence. This is especially true when there is conflict in information available on some parameters. Professional 

judgment should be exercised prior to making such a determination. Negative results from applicable validated skin 

corrosion/irritation in vitro tests are considered in the total weight of evidence evaluation. 

Classification criteria for mixtures

It should be noted that the classification criteria for the health hazards of mixtures usually 

include a tiered scheme (i.e., stepwise procedure based on a hierarchy principle) in which test 

data available on the complete mixture are considered as the first tier in the evaluation, followed 

by the applicable bridging principles, and lastly, cut-off values/concentration limits or additivity. 

Tier 1: Classification of mixtures when data are available for the complete mixture 

When skin corrosion/irritation test data on the mixture itself is available, this data should be used 

to classify the mixture using the criteria for substances, taking into account the tiered weight-ofevidence illustrated in Figure VII.2.1. 

When considering testing of the mixture, classifiers should use a tiered weight-of-evidence 

approach as included in the criteria for classification of substances for skin corrosion and 

irritation to help ensure an accurate classification. In the absence of any other information, a 

mixture is considered corrosive (Skin Category 1) if it has a pH ≤ 2 or a pH ≥ 11.5. However, if 
69

consideration of acid/alkaline reserve suggests the mixture may not be corrosive despite the low 

or high pH value, then further evaluation may be necessary. 

If appropriate test data for the mixture is not available, then the classifier must consider the 

application of the Bridging Principle criteria in Tier 2, if appropriate, or use the classification 

resulting from the application of criteria in Tier 3. 

Tier 2: Classification of mixtures when data are not available for the complete mixture –

bridging principles 

Where the mixture itself has not been tested to determine its skin corrosion/irritation potential, 

but there are sufficient data on BOTH the individual ingredients AND similar tested mixtures to 

adequately characterize the hazards of the mixture, these data are used in accordance with the 

below bridging principles. 

The bridging principles applicable to the skin corrosion/irritation hazard class include: 

 Dilution, 

 Batching, 

 Concentration of mixtures, 

 Interpolation within one toxicity category, 

 Substantially similar mixtures, 

 Aerosols. 

The application of bridging principles ensures that the classification process uses the available 

data to the greatest extent possible in characterizing the potential skin corrosion/irritation hazard. 

Dilution 

If a tested mixture is diluted with a diluent which has an equivalent or lower skin 

corrosivity/irritancy classification than the least corrosive/irritant original ingredient and 

which is not expected to affect the corrosivity/irritancy of other ingredients, then the new 

diluted mixture must be classified as equivalent to the original tested mixture. 

Batching 

The skin corrosion/irritation potential of a tested production batch of a mixture can be 

assumed to be substantially equivalent to that of another untested production batch of the 

same commercial product when produced by or under the control of the same 

manufacturer, unless there is reason to believe there is significant variation such that the 

skin corrosion/irritation potential of the untested batch has changed. If the latter occurs, a 

new classification is necessary. 

Concentration of mixtures 

If a tested mixture classified in the highest sub-category for skin corrosion is concentrated, 

the more concentrated untested mixture must be classified in the highest corrosion subcategory without additional testing. If a tested mixture classified for skin irritation 
70

(Category 2) is concentrated and does not contain skin corrosive ingredients, the more 

concentrated untested mixture should be classified for skin irritation (Category 2) without 

additional testing. 

Interpolation within one hazard category 

For three mixtures (A, B and C) with identical ingredients, where mixtures A and B have 

been tested and are in the same skin corrosion/irritation hazard category, and where 

untested mixture C has the same toxicologically active ingredients as mixtures A and B 

but has concentrations of toxicologically active ingredients intermediate to the 

concentrations in mixtures A and B, then mixture C is assumed to be in the same skin 

corrosion/irritation category as A and B. 

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

(ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) Data on skin corrosion/irritation for A and C are available and substantially 

equivalent, i.e., they are in the same hazard category and are not expected to 

affect the skin corrosion/irritation potential of B. 

If mixture (i) or (ii) is already classified by testing, then the other mixture can be 

classified in the same hazard category. 

Aerosols 

An aerosol form of a mixture must be classified in the same hazard category as the tested 

non-aerosolized form of the mixture provided that the added propellant does not affect 

the skin corrosion/irritation properties of the mixture upon spraying. 

If appropriate data is not available to apply the above bridging principles then the classifier 

applies the criteria in Tier 3. 
71

Tier 3: Classification of mixtures when data are available for all ingredients or only for some 

ingredients of the mixture 

Cut-off values/concentration limits: Additivity 

In general, the approach to classifying a mixture for skin corrosion/irritation in Tier 3 is based on 

the theory of additivity where each corrosive or irritant ingredient is considered to contribute to 

the overall corrosive or irritant properties of the mixture. The ingredients are summed in 

proportion to their concentration and potency (i.e., corrosives carry more weight in the irritation 

calculations). 

Table VII.2.3 provides the cut-off value/concentration limits to be used to determine if the 

mixture is considered to be corrosive or irritant to the skin. Three potential additivity calculations 

are given in the first column. Each equation has specific concentration cut-offs that will trigger 

the classification specified in columns 2 and 3, which correspond to Category 1 and Category 2, 

respectively. 

To better illustrate the order in which the calculations should be evaluated, an arrow has been 

added to the table. Following the arrow, the first calculation that exceeds the percentage cut-off 

trigger determines which classification is assigned to the mixture. If none of the sums exceed the 

cut-off triggers, then the mixture is not classified. 

Table VII.2.3. Concentration of ingredients of a mixture classified as skin Category 1 or 2 

that would trigger classification of the mixture as hazardous to skin (Category 1 or 2) 

Sum of ingredients classified as:

Concentration triggering 

classification of a mixture as:

Skin corrosive Skin irritant

Category 1

(see note below) Category 2

Skin Category 1  5%  1% but < 5%

Skin Category 2  10%

(10 × Skin Category 1) + Skin Category 2  10%

The Four Skin Corrosion/Irritation Mixture Additivity Calculations 

There are four possible calculations that may need to be performed to determine if the mixture 

should be classified. 
72

Sum of ingredients classified as:

Concentration triggering 

classification of a mixture as:

Skin corrosive Skin irritant

Category 1 Category 2

Skin Category 1  5% (1)  1% but < 5% (2)

Skin Category 2  10% (3)

(10 × Skin Category 1) + Skin Category 2  10% (4)

Skin corrosion Category 1 classification calculation: 

(1) Add the percentages of all ingredients classified as Skin Category 1. 

If the sum is ≥ 5% the mixture is classified as Category 1 Skin Corrosion.

∑ % Skin Category 1 ingredients ≥ 5%

Skin irritation Category 2 classification calculations: 

For Category 1 ingredients: 

(2) Add the percentages of all ingredients classified as Skin Category 1. 

If the sum is ≥ 1% but < 5%, the mixture is classified as Category 2 Skin Irritation. 

∑ % Skin Category 1 ingredients ≥ 1% but < 5%

For Category 2 ingredients: 

(3) Add the percentages of all ingredients classified as Skin Category 2. 

If the sum is ≥ 10%, the mixture is classified as Category 2 Skin Irritation. 

∑ % Skin Category 2 ingredients ≥ 10%

For Category 1 & 2 ingredients: 

(4) First add the percentages of all ingredients classified as Skin Category 1 and multiply 

that number by the weighting factor of 10. 

Then add the percentages of all ingredients classified as Skin Category 2. 

Add these two numbers together. If the sum is ≥ 10%, the mixture is classified as 

Category 2 Skin Irritation. 

(10 × (∑ % Skin Cat 1 ingredients)) + ∑ % Skin Cat 2 ingredients ≥ 10%
73

Shortcut Skin Corrosion/Irritation Mixture Additivity Calculations 

Shortcut 

For those doing the calculations manually, a shortcut that leads to the same classification is to 

only do the worst-case calculations for the Corrosive Category 1 classification and the Skin 

Irritation Category 2 classification. In the shortcut there are only two calculations. The first sum 

that exceeds the percentage cut-off trigger determines which classification is assigned to the 

mixture. If neither exceeds the cut-off triggers then the mixture is not classified. 

Sum of ingredients classified as:

Concentration triggering 

classification of a mixture as:

Skin corrosive Skin irritant

Category 1 Category 2

Skin Category 1  5%  1% but < 5% 

Skin Category 2  10% 

(10 × Skin Category 1) + Skin Category 2  10% 

Skin corrosion Category 1 classification calculation: 

(1) Add the percentages of all ingredients classified as of Skin Category 1. 

If the sum is ≥ 5% the mixture is classified as Category 1 Skin Corrosion.

∑ % Skin Category 1 ingredients ≥ 5%

Shortcut Skin irritation Category 2 classification calculation: 

For Category 1 & 2 ingredients: 

(4) Add the percentages of all ingredients classified as of Skin Category 1 and multiply 

that sum by the weighting factor of 10. 

Then add the percentages of all ingredients classified as of Skin Category 2. 

Add these two numbers together. If the sum is ≥ 10%, the mixture is classified as 

Category 2 Skin Irritation. 

(10 × (∑ % Skin Cat 1 ingredients)) + ∑ % Skin Cat 2 ingredients ≥ 10%

Cut-off values/concentration limits: when the additivity approach does not apply 

Particular care must be taken when classifying certain types of chemicals such as acids and 

bases, inorganic salts, aldehydes, phenols, and surfactants. The additivity approach might not 

work because many such substances are corrosive or irritant at concentrations < 1%, and the 

additivity approach may underestimate the overall corrosive or irritant properties of the mixture. 
74

For mixtures containing strong acids or bases, the pH should be used as the classification 

criterion since pH will be a better indicator of corrosion than the concentration limits in Table 

VII.2.3. A mixture containing corrosive or irritant ingredients that cannot be classified based on 

the additivity approach shown in Table VII.2.3, due to chemical characteristics that make this 

approach unworkable, should be classified using the more conservative cut-off/concentration 

limit approach summarized below: 

 Mixture is Skin Category 1 if it contains ≥ 1% of a corrosive Category 1 ingredient, and

 Mixture is Skin Category 2 if it contains ≥ 3% of an irritant ingredient. 

The cut-off value/concentration limits approach is summarized in HCS Table A.2.4. 

Table VII.2.4. Concentration of ingredients of a mixture when the additivity approach 

does not apply, that would trigger classification of the mixture as hazardous to skin 

Ingredient: Concentration

Mixture classified 

as: Skin

Acid with pH  2  1% Category 1

Base with pH  11.5  1% Category 1

Other corrosive (Category 1) ingredients for which 

additivity does not apply

 1% Category 1

Other irritant (Category 2) ingredients for which 

additivity does not apply, including acids and 

bases 

 3% Category 2

Cut-off values/concentration limits: Important Points to Consider 

To ensure consistent application of both the additivity and cut-off/concentration limit approaches 

for purposes of classifying the skin corrosion/irritation hazards of mixtures, the following 

principles need to be applied where appropriate: 

 Classification Above or Below Cut-Off Values/Concentration Limits 

On occasion, reliable data may show that the skin corrosion/irritation of an ingredient 

will not be evident when present at a level above the concentration limits/cut-off values 

mentioned in Tables VII.2.3 and VII.2.4. In these cases, the mixture could be classified 

according to those data (see also 29 CFR 1910.1200 A.0.4.3). On occasion, when it is 

expected that the skin corrosion/irritation of an ingredient will not be evident when 

present at a level above the concentration cut-off values mentioned in Tables VII.2.3 and 

VII.2.4, testing of the mixture may be considered. If testing is not performed, the tiered 

weight-of-evidence approach for skin corrosion/irritation should be used.

If there are data showing that (an) ingredient(s) may be corrosive or irritant to skin at a 

concentration of  1% (corrosive) or  3% (irritant), the mixture should be classified 

accordingly. 
75

 “Relevant Ingredient” Concept 

For the purpose of applying the cut-off values in Tables VII.2.3 and VII.2.4, only 

“relevant ingredients” need to be included in the calculation. 

The “relevant ingredients” of a mixture are those which are present in concentrations ≥ 

1% (w/w for solids, liquids, dusts, mists, and vapors and v/v for gases), unless there is a 

presumption (e.g., in the case of corrosive ingredients) that an ingredient present at a 

concentration < 1% can still be relevant for classifying the mixture for skin 

corrosion/irritation. If the classifier suspects that the ingredient could be relevant for 

classifying the mixture at < 1%, then the classifier must use expert judgment to determine 

at what concentration below 1% the corrosive Category 1 ingredient(s) should be 

included in the calculation. 

Classification Procedure and Guidance 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS requires 

collecting and evaluating the best available existing evidence on the hazards of each chemical. 

In classification the data are compared to the skin corrosion/irritation classification criteria. If 

valid data on skin irritation/corrosion of a substance or mixture are available, these data should 

be used for classification. To find the necessary data, a classifier is advised to try the following: 

 ask the manufacturer or supplier for the skin irritation/corrosion data for the product; or 

 check if the skin irritation/corrosion data is available in the SDS or any other 

documentation accompanying the product; or 

 find the data available in the open literature, if the chemical identity of the product is 

known (for a single-component chemical). 

Data that are generated in accordance with recognized scientific principles are acceptable under 

the HCS. 

Examples of scientifically validated test methods 

Methods that use recognized scientific principles for investigation of skin corrosion/irritation 

effects include: 

 OECD Test Guideline 404: Acute Dermal Irritation/Corrosion 

 OECD Test Guideline 430: In Vitro Skin Corrosion: Transcutaneous Electrical 

Resistance Test (TER) 

 OECD Test Guideline 431: In Vitro Skin Corrosion: Human Skin Model Test 

 OECD Test Guideline 435: In Vitro Skin Corrosion: Membrane Barrier Test Method 

 OECD Test Guideline 439: In Vitro Skin Irritation: Reconstructed Human Epidermis 

Test Method 

 USEPA OTS code: 798.4470; 

 USEPA OPP code: 81-5; 

 USEPA OPPTS code: 870.2500; 

 EEC Directive 92/32/EEC (B.4). 
76

In the in vivo test, the substance is applied in a single dose to the skin of an experimental animal 

(usually a healthy young albino rabbit) while untreated skin areas of the test animal serve as the 

control. In the in vitro test, the assessment of corrosivity is not carried out in live animals. 

Transcutaneous Electrical Resistance (TER) is a measure of the electrical impedance of the skin, 

as a resistance value in kilo Ohms. In the In Vitro Human Skin Model Test, the test material is 

applied topically to a three-dimensional human skin model, comprising at least a reconstructed 

epidermis with a functional stratum corneum. 

Guidance on evaluation of data from studies with more than three animals 

The classification criteria for skin corrosion/irritation are given in terms of a 3-animal test. Some 

older test methods may have used up to 6 animals. However, the skin corrosion/irritation criteria 

do not specify how to classify based on existing data from tests with more than 3 animals. 

Criteria for evaluation of a 4, 5 or 6-animal study are provided in the paragraphs below, 

depending on the number of animals tested. Scoring for erythema/eschar and edema is 

performed at 24, 48 and 72 hours after exposure or, if reactions are delayed, from grades on 3 

consecutive days after the onset of skin reactions. 

In the case of a study with 6 animals the following principles apply: 

(a) The substance or mixture is classified as skin corrosion Category 1 if destruction of 

skin tissue (that is, visible necrosis through the epidermis and into the dermis) occurs in 

at least one animal after exposure up to 4 hours in duration; 

(b) The substance or mixture is classified as skin irritation Category 2 if at least 4 out of 6 

animals show a mean score per animal of ≥ 2.3 and ≤ 4.0 for erythema/eschar or for 

edema.

In the case of a study with 5 animals the following principles apply: 

(a) The substance or mixture is classified as skin corrosion Category 1 if destruction of 

skin tissue (that is, visible necrosis through the epidermis and into the dermis) occurs in 

at least one animal after exposure up to 4 hours in duration; 

(b) The substance or mixture is classified as skin irritation Category 2 if at least 3 out of 5 

animals show a mean score per animal of ≥ 2.3 and ≤ 4.0 for erythema/eschar or for 

edema.

In the case of a study with 4 animals the following principles apply: 

(a) The substance or mixture is classified as skin corrosion Category 1 if destruction of 

skin tissue (that is, visible necrosis through the epidermis and into the dermis) occurs in 

at least one animal after exposure up to 4 hours in duration; 
77

(b) The substance or mixture is classified as skin irritation Category 2 if at least 3 out of 4 

animals show a mean score per animal of ≥ 2.3 and ≤ 4.0 for erythema/eschar or for 

edema.

Decision logic 

Two decision logics for classifying Skin Corrosion/Irritation are provided. The first decision 

logic is for substances and for mixtures with data on the mixture as a whole. Use the second 

decision logic for classifying mixtures on the basis of information/data on similar tested mixtures 

and/or ingredients. The decision logics are provided as additional guidance. It is strongly 

recommended that the person responsible for classification study the criteria before and during 

use of the decision logic. 

These decision logics are essentially flow charts for classifying substances and mixtures 

regarding skin corrosion/irritation. They present questions in a sequence that walks you through 

the classification steps and criteria for classifying skin corrosion/irritation. Once you answer the 

questions provided, you will arrive at the appropriate classification. 
78

Decision logic for skin corrosion/irritation 

Classification 

not possible

Mixture: Does the mixture as a whole have data/information 

to evaluate skin corrosion/irritation?

Substance: Are there data/information to evaluate skin corrosion/irritation?

See next decision 

logic for use with 

similar tested 

mixtures and

ingredients

No

Yes

Yes

Yes

Yes

Is the substance or mixture corrosive considering (total weight of evidence 

as needed):

(a) Existing human data showing irreversible damage to skin; 

(b) Destruction of skin in one or more test animals (see criteria and subcategorization);

(c) Other existing animal data indicating skin corrosion after single or 

repeated exposure;

(d) Existing ex vivo/in vitro data;

(e) pH extremes of  2 or  11.5 (taking into account acid/alkaline reserve)

(f) Information available from validated Structure Activity Relationship 

(SAR) methods?

Category 1

Danger

No

No

Is the substance or mixture an irritant considering (total weight of 

evidence as needed):

(a) Existing human data, single or repeated exposure;

(b) Skin irritation data from an animal study (see criteria);

(c) Other existing animal data including single or repeated exposure,

(d) Existing in vitro data;

(e) Information available from validated Structure Activity Relationship 

(SAR) methods?

No

Yes

No

Not classified

Classification 

not possible

Mixture: Does the mixture as a whole or its ingredients have 

data/information to evaluate skin corrosion/irritation?

Category 2

Warning
79

Mixtures decision logic for skin corrosion/irritation 

Classification of mixtures on the basis of information/data on similar tested mixtures and/or ingredients

(Cont’d on next page)

Classify in 

appropriate 

category

Does the mixture contain ≥ 1% of an ingredient which is 

corrosive when the additivity approach does not apply?

Does the mixture contain  3% of an ingredient which is irritant 

and when the additivity approach does not apply?

Can bridging principles be applied? Yes

No

Category 1

Danger

Category 2

Warning

Does the mixture contain one or more corrosive ingredients when 

the additivity approach applies and where the sum of 

concentrations of ingredients classified as skin Category 1  5%?

Category 1

Danger

No

No

No

Are there data on similar tested mixtures to evaluate skin 

corrosion/irritation?

No

Yes

Yes

Yes

Yes
80

Skin Corrosion/Irritation Classification Examples 

The following examples are provided to walk you through the skin corrosion/irritation 

calculation and classification processes. 

Examples of a substance fulfilling the criteria for classification: 

Substance Example #1

Skin Irritation

Test Data 

HCS 2012 

Classification Rationale

According to OECD Test 

Guideline 404 test substance was 

applied for 1 hour and three 

minutes. No scars or other 

irreversible effects were found. 

The scoring results obtained after 

4 hours application time are

 Erythema/Eschar: 2.7, 3, 0.66

 Edema: 1.7, 2, 1

Skin Irritant 

Category 2

Fulfills criteria 

 The classification is made on the 

basis of 2 of 3 animals exceeding 

a 2.3 mean score for erythema.

Not 

classified 

No

Does the mixture contain one or more corrosive or irritant 

ingredients when the additivity approach applies and where the sum 

of concentrations of ingredients classified as:

(a) skin Category 1 ≥ 1% but < 5%, or

(b) skin Category 2 ≥ 10%, or

(c) (10 × skin Category 1) + skin Category 2 ≥ 10%?

Yes

Category 2

Warning 

No
81

Substance Example #2

Skin Corrosion

Test Data 

HCS 2012 

Classification Rationale

In OECD Test 404 full 

necrosis/irreversible skin damage 

after 4-hour exposure within 14 

days were observed in one animal

Skin Corrosion 

Category 1C

Fulfills criteria 

 According to the classification 

criteria the production of 

irreversible damage to the skin 

after 4-hour exposure in at least 

one animal warrants 

classification in Category 1C.

Substance Example #3

Skin Corrosion

Test Data 

HCS 2012 

Classification Rationale

The material is a new aliphatic 

tertiary amine. No data is 

available. The test substance has 

Structure Activity Relationships 

(SAR) to substances with similar 

structure known to be corrosive.

Skin Corrosion 

Category 1

Using expert judgment and SAR 

information the classifier of this 

mixture concluded that Category 1 is 

justified, since there is much 

information indicating that aliphatic 

amines are corrosive. According to 

the criteria, the classifier of this 

mixture concluded that classification 

as corrosive Category 1 is warranted.

Substance Example #4

Skin Irritation

Test Data 

HCS 2012 

Classification Rationale

OECD Test Guidelines 404 

test results:

 Erythema/Eschar: mean value 

2.2 (in 2 of 3 animals)

 Edema: 2.4 (in all animals)

Skin Irritation 

Category 2

Fulfills criteria 

 The criteria for Category 2 

classification are fulfilled, since 

the mean value for edema over 

24, 48, and 72 hours in 2 of 3 

animals is > 2.3.
82

Examples of mixtures fulfilling the criteria for classification: 

Mixture Example #1

Skin Corrosion/Irritation

Data 

HCS 2012 

Classification Rationale

Component data:

Component 1: 4%, Skin 

Category 1, pH = 1.8

Component 2: 5%, Skin 

Category 2

Component 3: 5%, not classified

Component 4: 86%, No data 

available

Mixture pH = 4.0

Skin Corrosion 

Category 1

For this mixture, the classification 

was assigned as a Category 1 

because component 1 (Category 1) is 

in the mixture at  1% 

Rationale:

 The overall mixture pH of 4.0 

does not result in classification in 

Category 1 since this does not 

fall within the criteria of pH  2 

or pH  11.5

 Component 1 with a pH = 1.8 is 

an ingredient for which additivity 

might not apply. Expert judgment 

would be needed to determine 

whether or not additivity applies. 

Knowledge of the components is 

important. Given the limited

information in this example, the 

classifier of this mixture chose to 

apply non-additivity for a 

conservative approach. Without 

information on the mode of 

action of component 1, the 

mixture could be corrosive 

regardless of the overall pH. 

Therefore, the criteria described 

in 29 CFR 1910.1200 paragraph 

A.2.4.3.4 were applied (i.e., “A 

mixture containing corrosive or 

irritant ingredients that cannot be 

classified based on the additivity 

approach shown in [Table 

VII.2.3], due to chemical 

characteristics that make this 

approach unworkable, should be 

classified as Skin Category 1 if it 

contains ≥ 1% of a corrosive 

ingredient and as Skin Category 

2 when it contains ≥ 3% of an 

irritant ingredient”). 
83

Mixture Example #2

Skin Corrosion/Irritation

Data 

HCS 2012 

Classification Rationale

Tested mixture information

Animal 1: Mean Erythema/eschar 

3.8, Mean Edema: 2.5

Animal 2: Mean Erythema/eschar 

3.5, Mean Edema: 2.9

Animal 3: Mean Erythema/eschar 

4.0, Mean Edema: 3.2

Based on the test data the mixture 

is classified as Skin Irritant 

Category 2. The tested mixture is 

aerosolized using a 50/50 mixture 

of propane/butane as the 

propellant.

Aerosolized untested mixture 

information

Component 1: 50%, Tested 

mixture = Skin Category 2 

Component 2: 25%, Liquefied 

propane

Component 3: 25%, Liquefied 

butane

Skin Irritation 

Category 2

Applying the aerosols bridging 

principle, the aerosolized untested 

mixture can be classified as 

Skin Irritant Category 2 without 

additional testing.

Rationale:

 Classification via application of 

bridging principles can be 

considered since there are 

sufficient data on both the 

individual ingredients and a 

similar tested mixture

 The aerosols bridging principle 

can be applied because:

(i) The non-aerosolized mixture 

has been tested, and

(ii) The propellant (i.e., 50/50 

mixture of liquefied 

propane/butane) is not corrosive 

or an irritant, and

(iii) The propellant will not 

affect the irritation properties of 

the mixture upon spraying.
84

Mixture Example #3

Skin Corrosion/Irritation

Data 

HCS 2012 

Classification Rationale

Component data:

Component 1: 91%, no data 

available

Component 2: 5%, Skin 

Category 2

Component 3: 3%, Skin 

Category 2

Component 4: 0.9%, Skin 

Category 1

Component 5: 0.1%, no data 

available

Skin Irritation

Category 2

Use equations from Table VII.2.3 

Category 1 calculation:

a) ∑%Skin Category 1 = 0.9 which 

is not ≥ 5%

Category 2 calculations:

b) ∑%Skin Category 1= 0.9 which 

is not ≥ 1% but < 5%

c) ∑%Skin Category 2 = 5 + 3 = 8 

which is not ≥ 10%

d) ∑(10 x %Skin Category 1) + 

∑%Skin Category 2 = (10 x 0.9) 

+ (5 + 3) = 17 which is ≥ 10%

Rationale

 Classification of the mixture 

based on ingredient data can be 

considered 

 In the exercise of expert 

judgment in applying the 

“relevant ingredient” concept, the 

classifier took a conservative 

approach since component 4 

(Skin Category 1) is only slightly 

below 1% (i.e., 0.9%) and 

application of the additivity 

approach includes a weighting 

factor for Category 1 ingredients. 
85

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.2 Skin Corrosion/Irritation. 

29 CFR 1910.1200, Hazard Communication. Appendix C, Allocation of Label Elements. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

The Organization for Economic Co-operation and Development (OECD) Guidelines for the 

Testing of Chemicals. 

United States Environmental Protection Agency (EPA) Office of Prevention, Pesticides, and 

Toxic Substances (OPPTS) Health Effects Test Guidelines.
86

VII.3 Serious Eye Damage/Eye Irritation 

Introduction 

Changes at the site of first contact (e.g., skin, eye) can be caused regardless of whether a 

chemical can become systemically available. These changes are considered local effects. 

Chemicals causing local effects after a single exposure can be further distinguished as irritant or 

corrosive chemicals, depending on the reversibility of the effects observed. 

Corrosive chemicals are those which can destroy living tissues with which they come into 

contact. In toxicology, the term “corrosive” normally means causing visible destruction of the 

skin, eyes, or the lining of the respiratory tract or the gastrointestinal tract on contact. Corrosion 

is manifested by ulcers, cell death, and scar formation. 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. 

Irritant chemicals are non-corrosive substances which, through immediate contact with the 

tissue under consideration, may cause inflammation. Dermal irritation is a skin reaction resulting 

from a single or multiple exposures to a physical or chemical entity at the same site, 

characterized by the presence of inflammation. 

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 and irreparable. 

Appendix A.3 of the HCS addresses the classification of those chemicals which present a 

corrosion or irritation hazard to the eye. 

General Considerations 

Classification for serious eye damage/eye irritation should be conducted using a tiered weight–

of-evidence approach. In the tiered approach, emphasis should be placed upon existing human 

data, followed by existing animal data, followed by in vitro data and then other sources of 

information. Classification results directly when the data satisfy the criteria. However, in some 

cases, classification of a chemical is made on the basis of the weight-of-evidence within a tier. If 

no decision can be made about classification after following the tiered approach, then a total 

weight-of-evidence approach to classification should be used. In a total weight-of-evidence 

approach all available information bearing on the determination of serious eye damage /eye 

irritation is considered together, including the results of appropriate validated in vitro tests, 

relevant animal data, and human data such as epidemiological and clinical studies and welldocumented case reports and observations. 
87

Classification Criteria for Substances 

There are two categories assigned for eye effects in the HCS. In addition, the category for eye 

irritation is subdivided into two subcategories according to specific criteria outlined below. 

Substances are allocated to one of the categories within this hazard class, Category 1 (serious eye 

damage) or Category 2 (eye irritation), as follows: 

(a) Category 1 (serious eye damage/irreversible effects on the eye): Substances that have 

the potential to seriously damage the eyes (see Table VII.3.1);

(b) Category 2 (eye irritation/reversible effects on the eye): Substances that have the 

potential to induce reversible eye irritation (see Table VII.3.2). Category 2 has two 

subcategories, Category 2A and Category 2B, which are differentiated by the time it 

takes for the eye effects to reverse. 

Classification criteria for substances using animal test data

Serious eye damage (Category 1)/Irreversible effects on the eye 

Serious eye damage is the production of tissue damage in the eye, or serious physical decay of 

vision, following application of a test substance to the anterior surface of the eye, which is not 

fully reversible within 21 days of application. 

The criteria include animals with grade 4 cornea lesions and other severe reactions (e.g.,

destruction of cornea) observed at any time during the test, as well as persistent corneal opacity, 

discoloration of the cornea by a dye substance, adhesion, pannus, and interference with the 

function of the iris or other effects that impair sight. In this context, persistent lesions are 

considered those which are not fully reversible within an observation period of normally 21 days. 

Hazard classification as Category 1 also includes substances fulfilling the criteria of corneal 

opacity ≥3 and/or iritis > 1.5 detected in a Draize eye test with rabbits, because severe lesions 

like these usually do not reverse within a 21-day observation period. 
88

Table VII.3.1. Serious eye damage/Irreversible eye effects categorya,b 

Category Criteria

Category 1: 

Serious eye 

damage/Irreversible 

eye effects

A substance that produces:

(a) in at least one animal effects on the cornea, iris or conjunctiva that 

are not expected to reverse or have not fully reversed within an 

observation period of normally 21 days; and/or

(b) in at least 2 of 3 tested animals, a positive response of:

(i) corneal opacity  3; and/or

(ii) iritis > 1.5;

calculated as the mean scores following grading at 24, 48 and 72 

hours after instillation of the test material.

a Grading criteria correspond to those described in OECD Test Guideline 405. 

b Criteria for evaluation of a 4, 5 or 6-animal study are provided below under the heading “Guidance on evaluation 

of data from studies with more than three animals.” 

Eye irritation (Category 2)/Reversible effects on the eye 

Eye irritation is the production of changes in the eye following the application of test substance 

to the anterior surface of the eye, which are fully reversible within 21 days of application.

Substances that have the potential to induce reversible eye irritation should be classified in 

Category 2. When data are sufficient, substances may be classified in Category 2A or 2B in 

accordance with the criteria in Table VII.3.2. For substances inducing eye irritant effects 

reversing within an observation time of normally 21 days, Category 2A applies. For substances 

inducing eye irritant effects reversing within an observation time of 7 days, Category 2B applies. 

If there is insufficient data to subdivide into category 2B then the classifier may use the generic 

term of Category 2. The criteria for the generic Category 2 are equivalent to Category 2A. 

For those substances where there is pronounced variability among animal responses, this 

information may be taken into account in determining the classification. 
89

Table VII.3.2. Reversible eye effects categoriesa,b 

Criteria

Substances that have the potential to induce reversible eye irritation

Category 

2A

Substances that produce in at least 2 of 3 tested animals a positive response of:

(a) corneal opacity  1; and/or

(b) iritis  1; and/or

(c) conjunctival redness  2; and/or

(d) conjunctival edema (chemosis)  2

calculated as the mean scores following grading at 24, 48 and 72 hours after 

instillation of the test material, and which fully reverses within an observation 

period of normally 21 days.

Category 

2B

Within Category 2A an eye irritant is considered mildly irritating to eyes

(Category 2B) when the effects listed above are fully reversible within 7 days of 

observation.

a Grading criteria correspond to those described in OECD Test Guideline 405. 

b Criteria for evaluation of a 4, 5 or 6-animal study are provided below under the heading “Guidance on evaluation 

of data from studies with more than three animals.” 

Classification in a tiered approach

A tiered approach to the evaluation of initial information must be used, where applicable (Figure 

VII.3.1), recognizing that not all elements may be relevant. 

The tiered approach provides guidance on how to organize existing information on a substance 

and to make a weight-of-evidence decision about hazard assessment and hazard classification 

(ideally without conducting new animal tests). Although information might be gained from the 

evaluation of single parameters within a tier, consideration should be given to the totality of 

existing information and making an overall weight-of-evidence determination. This is especially 

true when there is conflict in information available on some parameters. 

Existing human and animal data should be the first line of evaluation, as they give information 

directly relevant to effects on the eye. Possible skin corrosion has to be evaluated prior to 

consideration of any testing for serious eye damage/eye irritation in order to avoid testing for 

local effects on eyes with skin corrosive substances. 

In vitro alternatives that have been scientifically validated and accepted must be used to make 

classification decisions. 
90

Likewise, pH extremes such as  2 and  11.5 may indicate serious eye damage, especially when 

associated with significant acid/alkaline reserve (buffering capacity).10 Generally, such 

substances are expected to produce significant effects on the eyes. In the absence of any other 

information, a substance is considered to cause serious eye damage (Category 1) if it has a pH ≤ 

2 or ≥ 11.5. However, if consideration of acid/alkaline reserve suggests the substance may not 

cause serious eye damage despite the low or high pH value, then further evaluation may be 

necessary. Data from an appropriate scientifically validated in vitro test is the preferred method 

for validation. 

In some cases sufficient information may be available from structurally related substances to 

make classification decisions. 

Figure VII.3.1. Tiered evaluation for serious eye damage/eye irritation

(see also Tiered evaluation for skin corrosion and irritation)

Step Parameter Finding Conclusion

1a: Existing human or animal serious eye 

damage/eye irritation data a

Serious eye damage Category 1

Eye irritant Category 2b

Negative data/Insufficient data/No data

1b: Existing human or animal data, skin 

corrosion

Skin corrosion Category 1

Negative data /Insufficient data/No data

1c: Existing human or animal serious eye 

damage/eye irritation data a

Existing data showing 

that substance does not 

cause serious eye 

damage or eye irritation

Not classified

No/Insufficient data

2: Other, existing skin/eye data in 

animals c

Yes; other existing data 

showing that substance 

may cause serious eye 

damage or eye irritation

Category 1 or Category 2b

No/Insufficient data

3: Existing ex vivo/in vitro eye data d

Positive: serious eye 

damage

Category 1

Positive: eye irritant Category 2b

No/Insufficient data/Negative response

 

10 For further information concerning acid/alkaline reserve, see (1) Young et al. 1988, “Classification as corrosive or 

irritant to skin of preparations containing acidic or alkaline substances, without test on animals,” Toxicology in Vitro

2, 19-26 and (2) Young and How, 1994, “Product classification as corrosive or irritant by measuring pH and acid / 

alkali reserve,” Alternative Methods in Toxicology vol. 10 - In Vitro Skin Toxicology: Irritation, Phototoxicity, 

Sensitization, 23-27. 
91

Figure VII.3.1. Tiered evaluation for serious eye damage/eye irritation

(see also Tiered evaluation for skin corrosion and irritation)

Step Parameter Finding Conclusion

4: pH-based assessment (with 

consideration of acid/alkaline reserve 

of the chemical) e

pH ≤ 2 or ≥ 11.5 with 

high acid/alkaline 

reserve or no data for 

acid/alkaline reserve

Category 1

Not pH extreme, no pH data or extreme 

pH with data showing low/no 

acid/alkaline reserve

 Severe damage to eyes Category 1

5: Validated Structure Activity 

Relationship (SAR) methods Eye irritant Category 2b

Skin corrosive Category 1

No/Insufficient data

6: Consideration of the total weight of 

evidence f

Serious eye damage Category 1

Eye irritant Category 2b

7: Not classified

a

 Existing human or animal data could be derived from single or repeated exposure(s), for example in occupational, 

consumer, transport, or emergency response scenarios; from ethically conducted human clinical studies; or from 

purposely generated data from animal studies conducted according to validated and internationally accepted test 

methods. Although human data from accident or poison center databases can provide evidence for classification, 

absence of incidents is not itself evidence for no classification. 

b

 Classify in the appropriate category/sub-category, as shown in Tables VII.3.1 and VII.3.2. 

c

 Existing animal data should be carefully reviewed to determine if sufficient serious eye damage/eye irritation 

evidence is available through other, similar information. It is recognized that not all skin irritants are eye irritants. 

Expert judgment should be exercised prior to making such a determination. 

d

 Evidence from studies using validated protocols with isolated human/animal tissues or other non-tissue-based, 

validated protocols should be assessed. Examples of scientifically validated test methods for identifying eye 

corrosives and severe irritants (i.e., Serious Eye Damage) include OECD TG 437 (Bovine Corneal Opacity and 

Permeability (BCOP)) and 438 (Isolated Chicken Eye (ICE)). Presently there are no scientifically validated and 

internationally accepted in vitro test methods for identifying eye irritation. A positive test result from a scientifically 

validated in vitro test on skin corrosion would lead to the conclusion to classify as causing serious eye damage. 

e

 Measurement of pH alone may be adequate, but assessment of acid or alkali reserve (buffering capacity) would be 

preferable. Presently, there is no scientifically validated method for assessing this parameter. 

f

 All information that is available on a substance should be considered and an overall determination made on the 

total weight of evidence. This is especially true when there is conflict in information available on some parameters. 

The weight of evidence including information on skin irritation may lead to classification for eye irritation. Negative 

results from applicable validated in vitro tests are considered in the total weight of evidence evaluation. 

Classification criteria for mixtures

It should be noted that the classification criteria for the health hazards of mixtures usually 

include a tiered scheme (i.e., stepwise procedure based on a hierarchy principle) in which test 

data available on the complete mixture are considered as the first tier in the evaluation, followed 

by the applicable bridging principles, and lastly, cut-off values/concentration limits or additivity. 
92

Tier 1: Classification of mixtures when data are available for the complete mixture 

When serious eye damage /eye irritation test data on the mixture itself is available, these data are 

used to classify the mixture using the criteria for substances and taking into account the tiered 

weight-of-evidence approach illustrated in Figure VII.3.1. 

When considering testing of the mixture, classifiers are encouraged to use a tiered weight-ofevidence approach as included in the criteria for classification of substances for skin corrosion 

and serious eye damage/eye irritation to help ensure an accurate classification. In the absence of 

any other information, a mixture is considered to cause serious eye damage (Eye Category 1) if it 

has a pH ≤ 2 or ≥ 11.5. However, if consideration of alkali/acid reserve suggests the mixture may 

not cause serious eye damage despite the low or high pH value, then further evaluation may be 

necessary. 

If appropriate test data for the mixture are not available, then the classifier must consider the 

application of the Bridging Principle criteria in Tier 2, if appropriate, or if application of bridging 

principles are not appropriate, use the classification resulting from the application of criteria in 

Tier 3. 

Tier 2: Classification of mixtures when data are not available for the complete mixture - 

bridging principles 

Where the mixture itself has not been tested to determine its skin corrosivity or serious eye 

damage/eye irritation potential, but there are sufficient data on BOTH the individual ingredients 

AND similar tested mixtures to adequately characterize the hazards of the mixture, these data are 

used in accordance with the bridging principles below. 

The bridging principles that are applicable to the serious eye damage/eye irritation hazard class 

include: 

 Dilution, 

 Batching, 

 Concentration of mixtures,

 Interpolation within one toxicity category, 

 Substantially similar mixtures,

 Aerosols. 

The application of bridging principles ensures that the classification process uses the available 

data to the greatest extent possible in characterizing the potential skin corrosion/irritation hazard. 

Dilution 

If a tested mixture is diluted with a diluent which has an equivalent or lower 

classification for serious eye damage/eye irritation classification than the least seriously 

eye damaging/eye irritant original ingredient and which is not expected to affect the 
93

serious eye damage/eye irritancy of other ingredients, then the new diluted mixture must 

be classified as equivalent to the original tested mixture. Alternatively, the cut-off 

values/concentration limits or additivity method could be applied. 

Batching 

The serious eye damage/eye irritation potential of a tested production batch of a mixture 

can be assumed to be substantially equivalent to that of another untested production batch 

of the same commercial product when produced by or under the control of the same 

manufacturer, unless there is reason to believe there is significant variation such that the 

serious eye damage/eye irritation potential of the untested batch has changed. If the latter 

occurs, a new classification is necessary. 

Concentration of mixtures 

If a tested mixture classified for serious eye damage (Category 1) is concentrated, the 

more concentrated untested mixture is classified for serious eye damage (Category 1) 

without additional testing. If a tested mixture classified for eye irritation (Category 2 or 

2A) is concentrated and does not contain serious eye damage ingredients, the more 

concentrated untested mixture should be classified in the same category (Category 2 or 

2A) without additional testing. 

Interpolation within one hazard category 

For three mixtures (A, B and C) with identical ingredients, where mixtures A and B have 

been tested and are in the same serious eye damage/eye irritation hazard category, and 

where untested mixture C has the same toxicologically active ingredients as mixtures A 

and B but has concentrations of toxicologically active ingredients intermediate to the 

concentrations in mixtures A and B, then mixture C is assumed to be in the same serious 

eye damage/eye irritation category as A and B. 

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

 (ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) Data on serious eye damage/eye irritation for A and C are available and 

substantially equivalent, i.e., they are in the same hazard category and are not 

expected to affect the serious eye damage/eye irritation potential of B. 

If mixture (i) or (ii) is already classified by testing, then the other mixture can be 

classified in the same hazard category. 
94

Aerosols 

An aerosol form of a mixture must be classified in the same hazard category as the tested 

non-aerosolized form of the mixture provided that the added propellant does not affect 

the serious eye damage/eye irritation properties of the mixture upon spraying. Bridging 

principles apply for the intrinsic hazard classification of aerosols. However, the need to 

evaluate the potential for “mechanical” eye damage from the physical force of the spray 

is recognized. 

If appropriate data is not available to apply the above bridging principles then the classifier 

applies the criteria in Tier 3. 

Tier 3: Classification of mixtures when data are available for all ingredients or only for some 

ingredients of the mixture 

Cut-off values/concentration limits: Additivity 

In general, the approach to classifying a mixture for serious eye damage/eye irritation in Tier 3 is 

based on the theory of additivity, where each corrosive or irritant ingredient is considered to 

contribute to the overall corrosive or irritant properties of the mixture. The ingredients are 

summed in proportion to their concentration and potency (i.e., corrosives carry more weight in 

the irritation calculations). 

Table VII.3.3 provides the cut-off value/concentration limits to be used to determine if the 

mixture is considered to be corrosive or irritant to the eyes. Six potential additivity calculations 

are given in the first column. Each calculation has specific concentration cut-offs that will trigger 

the classification specified in columns 2 and 3 which correspond to Category 1 and Category 2, 

respectively. 

To better illustrate the order in which the equations should be evaluated an arrow has been added 

to the table. Following the arrow, the first calculation that exceeds the percentage cut-off trigger 

determines which classification is assigned to the mixture. If none of the sums exceed the cut-off 

triggers then the mixture is not classified. 
95

Table VII.3.3. Concentration of ingredients of a mixture classified as skin Category 1 

and/or eye Category 1 or 2 that would trigger classification of the mixture as hazardous to 

the eye (Category 1 or 2)11

Sum of ingredients classified as

Concentration triggering 

classification of a mixture as

Serious eye damage Eye irritation

Category 1 Category 2

Eye Category 1 or Skin Category 1  3%  1% but < 3%

Eye Category 2  10%

(10 × Eye Category 1) + Eye Category 2  10%

Skin Category 1 + Eye Category 1a

 3%  1% but < 3%

10  (Skin Category 1 + Eye Category 1)a+ 

Eye Category 2 

 10%

a If an ingredient is classified as both skin Category 1 and eye Category 1 its concentration is considered only once 

in the calculation. 

Note: A mixture is classified as eye Category 2B when all relevant ingredients are classified as eye 

Category 2B.

The Nine Serious Eye Damage/Eye Irritation Mixture Additivity Calculations 

There are nine possible calculations that may need to be performed to determine if the mixture 

should be classified. 

Sum of ingredients classified as

Concentration triggering 

classification of a mixture as

Serious eye 

damage Eye irritation

Category 1 Category 2

Eye Category 1  3% (1)  1% but < 3% (4)

Skin Category 1  3% (2)  1% but < 3% (5)

Eye Category 2  10% (6)

(10 × Eye Category 1) + Eye Category 2  10% (7)

Skin Category 1 + Eye Category 1a

 3% (3)  1% but < 3% (8)

10  (Skin Category 1 + Eye Category 1)a+ 

Eye Category 2 

 10% (9)

 

11 Revision 6 of the GHS contains a similar table that may be easier to understand. See GHS Table 3.3.3. 
96

a

 If an ingredient is classified as both skin Category 1 and eye Category 1 its concentration is considered only once 

in the calculation

Note: A mixture is classified as eye Category 2B when all relevant ingredients are classified as eye 

Category 2B.

Serious eye damage Category 1 classification calculations: 

(1) Add the percentages of all ingredients classified as Eye Category 1. 

If the sum is ≥ 3% the mixture is classified as Category 1 Serious Eye Damage. 

∑ % Eye Category 1 ingredients ≥ 3% 

(2) Add the percentages of all ingredients classified as Skin Category 1. 

If the sum is ≥ 3% the mixture is classified as Category 1 Serious Eye Damage. 

∑ % Skin Category 1 ingredients ≥ 3% 

(3) First add the percentages of all ingredients classified as Eye Category 1. 

Then add the percentages of all ingredients classified as Skin Category 1. 

Add these two numbers together. If the sum is ≥ 3%, the mixture is classified as 

Category 1 Serious Eye Damage. 

∑ % Skin Category 1 ingredients + ∑ % Eye Category 1 ingredients ≥ 3%

Eye irritation Category 2 classification calculations: 

For Category 1 ingredients: 

(4) Add the percentages of all ingredients classified as Eye Category 1. 

If the sum is ≥ 1% but < 3%, the mixture is classified as Category 2 Eye Irritation. 

∑ % Eye Category 1 ingredients ≥ 1% but < 3% 

(5) Add the percentages of all ingredients classified as Skin Category 1. 

If the sum is ≥ 1% but < 3%, the mixture is classified as Category 2 Eye Irritation. 

∑ % Skin Category 1 ingredients ≥ 1% but < 3% 

For Category 2 ingredients: 

(6) Add the percentages of all ingredients classified as Eye Category 2. 

If the sum is ≥ 10% the mixture is classified as Category 2 Eye Irritation. 

∑ % Eye Category 2 ingredients ≥ 10% 
97

For Category 1 & 2 ingredients: 

(7) First add the percentages of all ingredients classified as Eye Category 1 and multiply 

this sum by 10. 

Then add the percentages of all ingredients classified as Eye Category 2. 

Add these two numbers together. If the sum is ≥ 1% but < 3%, the mixture is classified as 

Category 2 Eye Irritation.

10 (∑ % Eye Category 1 ingredients) + ∑ % Eye Category 2 ingredients ≥ 1% but < 3% 

For Skin & Eye Category 1 ingredients: 

(8) First add the percentages of all ingredients classified as Skin Category 1.

Then add the percentages of all ingredients classified as Eye Category 1. 

(If an ingredient is classified as both skin Category 1 and eye Category 1 its 

concentration is considered only once in the calculation.) 

Add these two numbers together. If the sum is ≥ 1% but < 3%, the mixture is 

classified as Category 2 Eye Irritation. 

∑ % Skin Category 1 ingredients + ∑ % Eye Category 1 ingredients ≥ 1% but < 3% 

For Skin & Eye Category 1 & Eye 2 ingredients: 

(9) Add the percentages of all ingredients classified as Skin Category 1. 

Add the percentages of all ingredients classified as Eye Category 1. 

Add these two numbers. Multiply that sum by 10. This is calculation one. 

In calculation two add the percentages of all ingredients classified as Eye 

Category 2. 

In calculation three add the numbers from calculation one and calculation two together. 

If the number in calculation 3 is ≥ 10%, the mixture is classified as Category 2 Eye 

Irritation. 

10 (∑ % Skin Category 1 ingredients + ∑ % Eye Category 1 ingredients) + ∑ % Eye 

Category 2 ingredients ≥ 10% 

Reminder: 

A mixture may be classified as eye Category 2B when all relevant ingredients are classified as 

eye Category 2B. Category 2A is equivalent to Category 2. 
98

Shortcut Serious Eye Damage/Eye Irritation Mixture Additivity Calculations 

Shortcut 

For those doing the calculations manually, a shortcut that leads to the same classification is to 

only do the worst-case calculations for the Serious Eye Damage Category 1 classification and the 

Eye Irritation Category 2 classification. In the shortcut there are only two calculations. The first 

sum that exceeds the percentage cut-off trigger determines which classification is assigned to the 

mixture. If neither exceeds the cut-off triggers then the mixture is not classified. 

Sum of ingredients classified as

Concentration triggering 

classification of a mixture as

Serious eye damage Eye irritation

Category 1 Category 2

Eye Category 1  3%  1% but < 3%

Skin Category 1  3%  1% but < 3%

Eye Category 2  10%

(10 × Eye Category 1) + Eye Category 2  10%

Skin Category 1 + Eye Category 1a

 3%  1% but < 3%

10  (Skin Category 1 + Eye Category 1)a+

Eye Category 2 

 10%

a

 If an ingredient is classified as both skin Category 1 and eye Category 1 its concentration is considered only once 

in the calculation

Note: A mixture is classified as eye Category 2B when all relevant ingredients are classified as eye 

Category 2B.

Shortcut Serious eye damage Category 1 classification calculation: 

(3) First add the percentages of all ingredients classified as Eye Category 1. 

Then add the percentages of all ingredients classified as Skin Category 1. 

Add these two numbers together. If the sum is ≥ 3%, the mixture is classified as 

Category 1 Serious Eye Damage. 

∑ % Skin Category 1 ingredients + ∑ % Eye Category 1 ingredients ≥ 3%

Shortcut Eye irritation Category 2 classification calculation: 

(9) Add the percentages of all ingredients classified as Skin Category 1. 

Add the percentages of all ingredients classified as Eye Category 1. 

Add these two numbers. Multiply that sum by 10. This is calculation one. 

In calculation two add the percentages of all ingredients classified as Eye 
99

Category 2. 

In calculation three add the numbers from calculation one and calculation two together. 

If the number in calculation 3 is ≥ 10%, the mixture is classified as Category 2 Eye 

Irritation. 

10 (∑ % Skin Category 1 ingredients + ∑ % Eye Category 1 ingredients) + ∑ % Eye 

Category 2 ingredients ≥ 10% 

Cut-off values/concentration limits: when the additivity approach does not apply 

Particular care must be taken when classifying certain types of chemicals such as acids and 

bases, inorganic salts, aldehydes, phenols, and surfactants. The additivity approach might not 

work because many such chemicals are seriously damaging or irritating to the eye at 

concentrations < 1% and additivity may underestimate the overall corrosive or irritant properties 

of the mixture. 

For mixtures containing strong acids or bases, the pH should be used as the classification 

criterion since pH will be a better indicator of serious eye damage (subject to consideration of 

acid/alkali reserve) than the concentration limits in Table VII.3.3. A mixture containing 

corrosive or serious eye damaging/eye irritating ingredients that cannot be classified based on the 

additivity approach applied in Table VII.3.3 due to chemical characteristics that make this 

approach unworkable should be classified using the more conservative cut-off/concentration 

limit approach summarized below: 

 Mixture is Eye Category 1 if it contains ≥ 1% of a corrosive ingredient, and 

 Mixture is Eye Category 2 if it contains ≥ 3% of an irritant ingredient. 

The cut-off value/concentration limits approach is summarized in HCS Table VII.3.4.

Table VII.3.4. Concentration of ingredients of a mixture when the additivity approach does 

not apply, that would trigger classification of the mixture as hazardous to the eye 

Ingredient Concentration

Mixture classified as:

Eye

Acid with pH  2  1% Category 1

Base with pH  11.5  1% Category 1

Other corrosive (Eye Category 1) ingredient  1% Category 1

Other eye irritant (Eye Category 2) ingredient

for which additivity does not apply , including 

acids and bases

 3% Category 2
100

Cut-off values/concentration limits: Important Points to Consider 

To ensure consistent application of both the additivity and cut-off/concentration limit approaches 

to classification for Serious Eye Damage/Eye Irritation, the following principles need to be 

applied where appropriate: 

 Classification Above or Below Cut-Off Values/Concentration Limits 

On occasion, reliable data may show that the irreversible/reversible eye effects of an 

ingredient will not be evident when present at a level above the cut-off 

values/concentration limits mentioned in Tables VII.3.3 and VII.3.4. In these cases the 

mixture could be classified according to those data (see also HCS 2012 A.0.4.3). Testing 

of the mixture may be considered. If testing is not performed, the tiered weight-ofevidence approach should be applied. 

If there are data showing that (an) ingredient(s) may be corrosive to the skin or seriously 

damaging to the eye/eye irritating at a concentration of  1% (corrosive to the skin or 

seriously damaging to the eye) or  3% (eye irritant), the mixture should be classified 

accordingly. 

 “Relevant Ingredient” Concept 

For the purpose of applying the cut-off values in Tables VII.3.3 and VII.3.4, only 

“relevant ingredients” need to be included in the calculation. 

The “relevant ingredients” of a mixture are those which are present in concentrations ≥ 

1% (w/w for solids, liquids, dusts, mists and vapors and v/v for gases), unless there is a 

presumption (e.g., in the case of corrosive ingredients) that an ingredient present at a 

concentration < 1% can still be relevant for classifying the mixture for serious eye 

damage/eye irritation. If the classifier suspects that the ingredient could be relevant for 

classifying the mixture at < 1%, then the classifier must use expert judgment to determine 

at what concentration below 1% the corrosive Category 1 ingredient(s) should be 

included in the calculation. 

Classification Procedure and Guidance 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS requires 

collecting and evaluating the best available existing evidence on the hazards of each chemical. 

In classification the data are compared to the serious eye damage/eye irritation classification 

criteria. If valid data on serious eye damage/eye irritation of a substance or mixture are available, 

these data should be used for classification. To find the necessary data, a classifier is advised to 

try the following: 

 ask the manufacturer or supplier for the serious eye damage/eye irritation data for the 

product; or 
101

 check if the serious eye damage/eye irritation data is available in the SDS or any other 

documentation accompanying the product; or 

 find the data available in the open literature, if the chemical identity of the product is 

known (for a single-component chemical). 

Data generated in accordance with internationally recognized scientific principles are acceptable 

under the HCS. 

Examples of scientifically validated test methods 

There are a number of methods that use recognized scientific principles for investigation of 

serious eye damage/eye irritation effects: 

 OECD Test Guideline 405: Acute Eye Irritation/Corrosion 

 USEPA OTS code: 798.4500; 

 USEPA OPP code: 81-4; 

 USEPA OPPTS code: 870.2400; 

 EEC Directive 92/32/EEC (B.5); 

 OECD Test Guideline 437: In Vitro Bovine Corneal Opacity and Permeability (BCOP); 

 OECD Test Guideline 438: In Vitro Isolated Chicken Eye (ICE). 

In the in vivo test, the substance is applied in a single dose to one of the eyes of an experimental 

animal (usually a healthy young albino rabbit) while the untreated eye serves as the control. 

Internationally accepted, validated in vivo test methods for identifying eye corrosives and severe 

irritants (i.e., Serious Eye Damage) include OECD TG 437 - Bovine Corneal Opacity and 

Permeability (BCOP) and OECD TG 438 - Isolated Chicken Eye (ICE). Presently there are no 

validated and internationally accepted in vitro test methods for identifying eye irritation. 

Guidance on evaluation of data from studies with more than three animals 

The classification criteria for serious eye damage/eye irritation are given in terms of a 3-animal 

test. Some older test methods may have used up to 6 animals. However, the serious eye 

damage/eye irritation criteria do not specify how to classify based on existing data from tests 

with more than 3 animals. 

Criteria for the evaluation of a 4, 5 or 6-animal study are provided in the paragraphs below, 

depending on the number of animals tested. Scoring is done at 24, 48 and 72 hours after 

instillation of the test material. 

In the case of a study with 6 animals the following principles apply: 

(a) The substance or mixture is classified as serious eye damage Category 1 if: 

(i) at least in one animal effects on the cornea, iris or conjunctiva are not expected 

to reverse or have not fully reversed within an observation period of normally 

21 days; and/or 
102

(ii) at least 4 out of 6 animals show a mean score per animal of  3 for corneal 

opacity and/or > 1.5 for iritis. 

(b) The substance or mixture is classified as eye irritation Category 2/2A if at least 4 out 

of 6 animals show a mean score per animal of: 

(i) ≥ 1 for corneal opacity; and/or 

(ii) ≥ 1 for iritis; and/or 

(iii) ≥ 2 for conjunctival redness; and/or 

(iv) ≥ 2 for conjunctival oedema (chemosis) 

and which fully reverses within an observation period of normally 21 days. 

(c) The substance or mixture is classified as irritating to eyes (Category 2B) if the effects 

listed in sub-paragraph (b) above are fully reversible within 7 days of observation. 

In the case of a study with 5 animals the following principles apply: 

(a) The substance or mixture is classified as serious eye damage Category 1 if: 

(i) at least in one animal effects on the cornea, iris or conjunctiva are not expected 

to reverse or have not fully reversed within an observation period of normally 21 

days; and/or 

(ii) at least 3 out of 5 animals show a mean score per animal of  3 for corneal 

opacity and/or > 1.5 for iritis. 

(b) The substance or mixture is classified as eye irritation Category 2/2A if at least 3 out 

of 5 animals show a mean score per animal of: 

(i) ≥ 1 for corneal opacity; and/or 

(ii) ≥ 1 for iritis; and/or 

(iii) ≥ 2 for conjunctival redness; and/or 

(iv) ≥ 2 for conjunctival oedema (chemosis) 

and which fully reverses within an observation period of normally 21 days. 

(c) The substance or mixture is classified as irritating to eyes (Category 2B) if the effects 

listed in sub-paragraph (b) above are fully reversible within 7 days of observation. 

In the case of a study with 4 animals the following principles apply: 

(a) The substance or mixture is classified as serious eye damage Category 1 if: 

(i) at least in one animal effects on the cornea, iris or conjunctiva are not expected 

to reverse or have not fully reversed within an observation period of normally 21 

days; and/or 

(ii) at least 3 out of 4 animals show a mean score per animal of  3 for corneal 

opacity and/or > 1.5 for iritis. 
103

(b) Classification as eye irritation Category 2/2A if at least 3 out of 4 animals show a 

mean score per animal of: 

(i) ≥ 1 for corneal opacity; and/or 

(ii) ≥ 1 for iritis; and/or 

(iii) ≥ 2 for conjunctival redness; and/or 

(iv) ≥ 2 for conjunctival oedema (chemosis) 

and which fully reverses within an observation period of normally 21 days. 

(c) The substance or mixture is classified as irritating to eyes (Category 2B) if the effects 

listed in sub-paragraph (b) above are fully reversible within 7 days of observation. 

Decision logic 

Two decision logics for classifying Serious Eye Damage/Eye Irritation are provided. The first 

decision logic is for substances and for mixtures with data on the mixture as a whole. Use the 

second decision logic for classifying mixtures on the basis of information/data on similar tested 

mixtures and/or ingredients. The decision logics are provided as additional guidance. It is 

strongly recommended that the person responsible for classification study the criteria before and 

during use of the decision logic. 

These decision logics are essentially flowcharts for classifying substances and mixtures 

regarding serious eye damage/eye irritation. They present questions in a sequence that walks you 

through the classification steps and criteria for classifying serious eye damage/eye irritation. 

Once you answer the questions provided, you will arrive at the appropriate classification. 
104

Decision logic for serious eye damage/eye irritation 

(Cont’d on next page)

Yes

Does the substance or mixturehave potential to cause irreversible eye 

damage (serious eye damage)considering(total weight of evidence as 

needed):

(a) Existing human experience, 

(b) Existing animal observations including single or repeated exposure,

(c) In vitro data,

(d) Information available from structurally related compounds,

(e) pH extremes of 2 or  11.5 (taking into account acid/alkaline reserve)

(f) Irreversible eye damage in one or more test animals? (see Table A.3.1 

for criteria and sub-categorization) for

See next decision logic 

for use with ingredients

Substance:Are there data/information to evaluate serious eye 

damage/eye irritation?

Classification 

not possible

Mixture: Does the mixture as a whole or its ingredients 

have data/information to evaluate serious eye 

damage/eye irritation?

No

Yes

No

Mixture:Does the mixture as a whole have 

data/information to evaluate serious eye 

damage/eye irritation?

Category 1

Danger

Yes

No

Yes

Classification 

not possible No
105

Is the substance or mixture an eye irritant considering(total weight of 

evidence as needed):

(a) Existing human experience and data, single or repeated exposure,

(b) Existing animal observations including single or repeated exposure,

(c) In vitro data,

(d) Information available from structurally related compounds,

(e) Eye irritation data from an animal study (see Table A.3.2 for 

criteria for Category 2A)?

Yes

Category 2A

Warning

Not classified

No

Yes

Category 2B

No symbol

Warning

Is the substance or mixture a mild irritant, Category 2B, considering

criteria in Table A.3.2?

No

No
106

Mixtures decision logic for serious eye damage/eye irritation 

Classification of mixtures on the basis of information/data on ingredients

Cont’d on next page)

Does the mixture contain ≥ 1% of an ingredient which causes 

irreversible eye damage & for which additivity may not apply, 

such as:

(a) Acids and bases with extreme pHs  2 or  11.5 

(considering acid/alkaline reserve), or 

(b) Inorganic salts, or

(c) Aldehydes, or

(d) Phenols, or

(e) Surfactants, or

(f) Other ingredients?

Can bridging principles be applied?

Does the mixture contain  3% of an ingredient which is irritant 

and for which additivity may not apply, including acids and 

bases?

Yes

Classify in 

appropriate 

category

No

Yes

Category 1

Danger 

Yes

Category 2

Warning

Does the mixture contain one or more corrosive or irritant 

ingredients for which additivity applies, and where the sum of 

concentrations of ingredients classified as:

(a) eye or skin Category 1:  3% or 

(b) skin Category 1 + eye Category 1:  3%? 

Yes

Category 1

Danger 

No

No

No
107

Not classified

Does the mixture contain one or more corrosive or irritant 

ingredients for which additivity applies, and where the sum of 

concentrations of ingredients classified as:

(a) eye or skin Category 1:  1% but < 3%, or

(b) eye Category 2A/2B: 10%, or

(c) (10 × eye Category 1) + eye Category 2A/2B:  10%, or

(d) skin Category 1 + eye Category 1:  1% but < 3%, or

(e) 10 × (skin Category 1 + eye Category 1) + eye Category 

2A/2B:  10%?

No

Yes

Category 2

Warning

No
108

Serious Eye Damage/Eye Irritation Classification Examples 

The following examples are provided to walk you through the serious eye damage/eye irritation 

calculation and classification processes. 

Examples of a substance fulfilling the criteria for classification: 

Substance Example #1

Serious Eye Damage

Test Data

HCS 2012

Classification Rationale

Toxicity data: neither in vivo data 

nor in vitro data available

Other relevant information: pH 

1.9; no info on buffering capacity

Serious Eye 

Damage

Category 1

Based on a pH < 2, the substance is a 

Serious Eye Damage Category 1 

according to Figure VII.3.1 Tiered 

evaluation for serious eye 

damage/eye irritation, Step 4.

Substance Example #2

Eye Irritation

Test Data 

HCS 2012

Classification Rationale

In an OECD Test Guideline 405 

study the test substance was 

applied on the eyes of three 

rabbits. The scoring results are

 Corneal opacity: 2, 2, 1.3

 Iritis: 1, 1, 1

 Conjunctival redness: 2, 1, 1

 Conjunctival edema 

(chemosis): 3, 1.7, 2.3

 Reversibility: The effects 

were reversible. 

Eye Irritation

Category 2

Fulfills criteria 

 The test results show:

Cornea ≥ 1 (in all animals)

Iritis ≥ 1 (in all animals)

Conjunctival redness ≥ 2 (in 1 

animal)

Conjunctival edema ≥2 (in 2 of 3 

animals)

 The Category 2 criteria are 

fulfilled by the Cornea, 

Conjunctiva and Iris scores.
109

Substance Example #3

Serious Eye Damage

Test Data 

HCS 2012

Classification Rationale

The material is a new aliphatic 

secondary amine. No data is 

available. The test substance has 

Structure Activity Relationships 

(SAR) to substances with similar 

structure known to be corrosive to 

the skin.

Serious Eye 

Damage 

Category 1

Based on expert judgment using 

SAR information the classifier 

concluded that Category 1 is 

justified, since there is much data on 

aliphatic amines which are skin 

corrosives Category 1 and thus 

deemed to cause irreversible eye 

effects resulting in Serious Eye 

Damage Category 1 according to 

Figure VII.3.1 Tiered evaluation for 

serious eye damage/eye irritation, 

Step 5.

Substance Example #4

Eye Irritation

Test Data 

HCS 2012

Classification Rationale

OECD Test Guideline 405: Acute 

Eye Irritation/Corrosion test 

results:

 Corneal opacity: mean score 

0.6

 Iritis: mean score 1.3

 Conjunctival redness: mean 

score 2.4 (from 2 of 3 

animals)

 Conjunctival edema 

(chemosis): mean score 1.4 

 Reversibility: The effects 

were fully reversible after 7 

days.

Eye Irritation 

Category 2B

Fulfills criteria 

 the mean score for redness over 

24, 48, and 72 hours in 2 of 3 

animals is 2.4 and therefore > 

2.3, 

 the effects are fully reversible in 

7 days, 

 the criteria for classification in 

Category 2B are fulfilled.
110

Examples of a mixture fulfilling the criteria for classification: 

Mixture Example #1

Eye Irritation

Data

HCS 2012

Classification Rationale

Component data:

Component 1: 0.5%, Eye 

Category 1

Component 2: 3.5%, Eye 

Category 2, surfactant

Component 3: 15%, No data 

available

Component 4: 15%, No data 

available

Component 5: 66%, No data 

available

Eye Irritation 

Category 2

Mixture is Eye Irritation Category 2 

because

 Mixture contains 0.5% of an Eye 

Category 1 which is not ≥ 1% so 

the mixture is not Category 1;

 Mixture contains 3.5% of an Eye 

Category 2 surfactant which is ≥

3.0% so the mixture is Category 

2.

 Classification of the mixture 

based on ingredient data can be 

considered.

 Component 2 (Surfactant) is a 

component for which additivity 

might not apply. Expert judgment 

would be needed to determine 

whether or not additivity applies. 

Knowledge of the components is 

important. Given the limited 

information in this example, the 

classifier of this mixture chose to 

apply non-additivity for a 

conservative approach. 

Therefore, the criteria described 

in 29 CFR 1910.1200 paragraph 

A.3.4.3.4 apply (i.e., “A mixture 

containing corrosive or irritant 

ingredients that cannot be 

classified based on the additivity 

approach shown in [Table 

VII.3.3], due to chemical 

characteristics that make this 

approach unworkable, should be 

classified as Eye Category 1 if it 

contains ≥ 1% of a corrosive 

ingredient and as Eye Category 

2/3 when it contains ≥ 3% of an 

irritant ingredient”).
111

Mixture Example #2

Serious Eye Damage

Data

HCS 2012

Classification Rationale

Component data:

Component 1: 22.06%, Eye 

Category 1

Component 2: 4%, Eye 

Category 1

Component 3: 5.5%, Eye 

Category 2A

Component 4: 8%, not classified 

based on test data

Component 5: 0.05%, not 

classified based on test data

Component 5: 0.2%, not 

classified based on test data

Water: 60.19%, %, not classified

pH of mixture (neat liquid): 7 – 8

Mixture BCOP test data:

Mean opacity value = 15

Mean permeability OD490 

value = 5

In Vitro Irritancy Score 

(IVIS) = 90

Serious Eye 

Damage 

Category 1

IVIS = mean opacity value + (15 x 

mean permeability OD490 value)

A test sample that induces an IVIS ≥

55.1 is defined as a corrosive or 

severe irritant to eyes.

Applying the Tiered evaluation for 

serious eye damage/eye irritation 

approach using serious eye 

damage/eye irritation in vitro data 

from a Bovine Corneal Opacity and 

Permeability (BCOP) test, the mixture 

is classified as Serious Eye Damage 

Category 1 based on test data.

 Test results derived using the 

BCOP test method indicate the 

mixture is a corrosive or severe 

eye irritant.
112

Mixture Example #3

Eye Irritation

Data

HCS 2012 

Classification Rationale

Component data:

Component 1: 4%, Eye Irritation 

Category 2A

Component 2: 5%, Eye Irritation 

Category 2A

Component 3: 5%, Eye Irritation 

Category 2A

Component 4: 86%, no data 

available

Eye Irritation 

Category 2A

Use equations from Table VII.3.3 

Category 1 calculation:

a) ∑% Eye Category 1 = 0 which is 

not ≥ 3%

b) ∑ % Skin Category 1 = 0 which 

is not ≥ 3%

c) ∑ % Skin Category 1 + ∑ % Eye 

Category 1 = 0 which is not ≥ 3%

Category 2 calculations:

d) ∑% Eye Category 1 = 0 which is 

not ≥ 1% but < 3%

e) ∑ % Skin Category 1 = 0 which is 

not ≥ 1% but < 3%

f) ∑ % Eye Category 2/2A = 4% + 

5% + 5% = 14% which is ≥ 10%

 Classification of the mixture 

based on ingredient data can be 

considered 

 Apply the calculations in Table 

VII.3.3

 The mixture is classified as 

Category 2A since all the 

classified components were 

Category 2A.
113

Example of a substance not fulfilling the criteria for classification: 

Substance Example #5

Eye Irritation

Test Data

HCS 2012

Classification Rationale

Toxicity data: Old non-guideline 

study in rabbits

 After 24 hours: questionable 

redness 

 Reversibility: full after 8 days 

Not classified According to the classification 

criteria the slight irritating effect 

with full reversibility does not justify 

classification in this hazard class.
114

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.3 Serious Eye Damage/Eye Irritation. 

29 CFR 1910.1200, Hazard Communication. Appendix C, Allocation of Label Elements. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

The Organization for Economic Co-operation and Development (OECD) Guidelines for the 

Testing of Chemicals. 

United States Environmental Protection Agency (EPA) Office of Prevention, Pesticides, and 

Toxic Substances (OPPTS) Health Effects Test Guidelines.
115

VII.4 Respiratory or Skin Sensitization 

Introduction

A sensitizer (allergen) causes little or no reaction in humans 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 have also been known to occur. Well-known examples of 

sensitizers are toluene diisocyanate, nickel compounds, and poison ivy. 

A sensitizer is an agent that can cause an allergic response in susceptible individuals. The 

consequence of this is that following an initial exposure which sensitizes the individual, 

subsequent exposures via the skin or by inhalation provoke the characteristic adverse health 

effects of allergic contact dermatitis or asthma (and related respiratory symptoms such as 

rhinitis), respectively. Although asthma and rhinitis are generally thought to be a result of an 

allergic reaction, the understanding, in recent years, that other, non-immunological, mechanisms 

may occur, makes it more appropriate to use a term based on disease rather than mechanism. 

Thus, the term “respiratory hypersensitivity” is a term that is used to describe asthma and other 

related respiratory conditions, irrespective of the mechanism by which they are caused. 

The term skin sensitization specifies an allergic mechanism of action, while respiratory 

hypersensitivity does not. For this reason, the two health hazards have been approached 

differently. 

For the purpose of this chapter, sensitization includes two phases: 

 induction of specialized immunological memory in an individual by exposure to an 

allergen; and 

 elicitation, i.e., production of a cell-mediated or antibody-mediated allergic response by 

exposure of a sensitized individual to an allergen. 

For respiratory sensitization, the pattern of induction followed by elicitation phases is shared in 

common with skin sensitization. For skin sensitization, an induction phase is required in which 

the immune system learns to react; clinical symptoms can then arise when subsequent exposure 

is sufficient to elicit a visible skin reaction (elicitation phase). Respiratory sensitization may be 

induced not only by inhalation but also by skin contact. 

Tests for sensitization usually follow the same pattern in which there is an induction phase, and 

then a response, which is measured by a standardized elicitation phase, typically involving a patch 

test. The local lymph node assay is the exception, directly measuring the induction response. 

Evidence of skin sensitization in humans normally is assessed by a diagnostic patch test. 

Usually, for both skin and respiratory sensitization, lower levels are necessary for elicitation than 

are required for induction. 
116

The hazard class “respiratory or skin sensitization” is differentiated into: 

(a) Respiratory sensitization and 

(b) Skin sensitization. 

Respiratory Sensitizers 

Definition and General Considerations 

Respiratory sensitizer means a chemical that will lead to hypersensitivity of the airways 

following inhalation of the chemical. 

Respiratory Sensitizer Classification Criteria for Substances 

Effects seen in either humans or animals will normally justify classification using a weight-ofevidence approach for respiratory sensitizers. Substances may be allocated to one of the two subcategories, 1A or 1B, using a weight-of-evidence approach in accordance with the criteria 

indicated below and on the basis of reliable and good quality evidence from human cases or 

epidemiological studies and/or observations from appropriate studies in experimental animals. 

Where data are not sufficient for sub-categorization, respiratory sensitizers shall be classified in 

Category 1. 

Table VII.4.1. Hazard category and sub-categories for respiratory sensitizers 

Category Respiratory Sensitizer Criteria

Category 1 A substance is classified as a respiratory sensitizer

(a) if there is evidence in humans that the substance can lead to 

specific respiratory hypersensitivity and/or

(b) if there are positive results from an appropriate animal test.12

Sub-category 1A Substances showing a high frequency of occurrence13 in humans, or a 

probability of occurrence of a high sensitization rate in humans based 

on animal or other tests.12Severity of reaction may also be considered.

Sub-category 1B Substances showing a low to moderate frequency of occurrence13 in 

humans; or a probability of occurrence of a low to moderate 

sensitization rate in humans based on animal or other tests.12Severity 

of reaction may also be considered.

 

12 At this writing, recognized and validated animal models for the testing of respiratory hypersensitivity are not 

available. Under certain circumstances, data from animal studies may provide valuable information in a weight-ofevidence assessment

13 With regard to the criteria for respiratory sensitization, the frequency of occurrence in humans is a matter of 

expert judgment. 
117

Human evidence 

Evidence that a substance can lead to specific respiratory hypersensitivity will normally be based 

on human experience. In this context, hypersensitivity is normally seen as asthma, but other 

hypersensitivity reactions such as rhinitis/conjunctivitis and alveolitis are also considered. The 

condition will have the clinical character of an allergic reaction. However, immunological 

mechanisms do not have to be demonstrated. 

When considering the human evidence, it is necessary that in addition to the evidence from the 

cases, the following factors should be taken into account: 

(a) The size of the population exposed; 

(b) The extent of exposure. 

The evidence referred to above could be: 

(a) Clinical history and data from appropriate lung function tests related to exposure to 

the substance, confirmed by other supportive evidence which may include: 

(i) In vivo immunological test (e.g., skin prick test); 

(ii) In vitro immunological test (e.g., serological analysis); 

(iii) Studies that may indicate other specific hypersensitivity reactions where 

immunological mechanisms of action have not been proven, e.g., repeated lowlevel irritation, pharmacologically mediated effects 

(iv) A chemical structure related to substances known to cause respiratory 

hypersensitivity; 

(b) Data from positive bronchial challenge tests with the substance conducted according 

to accepted guidelines for the determination of a specific hypersensitivity reaction. 

Clinical history should include both medical and occupational history to determine a relationship 

between exposure to a specific substance and development of respiratory hypersensitivity. 

Relevant information includes aggravating factors both in the home and workplace, the onset and 

progress of the disease, family history and medical history of the patient in question. The 

medical history should also include details of other allergic or airway disorders from childhood 

and smoking history. 

The results of positive bronchial challenge tests are considered to provide sufficient evidence for 

classification on their own. It is, however, recognized that in practice many of the examinations 

listed above will already have been carried out. 
118

Animal studies 

Data from appropriate animal studies which may be indicative of the potential of a substance to 

cause sensitization by inhalation in humans may include: 

(a) Measurements of Immunoglobulin E (IgE) and other specific immunological 

parameters, for example in mice 

(b) Specific pulmonary responses in guinea pigs. 

At this writing, recognized and validated animal models for the testing of respiratory 

hypersensitivity are not available. Under certain circumstances, data from animal studies may 

provide valuable information in a weight-of-evidence assessment. 

The mechanisms by which substances induce symptoms of asthma are not yet fully known. For 

preventive measures, these substances are considered respiratory sensitizers. However, if on the 

basis of the evidence, it can be demonstrated that these substances induce symptoms of asthma 

by irritation only in people with bronchial hyperactivity, they should not be considered as 

respiratory sensitizers. 

Classification Procedure and Guidance 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS requires 

collecting and evaluating the best available existing evidence on the hazards of each chemical. 

Classification procedure 

In classification, the data are compared to the respiratory sensitizer classification criteria. Data 

can be found in literature, on SDSs, or be determined by testing, (which is not required by the 

HCS). For classification of mixtures, follow the three-tier approach discussed below. 

To assess the respiratory sensitization hazard of a chemical, identify the relevant data. Effects 

seen in either humans or animals will normally justify classification using a weight-of-evidence 

approach for respiratory sensitizers. The weight-of-evidence approach uses expert judgment. All 

available information bearing on the respiratory sensitizer hazard classification is considered 

together, including the results of relevant animal data, and human experience, such as 

epidemiological and clinical studies and well-documented case reports and observations. 

The quality and consistency of the data should be considered. Information on chemicals related 

to the material being classified should be considered, as appropriate. Both positive and negative 

results shall be considered together in a weight-of-evidence determination. However, positive 

effects which are consistent with the respiratory sensitizer classification criteria, whether seen in 

humans or animals, normally justify classification.

Where evidence is available from both humans and animals and there is a conflict between the 

findings, evaluate the quality and reliability of the evidence from both sources. Reliable, good 
119

quality human data generally takes precedence over other data. Positive results from wellconducted animal studies are not necessarily negated by the lack of positive human experience 

but require an assessment of the robustness, quality and statistical power of both the human and 

animal data. 

If the data are available, then you must classify the chemical into the appropriate respiratory 

sensitization sub-category, i.e., category 1A or category 1B. If the data does not allow 

classification into a sub-category, then you must classify the chemical in respiratory sensitization 

category 1. 

Skin Sensitizers 

Definition and General Considerations 

Skin sensitizer means a chemical that will lead to an allergic response following skin contact. 

Skin Sensitizer Classification Criteria for Substances 

Effects seen in either humans or animals will normally justify classification using a weight-ofevidence approach for skin sensitizers. Substances may be allocated to one of the two subcategories, 1A or 1B, using a weight-of-evidence approach in accordance with the criteria given 

below, and on the basis of reliable and good quality evidence from human cases or 

epidemiological studies and/or observations from appropriate studies in experimental animals. 

Where data are not sufficient for sub-categorization, skin sensitizers shall be classified in 

Category 1. 

Table VII.4.2. Hazard category and sub-categories for skin sensitizers 

Category Skin Sensitizer Criteria

Category 1 A substance is classified as a skin sensitizer 

(a) if there is evidence in humans that the substance can lead to 

sensitization by skin contact in a substantial number of persons, or 

(b) if there are positive results from an appropriate animal test. 

Sub-category 1A Substances showing a high frequency of occurrence14 in humans 

and/or a high potency in animals can be presumed to have the 

potential to produce significant sensitization in humans. Severity of 

reaction may also be considered.

Sub-category 1B Substances showing a low to moderate frequency of occurrence14 in 

humans and/or a low to moderate potency in animals can be 

presumed to have the potential to produce sensitization in humans. 

Severity of reaction may also be considered.

 

14 With regard to the criteria for respiratory sensitization, the frequency of occurrence in humans is a matter of 

expert judgment. 
120

Human evidence 

Human evidence for sub-category 1A may include: 

(a) Positive responses at ≤ 500 μg/cm2(Human Repeat Insult Patch Test (HRIPT), 

Human Maximization Test (HMT) – induction threshold);

(b) Diagnostic patch test data where there is a relatively high and substantial incidence of 

reactions in a defined population in relation to relatively low exposure; 

(c) Other epidemiological evidence where there is a relatively high and substantial 

incidence of allergic contact dermatitis in relation to relatively low exposure. 

Human evidence for sub-category 1B may include: 

(a) Positive responses at > 500 μg/cm2

(HRIPT, HMT – induction threshold); 

(b) Diagnostic patch test data where there is a relatively low but substantial incidence of 

reactions in a defined population in relation to relatively high exposure; 

(c) Other epidemiological evidence where there is a relatively low but substantial 

incidence of allergic contact dermatitis in relation to relatively high exposure. 

Animal studies 

Two types of in vivo methods to investigate skin sensitization tests have been developed: an 

adjuvant test in which sensitization is potentiated by the injection of Freunds Complete Adjuvant 

(FCA), and non-adjuvant tests. There are three animal test methods used to evaluate skin 

sensitization for substances: the mouse local lymph node assay (LLNA), the guinea pig 

maximization test (GPMT), and the Buehler occluded patch test. The Organization for Economic 

Cooperation and Development (OECD) Guidelines describe test methods for skin sensitization: 

Guideline 406, the Guinea Pig Maximization test and the Buehler guinea pig test and Guideline 

429, the Local Lymph Node Assay. Other methods may be used provided that they are 

scientifically validated. The Mouse Ear Swelling Test (MEST), appears to be a reliable screening 

test to detect moderate to strong sensitizers, and can be used, in accordance with professional 

judgment, as a first stage in the assessment of skin sensitization potential. 
121

Animal test results for Skin Sensitization Category 1 include data with values indicated below: 

Table VII.4.3. Animal test results for Skin Sensitization Category 1 

Assay Criteria

Adjuvant type test method for skin 

sensitization

Response in at least 30% of the animals is considered 

positive.

Non-adjuvant Guinea pig test method Response in at least 15% of the animals is considered 

positive.

Local lymph node assay Stimulation index of three or more is considered a 

positive response.

Animal test results for Skin Sensitization sub-category 1A can include data with values indicated 

below: 

Table VII.4.4. Animal test results for Skin Sensitization sub-category 1A 

Assay Criteria

Local lymph node assay EC3 value ≤ 2% 

Guinea pig maximization 

test 

≥ 30% responding at ≤ 0.1% intradermal induction dose or 

≥ 60% responding at > 0.1% to ≤ 1% intradermal 

induction dose 

Buehler assay ≥ 15% responding at ≤ 0.2% topical induction dose or 

≥ 60% responding at > 0.2% to ≤ 20% topical induction dose 

Note: EC3 refers to the estimated concentration of the test chemical required to induce a 

stimulation index of 3 in the local lymph node assay. 

Animal test results for Skin Sensitization sub-category 1B can include data with values indicated 

below: 

Table VII.4.5. Animal test results for Skin Sensitization sub-category 1B 

Assay Criteria

Local lymph node assay EC3 value > 2% 

Guinea pig maximization 

test 

≥ 30% to < 60% responding at > 0.1% to ≤ 1% intradermal 

induction dose or 

≥ 30% responding at > 1% intradermal induction dose 

Buehler assay ≥ 15% to < 60% responding at > 0.2% to ≤ 20% topical 

induction dose or 

≥ 15% responding at > 20% topical induction dose 
122

Note: EC3 refers to the estimated concentration of the test chemical required to induce a 

stimulation index of 3 in the local lymph node assay. 

Immunological contact urticaria 

Substances which cause immunological contact urticaria with or without meeting the criteria for 

respiratory sensitizers shall be considered for classification as skin sensitizers. 

There is no recognized animal model available to identify substances which cause 

immunological contact urticaria. Therefore, classification will normally be based on human 

evidence, similar to that for skin sensitization. 

Classification procedure 

In classification, the data are compared to the skin sensitizer classification criteria. Data can be 

found in literature, on SDSs, or be determined by testing (which is not required by the HCS). For 

mixtures, follow the three-tier approach discussed below.

For classification of a substance, evidence shall include one or more of the following conditions 

using a weight-of-evidence approach: 

(a) Positive data from patch testing, normally obtained in more than one dermatology 

clinic; 

(b) Epidemiological studies showing allergic contact dermatitis caused by the substance; 

Situations in which a high proportion of those exposed exhibit characteristic symptoms 

are to be looked at with special concern, even if the number of cases is small; 

(c) Positive data from appropriate animal studies; 

(d) Positive data from experimental studies in humans; 

(e) Well-documented episodes of allergic contact dermatitis, normally obtained in more 

than one dermatology clinic; 

(f) Severity of reaction. 

Evidence from animal studies is usually much more reliable than evidence from human 

exposure. However, in cases where evidence is available from both sources, and there is conflict 

between the results, the quality and reliability of the evidence from both sources must be 

assessed in order to resolve the question of classification on a case-by-case basis. Normally, 

human data are not generated in controlled experiments with volunteers for the purpose of hazard 

classification but rather as part of risk assessment to confirm lack of effects seen in animal tests. 

Consequently, positive human data on skin sensitization are usually derived from case-control or 

other, less defined studies. Evaluation of human data must, therefore, be carried out with caution 

as the frequency of cases reflect, in addition to the inherent properties of the substances, factors 

such as the exposure situation, bioavailability, individual predisposition and preventive measures 
123

taken. Negative human data should not normally be used to negate positive results from animal 

studies. For both animal and human data, consideration should be given to the impact of the 

vehicle used. 

If none of the above-mentioned conditions ((a)-(f) above) are met, the substance need not be 

classified as a skin sensitizer. However, a combination of two or more indicators of skin 

sensitization, as listed below, may alter the decision. This shall be considered on a case-by-case 

basis. 

(a) Isolated episodes of allergic contact dermatitis; 

(b) Epidemiological studies of limited power, e.g., where chance, bias or confounders 

have not been ruled out fully with reasonable confidence; 

(c) Data from animal tests, performed according to existing guidelines, which do not 

meet the criteria for a positive result described in 29 CFR 1910.1200 Paragraph 

A.4.2.2.3, but which are sufficiently close to the limit to be considered significant; 

(d) Positive data from non-standard methods; 

(e) Positive results from close structural analogues.

If the data is available, then you must classify into the appropriate skin sensitization subcategory, i.e., category 1A or category 1B. If the data does not allow classification into a subcategory, then you must classify in skin sensitization category 1. 

Sensitizer Classification Criteria for Mixtures 

The approach to classifying mixtures for both skin and respiratory sensitizers incorporates a 

tiered approach (i.e., stepwise procedure based on a hierarchy). 

Tier 1: Classification of mixtures when data are available for the complete mixture 

When reliable and good evidence from human experience or appropriate animal studies is 

available for the mixture then it should be used in a weight-of-evidence approach using the same 

criteria as those specified for substances. Care should be exercised in evaluating such data to 

ensure the dose used does not render the results inconclusive. If test data for the mixture is not 

available, then the classifier should consider the application of the criteria in Tier 2 or 3, as 

appropriate. 
124

Tier 2: Classification of mixtures when data are not available for the complete mixture –

bridging principles 

Where the mixture itself has not been tested to determine its sensitizing properties, but there are 

sufficient data on BOTH the individual ingredients AND similar tested mixtures to adequately 

characterize the hazard of the mixture, these data can be used in accordance with the following 

bridging principles. 

All six bridging principles are applicable to the skin and respiratory sensitization classes: 

 Dilution, 

 Batching, 

 Concentration of mixtures,

 Interpolation within one toxicity category, 

 Substantially similar mixtures, and 

 Aerosols. 

The application of bridging principles ensures that the classification process uses the available 

data to the greatest extent possible in characterizing the potential skin or respiratory sensitization 

hazard. 

Dilution 

If a tested mixture is diluted with a diluent which is not a sensitizer and which is not 

expected to affect the sensitization of other ingredients, then the new diluted mixture may 

be classified as equivalent to the original tested mixture. 

Batching 

The sensitizing properties of a tested production batch of a mixture can be assumed to be 

substantially equivalent to that of another untested production batch of the same 

commercial product when produced by or under the control of the same manufacturer, 

unless there is reason to believe there is significant variation such that the sensitization 

potential of the untested batch has changed. If the latter occurs, a new classification is 

necessary. 

Concentration of mixtures 

If a tested mixture is classified in Category 1 or sub-category 1A, and the concentration 

of the ingredients of the tested mixture that are in Category 1 and sub-category 1A is 

increased, the resulting untested mixture should be classified in Category 1 or subcategory 1A without additional testing. 
125

Interpolation within one category/sub-category 

For three mixtures (A, B and C) with identical ingredients, where mixtures A and B have 

been tested and are in the same sensitizer category/sub-category, and where untested 

mixture C has the same sensitization toxicologically active ingredients as mixtures A and 

B but has concentrations of sensitization toxicologically active ingredients intermediate 

to the concentrations in mixtures A and B, then mixture C is assumed to be in the same 

sensitizer category/sub-category as A and B. 

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

(ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) Ingredient B is a sensitizer and ingredients A and C are not sensitizers; 

(e) A and C are not expected to affect the sensitizing properties of B. 

If mixture (i) or (ii) is already classified by testing for sensitization, then the other 

mixture can be assigned the same hazard category. 

Aerosols 

An aerosol form of the mixture may be classified in the same hazard category as the 

tested non-aerosolized form of the mixture provided that the added propellant does not 

affect the sensitizing properties of the mixture upon spraying. 

If appropriate data is not available to apply the above bridging principles then the classifier 

should consider the application of the cut-off value/concentration limit approach described in 

Tier 3. 

Tier 3: Classification of mixtures when data are available for all ingredients or only for some 

ingredients of the mixture 

If there are not sufficient data to apply the bridging principles, then the third tier for sensitizers is 

to classify the mixture using the cut-off/concentration limit approach. 
126

The mixture shall be classified as a respiratory sensitizer when at least one ingredient has been 

classified as a respiratory sensitizer and is present at or above the appropriate respiratory 

sensitizer cut-off value/concentration limit for a solid/liquid or gas. See table below. 

Table VII.4.6. Cut-off values/concentration limits of ingredients of a mixture classified as 

respiratory sensitizers that would trigger classification of the mixture 

Ingredient classified as:

Cut-off values/concentration limits 

triggering classification of a mixture as:

Respiratory sensitizer Category 1

Solid/Liquid Gas

Respiratory sensitizer Category 1  0.1%  0.1%

Respiratory sensitizer Sub-category 1A  0.1%  0.1%

Respiratory sensitizer Sub-category 1B  1.0%  0.2%

The mixture shall be classified as a skin sensitizer when at least one ingredient has been 

classified as a skin sensitizer and is present at or above the appropriate skin sensitizer cut-off 

value/concentration limit. See table below. 

Table VII.4.7. Cut-off values/concentration limits of ingredients of a mixture classified as 

skin sensitizers that would trigger classification of the mixture 

Ingredient classified as:

Cut-off values/concentration limits 

triggering classification of a mixture as:

Skin sensitizer Category 1

All physical states

Skin sensitizer Category 1  0.1% 

Skin sensitizer Sub-category 1A  0.1%

Skin sensitizer Sub-category 1B  1.0%

The respiratory and skin sensitization assessments are carried out separately. 

Some chemicals that are classified as sensitizers may elicit a response, when present in a mixture 

in quantities below the cut-offs established in the above tables in individuals who are already 

sensitized to the chemical. 29 CFR 1910.1200 paragraph A.0.4.3.2 states that if the classifier has 

information that the hazard of an ingredient will be evident (i.e., it presents a health risk) below 

the above cut-off values/concentration limits, then the mixture should be classified according to 

those lower cut-off values. 

 If the classifier has reliable data that show the respiratory or skin sensitization potential of 

an ingredient will not be evident above the cut-off values/concentration limits then the 

mixture may be classified according to those higher substance specific cut-off values. 
127

Decision logic 

Decision logics for classifying respiratory and skin sensitizers are provided. The decision logics 

are for both substances and mixtures and are provided as additional guidance. It is strongly 

recommended that the person responsible for classification study the criteria before and during 

use of the decision logics. 

The decision logics are essentially flowcharts for classifying substances and mixtures regarding 

sensitization. It presents questions in a sequence that walks you through the classification steps 

and criteria for classifying respiratory and skin sensitizers. Once you answer the questions 

provided, you will arrive at the appropriate classification. 
128

Decision logic for respiratory sensitization

Substance: Does the substance have respiratory sensitization data? No

Mixture: Does the mixture as a whole or its 

ingredients have respiratory sensitization data?

Can bridging principles be applied?

Classification 

not possible

No

Yes

(a) Is there evidence in humans that the 

substance/mixture can lead to specific 

respiratory hypersensitivity, and/or 

(b) are there positive results from an appropriate 

animal test? 

Yes

Category 1

Danger 

Not classified

Yes

Yes

Classify in 

appropriate 

category 

No

Does the mixture contain one or more ingredients classified 

as a respiratory sensitizer at:

(a)  0.1% w/w (solid/liquid)? 

(b)  1.0% w/w (solid/liquid)? 

or

(c)  0.1% v/v (gas)? 

(d)  0.2% v/v (gas)? 

Yes

Not classified

Category 1

Danger 

Classification 

not possible Does the mixture as a whole have 

respiratory sensitization data? 

No

No

No

Yes
129

Decision logic for skin sensitization

Substance: Does the substance have skin sensitization data?

Mixture: Does the mixture as a whole or its 

ingredients have skin sensitization data?

No Classification 

not possible

No

Yes

(a) Is there evidence in humans that the 

substance/mixture can lead to sensitization 

by skin contact in a substantial number of 

persons, or 

(b) Are there positive results from an appropriate 

animal test?

Yes

Category 1

Warning 

Not classified

Yes

Classification 

not possible

Does the mixture as a whole have skin 

sensitization data?

No

No Yes

Can bridging principles be applied? Yes

Classify in 

appropriate 

category

Does the mixture contain one or more ingredients classified 

as a skin sensitizer at:

(a)  0.1% ? 

(b)  1.0%?

Yes

Not classified

No

Category 1

Warning 

No
130

Respiratory and Skin Sensitization Classification Examples 

The following examples are provided to walk you through respiratory and/or skin sensitization 

classification. 

Examples of a substance fulfilling the criteria for classification: 

Substance Example #1

Respiratory and Skin Sensitization

Test Data

HCS 2012 

Classification Rationale

The material is a new isocyanate. 

No data are available for the new 

material. The test substance has 

Structure Activity Relationships 

(SAR) to substances with similar 

structure known to be respiratory 

and skin sensitizers in humans 

(e.g., methyl isocyanate).

Respiratory 

Sensitizer

Category 1

Skin Sensitizer 

Category 1

(cannot 

differentiate subcategories since 

this is not based on 

data for the actual 

substance)

Fulfills criteria.

Based on expert judgment using 

SAR information the classifier 

concluded that classification as a 

Category 1 Respiratory Sensitizer

and Category 1 Skin Sensitizer is 

justified, since there is ample 

available data on isocyanates that are 

respiratory and skin sensitizers in 

humans.

Substance Example #2

Respiratory Sensitization

Test Data 

HCS 2012 

Classification Rationale

The material is an enzyme with 

many well-documented human 

case studies for respiratory 

sensitization occurring in workers 

exposed during the manufacturing 

process. 

Respiratory 

Sensitizer

Category 1

Fulfills criteria.

Because of the clear evidence from 

valid human studies, classification 

for respiratory sensitization is

warranted.
131

Substance Example #3

Skin Sensitization

Test Data

HCS 2012 

Classification Rationale

In an OECD Test Guideline 406 

Skin Sensitization study, 4 

animals out of 10 had a positive 

response.

In a Freund’s Complete Adjuvant 

test in guinea pigs, 4 animals out 

of 8 showed a positive reaction.

Skin Sensitizer 

Category 1

Fulfills Category 1 criteria.

The criteria for Skin Sensitizer 

Category 1 classification are 

fulfilled, since in two independent 

adjuvant tests the response was ≥ 

30% positive.

Substance Example #4

Skin Sensitization

Test Data

HCS 2012 

Classification Rationale

Toxicity data: A high frequency 

of well documented human case 

reports on contact sensitization at 

very low concentrations (≤ 500 

μg/cm2) and in addition positive 

animal study results showing a 

high potency

Skin Sensitizer, 

Category 1A

Fulfills Category 1A criteria.

The classification criteria are 

fulfilled based both on human and 

animal evidence.

Substance Example #5

Skin Sensitization

Test Data

HCS 2012 

Classification Rationale

Substance X gave a positive 

result in the Local Lymph Node 

Assay (LLNA) with an EC3-

value of 10.4%.

Skin Sensitizer 

Category 1B

Fulfills Category 1B criteria.

This EC3-value is above the 

Category 1A criteria cut-off of 2% 

and meets the Category 1B criteria.
132

Substance Example #6

Skin Sensitization

Test Data

HCS 2012 

Classification Rationale

Substance Y tested positive in 

the LLNA with an EC3-value of 

0.5%. 

In the Guinea Pig Maximization 

Test (GPMT) a dermal induction 

concentration of 0.375% 

produced a positive response in 

70% of the animals.

Skin Sensitizer 

Category 1A

Fulfills Category 1A criteria

on the basis of the EC3-value and the 

response in the GPMT.

Example of a mixture fulfilling the criteria for classification: 

Mixture Example #1

Skin Sensitization

Data 

HCS 2012 

Classification Rationale

Component data:

Component 2: 20%, Skin 

Sensitization Category 1B

Skin Sensitization 

Category 1B

Fulfills cutoff value criteria.

Component 2 is 20% which is ≥1%

Skin Sensitization Category 1B 

criteria are fulfilled.
133

Examples of mixtures and substances not fulfilling the criteria for classification: 

Mixture Example #2

Skin Sensitization

Data 

HCS 2012 

Classification Rationale

Component data:

Component 3: 0.8%, Skin 

Sensitization Category 1B

Not classified for 

skin sensitization

While a component meets the criteria 

for Skin Sensitization Category 1B, 

the component is present in the 

mixture at less than the cutoff value 

for Skin Sensitization Category 1B.

The mixture criteria for Skin 

Sensitization Category 1B are not 

fulfilled.

Substance Example #7

Skin Sensitization

Test Data

HCS 2012 

Classification Rationale

In the LLNA a maximum 

stimulation index of 2.2 was 

reported.

Not classified for 

skin sensitization

The criteria for Skin Sensitization 

Category 1 is not met since the 

maximum stimulation index is less 

than 3.
134

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.4, Respiratory or Skin Sensitization 

29 CFR 1910.1200, Hazard Communication, Appendix C, Allocation of Label Elements 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 
135

VII.5 Germ Cell Mutagenicity 

Introduction 

Genotoxicity is a toxic end-point which may be associated with somatic mutation and germ cell 

mutation. A chemical’s ability to induce germ cell mutations, which may continue to affect 

future generations, is an important consideration in the protection of human health.

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 several 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.

Mutagenicity refers to the ability of some chemicals to modify the genetic material in the nucleus 

of cells in ways that allow the changes to be transmitted during cell division. Germ cell 

mutations occur in germinal cells – (sperm and ova) – where there is no effect on the exposed 

person; rather the effect is passed on to future generations. Somatic mutations occur in other cell 

types (all body cells except sperm and ova), and may result in cell death (e.g., teratogenesis) or 

the transmission of a genetic defect to other cells in the same tissue. Current genotoxicity tests 

are aimed largely at detecting somatic cell mutations and are used as predictive indicators of 

carcinogenic potential. Relatively few genotoxic agents have been demonstrated to affect germ 

cells in vivo. 

Definition and General Considerations 

A mutation is defined as a permanent change in the amount or structure of the genetic material in 

a cell. The term mutation applies both to heritable genetic changes that may be manifested at the 

phenotypic level and to the underlying DNA modifications when known (including, for example, 

specific base pair changes and chromosomal translocations). The terms mutagenic and mutagen 

will be used for agents giving rise to an increased occurrence of mutations in populations of cells 

and/or organisms. 

The more general terms genotoxic and genotoxicity apply to agents or processes which alter the 

structure, information content, or segregation of DNA, including those which cause DNA 

damage by interfering with normal replication processes, or which in a non-physiological 

manner (temporarily) alter its replication. Genotoxicity test results are usually taken as indicators 

for mutagenic effects. 

This hazard class is primarily concerned with chemicals that may cause mutations in the germ 

cells of humans that can be transmitted to the progeny. However, mutagenicity/genotoxicity tests 

in vitro and in mammalian somatic cells in vivo are also considered in classifying substances and 

mixtures within this hazard class. 
136

Classification Criteria for Substances

There are two hazard categories for germ cell mutagens to accommodate the weight-of-evidence 

available. Category 1 is subdivided into two subcategories according to specific criteria outlined 

below. 

Table VII.5.1. Hazard categories for germ cell mutagens 

Category Criteria

CATEGORY 1 Substances known to induce heritable mutations or to be regarded 

as if they induce heritable mutations in the germ cells of humans

Category 1A Substances known to induce heritable mutations in 

germ cells of humans

Positive evidence from human epidemiological studies.

Category 1B Substances which should be regarded as if they induce heritable 

mutations in the germ cells of humans

(a) Positive result(s) from in vivo heritable germ cell mutagenicity tests 

in mammals; or

(b) Positive result(s) from in vivo somatic cell mutagenicity tests in 

mammals, in combination with some evidence that the substance has 

potential to cause mutations to germ cells. This supporting evidence 

may, for example, be derived from mutagenicity/genotoxicity tests in 

germ cells in vivo, or by demonstrating the ability of the substance or its 

metabolite(s) to interact with the genetic material of germ cells; or

(c) Positive results from tests showing mutagenic effects in the germ 

cells of humans, without demonstration of transmission to progeny; for 

example, an increase in the frequency of aneuploidy in sperm cells of 

exposed people.

CATEGORY 2 Substances which cause concern for humans 

owing to the possibility that they may induce heritable 

mutations in the germ cells of humans

Positive evidence obtained from experiments in mammals and/or in 

some cases from in vitro experiments, obtained from:

(a) Somatic cell mutagenicity tests in vivo, in mammals; or

(b) Other in vivo somatic cell genotoxicity tests which are supported by 

positive results from in vitro mutagenicity assays.

Note: Substances which are positive in in vitro mammalian 

mutagenicity assays, and which also show a chemical structure activity 

relationship to known germ cell mutagens, should be considered for 

classification as Category 2 mutagens.
137

Specific considerations for classification of substances as germ cell mutagens 

The HCS is hazard-based, classifying chemicals on the basis of their intrinsic ability to induce 

mutations in germ cells. The HCS criteria are not meant for the quantitative risk assessment of 

chemical substances. 

For classification, test results are considered from experiments determining mutagenic and/or 

genotoxic effects in germ and/or somatic cells of animals. Mutagenic and/or genotoxic effects 

determined in in vitro tests shall also be considered. Examples of various tests for mutagenic 

effects are given later in this chapter. 

Classification for heritable effects in human germ cells is made on the basis of scientifically 

validated tests. Evaluation of the test results shall be done using expert judgment and all the 

available evidence shall be weighed for classification. 

The classification of substances shall be based on the total weight-of-evidence available, using 

expert judgment. In those instances where a single well-conducted test is used for classification, 

it shall provide clear and unambiguously positive results. The relevance of the route of exposure 

used in the study of the substance compared to the route of human exposure should also be taken 

into account. 

Classification criteria for mixtures 

It should be noted that the HCS classification criteria for health hazards often include a tiered 

scheme in which test data available on the complete mixture are considered as the first tier in the 

evaluation, followed by the applicable bridging principles, and lastly, cut-off 

values/concentration limits or additivity. However, this approach is not used for Germ Cell 

Mutagenicity. The criteria for Germ Cell Mutagenicity consider the cut-off values/concentration 

limits as the primary tier and allow the classification to be modified only on a case-by-case 

evaluation based on available test data for the mixture as a whole. 

Tier 1: Classification of mixtures when data are available for all ingredients or only for some 

ingredients of the mixture 

The mixture will be classified as a mutagen when at least one ingredient has been classified as a 

Category 1A, Category 1B or Category 2 mutagen and is present at or above the appropriate cutoff value/concentration limit specified below for Category 1 and Category 2, respectively. 

An assessment is carried out separately for each Category 1A, Category1B or Category 2 

ingredient in the mixture. In the case where the mixture has Category 1A, Category 1B and 

Category 2 ingredients above the cut-off/concentration limit the mixture is classified in the most 

severe category. 
138

Table VII.5.2. Cut-off values/concentration limits of ingredients of a mixture classified as 

germ cell mutagens that would trigger classification of the mixture 

Ingredient 

classified as:

Cut-off/concentration limits triggering 

classification of a mixture as:

Category 1 mutagen

Category 1A Category 1B Category 2 mutagen

Category 1A mutagen  0.1% -- --

Category 1B mutagen --  0.1% --

Category 2 mutagen -- --  1.0%

Note: The cut-off values/concentration limits in the table above apply to solids and liquids (w/w 

units) as well as gases (v/v units). 

Tier 2: Classification of mixtures when data are available for the complete mixture 

On a case-by-case basis the Germ Cell Mutagenicity classification, which normally considers 

results obtained with the individual ingredients, may be modified using available test data for the 

mixture as a whole. 

The concern with using test data for the mixture as a whole is that as the concentration of a germ 

cell mutagen is reduced in a mixture, the dilution effect may result in a misleading test result 

(i.e., false negative) if the study was not appropriately designed to factor in the concentration of 

the germ cell mutagen in the mixture. In these cases, mixtures that could cause Germ Cell 

Mutation would not be classified and labeled. Accordingly, the HCS states that the test results 

for the mixture as a whole must be conclusive taking into account dose, and other factors such as 

duration, observations and analysis (e.g., statistical analysis, test sensitivity) of germ cell 

mutagenicity test systems. If appropriate test data for the mixture is not available then the 

classifier can consider the application of the Bridging Principle criteria in Tier 3, if appropriate, 

or as stated above use the classification resulting from the application of criteria in Tier 1. 

Tier 3: Classification of mixtures when data are not available for the complete mixture - 

bridging principles 

Where the mixture itself has not been tested to determine its germ cell mutagenicity hazard, but 

there are sufficient data on BOTH the individual ingredients AND similar tested mixtures to 

adequately characterize the hazards of the mixture, these data can be used in accordance with the 

below bridging principles. If data on another mixture are used in the application of the bridging 

principles, the data on that mixture must be conclusive as discussed above in Tier 2.
139

Only the following bridging principles are applicable to the Germ Cell Mutagenicity 

hazard class: 

 Dilution, 

 Batching, 

 Substantially similar mixtures. 

Dilution 

If a tested mixture is diluted with a diluent which is not expected to affect the germ cell 

mutagenicity of other ingredients, then the new diluted mixture may be classified as 

equivalent to the original tested mixture. 

Batching 

The germ cell mutagenic potential of a tested production batch of a mixture can be 

assumed to be substantially equivalent to that of another untested production batch of the 

same commercial product, when produced by or under the control of the same 

manufacturer, unless there is reason to believe there is significant variation in 

composition such that the germ cell mutagenic potential of the untested batch has 

changed. If the latter occurs, a new classification is necessary. 

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

(ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) Data on toxicity for A and C are available and substantially equivalent, i.e. 

they are in the same hazard category and are not expected to affect the germ cell 

mutagenicity of B. 

If mixture (i) or (ii) is already classified by testing, then the other mixture can be 

classified in the same hazard category. 
140

Classification Procedure and Guidance 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS requires 

collecting and evaluating the best available existing evidence on the hazards of each chemical. 

Examples of scientifically validated test methods 

There are a number of scientifically recognized methods for investigation of mutagenic effects. 

Examples of in vivo heritable germ cell mutagenicity tests are: 

(a) Rodent dominant lethal mutation test (OECD 478) 

(b) Mouse heritable translocation assay (OECD 485) 

(c) Mouse specific locus test 

Examples of in vivo somatic cell mutagenicity tests are: 

(a) Mammalian bone marrow chromosome aberration test (OECD 475) 

(b) Mouse spot test (OECD 484) 

(c) Mammalian erythrocyte micronucleus test (OECD 474) 

Examples of mutagenicity/genotoxicity tests in germ cells are: 

(a) Mutagenicity tests: 

(i) Mammalian spermatogonial chromosome aberration test (OECD 483) 

(ii) Spermatid micronucleus assay 

(b) Genotoxicity tests: 

(i) Sister chromatid exchange analysis in spermatogonia 

(ii) Unscheduled DNA synthesis test (UDS) in testicular cells 

Examples of genotoxicity tests in somatic cells are: 

(a) Liver Unscheduled DNA Synthesis (UDS) in vivo (OECD 486) 

(b) Mammalian bone marrow Sister Chromatid Exchanges (SCE) 

Examples of in vitro mutagenicity tests are: 

(a) In vitro mammalian chromosome aberration test (OECD 473) 

(b) In vitro mammalian cell gene mutation test (OECD 476) 

(c) Bacterial reverse mutation tests (OECD 471) 

As new, scientifically validated tests arise, these may also be used in the total weight-of-evidence 

to be considered. 

Classification procedure 

In classification, the data are compared to the germ cell mutagenicity classification criteria. Data 

can be found in literature, on SDSs, or be determined by testing (which is not required by the 

HCS). For mixtures, follow the above modified three-tier approach. 
141

Classification is made on the basis of the appropriate criteria and an assessment of the total

weight-of-evidence. The validity and usefulness of each of the data sets to the overall assessment 

of mutagenicity should be individually assessed, taking account of protocol design (including 

route of administration) and current expert views on the value of the test systems. See 

considerations below. 

If the data is available, then you must classify into the appropriate germ cell mutagenicity subcategory, i.e., Category 1A or Category 1B. If the data does not allow classification into a subcategory, then you must classify in germ cell mutagenicity category 1. 

Currently, there is no example of a substance classified in germ cell mutagen category 1A. To 

date, epidemiological studies have not provided evidence to classify a substance as a Category 

1A mutagen. Hereditary diseases in humans for the most part have an unknown origin and show 

a varying distribution in different populations. Due to the random distribution of mutations in the 

genome it is not expected that one particular substance would induce one specific genetic 

disorder. It is unlikely that epidemiological studies will provide evidence for classifying a 

substance as a Category 1A mutagen. 

Considerations 

Considerations When Evaluating Negative Test Results

Doses or concentrations Were the doses or concentrations of test substance used high 

enough?

Sensitivity of test system Was the test system used sensitive to the nature of 

the genotoxic changes that might have been expected? 

Volatility of the test 

substance

Were the concentrations maintained in tests conducted in vitro?

Metabolism Was the metabolic activation suitable in the test systems in vitro?

Exposure to target organ Was the substance reaching the target organ, for studies in vivo? 

(taking also toxicokinetic data into consideration)

Reactivity of the substance Was the test substance reactive? (e.g., rate of hydrolysis, 

electrophilicity, presence or absence of structural alerts and other 

available indications)

Response in the control What was the response of the positive and negative controls?
142

Considerations When Evaluating Positive/Contradictory Test Results

Conflicting results Conflicting results obtained in non-mammalian systems and in 

mammalian cell tests may be addressed by considering possible 

differences in substance uptake, metabolism or in the 

organization of genetic material. The results of mammalian tests 

may be considered of higher significance.

Positive in the in vitro

SCE assay

Positive results in the in vitro SCE assay should be viewed with

caution, as this assay is associated with a relatively high 

incidence of false positive results. Thus, a positive result in this 

assay would not be considered to be evidence of a significant 

clastogenic potential in vitro if negative results were available in 

an in vitro chromosome aberration assay.

Positive in the DNA 

binding assay

Interpretation of results from DNA binding assays should be 

viewed with caution as these assays are only considered to be 

indicators of DNA damage. Consequently, the observance of in 

vivo DNA adducts alone in the absence of positive findings from 

in vitro assays is generally not considered sufficient evidence of 

a significant genotoxic potential in vivo.

Contradiction between in 

vitro and in vivo

If contradictory findings are obtained in vitro and in vivo, in 

general, the results of in vivo tests indicate a higher degree of 

reliability. However, for evaluation of negative results in vivo, it 

should be considered whether there is adequate evidence of 

target tissue exposure.

Sensitivity and specificity 

of test systems

The sensitivity and specificity of different test systems varies for

different classes of substances. If available testing data for other

related substances permits assessment of the performance of

difference assays for the class of substance under evaluation, the

result from the test system known to produce more accurate

responses would be given higher priority.

Positive in high toxic 

concentration

The consequences of “positive” findings only at highly 

toxic/cytotoxic concentrations, and the presence or absence of a 

dose-response relationship should be considered. The default 

assumption for genotoxic chemicals, in the absence of 

mechanistic evidence to the contrary, is that they have a linear 

dose response relationship. However, both direct and indirect 

mechanisms of genotoxicity can be non-linear or threshold, and 

sometimes this default assumption may be inappropriate. When 

interpreting positive results, considerations of the dose-response 

relationship and of possible mechanisms of action are important 

components of a hazard assessment.
143

Considerations When Evaluating Positive/Contradictory Test Results

Expert judgment Conflicting results may also be available from the same test, 

performed by different laboratories or on different occasions. In 

this case, expert judgment should be used to reach an overall 

evaluation of the data. In particular, the quality of each of the 

studies and of the data provided should be evaluated, with 

special consideration of the study design, reproducibility of data, 

dose-effect relationships, and biological relevance of the 

findings. The purity of the test substance may also be a factor to 

take into account. In the case where an OECD guideline is 

available for a test method, the quality of a study using the 

method is regarded as being higher if it was conducted in 

compliance with the requirements stated in the guideline. 

Furthermore, studies compliant with Good Laboratory Practices 

(GLP) may be regarded as being of a higher quality.

Decision Logic 

Two decision logics for classifying germ cell mutagenicity are provided. The first decision logic 

is for substances. Use the second decision logic for classifying mixtures. The decision logics are 

provided as additional guidance. It is strongly recommended that the person responsible for 

classification study the criteria before and during use of the decision logics. 

These decision logics are essentially flowcharts for classifying substances and mixtures 

regarding germ cell mutagenicity. They present questions in a sequence that walks you through 

the classification steps and criteria for classifying germ cell mutagenicity. Once you answer the 

questions provided, you will arrive at the appropriate classification. 
144

Substance decision logic for germ cell mutagenicity

Continued on next page 

Substance: Does the substance have data on mutagenicity? No Classification 

not possible

Yes

According to the criteria, is the substance:

(a) Known to induce heritable mutations in germ cells of humans, or 

(b) Should it be regarded as if it induces heritable mutations in the 

germ cells of humans? 

Application of the criteria needs expert judgment in a weight-ofevidence approach.

Yes

Category 1

Danger 

Category 2

Warning 

Not classified 

According to the criteria, does the substance cause concern for 

humans owing to the possibility that it may induce heritable 

mutations in the germ cells of humans?

Application of the criteria needs expert judgment in a weight-ofevidence approach.

No

Yes

No
145

Mixtures decision logic for germ cell mutagenicity

Mixture:

Classification of mixtures will be based on the available test data for the individual ingredients of the 

mixture, using cut-off values/concentration limits for those ingredients. The classification may be 

modified on a case-by-case basis based on the available test data for the mixture itself or based on 

bridging principles. See modified classification on a case-by-case basis below. 

Yes

Does the mixture contain one or more ingredients classified as 

a Category 2 mutagen at:

 1.0%?

Does the mixture contain one or more ingredients classified 

as a Category 1 mutagen at:

 0.1%?

No

No

Not classified

Yes

Category 2

Warning 

Classification based on individual ingredients of the mixture Category 1

Danger 

Are test data available 

for the mixture itself? Yes

Can bridging principles be applied? If data on another 

mixture are used, data on that mixture must be conclusive.

Are the test results on the mixture 

conclusive taking into account dose 

and other factors such as duration,

observations and analysis (e.g. 

statistical analysis, test sensitivity) of 

germ cell mutagenicity test systems? 

Classify in 

appropriate 

category 

Danger 

or 

Warning 

or 

No 

classification

Classification based on individual 

ingredients of the mixture (see above).

No

Yes

No

No

Yes

Classification based on a case-by-case basis
146

Germ cell mutagenicity Classification Examples 

The following examples are provided to walk you through germ cell mutagenicity classification. 

Examples of a substance fulfilling the criteria for classification: 

Substance Example #1

Germ Cell Mutagenicity

Test Data

HCS 2012 

Classification Rationale

Positive result in the Rodent 

Dominant Lethal Mutation Test 

(OECD Test Guideline 478)

Germ Cell 

Mutagenicity 

Category 1B

The test result fulfills the Germ Cell 

Mutagenicity Category 1B 

classification criteria of a positive 

result from an in vivo heritable germ 

cell mutagenicity test in mammals.

Substance Example #2

Germ Cell Mutagenicity

Test Data

HCS 2012 

Classification Rationale

Positive result in the Mammalian 

Bone Marrow Chromosome 

Aberration Test (OECD Test 

Guideline 475)

Germ Cell 

Mutagenicity 

Category 2

The test result fulfills the Germ Cell 

Mutagenicity Category 2

classification criteria of positive 

evidence obtained from a somatic 

cell mutagenicity test in vivo in 

mammals
147

Example of a mixture fulfilling the criteria for classification: 

Mixture Example #1

Germ Cell Mutagenicity

Data 

HCS 2012 

Classification Rationale

Component data:

Component 1:0.09%, GCM 

Category 1B

Component 2: 3%, GCM

Category 2

Component 3: 2%, GCM

Category 1B

Germ Cell 

Mutagenicity 

Category 1B

The GCM cut-off 

values/concentration limits are used 

for classification.

 Component 1 is not ≥ 0.1% so the 

mixture does not meet the 

Category 1B criteria.

 Component 2 is ≥ 1.0% so the 

mixture meets the Category 2 

criteria.

 Component 3 is ≥ 0.1% so the 

mixture meets the Category 1B 

criteria.

When the criteria are satisfied by 

more than one ingredient for more 

than one category the most severe 

category is used to classify the 

mixture. Therefore, this mixture is 

classified as Germ Cell Mutagen 

Category 1B.
148

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.5 Germ Cell Mutagenicity 

29 CFR 1910.1200, Hazard Communication, Appendix C, Allocation of Label Elements 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 
149

VII.6 Carcinogenicity 

Introduction

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. 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 list the specific chemicals 

they consider to be carcinogens. These lists will be discussed later in this chapter. 

Definition and General Considerations

Carcinogen means a substance or a mixture of substances which induces cancer or increases its 

incidence. Substances and mixtures which have induced benign and malignant tumors in wellperformed experimental studies on animals are considered also to be presumed or suspected 

human carcinogens unless there is strong evidence that the mechanism of tumor formation is not 

relevant for humans. 

Classification of a substance or mixture as posing a carcinogenic hazard is based on its inherent 

properties and does not provide information on the level of the human cancer risk which the use 

of the substance or mixture may represent. 

Classification Criteria for Substances

For the purpose of classification for carcinogenicity, substances are allocated to one of two 

categories based on strength of evidence and additional weight-of-evidence considerations. In 

certain instances, route-specific classification may be warranted. 
150

Table VII.6.1 Hazard categories for carcinogens 

Category Criteria

CATEGORY 1 Known or presumed human carcinogens

The classification of a substance as a Category 1 carcinogen is done on 

the basis of epidemiological and/or animal data. This classification is 

further distinguished on the basis of whether the evidence for 

classification is largely from human data (Category 1A) or from animal 

data (Category 1B).

Category 1A Known to have carcinogenic potential for humans.

Classification in this category is largely based on human evidence.

Category 1B Presumed to have carcinogenic potential for humans.

Classification in this category is largely based on animal evidence.

The classification of a substance in Category 1A and 1B is based on 

strength of evidence together with weight-of-evidence considerations. 

Such evidence may be derived from:

- human studies that establish a causal relationship between 

human exposure to a substance and the development of cancer 

(known human carcinogen); or

- animal experiments for which there is sufficient evidence to 

demonstrate animal carcinogenicity (presumed human 

carcinogen).

In addition, on a case-by-case basis, scientific judgment may warrant a 

decision of presumed human carcinogenicity derived from studies 

showing limited evidence of carcinogenicity in humans together with 

limited evidence of carcinogenicity in experimental animals.

CATEGORY 2 Suspected human carcinogens 

The classification of a substance in Category 2 is done on the basis of 

evidence obtained from human and/or animal studies, but which is not 

sufficiently convincing to place the substance in Category 1A or B. This 

classification is based on strength of evidence together with weight-ofevidence considerations. Such evidence may be from either limited 

evidence of carcinogenicity in human studies or from limited evidence 

of carcinogenicity in animal studies.

Other considerations Where the weight of evidence for the carcinogenicity of a substance 

does not meet the above criteria, any positive study conducted in 

accordance with established scientific principles, and which reports 

statistically significant findings regarding the carcinogenic potential of 

the substance, must be noted on the safety data sheet. 
151

Where OSHA has included cancer as a health hazard to be considered by classifiers for a 

chemical covered by 29 CFR part 1910, Subpart Z, Toxic and Hazardous Substances, chemical 

manufacturers, importers, and employers shall classify the chemical as a carcinogen. See the 

table below for the substance-specific OSHA standards listing cancer as a health effect. 

Table VII.6.2 Standards listing cancer as a health effect 

Standard Number Substance

1910.1001 Asbestos

1910.1003 4-Nitrobiphenyl

1910.1004 alpha-Naphthylamine 

1910.1006 Methyl chloromethyl ether 

1910.1007 3,'-Dichlorobenzidine (and its salts) 

1910.1008 bis-Chloromethyl ether 

1910.1009 beta-Naphthylamine 

1910.1010 Benzidine 

1910.1011 4-Aminodiphenyl 

1910.1012 Ethyleneimine

1910.1013 beta-Propiolactone 

1910.1014 2-Acetylaminofluorene

1910.1015 4-Dimethylaminoazobenzene 

1910.1016 N-Nitrosodimethylamine 

1910.1017 Vinyl chloride

1910.1018 Inorganic arsenic

1910.1026 Chromium VI

1910.1027 Cadmium

1910.1028 Benzene

1910.1029 Coke oven emissions

1910.1044 1,2-dibromo-3-chloropropane 

1910.1045 Acrylonitrile 

1910.1047 Ethylene oxide 

1910.1048 Formaldehyde

1910.1050 Methylenedianiline 

1910.1051 1,3-Butadiene 

1910.1052 Methylene chloride

Specific considerations for classification of substances as carcinogens 

Classification as a carcinogen is made on the basis of evidence from reliable and acceptable 

methods, and is intended to be used for substances which have an intrinsic property to produce 

such toxic effects. The evaluations are to be based on all existing data, peer-reviewed published 

studies and additional data accepted by regulatory agencies. 
152

Carcinogen classification is a one-step, criterion-based process that involves two interrelated 

determinations: evaluations of strength of evidence and consideration of all other relevant 

information to place substances with human cancer potential into hazard categories. 

Strength of evidence involves the enumeration of tumors in human and animal studies and 

determination of their level of statistical significance. Sufficient human evidence demonstrates 

causality between human exposure and the development of cancer, whereas sufficient evidence 

in animals shows a causal relationship between the agent and an increased incidence of tumors. 

Limited evidence in humans is demonstrated by a positive association between exposure and 

cancer, but a causal relationship cannot be stated. Limited evidence in animals is provided when 

data suggest a carcinogenic effect, but are less than sufficient to demonstrate causation. 

(Guidance on consideration of important factors in the classification of carcinogenicity and a 

more detailed description of the terms “limited” and “sufficient” have been developed by the 

International Agency for Research on Cancer (IARC) and are provided in non-mandatory 

Appendix F to the HCS. See below detailed discussion.) 

Weight-of-evidence: Beyond the determination of the strength of evidence for carcinogenicity, a 

number of other factors should be considered that influence the overall likelihood that an agent 

may pose a carcinogenic hazard in humans. These factors will be discussed later in this chapter. 

Sources for establishing that a substance is a carcinogen or potential carcinogen 

The following sources may be treated as establishing that a substance is a carcinogen or potential 

carcinogen for hazard communication purposes in lieu of applying the criteria described in Table 

VII.6.1: 

 National Toxicology Program (NTP), “Report on Carcinogens” (latest edition) 

 International Agency for Research on Cancer (IARC) “Monographs on the Evaluation of 

Carcinogenic Risks to Humans” (latest editions). 

When performing classifications, the HCS provides classifiers with the option of relying on the 

classification listings of IARC and NTP to make classification decisions regarding 

carcinogenicity, rather than applying the criteria themselves. This will make classification easier, 

as well as lead to greater consistency in carcinogen classification. In addition, the HCS has 

provided guidance on hazard classification for carcinogenicity in non-mandatory Appendix F to

29 CFR 1910.1200. Part A of Appendix F includes background guidance provided by the GHS 

based on the Preamble of the IARC “Monographs on the Evaluation of Carcinogenic Risks to 

Humans” (2006). Part B provides IARC classification information. Part C provides background 

guidance from the National NTP “Report on Carcinogens” (RoC), and Part D is a table that 

compares HCS carcinogen hazard categories to carcinogen classifications under IARC and NTP, 

allowing classifiers to be able to use information from IARC and NTP RoC carcinogen 

classifications to complete their classifications under the HCS. The table relating carcinogen 

classification information from IARC and NTP to the HCS is provided below.
153

Table VII.6.3 Approximate Equivalences Among Carcinogen Classification Schemes 

Approximate Equivalences Among Carcinogen Classification Schemes

IARC HCS NTP RoC

Group 1 Category 1A Known

Group 2A Category 1B Reasonably Anticipated (See Note 1)

Group 2B Category 2 Reasonably Anticipated (See Note 1)

Note 1: 

1. Limited evidence of carcinogenicity from studies in humans (corresponding to IARC 

2A/HCS 1B); 

2. Sufficient evidence of carcinogenicity from studies in experimental animals (again, 

essentially corresponding to IARC 2A/HCS 1B); 

3. Less than sufficient evidence of carcinogenicity in humans or laboratory animals; however: 

a. The agent, substance, or mixture belongs to a well-defined, structurally-related class of 

substances whose members are listed in a previous RoC as either ‘‘Known’’ or 

‘‘Reasonably Anticipated’’ to be a human carcinogen, or 

b. There is convincing relevant information that the agent acts through mechanisms 

indicating it would likely cause cancer in humans. 

OSHA considers the determinations of IARC and NTP as sufficient evidence in establishing the 

classification of a carcinogen. If the classifier uses the determinations of IARC or NTP then they 

do not have to conduct their own weight-of-evidence evaluation with regards to carcinogenicity. 

However, if the classifier does perform their own hazard evaluation and their determination 

differs from that of IARC and/or NTP, they would need to justify with evidence why their 

classification result differs from that of IARC and/or NTP. 

In addition, the National Institute for Occupational Safety and Health (NIOSH) has revised its 

policy for classifying carcinogens. The updated policy evaluates the carcinogen hazard 

assessments made by NTP, IARC, and the Environmental Protection Agency (EPA) and aligns 

their cancer designations into the appropriate HCS carcinogen categories. The classification 

scheme developed by NIOSH is an acceptable alternative to using Table VII.6.3. 

Classification Procedure and Guidance 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS requires 

collecting and evaluating the best available existing evidence on the hazards of each chemical. 
154

Examples of scientifically validated test methods 

There are a number of scientifically validated methods for investigation of carcinogenic effects: 

 OECD Test Guideline 451: Carcinogenicity Studies 

 OECD Test Guideline 453: Combined Chronic Toxicity/Carcinogenicity Studies 

Other test methodologies that meet the requirements for testing carcinogenicity potential include: 

Carcinogenicity Studies: 

 USEPA OTS code: 798.3300; 

 USEPA OPP code: 83-2; 

 USEPA OPPTS code: 870.4200; 

Combined Chronic Toxicity and Carcinogenicity Studies: 

 USEPA OTS code: 798.3320; 

 USEPA OPP code: 83-5; 

 USEPA OPPTS code: 870.4300; 

The objective of a long-term carcinogenicity study is to observe test animals for a major portion 

of their life span for the development of neoplastic lesions during or after exposure to various 

doses of a test substance by an appropriate route of administration.

Carcinogenicity Studies (also known as Oncogenicity Studies) are performed to determine the 

carcinogenic potential and dose-response relationships of the test chemical. They produce data 

on the production of tumors as well as pre-neoplastic lesions and other indications of chronic 

toxicity that may provide evidence of treatment-related effects and insights into the mechanism 

of carcinogenesis. Given that development of tumors is age-related and that large groups are 

required to detect increases in treated animals, carcinogenicity studies are normally conducted in 

small rodents (usually mice and rats) over most of their life span. 

Combined Chronic Toxicity/Carcinogenicity Studies encompass both neoplastic effects and 

general toxicity, including neurological, physiological, biochemical, hematological and 

pathological effects. Typically, rats are used for combined chronic toxicity/carcinogenicity 

assessment except in respect of the dermal route, for which mice are preferred. The study design 

incorporates groups of treated and control animals scheduled for interim sacrifice after 12 

months of study for investigation of pathological abnormalities that are uncomplicated by agerelated changes. OECD Test Guideline 453 and US EPA Health Effects Test Guidelines 

870.4300 specify the same duration of exposure as in carcinogenicity studies. 
155

Classification procedure 

In classification, the data are compared to the carcinogenicity classification criteria. Data can be 

found in literature, on SDSs, or be determined by testing (which is not required by the HCS). For 

mixtures follow the modified three-tier approach discussed below. 

If the data is available, then you must classify into the appropriate carcinogenicity sub-category, 

i.e., category 1A or category 1B. If the data does not allow classification into a sub-category,

then you must classify in carcinogenicity category 1. 

This guidance discusses some additional considerations in classification and an approach to 

analysis, rather than hard-and-fast rules. It is consistent with 29 CFR 1910.1200 Appendix A.6, 

and should help in evaluating information to determine carcinogenicity. 

The terms “sufficient” and “limited” evidence are used in the HCS as they have been defined by 

IARC and are outlined below. 

Carcinogenicity in humans

The evidence relevant to carcinogenicity from studies in humans is classified into one of the

following 2 categories:

Sufficient evidence of 

carcinogenicity in humans:

A causal relationship has been established between exposure to 

the agent and human cancer. That is, a positive relationship has 

been observed between the exposure and cancer in studies in 

which chance, bias and confounding could be ruled out with 

reasonable confidence.

Limited evidence of 

carcinogenicity in humans:

A positive association has been observed between exposure to the 

agent and cancer for which a causal interpretation is considered 

by the Working Group to be credible, but chance, bias or 

confounding could not be ruled out with reasonable confidence. 
156

Carcinogenicity in experimental animals

The evidence relevant to carcinogenicity in experimental animals is classified into one of the 

following 2 categories:

Sufficient evidence of 

carcinogenicity in 

experimental animals:

A causal relationship has been established between the agent and 

an increased incidence of malignant neoplasms or of an 

appropriate combination of benign and malignant neoplasms in 

two or more species of animals or two or more independent 

studies in one species carried out at different times or in different 

laboratories or under different protocols. An increased incidence 

of tumors in both sexes of a single species in a well-conducted 

study, ideally conducted under Good Laboratory Practices, can 

also provide sufficient evidence.

Exceptionally, a single study in one species and sex might be 

considered to provide sufficient evidence of carcinogenicity when 

malignant neoplasms occur to an unusual degree with regard to

incidence, site, type of tumor or age at onset, or when there are 

strong findings of tumors at multiple sites.

Limited evidence of 

carcinogenicity in 

experimental animals:

The data suggest a carcinogenic effect but are limited for making 

a definitive evaluation because, e.g., the evidence of 

carcinogenicity is restricted to a single experiment; there are 

unresolved questions regarding the adequacy of the design, 

conduct or interpretation of the studies; the agent increases the 

incidence only of benign neoplasms or lesions of uncertain 

neoplastic potential; or the evidence of carcinogenicity is 

restricted to studies that demonstrate only promoting activity in a 

narrow range of tissues or organs.

Guidance on how to consider important factors in classification of carcinogenicity 

Carcinogenicity classification is based on strength of evidence and additional weight-of-evidence 

considerations. The weight-of-evidence analysis called for in the HCS is an integrative approach 

that considers important factors in determining carcinogenic potential along with the strength of 

evidence analysis. 

The full list of factors that influence this determination is very lengthy, but some of the important 

ones are considered here. Factors can be viewed as either increasing or decreasing the level of 

concern for human carcinogenicity. The relative emphasis accorded to each factor depends upon 

the amount and coherence of evidence bearing on each. Generally there is a requirement for 

more complete information to decrease than to increase the level of concern. 

Additional considerations (weight-of-evidence) should be used in evaluating the tumor findings 

and the other factors in a case-by-case manner. Some important factors which may be taken into 

consideration, when assessing the overall level of concern are summarized below. 
157

Factors that increase concerns

Tumor type and 

background incidence

A carcinogen that increases the incidence of a neoplastic disease 

that is rare in the test species or strain is of greater concern than a 

carcinogen that increases the incidence of a neoplasm having a 

high spontaneous incidence.

Unusual tumor types or tumors occurring with reduced latency 

may add to the weight-of-evidence for the carcinogenic potential 

of a substance, even if the tumors are not statistically significant.

Reduced tumor latency Unusual tumor types or tumors occurring with reduced latency 

may add to the weight-of-evidence for the carcinogenic potential 

of a substance, even if the tumors are not statistically significant.

Progression of lesions to 

malignancy

At first, it may appear logical that a carcinogen that increases 

only benign tumors in experimental animals is of lesser 

significance to human health than a test chemical that causes 

malignancies. However, it should never be assumed that an agent 

that causes benign tumors in animals will not cause malignancy 

in humans. In any case, benign tumors are potentially serious, 

even lethal, depending on their size, growth rate and site of 

origin.

Multiple responses The formation of tumors at several sites is viewed with greater 

concern than tumor formation at a single site.

Whether responses are in 

single or both sexes

It is worth observing that a carcinogenic response in experimental 

animals is more significant for human health if it occurs in more 

than one species and/or in both sexes.

If tumors are seen only in one sex of an animal species, the mode 

of action should be carefully evaluated to see if the response is 

consistent with the postulated mode of action. Effects seen only 

in one sex in a test species may be less convincing than effects 

seen in both sexes, unless there is a clear patho-physiological 

difference consistent with the mode of action to explain the single 

sex response.

Whether responses are in a 

single species or several

species

Positive responses in several species add to the weight-ofevidence that a chemical is a carcinogen.

Responses in multiple 

animal experiments

A carcinogenic response confined to one species assumes greater 

human significance if it is seen in two or more studies conducted at 

different times, in different laboratories or under different protocols.
158

Factors that increase concerns

Taking into account all of the factors discussed here, chemicals 

with positive outcomes in two or more species would be 

provisionally considered to be classified in Category 1B until 

human relevance of animal results are assessed in their entirety. It 

should be noted, however, that positive results for one species in 

at least two independent studies, or a single positive study 

showing unusually strong evidence of malignancy may also lead 

to Category 1B.

Structural similarity to a 

chemical(s) for which there 

is good evidence of 

carcinogenicity

Mode of action and its 

relevance to humans, such 

as mutagenicity, 

cytotoxicity with growth 

stimulation, mitogenesis,

immunosuppression

A chemical that has not been tested for carcinogenicity may in 

certain instances be classified for carcinogenicity based on tumor 

data from a structural analogue together with substantial support 

from consideration of other important factors such as formation 

of common significant metabolites (e.g., for benzidine congener 

based dyes)

Animal carcinogens that are genotoxic, or structurally similar to 

known human carcinogens, also assume greater significance.

It is recognized that genetic events are central in the overall 

process of cancer development. Therefore evidence of mutagenic 

activity in vivo may indicate that a chemical has a potential for 

carcinogenic effects.

Factors that reduce concerns

Comparison of absorption, 

distribution, metabolism 

and excretion between test 

animals and humans

Routes of exposure

If a metabolism and toxicokinetic behavior of a chemical in 

humans is fundamentally different from its behavior in the 

species in which it is carcinogenic, or if the animal study employs 

an inappropriate route of administration, or demonstrates 

carcinogenic activity only at doses that causes excessive toxicity.

Certain tumor types in animals may be associated with 

toxicokinetics or toxicodynamics that are unique to the animal 

species tested and may not be predictive of carcinogenicity in 

humans (e.g., the lack of human relevance of kidney tumors in 

male rats associated with compounds causing α2υ-globulin 

nephropathy). Even when a particular tumor type may be 

discounted, expert judgment must be used in assessing the total 

tumor profile in any animal experiment.
159

Factors that reduce concerns

The possibility of a 

confounding effect of 

excessive toxicity at test 

doses

Localized effects

Tumors occurring only at excessive doses associated with severe 

toxicity generally have doubtful potential for carcinogenicity in 

humans.

In addition, tumors occurring only at sites of contact and/or only 

at excessive doses need to be carefully evaluated for human 

relevance for carcinogenic hazard (e.g., forestomach tumors, 

following administration by gavage of an irritating or corrosive, 

non-mutagenic chemical, may be of questionable relevance). 

However, such determinations must be evaluated carefully in 

justifying the carcinogenic potential for humans; any occurrence 

of other tumors at distant sites must also be considered.

Mode of action not 

relevant to humans

One must look closely at any mode of action in animal 

experiments taking into consideration comparative 

toxicokinetics/toxicodynamics between the animal test species 

and humans to determine the relevance of the results to humans. 

This may lead to the possibility of discounting very specific 

effects of certain types of chemicals. Life-stage-dependent effects 

on cellular differentiation may also lead to qualitative differences 

between animals and humans. Only if a mode of action of tumor 

development is conclusively determined not to be operative in 

humans may the carcinogenic evidence for that tumor be 

discounted. However, a weight-of-evidence evaluation for a 

substance calls for any other tumorigenic activity to be evaluated, 

as well.

In addition to the factors listed above, another important consideration with regard to carcinogen 

classification is the significance of a single positive study. In evaluating the weight-of-evidence, 

the carcinogen classification criteria indicate that one positive study conducted according to good 

scientific principles and with statistically and biologically significant positive results may justify 

classification. OSHA expects classification of a chemical if one positive study is available. 

However, if following the evaluation of available scientific data, the classifier deems nonclassification to be the appropriate result, the one positive carcinogen study must still be 

communicated on the SDS. 

Classification criteria for mixtures 

It should be noted that the classification criteria for health hazards often include a tiered scheme 

in which test data available on the complete mixture are considered as the first tier in the 

evaluation, followed by the applicable bridging principles, and lastly, cut-off 
160

values/concentration limits or additivity. However, this approach is not used for Carcinogenicity. 

The criteria for Carcinogenicity consider the cut-off values/concentration limits as the primary 

tier and allow the classification to be modified only on a case-by-case evaluation based on 

available test data for the mixture as a whole. 

Tier 1: Classification of mixtures when data are available for all ingredients or only for some 

ingredients of the mixture 

The approach to classifying a mixture for carcinogenicity in Tier 1 is to use a cutoff/concentration limit. An assessment is carried out separately for each Category 1A, Category 

1B or Category 2 ingredient in the mixture. In the case where the mixture has Category 1A, 

Category 1B and Category 2 ingredients above the cut-off/concentration limit the mixture is 

classified in the most severe category. 

The mixture will be classified as a carcinogen when at least one ingredient has been classified as 

a Category 1A, Category 1B or Category 2 Carcinogen and is present at or above the appropriate 

cut-off value/concentration limit specified below for Category 1 and Category 2, respectively. 

Table VII.6.4. Cut-off values/concentration limits of ingredients of a mixture classified as a 

carcinogen that would trigger classification of the mixture 

Ingredient classified as: 

Cut-off/concentration limits triggering 

classification of a mixture as:

Category 1 carcinogen

Category 1A Category 1B Category 2 carcinogen

Category 1A carcinogen  0.1 % -- --

Category 1B carcinogen --  0.1 % --

Category 2 carcinogen -- --  0.1% (Note)

Note: If a Category 2 carcinogen ingredient is present in the mixture at a concentration between 

0.1% and 1%, information is required on the SDS for the mixture. However, a label warning is 

optional. If a Category 2 carcinogen ingredient is present in the mixture at a concentration of ≥ 

1%, both an SDS and a label are required and the information must be included on each. 

Tier 2: Classification of mixtures when data are available for the complete mixture 

On a case-by-case basis the classification which normally considers results obtained with the 

individual ingredients may be modified using available test data for the mixture as a whole. 

The concern with using test data for the mixture as a whole is that as the concentration of a 

carcinogenic ingredient is reduced in a mixture the dilution effect may result in misleading test 

results (i.e., false negative) if the study was not appropriately designed to factor in the 

concentration of the carcinogenic ingredient in the mixture. In these cases, mixtures that would 
161

cause cancer would not be classified and labeled. Accordingly, the GHS provides guidance that 

the test results for the mixture as a whole must be conclusive taking into account dose, and other 

factors such as duration, observations and analysis (e.g., statistical analysis, test sensitivity) of 

carcinogenicity test systems. If appropriate test data for the mixture is not available then the 

classifier can consider the application of the Bridging Principle criteria in Tier 3, if appropriate, 

or as stated above use the classification resulting from the application of criteria in Tier 1. 

Tier 3: Classification of mixtures when data are not available for the complete mixture - 

bridging principles 

Where the mixture itself has not been tested to determine its carcinogenic hazard, but there are 

sufficient data on BOTH the individual ingredients AND similar tested mixtures to adequately 

characterize the hazards of the mixture, these data can be used in accordance with the below 

bridging principles. If data on another mixture are used in the application of the bridging 

principles, the data on that mixture must be conclusive as discussed above in Tier 2. 

Only the following bridging principles are applicable to the Carcinogenicity hazard class: 

 Dilution, 

 Batching, 

 Substantially similar mixtures. 

Dilution 

If a tested mixture is diluted with a diluent that is not expected to affect the 

carcinogenicity of other ingredients, then the new diluted mixture may be classified as 

equivalent to the original tested mixture. 

Batching 

The carcinogenic potential of a tested production batch of a mixture can be assumed to be 

substantially equivalent to that of another untested production batch of the same 

commercial product, when produced by or under the control of the same manufacturer 

unless there is reason to believe there is significant variation in composition such that the 

carcinogenic potential of the untested batch has changed. If the latter occurs, a new 

classification is necessary. 

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

(ii) C + B; 
162

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) Data on toxicity for A and C are available and substantially equivalent, i.e.,

they are in the same hazard category and are not expected to affect the 

carcinogenicity of B. 

If mixture (i) or (ii) is already classified by testing, then the other mixture can be 

classified in the same hazard category. 

Decision Logic 

Two decision logics for classifying carcinogenicity are provided. The first decision logic is for 

substances. Use the second decision logic for classifying mixtures. The decision logics are 

provided as additional guidance. It is strongly recommended that the person responsible for 

classification study the criteria before and during use of the decision logic. 

These decision logics are essentially flowcharts for classifying substances and mixtures 

regarding carcinogenicity. They present questions in a sequence that walks you through the 

classification steps and criteria for classifying carcinogenicity. Once you answer the questions 

provided, you will arrive at the appropriate classification. 
163

Substance decision logic for carcinogenicity

According to the criteria, is the substance:

(a) Known to have carcinogenic potential for humans, or 

(b) Presumed to have carcinogenic potential for humans?

Application of the criteria needs expert judgment in a 

strength and weight-of-evidence approach.

No

Yes

Category 1

Danger 

Not classified

According to the criteria, is the substance a suspected

human carcinogen?

Application of the criteria needs expert judgment in a

strength and weight-of-evidence approach

Substance: Does the substance have carcinogenicity data?

Yes

No

Classification

not possible

Yes

Category 2

Warning 

No
164

Mixtures decision logic for carcinogenicity 

1 Between 0.1% and 1% information is required on the SDS and a label warning is optional. At 

≥ 1% both an SDS and a label are required. 

Classification based on individual ingredients of the mixture

Modified classification on a case-by-case basis

Mixture:

Classification of mixtures will be based on the available test data for the individual ingredients of the 

mixture, using cut-off values/concentration limits for those ingredients. The classification may be 

modified on a case-by-case basis based on the available test data for the mixture as a whole or based 

on bridging principles. See modified classification on a case-by-case basis below. 

Does the mixture contain one or more ingredients 

classified as a Category 1 carcinogen at:

 0.1%? Yes

No

Does the mixture contain one or more ingredients 

classified as a Category 2 carcinogen at:

 0.1%?

Yes

No

Not classified

Are test data available 

for the mixture itself? Yes

Are the test results on the mixture 

conclusive taking into account 

dose and other factors such as 

duration, observations and analysis 

(e.g., statistical analysis, test 

sensitivity) of carcinogenicity test 

systems?

Yes

Classify in 

appropriate 

category 

Danger 

or 

Warning 

or 

No classification

No

Can bridging principles be applied? If data on 

another mixture are used, data on that mixture 

must be conclusive.

Classification based on individual 

ingredients of the mixture (see above).

No

Category 1

Danger 

Category 21

Warning 

Yes

No

No
165

Carcinogenicity Classification Examples 

The following examples are provided to walk you through carcinogenicity classification. 

Examples of a substance fulfilling the criteria for classification: 

Substance Example #1: S32

Carcinogenicity

Test Data

HCS 2012 

Classification Rationale

Occupational exposure has been strongly 

associated with bladder cancer in numerous 

case reports from many countries. The 

association has also been observed in several 

epidemiological studies. In one extreme 

instance, all five of a group of workers 

continuously employed in S32 manufacture 

for 15 years or more developed bladder 

cancer.

S32 was tested in mice, rats and hamsters by

oral administration, in mice and rats by 

subcutaneous administration and in rats by 

inhalation and intraperitoneally. Following its 

oral administration to mice of different 

strains, both sexes, newborn and adult, and 

following its subcutaneous administration, it 

significantly increased the incidence of livercell tumors (benign and malignant). In female 

rats, it markedly increased the incidence of 

mammary tumors; and in male and female 

hamsters, it increased the incidence of liver 

tumors following its oral administration. S32 

induced bladder carcinomas in dogs.

The subcutaneous administration of S32 to 

rats produced a high incidence of Zymbalgland tumors; colonic tumors were also 

reported. The results of the inhalation study in 

rats could not be interpreted. The 

intraperitoneal administration of S32 to rats 

resulted in a marked increase in the incidence 

of mammary and Zymbal-gland tumors. It 

was also tested in dogs by oral administration, 

producing bladder carcinomas. Studies in fish, 

rabbits and frogs could not be evaluated.

No data were available on the genetic and 

related effects of S32 in humans.

Carcinogenicity 

Category 1A

Fulfills criteria 

 There is sufficient evidence 

that S32 is carcinogenic to 

mice, rats, hamsters and dogs 

and there is sufficient 

evidence that S32 is 

carcinogenic to humans

 Sufficient human evidence 

demonstrates causality 

between human exposure and 

the development of cancer, 

and sufficient evidence in 

animals shows a causal 

relationship between S32 and 

an increased incidence of 

tumors fulfills HCS criteria
166

Substance Example #2: S33

Carcinogenicity

Test Data

HCS 2012 

Classification Rationale

Five S33 samples all produced skin tumors, 

including carcinomas, when applied to the 

skin of mice. One of the S33 samples also 

produced lung tumors in mice after skin 

application. In two limited studies, a basic 

fraction of S33 was not carcinogenic for the 

skin of mice.

S33 was mutagenic in S. typhimurium and 

was positive in the mouse lymphoma 

L5178Y system, in the presence of an 

exogenous metabolic system. The urine from 

rats administered S33 was mutagenic in S. 

typhimurium in the presence of an 

exogenous metabolic system.

A mortality analysis of many occupations 

indicated an increased risk of mortality from 

scrotal cancer for S33-exposed workers. 

Malignant epitheliomas, about a third of 

which were of the scrotum, have been 

reported in several case reports of workers 

exposed to S33. 

A cohort study of workers in Norway and 

Sweden who had been exposed to S33 

reported a statistically significant excess 

incidence of non-melanoma skin cancer. A 

study of workers in Norway did not report 

any statistically significant increase in the 

incidence of cancer, although the risk for 

non-melanoma cancer was slightly increased. 

A nested case–control study of lung cancer 

among a cohort of workers in France 

reported an increased risk for exposure to 

S33. A cohort study of workers in the USA 

who had used S33 indicated the possibility of 

an increase in mortality from lung cancer; a 

nested case–control study found no evidence 

of an exposure–response relationship 

between exposure to S33 and cancer. A study 

that applied a job–exposure matrix to job 

titles in the Swedish census and linked this to 

cancer incidence found an increase in the 

incidence of urinary bladder cancer that was 

related to S33.

Carcinogen Category 1B Fulfills criteria 

 There is sufficient 

evidence for the 

carcinogenicity in 

experimental animals of 

S33. There is limited 

evidence that S33 is 

carcinogenic in humans. 

The data indicate that S33 

is probably carcinogenic 

to humans.

 The category 1B criteria 

are fulfilled by evidence 

from animal experiments 

for which there is 

sufficient evidence to 

demonstrate animal 

carcinogenicity 

(presumed human 

carcinogen) and limited 

evidence in humans.
167

Substance Example #3

Carcinogenicity

Test Data

HCS 2012 

Classification Rationale

NTP listed as Reasonably 

Anticipated to be Human 

Carcinogen

IARC listed as Group 2B: 

Possibly Carcinogenic to Humans

ACGIH listed as Category A3: 

Confirmed Animal Carcinogen 

with Unknown Relevance to 

Humans

Listed in EU CLP Table 3.1 as 

Category 2/Table 3.2 Category 3

Carcinogen 

Category 2

Fulfills criteria 

 Due to the fact that the substance 

is listed by NTP as Reasonably 

Anticipated to be Human 

Carcinogen and by IARC as 

Group 2B

 Per 29 CFR 1910.1200 A.6.4, 

NTP and IARC may be treated 

as establishing that a substance 

is a carcinogen or potential 

carcinogen for hazard 

communication purposes in lieu 

of applying the criteria 

 Per 29 CFR 1910.1200 Annex F 

Part D, IARC Group 2B is 

Carcinogen Category 2 

Substance Example #4

Carcinogenicity

Test Data

HCS 2012 

Classification Rationale

Listed by NTP as Reasonably 

Anticipated to be Human 

Carcinogen)

Listed by IARC as Group 2A: 

Probably Carcinogenic to Humans

Listed as 2A: Probably 

Carcinogenic to Humans by the 

Japan Society for Occupational 

Health

Carcinogen 

Category 1B

Fulfills criteria 

 Due to the fact that the substance 

is listed by NTP as Reasonably 

Anticipated to be Human 

Carcinogen and by IARC as 

Group 2A

 Per 29 CFR 1910.1200 A.6.4, 

NTP and IARC may be treated as 

establishing that a substance is a 

carcinogen or potential 

carcinogen for hazard 

communication purposes in lieu 

of applying the criteria 

 Per 29 CFR 1910.1200 Annex F 

Part D, IARC Group 2A is 

Carcinogen Category 1B 
168

Example of a substance not fulfilling the criteria for classification: 

Substance Example #5

Carcinogenicity

Test Data 

HCS 2012 

Classification Rationale

Listed by IARC as Group 3: Not 

Classifiable as to Carcinogenicity 

to Humans

Listed by ACGIH as Category 

A4: Not Classifiable as a Human 

Carcinogen

Listed by EPA as Category D: 

Not Classifiable as to Human 

Carcinogenicity

Not classified for 

Carcinogenicity

Does not fulfill criteria 

 The substance is listed by IARC 

as Group 3

 Per 29 CFR 1910.1200 A.6.4, 

NTP and IARC may be treated as 

establishing that a substance is a 

carcinogen or potential 

carcinogen for hazard 

communication purposes in lieu 

of applying the criteria 

 Per 29 CFR 1910.1200 Annex F 

Part D, IARC Group 3 is not an 

equivalent cancer HCS 2012 

classification 

Example of a mixture fulfilling the criteria for classification: 

Mixture Example #1

Carcinogenicity

Data

HCS 2012 

Classification Rationale

Component data:

Component 1: 0.05%, Carcinogen 

Category 1B

Component 2: 0.5%, Carcinogen 

Category 2

Carcinogen 

Category 2

Fulfills the criteria

 Component 1 is not ≥ 0.1% so 

the mixture does not meet the 

Carcinogen Category 1B criteria.

 Component 2 is ≥ 0.1% so the 

mixture meets the Carcinogen 

Category 2 criteria.

This mixture is classified as 

Carcinogen Category 2 and a label 

warning is optional.
169

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.6 Carcinogenicity 

29 CFR 1910.1200, Hazard Communication, Appendix F Guidance for Hazard Classifications 

Re: Carcinogenicity (Non-Mandatory) 

29 CFR 1910.1200, Hazard Communication, Appendix C, Allocation of Label Elements 

National Toxicology Program (NTP), “Report on Carcinogens” (latest edition) 

International Agency for Research on Cancer (IARC) “Monographs on the Evaluation of 

Carcinogenic Risks to Humans” (latest editions). 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 
170

VII.7 Reproductive Toxicity 

Introduction

The term “reproductive toxicity” is used to describe the adverse effects induced by a chemical on 

any aspect of mammalian reproduction. It covers all phases of the reproductive cycle, including 

impairment of male or female reproductive organs and/or function or capacity and the induction 

of non-heritable adverse effects in the progeny such as death, growth retardation, structural and 

functional effects. 

Definition and General Considerations 

Reproductive toxicity includes adverse effects on sexual function and fertility in adult males and 

females, as well as adverse effects on development of the offspring. Some reproductive toxic 

effects cannot be clearly assigned to either impairment of sexual function and fertility or to 

developmental toxicity. Nonetheless, chemicals with these effects shall be classified as 

reproductive toxicants. 

For classification purposes, the known induction of genetically based inheritable effects in the 

offspring is addressed in the Germ cell mutagenicity hazard class (see Chapter VII.5). 

Adverse effects on sexual function and fertility means any effect of a chemical that interferes 

with reproductive ability or sexual capacity. This includes, but is not limited to, alterations to the 

female and male reproductive system; adverse effects on onset of puberty, gamete production 

and transport, reproductive cycle normality, sexual behavior, fertility, parturition, or pregnancy 

outcomes; premature reproductive senescence; or modifications in other functions that are 

dependent on the integrity of the reproductive systems. 

Adverse effects on development of the offspring means any effect of a chemical that interferes 

with normal development of the conceptus either before or after birth, which is induced during 

pregnancy or results from parental exposure. These effects can be manifested at any point in the 

life span of the organism. The major manifestations of developmental toxicity include death of 

the developing organism, structural abnormality, altered growth and functional deficiency. A 

term often used to describe effects manifested as malformations of the newborn is teratogenicity. 

Adverse effects on or via lactation are also included in reproductive toxicity, but for 

classification purposes, such effects are treated in a separate hazard category. 

Classification Criteria for Substances 

For the purpose of classification for reproductive toxicity, substances shall be classified in one of 

two categories. Category 1, known or presumed human reproductive toxicant, is subdivided into 

two subcategories according to specific criteria outlined below. Category 2 includes criteria for 

suspected human reproductive toxicants. Effects on sexual function and fertility, and on 

development, shall also be considered. In addition, effects on or via lactation shall be classified 

in a separate hazard category. 
171

Table VII.7.1. Hazard categories for reproductive toxicants 

Category Criteria

CATEGORY 1 Known or presumed human reproductive toxicant

A substance shall be classified in Category 1 for reproductive toxicity 

when it is known to have produced an adverse effect on sexual function 

and fertility or on development in humans or when there is evidence 

from animal studies, possibly supplemented with other information, to 

provide a strong presumption that the substance has the capacity to 

interfere with reproduction in humans. The classification of a substance 

is further distinguished on the basis of whether the evidence for 

classification is primarily from human data (Category 1A) or from 

animal data (Category 1B).

Category 1A Known human reproductive toxicant

The classification of a substance in this category is largely based on 

evidence from humans.

Category 1B Presumed human reproductive toxicant

The classification of a substance in this category is largely based on 

evidence from experimental animals. Data from animal studies shall 

provide sufficient evidence of an adverse effect on sexual function and 

fertility or on development in the absence of other toxic effects, or if 

occurring together with other toxic effects the adverse effect on 

reproduction is considered not to be a secondary non-specific 

consequence of other toxic effects. However, when there is mechanistic 

information that raises doubt about the relevance of the effect for 

humans, classification in Category 2 may be more appropriate.

CATEGORY 2 Suspected human reproductive toxicant

A substance shall be classified in Category 2 for reproductive toxicity 

when there is some evidence from humans or experimental animals, 

possibly supplemented with other information, of an adverse effect on 

sexual function and fertility, or on development, in the absence of other 

toxic effects, or if occurring together with other toxic effects the adverse 

effect on reproduction is considered not to be a secondary non-specific 

consequence of the other toxic effects, and where the evidence is not 

sufficiently convincing to place the substance in Category 1. For 

instance, deficiencies in the study may make the quality of evidence less 

convincing, and in view of this, Category 2 would be the more 

appropriate classification.
172

Table VII.7.2. Hazard category for effects on or via lactation 

Category Criteria

Effects On or Via 

Lactation

Effects on or via lactation shall be classified in a separate single 

category. Chemicals that are absorbed by women and have been shown 

to interfere with lactation or that may be present (including metabolites) 

in breast milk in amounts sufficient to cause concern for the health of a 

breastfed child, shall be classified to indicate this property.15

Classification for effects via lactation shall be assigned on the basis of:16

(a) absorption, metabolism, distribution and excretion studies that 

indicate the likelihood the substance would be present in potentially 

toxic levels in breast milk; and/or

(b) results of one or two generation studies in animals which provide 

clear evidence of adverse effect in the offspring due to transfer in the 

milk or adverse effect on the quality of the milk; and/or

(c) human evidence indicating a hazard to babies during the lactation 

period.

Basis of classification for Reproductive Toxicity 

Classification for reproductive toxicity is on the basis of the criteria, an assessment of the total 

weight-of-evidence, and the use of expert judgment. Classification as a reproductive toxicant is 

intended to be used for chemicals that have an intrinsic, specific property to produce an adverse 

effect on reproduction; chemicals should not be so classified if such an effect is produced solely 

as a non-specific secondary consequence of other toxic effects. 

In the evaluation of toxic effects on the developing offspring, it is important to consider the 

possible influence of maternal toxicity. 

CATEGORY 1 

Classification in Category 1A is largely based on evidence from humans. Evidence used for 

classification shall be from well-conducted epidemiological studies, if available, which include 

the use of appropriate controls, balanced assessment, and consideration of bias or confounding 

factors. Less rigorous data from studies in humans may be sufficient for a Category 1A 

classification if supplemented with adequate data from studies in experimental animals, but 

classification in Category 1B may also be considered. 

 

15 In Figure A.7.1(b) of Appendix A of 29 CFR 1910.1200 this sentence ends with the phrase “hazardous to 

breastfed babies.” The inclusion of that language renders the sentence grammatically incorrect, and incorrect as a 

matter of substance, because classification can also be based on effects on lactation, rather than only effects via 

lactation. OSHA intends to correct the sentence in the standard. 

16 The words “for effects via lactation” do not appear in Figure A.7.1.(b) of Appendix A of 29 CFR 1910.1200, but 

the words are inserted here to make clear that the stated criteria only apply to that effect, and do not apply to exclude 

classification for effects on lactation. OSHA intends to correct the sentence in the standard. 
173

Weight-of-evidence 

Classification as a reproductive toxicant is made on the basis of an assessment of the total 

weight-of-evidence using expert judgment. This means that all available information that bears 

on the determination of reproductive toxicity is considered together. Included is information such 

as epidemiological studies and case reports in humans and specific reproduction studies along 

with sub-chronic, chronic and special study results in animals that provide relevant information 

regarding toxicity to reproductive and related endocrine organs. Evaluation of substances 

chemically related to the material under study may also be included, particularly when 

information on the material is scarce. The weight given to the available evidence will be 

influenced by factors such as 

 the quality of the studies; 

 consistency of results; 

 nature and severity of effects; 

 level of statistical significance for intergroup differences; 

 number of endpoints affected; 

 relevance of route of administration to humans; and 

 freedom from bias. 

Both positive and negative results are considered together in a weight-of-evidence determination. 

However, a single, positive study performed according to good scientific principles and with 

statistically or biologically significant positive results should be enough to justify classification 

unless the classifier shows that there is no relevance to humans or exposure as discussed below. 

Considerations When Evaluating Weight-of-Evidence 

Factors Weight-of-Evidence Evaluation

Experimental 

data quality/

adequacy:

A number of internationally accepted test methods are available; these 

include methods for developmental toxicity testing, methods for perinatal and post-natal toxicity testing and methods for one- or twogeneration toxicity testing.

Results obtained from screening tests can also be used to justify 

classification, although it is recognized that the quality of this evidence is 

less reliable than that obtained through full studies.

Adverse effects or changes, seen in short- or long-term repeated dose 

toxicity studies, which are judged likely to impair reproductive function 

and which occur in the absence of significant generalized toxicity, may 

be used as a basis for classification, e.g., histopathological changes in 

the gonads.
174

Factors Weight-of-Evidence Evaluation

Evidence from in vitro assays, or non-mammalian tests, and from 

analogous substances using structure-activity relationship (SAR), can 

contribute to the procedure for classification. In all cases of this nature, 

expert judgment must be used to assess the adequacy of the data. 

Inadequate data should not be used as a primary support for 

classification. A single, positive study performed according to good 

scientific principles and with statistically or biologically significant 

positive results should justify classification. 

Toxicokinetics/

mode of action:

If it can be conclusively demonstrated that the clearly identified 

mechanism or mode of action has no relevance for humans or when the 

toxicokinetic differences are so marked that it is certain that the 

hazardous property will not be expressed in humans, then a substance 

that produces an adverse effect on reproduction in experimental animals 

should not be classified.

Routes of 

administration:

It is preferable that animal studies are conducted using appropriate routes 

of administration which relate to the potential route of human exposure. 

However, in practice, reproductive toxicity studies are commonly 

conducted using the oral route, and such studies will normally be suitable 

for evaluating the hazardous properties of the substance with respect to 

reproductive toxicity.

Studies involving routes of administration such as intravenous or 

intraperitoneal injection, which may result in exposure of the 

reproductive organs to unrealistically high levels of the test substance, or 

which elicit local damage to the reproductive organs, (e.g., by irritation)

must be interpreted with extreme caution, such studies on their own 

would not normally be the basis for classification.

Limit dose: There is general agreement about the concept of a limit dose, above 

which the production of an adverse effect may be considered to be 

outside the criteria which lead to classification. Some test guidelines 

specify a limit dose; other test guidelines qualify the limit dose with a 

statement that higher doses may be necessary if anticipated human 

exposure is sufficiently high that an adequate margin of exposure would 

not be achieved. Also, due to species differences in toxicokinetics, 

establishing a specific limit dose may not be adequate for situations 

where humans are more sensitive than the animal model.
175

Factors Weight-of-Evidence Evaluation

In principle, adverse effects on reproduction seen only at very high dose 

levels in animal studies (for example, doses that induce prostration, 

severe inappetence, excessive mortality) would not normally lead to 

classification, unless other information is available, e.g., toxicokinetics 

information indicating that humans may be more susceptible than 

animals, to suggest that classification is appropriate.

Specification of the actual “limit dose” will depend upon the test method 

that has been used to provide the test results (e.g., in the OECD Test 

Guideline for repeated dose toxicity studies by the oral route, an upper 

dose of 1000 mg/kg) unless expected human response indicates the need 

for a higher dose level to be used as a limit dose.

Effects of 

minimal or low 

toxicological 

significance:

In some reproductive toxicity studies in experimental animals the only 

effects recorded may be considered of low or minimal toxicological 

significance and classification may not necessarily be the outcome. 

These include, for example, small changes in semen parameters or in the 

incidence of spontaneous defects in the fetus, small changes in the 

proportions of common fetal variants such as are observed in skeletal 

examinations, or in fetal weights, or small differences in postnatal 

developmental assessments.

Maternal 

toxicity:

If developmental toxicity occurs together with other toxic effects in the 

dam (mother), the potential influence of the generalized adverse effects 

should be assessed to the extent possible. The preferred approach is to 

consider adverse effects in the embryo/fetus first, and then evaluate 

maternal toxicity, along with any other factors, which are likely to have 

influenced these effects. Generally, the presence of maternal toxicity 

should not be used to negate findings of embryo/fetal effects, unless it 

can be clearly demonstrated that the effects are secondary non-specific 

effects (e.g., maternal stress, disruption of homeostasis).

Developmental effects, which occur even in the presence of maternal 

toxicity, are considered to be evidence of developmental toxicity, unless 

it can be unequivocally demonstrated on a case-by-case basis that the 

developmental effects are secondary to maternal toxicity. Moreover, 

classification should be considered where there is significant toxic effect 

in the offspring, e.g., irreversible effects such as structural 

malformations, embryo/fetal lethality, or significant post-natal functional 

deficiencies.
176

Factors Weight-of-Evidence Evaluation

Classification should not automatically be discounted for chemicals that 

produce developmental toxicity only in association with maternal 

toxicity, even if a specific maternally-mediated mechanism has been 

demonstrated. In such a case, classification in Category 2 may be 

considered more appropriate than Category 1. However, when a 

chemical is so toxic that maternal death or severe inanition results, or 

when the dams (mothers) are prostrate and incapable of nursing the pups, 

it may be reasonable to assume that developmental toxicity is produced 

solely as a secondary consequence of maternal toxicity and discount the 

developmental effects. Classification may not necessarily be the outcome 

in the case of minor developmental changes (e.g., small reduction in 

fetal/pup body weight, or retardation of ossification when seen in 

association with maternal toxicity).

Maternal toxicity 

Maternal toxicity deserves careful consideration. Development of the offspring throughout 

gestation and during the early postnatal stages can be influenced by toxic effects in the mother 

either through non-specific mechanisms related to stress and the disruption of maternal 

homeostasis, or by specific maternally-mediated mechanisms. So, in the interpretation of the 

developmental outcome that is used to decide classification for developmental effects, it is 

important to consider the possible influence of maternal toxicity. This is a complex issue because 

of uncertainties surrounding the relationship between maternal toxicity and developmental 

outcome. Expert judgment and a weight-of-evidence approach, using all available studies, shall 

be used to determine the degree of influence to be attributed to maternal toxicity when 

interpreting the criteria for classification for developmental effects. As weight-of-evidence to 

help reach a conclusion about classification, the adverse effects in the embryo/fetus shall be first 

considered; and then maternal toxicity, along with any other factors which are likely to have 

influenced these effects. 

Based on pragmatic observation, it is believed that maternal toxicity may, depending on severity, 

influence development via non-specific secondary mechanisms, producing effects such as 

depressed fetal weight, retarded ossification, and possibly resorptions and certain malformations 

in some strains of certain species. However, the limited number of studies which have 

investigated the relationship between developmental effects and general maternal toxicity have 

failed to demonstrate a consistent, reproducible relationship across species. 

Some of the endpoints used to assess maternal toxicity are provided below. Data on these 

endpoints, if available, shall be evaluated in light of their statistical or biological significance and 

dose-response relationship. 
177

(a) Maternal mortality: An increased incidence of mortality among the treated dams over 

the controls shall be considered evidence of maternal toxicity if the increase occurs in a 

dose-related manner and can be attributed to the systemic toxicity of the test material. 

Maternal mortality greater than 10% is considered excessive and the data for that dose 

level shall not normally be considered to need further evaluation. 

(b) Mating index (Number of animals with seminal plugs or sperm/Number of matings × 

100) 

(c) Fertility index (Number of animals with implants/Number of matings × 100) 

(d) Gestation length (If allowed to deliver) 

(e) Body weight and body weight change: Consideration of the maternal body weight 

change and/or adjusted (corrected) maternal body weight shall be included in the 

evaluation of maternal toxicity whenever such data are available. The calculation of an 

adjusted (corrected) mean maternal body weight change, which is the difference between 

the initial and terminal body weight minus the gravid uterine weight (or alternatively, the 

sum of the weights of the fetuses), may indicate whether the effect is maternal or 

intrauterine. In rabbits, the body weight gain may not be a useful indicator of maternal 

toxicity because of normal fluctuations in body weight during pregnancy. 

(f) Food and water consumption (if relevant): The observation of a significant decrease in 

the average food or water consumption in treated dams (mothers) compared to the control 

group may be useful in evaluating maternal toxicity, particularly when the test material is 

administered in the diet or drinking water. Changes in food or water consumption must 

be evaluated in conjunction with maternal body weights when determining if the effects 

noted are reflective of maternal toxicity or, more simply, unpalatability of the test 

material in feed or water. 

(g) Clinical evaluations (including clinical signs, markers, and hematology and clinical 

chemistry studies): The observation of increased incidence of significant clinical signs of 

toxicity in treated dams (mothers) relative to the control group is useful in evaluating 

maternal toxicity. If this is to be used as the basis for the assessment of maternal toxicity, 

the types, incidence, degree and duration of clinical signs shall be reported in the study. 

Clinical signs of maternal intoxication include, but are not limited to: coma, prostration, 

hyperactivity, loss of righting reflex, ataxia, or labored breathing. 

(h) Post-mortem data: Increased incidence and/or severity of post-mortem findings may 

be indicative of maternal toxicity. This can include gross or microscopic pathological 

findings or organ weight data, including absolute organ weight, organ-to-body weight 

ratio, or organ-to-brain weight ratio. When supported by findings of adverse 

histopathological effects in the affected organ(s), the observation of a significant change 
178

in the average weight of suspected target organ(s) of treated dams (mothers), compared to 

those in the control group, may be considered evidence of maternal toxicity. 

Classification criteria for mixtures 

It should be noted that the classification criteria for health hazards often include a tiered scheme 

in which test data available on the complete mixture are considered as the first tier in the 

evaluation, followed by the applicable bridging principles, and lastly, cut-off 

values/concentration limits or additivity. However, this approach is not used for Reproductive 

Toxicity. The criteria for Reproductive Toxicity consider the cut-off values/concentration limits 

as the primary tier and allow the classification to be modified only on a case-by-case evaluation 

based on available test data for the mixture as a whole. 

Tier 1: Classification of mixtures when data are available for all ingredients or only for some 

ingredients of the mixture 

The approach to classifying a mixture for reproductive toxicity in Tier 1 is to use a cutoff/concentration limit. An assessment is carried out separately for each Category 1A, Category 

1B or Category 2 ingredient in the mixture. In the case where the mixture has Category 1A, 

Category 1B and Category 2 ingredients above the cut-off/concentration limit, the mixture is 

classified in the most severe category. 

The mixture will be classified as a reproductive toxicant when at least one ingredient has been 

classified as a Category 1A, Category 1B or Category 2 reproductive toxicant and is present at or 

above the appropriate cut-off value/concentration limit specified below for Category 1 and 

Category 2, respectively. 

Additionally, a separate evaluation will be made to determine if the mixture will be classified for 

effects on or via lactation. If at least one ingredient in the mixture is classified in the category for 

effects on or via lactation and is present at or above the appropriate cut-off/concentration limit,

then the mixture will be classified for effects on or via lactation. 
179

Table VII.7.3. Cut-off values/concentration limits of ingredients of a mixture classified as 

reproductive toxicants or for effects on or via lactation that would trigger classification of 

the mixture 

Ingredient 

classified as:

Cut-off/concentration limits triggering classification of a mixture as:

Category 1 reproductive 

toxicant Category 2 

reproductive 

toxicant

Additional 

category for 

effects on or via 

Category 1A Category 1B lactation

Category 1A 

reproductive 

toxicant

 0.1% 

-- -- --

Category 1B

reproductive 

toxicant

--

 0.1% 

-- --

Category 2 

reproductive 

toxicant

-- --

 0.1% 

--

Additional 

category for 

effects on or via 

lactation 

-- -- --

 0.1% 

Tier 2: Classification of mixtures when data are available for the complete mixture 

On a case-by-case basis the Reproductive Toxicity classification, which normally considers 

results obtained with the individual ingredients, may be modified using available test data for the 

mixture as a whole. 

The concern with using test data for the mixture as a whole is that as the concentration of a 

reproductive toxicant is reduced in a mixture the dilution effect may result in a misleading test 

results (i.e., false negative) if the study was not appropriately designed to factor in the 

concentration of the reproductive toxicant in the mixture. In these cases, mixtures that would 

cause Reproductive Toxicity would not be classified and labeled. Accordingly, the HCS 

provides guidance that the test results for the mixture as a whole must be conclusive, taking into 

account dose, and other factors such as duration, observations and analysis (e.g., statistical 

analysis, test sensitivity) of reproduction test systems. 

If appropriate test data for the mixtures is not available, then the classifier can consider the 

application of the Bridging Principle criteria in Tier 3, if appropriate, or use the classification 

resulting from the application of the criteria in Tier 1. 
180

Tier 3: Classification of mixtures when data are not available for the complete mixture - 

bridging principles 

Where the mixture itself has not been tested to determine its reproductive toxicity, but there are 

sufficient data on BOTH the individual ingredients AND similar tested mixtures to adequately 

characterize the hazards of the mixture, then these data can be used in accordance with the 

bridging principles below. If data on another mixture are used in the application of the bridging 

principles, the data on that mixture must be conclusive as discussed in Tier 2 above. 

Only the following bridging principles are applicable to the Reproductive Toxicity hazard class: 

 Dilution, 

 Batching, 

 Substantially similar mixtures.

The application of bridging principles ensures that the classification process uses the available 

data to the greatest extent possible in characterizing the potential reproductive toxicity hazard. 

Dilution 

If a tested mixture is diluted with a diluent which is not expected to affect the 

reproductive toxicity of other ingredients, then the new diluted mixture may be classified 

as equivalent to the original tested mixture. 

Batching 

The reproductive toxicity potential of a tested production batch of a mixture can be 

assumed to be substantially equivalent to that of another untested production batch of the 

same commercial product, when produced by or under the control of the same 

manufacturer, unless there is reason to believe there is significant variation in 

composition such that the reproductive toxicity potential of the untested batch has 

changed. If the latter occurs, a new classification is necessary. 

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

(ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 
181

(d) Data on toxicity for A and C are available and substantially equivalent (i.e., 

they are in the same hazard category and are not expected to affect the 

reproductive toxicity of B). 

If mixture (i) or (ii) is already classified by testing, then the other mixture can be 

classified in the same hazard category. 

Classification Procedure and Guidance 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS requires 

collecting and evaluating the best available existing evidence on the hazards of each chemical. 

Data generated in accordance with internationally recognized scientific principles are acceptable 

under the HCS. 

Examples of scientifically validated test methods 

There are a number of internationally recognized methods for investigation of reproductive 

toxicity effects: 

 Prenatal Developmental Toxicity Study (OECD Test Guideline 414) 

 One-Generation Reproduction Toxicity Study (OECD Test Guideline 415) 

 Two-Generation Reproduction Toxicity Study (OECD Test Guideline 416) 

 Reproduction/Developmental Toxicity Screening Test (OECD Test Guideline 421) 

 Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity 

Screening Test (OECD Test Guideline 422) 

Other test methodologies that meet the requirements for testing of reproductive toxicity include: 

 Preliminary developmental toxicity screen (EPA 798.4420/870.3500) 

 Inhalation developmental toxicity study (EPA 798.4350/870.3600) 

 Prenatal developmental toxicity study (EPA 798.4900/ 870.3700) 

 Prenatal developmental toxicity study (EEC Directive 92/32/EEC B.31) 

 Reproduction and fertility effects (EPA 798.4700/870.3800) 

 One‐generation reproduction toxicity test study (EEC Directive 92/32/EEC B.34) 

 Two‐generation reproduction toxicity study (EEC Directive 92/32/EEC B.35) 
182

Classification procedure 

In classification, the data are compared to the reproductive toxicity classification criteria. If valid 

data on the reproductive toxicity of a substance or mixture are available, then these data should 

be used for classification. To find the necessary data, a classifier is advised to try the following: 

 ask the manufacturer or supplier for the reproductive toxicity data for the product; or 

 check to see if the reproductive toxicity data is available in the SDS or any other 

documentation accompanying the product; or 

 find the data available in the open literature if the chemical identity of the product is 

known (for a single-component chemical). 

For mixtures follow the three-tier approach discussed above. 

Considerations 

Classification is made on the basis of the appropriate HCS criteria and an assessment of the total 

weight-of-evidence. The validity and usefulness of each test data set to the overall assessment of 

reproductive toxicity should be individually assessed, taking account of protocol design 

(including route of administration) and current expert views on the value of the test systems. 

If the data are available, then you must classify into the appropriate reproductive toxicity subcategory (i.e., category 1A or category 1B). If the data does not allow classification into a subcategory, then you must classify in reproductive toxicity category 1. 

Decision logic 

Three decision logics for classifying reproductive toxicity are provided. The first decision logic 

is for reproductive toxic substances. Use the second decision logic for classifying reproductive 

toxic mixtures. There is an additional decision logic for classifying effects on or via lactation for 

both substances and mixtures. The decision logics are provided as additional guidance. It is 

strongly recommended that the person responsible for classification study the criteria before and 

during use of the decision logic. 

These decision logics are essentially flowcharts for classifying substances and mixtures 

regarding reproductive toxicity. They present questions in a sequence that walks you through the 

classification steps and criteria for classifying reproductive toxicity. Once you answer the 

questions provided, you will arrive at the appropriate classification. 
183

Substance decision logic for reproductive toxicity 

According to the criteria, is the substance:

(a) Known human reproductive toxicant, or 

(b) Presumed human reproductive toxicant? 

Application of the criteria needs expert judgment in a 

weight-of-evidence approach.

No

Yes

Category 1

Danger 

Not classified

According to the criteria, is the substance a suspected 

human reproductive toxicant?

Application of the criteria needs expert judgment in a 

strength and weight-of-evidence approach.

Substance: Does the substance have data on reproductive 

toxicity?

Yes

No Classification

not possible

Yes

Category 2

Warning 

No
184

Mixtures decision logic for reproductive toxicity

Classification based on individual ingredients of the mixture 

Modified classification on a case-by-case basis 

Mixture: Classification of mixtures will be based on the available test data for the individual 

ingredients of the mixture, using cut-off values/concentration limits for those ingredients. The 

classification may be modified on a case-by-case basis based on the available test data for the mixture 

as a whole or based on bridging principles. See modified classification on a case-by-case basis below. 

For further details see criteria (See 3.7.3.1, 3.7.3.2 and 3.Does the substance according to the criteria 

cause concern for the health of breastfed children?

Does the mixture contain one or more ingredients classified 

as a Category 1 reproductive toxicant at  0.1%? 

Yes

Category 1

Danger 

No

Does the mixture contain one or more ingredients 

classified as a Category 2 reproductive toxicant at  0.1%?

Yes

Category 2

Warning

No

Not Classified

Are test data available for 

the mixture itself? Yes

Are the test results on the 

mixture conclusive, taking into 

account dose and other factors 

such as duration, observations 

and analysis (e.g., statistical 

analysis, test sensitivity) of 

reproduction test systems?

Classify in 

appropriate 

category 

Danger 

or 

Warning 

or

No classification

Yes

No

No

Classification based on individual 

ingredients of the mixture (See above).

Can bridging principles be applied? If data on another 

mixture are used in the application of bridging principles, 

the data on that mixture must be conclusive. See criteria.

Yes

Mixture: Classification of mixtures will be based on the available test data for the individual 

ingredients of the mixture, using cut-off values/concentration limits for those ingredients. The 

classification may be modified on a case-by-case basis based on the available test data for the mixture 

as a whole or based on bridging principles. See modified classification on a case-by-case basis below. 

For further details see criteria.

No

No
185

Decision logic for effects on or via lactation 

Decision logic for substances

Decision logic for mixtures 

Does the substance according to the criteria cause concern 

for the health of breastfed children or interfere with 

lactation?

Yes

Additional category 

for effects on or via 

lactation 

No symbol 

No signal word

Not classified 

No

Mixture: Classification of mixtures will be based on the available test data for the individual 

ingredients of the mixture, using cut-off values/concentration limits for those ingredients. The 

classification may be modified on a case-by-case basis based on the available test data for the mixture 

as a whole or based on bridging principles. See modified classification on a case-by-case basis below. 

For further details see criteria.

Does the mixture contain one or more ingredients classified for 

effects on or via lactation at  0.1%? Yes

No

Not classified

Are test data available for 

the mixture itself? Yes

Are the test results on the mixture 

conclusive taking into account dose 

and other factors such as duration, 

observations and analysis (e.g., 

statistical analysis, test sensitivity) 

of reproduction test systems?

Yes

No

No

Classification based on individual 

ingredients of the mixture (See above).

Can bridging principles be applied? If data on another 

mixture are used in the application of bridging principles, 

the data on that mixture must be conclusive. See criteria.

No

Additional category 

for effects on or via 

lactation 

No symbol 

No signal word

Additional 

category for 

effects on or 

via lactation

No symbol

No signal 

word

or

No 

classification

Yes

Classification based on individual ingredients of the mixture 

Modified classification on a case-by-case basis
186

Reproductive Toxicity Classification Examples 

The following examples are provided to walk you through reproductive toxicity classification.

Examples of a substance fulfilling the criteria for classification: 

Substance Example #1

Reproductive Toxicity

Test Data 

HCS 2012

Classification Rationale

Evidence of decreased number of fetuses 

per brood, decline in the ability of males 

to impregnate females, increased 

incidence of preimplantation embryo 

death, etc. at dosing levels causing no 

general toxicity.

Reproductive 

Toxicity

Category 1B

Fulfills criteria 

 Data from animal studies providing 

clear evidence of an adverse effect 

on sexual function and fertility or on 

development in the absence of other 

toxic effects.

Substance Example #2

Reproductive Toxicity

Test Data

HCS 2012

Classification Rationale

Human epidemiological studies in IRIS 

Toxicological review (2005) and 

ATSDR (2000), describe increased 

incidence of natural abortion after 

exposure, abnormal development and 

malformation of newborns caused by 

prenatal abuse and decreased plasma 

concentrations of luteinizing hormone 

and testosterone after exposure.

Increased risk of late spontaneous 

abortions associated with exposure at 

levels around 88 ppm (range 50-150 

ppm).

Evidence of increased incidences of fetal 

death and delayed ossification, a 

decrease and unossification of 

sternebrae, a shift in rib profile, excess 

ribs, retarded skeletal development, 

delayed reflex response, learning 

disability and early vaginal opening and 

testes descent at dosing levels not toxic 

to dams from rat and mouse 

teratogenicity tests. 

Reproductive 

Toxicity

Category 1A

Fulfills criteria 

 Evidence of adverse effects on 

development in humans and in 

animal studies.
187

Example of a mixture fulfilling the criteria for classification: 

Mixture Example #1

Reproductive Toxicity

Data

HCS 2012

Classification Rationale

Component data:

Component 1: 0.05%, Category 1B

Component 2: 2%, Category 2

Component 3: 0.2%, Effect on or 

via lactation

Component 4: 97.75%

Reproductive 

Toxicity

Category 2 and 

Additional 

category for effects

on or via lactation

The Reproductive Toxicity cut-off 

values/concentration limits are used 

for classification.

Fulfills criteria

 Component 1 is not ≥ 0.1% so 

the mixture does not meet the 

Category 1B criteria.

 Component 2 is ≥ 0.1% so the 

mixture meets the Category 2 

criteria.

 Component 3 is ≥ 0.1% so the 

mixture meets the effect on or via 

lactation criteria.
188

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.7 Reproductive Toxicity 

29 CFR 1910.1200, Hazard Communication, Appendix C Allocation of Label Elements 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

The Organization for Economic Co-operation and Development (OECD) Guidelines for the 

Testing of Chemicals. 

United States Environmental Protection Agency (EPA), Office of Prevention, Pesticides, and 

Toxic Substances (OPPTS) Health Effects Test Guidelines. 
189

VII.8 Specific Target Organ Toxicity – Single Exposure 

Introduction

Chemical exposures can potentially result in adverse effects on one or more of the body’s organ 

systems such as the renal or nervous systems. The HCS provides criteria for the evaluation of 

data related to a specific target organ or type of effect. 

The specific target organ toxicity (STOT) classification addresses chemicals that affect various 

target organ systems of the body after either a single or repeated exposure. These criteria address 

those target organ systems that are not covered by the HCS criteria for acute toxicity, skin 

corrosion/irritation, serious eye damage/eye irritation, respiratory or skin sensitization, germ cell 

mutagenicity, carcinogenicity, reproductive toxicity and aspiration toxicity. Specific target organ 

toxicity criteria apply to significant health effects that can impair function, both reversible and 

irreversible, which can be immediate and/or delayed. Specific target organ toxicity can occur by 

any route that is relevant for human exposures (i.e., principally oral, dermal or inhalation). 

The HCS addresses two different types of STOT hazards: toxicity that occurs after a single 

exposure to a chemical, and toxicity that occurs after repeated exposures to a chemical. To 

conform to the HCS, this guidance addresses the two STOT hazard classes separately: STOT –

single exposure in Chapter VII.8 and STOT – repeated exposure in Chapter VII.9. 

Substances and mixtures shall be classified for either or both single and repeated dose toxicity 

independently. 

Definition and General Considerations 

Specific target organ toxicity - single exposure (STOT-SE) means specific, non-lethal target 

organ toxicity arising from a single exposure to a chemical. All significant health effects that can 

impair function, both reversible and irreversible, immediate and/or delayed and not specifically 

addressed in Chapters VII.1 to VII.7 and VII.10 are included. Specific target organ toxicity 

following repeated exposure is classified in accordance with Specific Target Organ Toxicity –

Repeated Exposure and is not included here but is discussed in the next chapter, VII.9. 

The adverse health effects produced by a single exposure include consistent and identifiable 

toxic effects in humans; or, in experimental animals, toxicologically significant changes which 

have affected the function or morphology of a tissue/organ, or have produced serious changes to 

the biochemistry or hematology of the organism, and these changes are relevant for human 

health. Human data is the primary source of evidence for this hazard class. 

Assessment shall take into consideration not only significant changes in a single organ or 

biological system but also generalized changes of a less severe nature involving several organs. 

Specific target organ toxicity can occur by any route that is relevant for humans (i.e., principally 

oral, dermal or inhalation). 
190

The classification criteria for specific organ systemic toxicity – single exposure are organized as 

criteria for substances Categories 1 and 2, criteria for substances Category 3 and criteria for 

mixtures. 

Classification Criteria for Substances 

Substances of Category 1 and Category 2 

Substances shall be classified for immediate or delayed effects separately, by the use of expert 

judgment on the basis of the weight of all evidence available, including the use of recommended 

guidance values. Substances shall then be classified in Category 1 or 2, depending upon the 

nature and severity of the effect(s) observed. 

Figure VII.8.1. Hazard categories for specific target organ toxicity following single exposure 

Category Criteria

Category 1 Substances that have produced significant toxicity in humans, or 

that, on the basis of evidence from studies in experimental animals 

can be presumed to have the potential to produce significant toxicity 

in humans following single exposure

Substances are classified in Category 1 for STOT-SE on the basis of:

(a) reliable and good quality evidence from human cases or 

epidemiological studies; or

(b) observations from appropriate studies in experimental animals in 

which significant and/or severe toxic effects of relevance to human 

health were produced at generally low exposure concentrations. 

Guidance dose/concentration values are provided below to be used as 

part of weight-of-evidence evaluation.

Category 2 Substances that, on the basis of evidence from studies in 

experimental animals, can be presumed to have the potential to be 

harmful to human health following single exposure

Substances are classified in Category 2 for STOT-SE on the basis of 

observations from appropriate studies in experimental animals in which 

significant toxic effects, of relevance to human health, were produced at 

generally moderate exposure concentrations. Guidance 

dose/concentration values are provided below in order to help in 

classification.

In exceptional cases, human evidence can also be used to place a 

substance in Category 2.
191

Category Criteria

Category 3 Transient target organ effects

There are target organ effects for which a substance does not meet the 

criteria to be classified in Categories 1 or 2 indicated above. These are 

effects which adversely alter human function for a short duration after 

exposure and from which humans may recover in a reasonable period 

without leaving significant alteration of structure or function. This 

category includes only narcotic effects and respiratory tract irritation. 

Substances are classified specifically for these.

Note: The primary target organ/system shall be identified where possible, and where this is not 

possible, the substance shall be identified as a general toxicant. The data shall be evaluated and, 

where possible, shall not include secondary effects (e.g., a hepatotoxicant can produce secondary 

effects in the nervous or gastro-intestinal systems). 

Specific considerations for classification of substances as specific target organ toxicity – single 

exposure 

Classification is determined by expert judgment, on the basis of the weight of all evidence 

available. 

Weight-of-evidence of all available data, including human incidents, epidemiology, and studies 

conducted in experimental animals is used to substantiate specific target organ toxic effects that 

merit classification. 

The relevant route(s) of exposure by which the classified substance produces damage shall be 

identified. 

The information required to evaluate specific target organ toxicity comes either from single 

exposure in humans (e.g., exposure at home, in the workplace or environmentally), or from 

studies conducted in experimental animals. The standard animal studies in rats or mice that 

provide this information are acute toxicity studies which can include clinical observations and 

detailed macroscopic and microscopic examination to enable the toxic effects on target 

tissues/organs to be identified. Results of acute toxicity studies conducted in other species may 

also provide relevant information. 

In most cases chemicals with human evidence of target organ toxicity will be classified in 

Category 1. Only in exceptional cases, based on expert judgment, it may be appropriate to place 

certain substances with human evidence of target organ toxicity in Category 2: (a) when the 

weight of human evidence is not sufficiently convincing to warrant Category 1 classification, 

and/or (b) based on the nature and severity of effects. However, the following considerations 

should be kept in mind when applying this concept. Dose/concentration levels in humans shall 

not be considered in the classification. Additionally, any available evidence from animal studies 
192

shall be consistent with the Category 2 classification. In other words, if there are also animal data 

available on the substance that warrant Category 1 classification, the chemical shall be classified 

as Category 1. 

Effects considered to support classification for Categories 1 and 2

Classification is supported by evidence associating single exposure to the substance with a 

consistent and identifiable toxic effect. 

Evidence from human experience/incidents is usually restricted to reports of adverse health 

consequences, often with uncertainty about exposure conditions, and may not provide the 

scientific detail that can be obtained from well-conducted studies in experimental animals. 

Therefore, evidence from appropriate studies in experimental animals can furnish much more 

detail, in the form of clinical observations and macroscopic and microscopic pathological 

examination; this can often reveal hazards that may not be life-threatening but could indicate 

functional impairment. Consequently, all available evidence, including evidence relevant to 

human health, must be taken into consideration in the classification process. Relevant toxic 

effects in humans and/or animals include, but are not limited to: 

(a) Morbidity resulting from single exposure; 

(b) Significant functional changes, more than transient in nature, in the respiratory 

system, central or peripheral nervous systems, other organs or other organ systems, 

including signs of central nervous system depression and effects on special senses (e.g., 

sight, hearing and sense of smell); 

(c) Any consistent and significant adverse change in clinical biochemistry, hematology, 

or urinalysis parameters; 

(d) Significant organ damage that may be noted at necropsy and/or subsequently seen or 

confirmed at microscopic examination; 

(e) Multi-focal or diffuse necrosis, fibrosis or granuloma formation in vital organs with 

regenerative capacity; 

(f) Morphological changes that are potentially reversible but provide clear evidence of 

marked organ dysfunction; and 

(g) Evidence of appreciable cell death (including cell degeneration and reduced cell 

number) in vital organs incapable of regeneration. 
193

Effects considered not to support classification for Categories 1 and 2

Effects may be seen in humans and/or animals that do not justify classification. Such effects 

include, but are not limited to: 

(a) Clinical observations or small changes in body weight gain, food consumption or 

water intake that may have some toxicological importance but that do not, by themselves, 

indicate “significant” toxicity; 

(b) Small changes in clinical biochemistry, hematology or urinalysis parameters and/or 

transient effects, when such changes or effects are of doubtful or of minimal toxicological 

importance; 

(c) Changes in organ weights with no evidence of organ dysfunction; 

(d) Adaptive responses that are not considered toxicologically relevant; and 

(e) Substance-induced species-specific mechanisms of toxicity, i.e., demonstrated with 

reasonable certainty to be not relevant for human health. 

Guidance values to assist with classification based on the results obtained from studies 

conducted in experimental animals for Categories 1 and 2 

In order to help reach a decision about whether a substance shall be classified or not, and to what 

degree it shall be classified (Category 1 vs. Category 2), dose/concentration “guidance values” 

are provided for consideration of the dose/concentration which has been shown to produce 

significant health effects. The principal argument for proposing such guidance values is that all 

chemicals are potentially toxic and there has to be a reasonable dose/concentration above which 

a degree of toxic effect is acknowledged. 

Thus, in animal studies, when significant toxic effects are observed that indicate classification, 

consideration of the dose/concentration at which these effects were seen, in relation to the 

suggested guidance values, provides useful information to help assess the need for classification 

(since the toxic effects are a consequence of the hazardous property(ies) and also the 

dose/concentration). 

The guidance value ranges for single-dose exposure which has produced a significant non-lethal 

toxic effect apply to acute toxicity testing, as shown in the table below. 
194

Table VII.8.1. Guidance value ranges for single-dose exposures 

Route of exposure Units

Guidance values (dose/concentration)

Category 1 Category 2 Category 3

Oral (rat) mg/kg 

body weight

< 300 > 300 and  2000 Guidance 

values do not 

apply Dermal 

(rat or rabbit)

mg/kg 

body weight

< 1000 > 1000 and  2000

Inhalation (rat) gas ppm < 2500 > 2500 and  5000

Inhalation (rat) vapor mg/1 < 10 > 10 and  20

Inhalation (rat) 

dust/mist/fume

mg/l/4h < 1.0 > 1.0 and  5.0

The guidance values and ranges mentioned in the above table are intended only for guidance 

purposes, i.e., to be used as part of the weight-of-evidence approach, and to assist with decisions 

about classification. They are not intended as strict demarcation values. Guidance values are not 

provided for Category 3 since this classification is primarily based on human data; animal data 

may be included in the weight-of-evidence evaluation. 

It is possible that even where a specific profile of toxicity occurs at a dose/concentration below 

the guidance value, e.g., < 2000 mg/kg body weight by the oral route, the nature of the effect 

may result in the decision not to classify. Conversely, a specific profile of toxicity may be seen 

in animal studies occurring at above a guidance value, e.g., ≥ 2000 mg/kg body weight by the 

oral route, and in addition there is supplementary information from other sources, e.g., other 

single dose studies, or human case experience, which supports a conclusion that, in view of the 

weight-of-evidence, classification is the prudent action to take. 

Other considerations when classifying using animal data 

When a substance is characterized only by use of animal data, the classification process must 

include reference to dose/concentration guidance values as one of the elements that contribute to 

the weight-of-evidence approach. 

Evidence in humans 

When well-substantiated human data are available showing a specific target organ toxic effect 

that can be reliably attributed to a single exposure to a substance, the substance shall be 

classified. Positive human data, regardless of probable dose, predominates over animal data. 

Thus, if a substance is unclassified because specific target organ toxicity observed was 

considered not relevant or significant to humans, if subsequent human incident data become 

available showing a specific target organ toxic effect, the substance shall be classified. 
195

Non-test data 

A substance that has not been tested for specific target organ toxicity shall, where appropriate, be 

classified on the basis of data from a scientifically validated structure activity relationship and 

expert judgment-based extrapolation from a structural analogue that has previously been 

classified together with substantial support from consideration of other important factors such as 

formation of common significant metabolites. 

Substances of Category 3 

Criteria for respiratory tract irritation 

The criteria for classifying substances as Category 3 for respiratory tract irritation are: 

(a) Respiratory irritant effects (characterized by localized redness, edema, pruritus and/or 

pain) that impair function with symptoms such as cough, pain, choking, and breathing 

difficulties are included. It is recognized that this evaluation is based primarily on human 

data;

(b) Subjective human observations supported by objective measurements of clear 

respiratory tract irritation (RTI) (e.g., electrophysiological responses, biomarkers of 

inflammation in nasal or bronchoalveolar lavage fluids);

(c) The symptoms observed in humans shall also be typical of those that would be 

produced in the exposed population rather than being an isolated idiosyncratic reaction or 

response triggered only in individuals with hypersensitive airways. Ambiguous reports 

simply of “irritation” should be excluded as this term is commonly used to describe a 

wide range of sensations including those such as smell, unpleasant taste, a tickling 

sensation, and dryness, which are outside the scope of classification for respiratory tract 

irritation; 

(d) There are currently no scientifically validated animal tests that deal specifically with 

RTI; however, useful information may be obtained from the single and repeated 

inhalation toxicity tests. For example, animal studies may provide useful information in 

terms of clinical signs of toxicity (dyspnea, rhinitis, etc.) and histopathology (e.g., 

hyperemia, edema, minimal inflammation, thickened mucous layer) which are reversible 

and may reflect the characteristic clinical symptoms described above. Such animal 

studies can be used as part of the weight-of-evidence evaluation; and 

(e) This special classification will occur only when more severe organ effects including 

the respiratory system are not observed, as those effects would require a higher 

classification. 
196

Criteria for narcotic effects 

The criteria for classifying substances in Category 3 for narcotic effects are: 

(a) Central nervous system depression including narcotic effects in humans such as 

drowsiness, narcosis, reduced alertness, loss of reflexes, lack of coordination, and vertigo 

are included. These effects can also be manifested as severe headache or nausea, and can 

lead to reduced judgment, dizziness, irritability, fatigue, impaired memory function, 

deficits in perception and coordination, reaction time, or sleepiness; and 

(b) Narcotic effects observed in animal studies may include lethargy, lack of coordination 

righting reflex, narcosis, and ataxia. If these effects are not transient in nature, then they 

shall be considered for classification as Category 1 or 2. 

Classification criteria for mixtures 

Mixtures are classified using the same criteria that are used to classify substances; or 

alternatively, as described below. As with substances, mixtures may be classified for specific 

target organ toxicity following single exposure, repeated exposure, or both. 

The approach to classifying mixtures for specific target organ toxicity – single exposure 

incorporates the tiered approach (i.e., stepwise procedure based on a hierarchy). 

Tier 1: Classification of mixtures when data are available for the complete mixture 

When reliable and good evidence from human experience or appropriate animal studies is 

available for the mixture, then the mixture can be classified by use of a weight-of-evidence 

approach using the same criteria as specified for substances. Specifically for mixtures, care 

should be exercised in evaluating data so that the dose, duration of exposure, observation or 

analysis, does not render the results inconclusive. If test data for the mixture is not available then 

the classifier should consider application of the criteria in Tier 2 or Tier 3 below, as appropriate. 

Tier 2: Classification of mixtures when data are not available for the complete mixture - 

bridging principles 

Where the mixture itself has not been tested to determine its specific target organ toxicity, but 

there are sufficient data on BOTH the individual ingredients AND similar tested mixtures to 

adequately characterize the hazards of the mixture, these data can be used in accordance with the 

below bridging principles. 

All six bridging principles are applicable to the specific target organ toxicity-single exposure 

hazard class: 

 Dilution, 

 Batching, 
197

 Concentration of mixtures,

 Interpolation within one toxicity category, 

 Substantially similar mixtures,

 Aerosols. 

The application of bridging principles ensures that the classification process uses the available 

data to the greatest extent possible in characterizing the potential specific target organ toxicitysingle exposure hazard. 

Dilution 

If a tested mixture is diluted with a diluent which has the same or a lower toxicity 

classification as the least toxic original ingredient and which is not expected to affect the 

specific target organ toxicity of other ingredients, then the new diluted mixture may be 

classified as equivalent to the original tested mixture. 

Batching 

The specific target organ toxicity of a tested production batch of a mixture can be 

assumed to be substantially equivalent to that of another untested production batch of the 

same commercial product when produced by or under the control of the same 

manufacturer, unless there is reason to believe there is significant variation such that the 

specific target organ toxicity of the untested batch has changed. If the latter occurs, a new 

classification is necessary. 

Concentration of mixtures 

If in a tested mixture of STOT-SE Category 1, the concentration of a specific target organ 

toxic ingredient is increased, the resulting concentrated mixture should be classified in 

STOT-SE Category 1 without additional testing. 

Interpolation within one toxicity category 

For three mixtures (A, B and C) with identical ingredients, where mixtures A and B have 

been tested and are in the same STOT-SE category, and where untested mixture C has the 

same specific target organ toxicologically active ingredients as mixtures A and B but has 

concentrations of specific target organ toxicologically active ingredients intermediate to 

the concentrations in mixtures A and B, then mixture C is assumed to be in the same 

STOT-SE category as A and B. 
198

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

(ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) Data on toxicity for A and C are available and substantially equivalent, i.e., 

they are in the same hazard category and are not expected to affect the specific 

target organ toxicity of B. 

If mixture (i) or (ii) is already classified by testing, then the other mixture can be 

classified in the same hazard category. 

Aerosols 

An aerosol form of a mixture may be classified in the same hazard category as the tested, 

non-aerosolized form of the mixture for oral and dermal specific target organ toxicity 

provided the added propellant does not affect the toxicity of the mixture on spraying. 

Classification of aerosolized mixtures for specific target organ toxicity by the inhalation 

route should be considered separately. 

If appropriate data is not available to apply the above bridging principles then the classifier 

should consider application of the criteria in Tier 3. 

Tier 3: Classification of mixtures when data are available for all ingredients or only for some 

ingredients of the mixture 

The approach to classifying a mixture for specific target organ toxicity in Tier 3 is to use a cutoff/concentration limit.

Where there is no reliable evidence or test data for the specific mixture itself, and the bridging 

principles cannot be used to enable classification, then classification of the mixture is based on 

the classification of the ingredient substances. In this case, the mixture shall be classified as a 

specific target organ toxicant (specific organ specified), following a single exposure when at 

least one ingredient has been classified as a Category 1 or Category 2 specific target organ 

toxicant and is present at or above the appropriate cut-off value/concentration limit specified in 

the below table for Categories 1 and 2, respectively. 
199

Table VII.8.2. Cut-off values/concentration limits of ingredients of a mixture classified as a 

specific target organ toxicant that would trigger classification of the mixture as Category 1 

or 2

Ingredient Classified as:

Cut-off/concentration limits

triggering classification of a mixture as:

Category 1 Category 2

Category 1

Target organ toxicant ≥ 1.0%

Category 2

Target organ toxicant - ≥ 1.0%

Care shall be exercised when toxicants affecting more than one organ system are combined that 

the potentiation or synergistic interactions are considered, because certain substances can cause 

target organ toxicity at < 1% concentration when other ingredients in the mixture are known to 

potentiate its toxic effect. 

Additionally, a mixture can also be classified in STOT – Single Exposure Category 3 for 

respiratory tract irritation and/or narcotic effects using a cut off/concentration limit of 20%, as 

appropriate. 

Table VII.8.3. Cut-off values/concentration limits of ingredients of a mixture classified as a 

specific target organ toxicant that would trigger classification of the mixture as Category 3 

Sum of Ingredients Classified as:

Cut-off/concentration limits triggering

classification of a mixture as STOT SE:

Category 3

Respiratory Tract Irritant

Category 3

Narcotic Effects

STOT SE Category 3 -

Respiratory Tract Irritant 20% -

STOT SE Category 3 -

Narcotic Effects - 20%

Care shall be exercised when extrapolating the toxicity of a mixture that contains Category 3 

ingredient(s). A cut-off value/concentration limit of 20%, considered as an additive of all Category 

3 ingredients for each hazard endpoint, is appropriate; however, this cut-off value/concentration 

limit may be higher or lower depending on the Category 3 ingredient(s) involved and the fact that 

some effects such as respiratory tract irritation may not occur below a certain concentration while 

other effects such as narcotic effects may occur below this 20% value. Expert judgment shall be 
200

exercised. Respiratory tract irritation and narcotic effects are to be evaluated separately. When 

conducting classifications for these hazards, the contribution of each ingredient should be 

considered additive, unless there is evidence that the effects are not additive. 

Since the mixture criteria for STOT-SE Category 3 ingredients are generally additive, the 

concept of relevant ingredients can be considered. The “relevant ingredients” of a mixture are 

those which are present in concentration ≥ 1% (w/w for solids, liquids, dusts, mists and vapors 

and v/v for gases), unless there is a reason to suspect that an ingredient present at a concentration 

< 1% can still be relevant for classifying the mixture for respiratory tract irritation or narcotic 

effects. 

Note that the additivity approach does NOT apply when classifying mixtures for STOT-SE 

categories 1 and 2. 

Mixtures containing from 1% to less than 10% of Category 1 STOT-SE ingredients may be 

classified as Category 2 STOT-SE under the limited following circumstances. The criteria allow 

for the classification of mixtures under the criteria as used for substances. Where the 

classification of the ingredients is based on animal data only, the use of the guidance values in 

Table VII.8.1 is appropriate as a part of the total weight-of-evidence approach. It may be 

appropriate, in light of the guidance values, to classify a mixture containing from 1% to less than 

10% of Category 1 STOT-SE substances as a Category 2 STOT-SE hazard, where warranted by 

the weight of evidence. Such a classification must be consistent with all of the criteria in 29 CFR 

1910.1200 A.8.2.1 ("Substances of Category 1 and Category 2"), including consideration of the 

severity of the effect observed. However, OSHA would not accept a determination not to classify 

a mixture based on this approach. 

Classification Procedure and Guidance 

Test data 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS requires 

collecting and evaluating the best available existing evidence on the hazards of each chemical. 

Old-style acute toxicity tests on animals use death as the main observational endpoint, usually in 

order to determine LD50 or LC50 values. These tests will generally not provide useful information 

for STOT-SE categories 1 and 2. Findings of narcosis and respiratory tract irritation are 

sometimes reported in clinical observations in standard acute toxicity tests. 

Some of the current acute toxicity tests, such as the fixed dose and up-down procedures (e.g., 

OECD Test Guideline 420 Acute oral toxicity – Fixed dose procedure and OECD Test Guideline 

425 Acute oral toxicity – Up-and-down procedure), have observations on signs of non-lethal 

toxicity and may provide useful information for STOT-SE.
201

Classification procedure 

Specific target organ toxicity after a single exposure addresses effects on the body other than 

death (which is addressed by acute toxicity criteria). These effects may be reversible or 

irreversible, and immediate or delayed. The criteria specifically note that, if available, human 

data will be the primary source of evidence for this hazard class. 

Relevant information with respect to toxicity after a single exposure may be available from case 

reports, epidemiological studies, medical surveillance and poison centers. 

Classification for STOT-SE Category 1 and 2 is based on findings of “significant” or “severe” 

toxic effects. Significant effects mean changes which clearly indicate functional disturbance or 

morphological changes which are toxicologically relevant. Severe effects are generally more 

profound or serious than significant effects and are of a considerably adverse nature with 

substantial impact on health. Both factors have to be evaluated by weight-of-evidence and expert 

judgment. 

Considerations 

The STOT criteria are applied independently for STOT – single exposure and STOT – repeated 

exposure (RE). Substances and mixtures can be classified into both hazard classes and either 

Category 1 or Category 2 for each hazard class, as well as the additional STOT - SE Category 3 

where respiratory tract irritation and/or narcotic effects are evaluated separately. 

If the chemical is classified into more than one STOT hazard class and/or category, then all 

relevant classifications should be communicated on the Safety Data Sheet in Section 2 and all 

appropriate hazard statements should be communicated along with the specific affected organs 

on the label. 

Classification for STOT-SE and acute toxicity are independent of each other and both may be 

assigned to a chemical if the respective criteria are met. However, it is not necessary to classify 

in both classes for the same toxic effect. See Substance Example #5 at the end of this chapter. 

Classification for STOT-SE is warranted where there is clear evidence of specific organ toxicity 

especially in absence of lethality which then may be classified under a separate hazard class such 

as acute toxicity.(e.g., methanol and tricresylphosphate). 

The specific target organ(s) should be identified for both substances and mixtures whenever 

known. All known specific target organs should be identified for mixtures classified by any of 

the three tiers. If the mixture is classified on the basis of ingredients, then the target organs 

effects from the ingredients should be identified. This information should be provided on SDSs 

and labels. 
202

Decision Logic 

Two decision logics for classifying specific target organ toxicity – single exposure are provided. 

The first decision logic is for substances and tested mixtures. The second decision logic is for 

classifying mixtures not tested as a whole. The decision logics are provided as additional 

guidance. It is strongly recommended that the person responsible for classification study the 

criteria before and during use of the decision logic. 

These decision logics are essentially flowcharts for classifying substances and mixtures 

regarding specific target organ toxicity – single exposure. They present questions in a sequence 

that walks you through the classification steps and criteria for classifying specific target organ 

toxicity – single exposure. Once you answer the questions provided, you will arrive at the 

appropriate classification. 
203

Decision logic for specific target organ toxicity – single exposure 

Substances and tested mixtures 

Substance: Does the substance have data and/or information to evaluate specific 

target organ toxicity following single exposure?

No

Classification 

not possible 

Mixture: Does the mixture as a whole or its ingredients have 

data/information to evaluate specific target organ toxicity 

following single exposure?

Yes

Following single exposure,

(a) Can the substance or mixture produce significant toxicity in humans, 

or 

(b) Can it be presumed to have the potential to produce significant 

toxicity in humans on the basis of evidence from studies in 

experimental animals? 

See criteria and guidance values. Application of the criteria needs expert 

judgment in a weight of evidence approach.

No

Yes

Category 2

Warning 

Following single exposure,

Can the substance or mixture be presumed to have the potential to 

be harmful to human health on the basis of evidence from studies in 

experimental animals? 

See criteria and guidance values. Application of the criteria needs 

expert judgment in a weight-of-evidence approach.

Yes

No

Classification 

not possible 

See decision 

logic #2 

Category 1

Danger 

Does the mixture as a whole have data/information to 

evaluate specific target organ toxicity following single 

exposure?

Yes

No

Yes

Following single exposure,

Can the substance or mixture produce transient narcotic effects or 

respiratory tract irritation or both? Classification in Category 3 would 

only occur when classification into Category 1 or 2 (based on more 

severe respiratory effects or narcotic effects that are not transient) is not 

warranted 

See criteria. Application of the criteria needs expert judgment in a weight-ofevidence approach.

Yes

Category 3

Warning 

Not classified

Yes

No

No
204

Decision logic for specific target organ toxicity – single exposure 

Mixtures not tested as a whole

Category 3

Warning 

Can bridging principles be applied?

No

Yes

Category 2

Warning 

Does the mixture contain one or more ingredients classified as a 

Category 2 specific target organ toxicant at a concentration of 

 1.0%? 

See Table for explanation of cut-off values.

Yes

Does the mixture contain one or more ingredients classified as a 

Category 1 specific target organ toxicant at a concentration of 

 1.0%? 

See Table for explanation of cut-off values.

No

Is the sum of the ingredients classified as a Category 3 specific target 

organ toxicant at a concentration  20%? 

Care should be exercised when classifying such mixtures. See criteria.

Yes

Not classified

No

 No

 No

Classify in 

appropriate 

category

Yes

Category 1

Danger
205

Specific Target Organ Toxicity – Single Exposure Classification Examples 

The following examples are provided to walk you through the specific target organ toxicity –

single exposure classification.

Examples of a substance fulfilling the criteria for classification: 

Substance Example #1

Specific Target Organ Toxicity – Single Exposure

Test Data

HCS 2012

Classification Rationale

There is broad human experience 

from many case reports of 

blindness following oral 

ingestion.

Acute oral toxicity in rats is low 

(LD50 values > 7,000 mg/kg 

body weight with no evidence of 

specific target organ toxicity 

observed in rats).

STOT – SE

Category 1

Fulfills criteria 

 The classification criteria for 

STOT-SE Category 1 are 

fulfilled, as there is clear human 

evidence of a specific target 

organ toxicity effect.

 The rat is the standard animal 

species for single exposure tests 

and is not sensitive as it did not 

predict the specific target organ 

toxicity potential seen in humans.

Substance Example #2

Specific Target Organ Toxicity – Single Exposure

Test Data

HCS 2012

Classification Rationale

Human experience: There are 

well-documented case reports of 

strong neurotoxic effects 

(peripheral neuropathy; cramps in 

calves, paresthesia in feet or 

hands; weak feet, wrist drop, 

paralysis).

Animal data: Serious neurotoxic 

effects (Paralysis) were observed 

after single exposure of doses < 

200 mg/kg body weight.

STOT–SE

Category 1

Fulfills criteria 

 The classification criteria for 

STOT-SE Category 1 are 

fulfilled based on human 

experience as well as on results 

of animal studies, with the same 

target organ toxicity being 

observed in humans and 

experimental animals.
206

Substance Example #3

Specific Target Organ Toxicity – Respiratory Tract Irritation

Test Data

HCS 2012

Classification Rationale

There is broad well-documented 

human experience on irritating 

effect to the respiratory system 

following inhalation.

STOT – SE

Category 3 

respiratory tract 

irritation

Fulfills criteria 

 The classification criteria for 

respiratory tract irritation STOT 

Category 3 are fulfilled based on 

well-documented experience in 

humans.

Substance Example #4

Specific Target Organ Toxicity – Narcotic Effects

Test Data

HCS 2012

Classification Rationale

In valid animal experiments 

narcotic effects (transient effect 

on the nervous system including 

lethargy, lack of coordination and 

narcosis) were observed 

following a single inhalation 

exposure at ≥ 8 mg/l.

STOT – SE

Category 3 

Narcotic effects

Fulfills criteria 

 The classification criteria for 

narcotic effects STOT Category 3 

are fulfilled based on results in an 

animal experiment.
207

Example of a mixture fulfilling the criteria for classification: 

Mixture Example #1

Specific Target Organ Toxicity – Single Exposure

Data

HCS 2012

Classification Rationale

Component data:

Component 1: 0.5%

Component 2: 3.5%, Category 3 -

Respiratory Tract Irritation

Component 3: 15%, Category 3 -

Narcotic effects

Component 4: 15%, Category 3 -

Narcotic effects

Component 5: 66%

STOT – SE

Category 3 

Narcotic effects

Respiratory tract irritation and 

narcotic effects are evaluated 

separately

∑%Category 3 – Narcotic effects = 

15% + 15% = 30% which is > 20%, 

therefore classify as Category 3 –

Narcotic Effects

∑%Category 3 – Respiratory 

Irritation = 3.5%, which is < 20%, 

not classified for Respiratory 

Irritation

Expert judgment is necessary. A cutoff value of 20% is appropriate, but 

the cut-off value at which effects 

occur may be higher or lower

depending on the Category 3 

ingredient(s). In this case, the 

classifiers judged that 30% is 

sufficient to classify.
208

Example of a substance not fulfilling the criteria for classification: 

Substance Example #5

Specific Target Organ Toxicity – Single Exposure

Data

HCS 2012

Classification Rationale

In a study in rats after single 

exposure at 2,000mg/kg body 

weight severe liver damage 

together with mortality was 

observed in 6/10 animals.

Not classified for

STOT – SE 

Though specific target organ toxicity 

was observed in experimental 

animals, the substance will be 

classified as Acute Oral Toxicity 

(Cat 4), since the lethality was due to 

the target organ toxicity, i.e., liver 

impairment. The substance would be 

classified as Acute Oral Toxicity 

Category 4 as it is assumed that the 

LD50 is >300 and ≤ 2,000 mg/kg. 

Thus, classification for STOT single 

exposure is not required as this 

would result in double classification 

for the same effect/mechanism. 

Death is not generally an effect that 

supports classification as STOT 

single exposure.
209

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.8 Specific Target Organ ToxicitySingle Exposure 

29 CFR 1910.1200, Hazard Communication, Appendix C Allocation of Label Elements 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

The Organization for Economic Co-operation and Development (OECD). Guidelines for the 

Testing of Chemicals. 
210

VII.9 Specific Target Organ Toxicity – Repeated or 

Prolonged Exposure 

Introduction

Chemical exposures can potentially result in adverse effects on one or more of the body’s target 

organ systems such as the renal or nervous systems. The HCS provides criteria for the evaluation 

of data related to a specific target organ or type of effect. 

Specific target organ toxicity (STOT) classification addresses chemicals that affect various target 

organ systems of the body after either a single or repeated exposure. These criteria address those 

target organ systems that are not covered by the HCS criteria for acute toxicity, skin 

corrosion/irritation, serious eye damage/eye irritation, respiratory or skin sensitization, germ cell 

mutagenicity, carcinogenicity, reproductive toxicity and aspiration toxicity. Specific target organ 

toxicity criteria apply to significant health effects that can impair function, both reversible and 

irreversible, which can be immediate and/or delayed. Specific target organ toxicity can occur by 

any route that is relevant for human exposures, i.e., principally oral, dermal or inhalation. 

The HCS addresses two different types of STOT hazards: toxicity that occurs after a single 

exposure to a chemical, and toxicity that occurs after repeated exposures to a chemical. To 

conform to the HCS, this guidance addresses the two STOT hazard classes separately: STOT –

single exposure in Chapter VII.8 and STOT – repeated exposure in Chapter VII.9. 

Substances and mixtures shall be classified for either or both single and repeated dose toxicity 

independently. 

Definition and General Considerations 

Specific target organ toxicity - repeated exposure (STOT-RE) means specific target organ 

toxicity arising from repeated exposure to a chemical. All significant health effects that can 

impair function, both reversible and irreversible, immediate and/or delayed and not specifically 

addressed in VII.1 to VII.7 and VII.10 are included. Specific target organ toxicity following a 

single-event exposure is classified in accordance with Specific Target Organ Toxicity – Single 

Exposure and is therefore not included here but discussed in the previous chapter, VII.8. 

The adverse health effects produced by a repeated exposure include consistent and identifiable 

toxic effects in humans; or, in experimental animals, toxicologically significant changes which 

have affected the function or morphology of a tissue/organ, or have produced serious changes to 

the biochemistry or hematology of the organism, and these changes are relevant for human 

health. Human data is the primary source of evidence for this hazard class. 

Assessment shall take into consideration not only significant changes in a single organ or 

biological system but also generalized changes of a less severe nature involving several organs. 
211

Specific target organ toxicity can occur by any route that is relevant for humans, i.e., principally 

oral, dermal or inhalation. 

The classification criteria for specific organ systemic toxicity – repeated exposure are organized 

as criteria for substances Categories 1 and 2 and criteria for mixtures. 

Classification Criteria for Substances 

Substances shall be classified as STOT - RE by expert judgment on the basis of the weight of all 

evidence available, including the use of recommended guidance values which take into account the 

duration of exposure and the dose/concentration which produced the effect(s). Substances shall be 

placed in one of two categories, depending upon the nature and severity of the effect(s) observed. 

Figure VII.9.1. Hazard categories for specific target organ toxicity following 

repeated exposure 

Category Criteria

Category 1 Substances that have produced significant toxicity in humans, or 

that, on the basis of evidence from studies in experimental animals 

can be presumed to have the potential to produce significant toxicity 

in humans following repeated or prolonged17 exposure

Substances are classified in Category 1 for STOT-RE on the basis of:

(a) reliable and good quality evidence from human cases or 

epidemiological studies; or,

(b) observations from appropriate studies in experimental animals in 

which significant and/or severe toxic effects, of relevance to human 

health, were produced at generally low exposure concentrations. 

Guidance dose/concentration values are provided below to be used 

as part of weight-of-evidence evaluation.

Category 2 Substances that, on the basis of evidence from studies in 

experimental animals can be presumed to have the potential to be 

harmful to human health following repeated or prolonged exposure

Substances are classified in Category 2 for STOT-RE on the basis of 

observations from appropriate studies in experimental animals in which 

significant toxic effects, of relevance to human health, were produced at 

generally moderate exposure concentrations. Guidance dose/concentration 

values are provided below in order to help in classification. 

In exceptional cases, human evidence can also be used to place a 

substance in Category 2.

 

17 Significant toxic effects observed in a 90-day repeated-dose study conducted in experimental animals. 
212

Note: The primary target organ/system shall be identified where possible, and where this is not 

possible, the substance shall be identified as a general toxicant. The data shall be evaluated and, 

where possible, shall not include secondary effects (e.g., a hepatotoxicant can produce secondary 

effects in the nervous or gastro-intestinal systems). 

Specific considerations for classification of substances as specific target organ toxicity –

repeated exposure 

Classification is determined by expert judgment, on the basis of the weight of all evidence 

available. 

Weight-of-evidence of all available data, including human incidents, epidemiology, and studies 

conducted in experimental animals is used to substantiate specific target organ toxic effects that 

merit classification. 

The relevant route(s) of exposure by which the classified substance produces damage shall be 

identified. 

The information required to evaluate specific target organ toxicity comes either from repeated 

exposure in humans, (e.g., exposure at home, in the workplace or environmentally), or from 

studies conducted in experimental animals. The standard animal studies in rats or mice that 

provide this information are 28-day, 90-day or lifetime studies (up to 2 years) that include 

hematological, clinico-chemical and detailed macroscopic and microscopic examination to 

enable the toxic effects on target tissues/organs to be identified. Data from repeat dose studies 

performed in other species may also be used. Other long-term exposure studies, e.g., for 

carcinogenicity, neurotoxicity or reproductive toxicity, may also provide evidence of specific 

target organ toxicity that could be used in the assessment of classification. 

In most cases chemicals with human evidence of target organ toxicity will be classified in 

Category 1. Only in exceptional cases, based on expert judgment, it may be appropriate to place 

certain substances with human evidence of target organ toxicity in Category 2: (a) when the 

weight of human evidence is not sufficiently convincing to warrant Category 1 classification, 

and/or (b) based on the nature and severity of effects. However, the following considerations 

should be kept in mind when applying this concept. Dose/concentration levels in humans shall 

not be considered in the classification. Additionally, any available evidence from animal studies 

shall be consistent with the Category 2 classification criteria. In other words, if there are also 

animal data available on the substance that warrant Category 1 classification, the chemical shall 

be classified as Category 1. 

Effects considered to support classification for Categories 1 and 2

Classification is supported by reliable evidence associating repeated exposure to the substance 

with a consistent and identifiable toxic effect. 
213

Evidence from human experience/incidents is usually restricted to reports of adverse health 

consequences, often with uncertainty about exposure conditions, and may not provide the 

scientific detail that can be obtained from well-conducted studies in experimental animals. 

Therefore, evidence from appropriate studies in experimental animals can furnish much more 

detail, in the form of clinical observations and macroscopic and microscopic pathological 

examination; this can often reveal hazards that may not be life-threatening but could indicate 

functional impairment. Consequently, all available evidence, including evidence relevant to 

human health, must be taken into consideration in the classification process. Relevant toxic 

effects in humans and/or animals include, but are not limited to: 

(a) Morbidity resulting from repeated or long-term exposure. Morbidity or death may 

result from repeated exposure, even to relatively low doses/concentrations, due to 

bioaccumulation of the substance or its metabolites, or due to overwhelming of the detoxification process by repeated exposure; 

(b) Significant functional changes in the central or peripheral nervous systems, or other 

organs or other organ systems, including signs of central nervous system depression and 

effects on special senses (e.g., sight, hearing and sense of smell); 

(c) Any consistent and significant adverse change in clinical biochemistry, hematology, 

or urinalysis parameters; 

(d) Significant organ damage that may be noted at necropsy and/or subsequently seen or 

confirmed at microscopic examination; 

(e) Multi-focal or diffuse necrosis, fibrosis or granuloma formation in vital organs with 

regenerative capacity; 

(f) Morphological changes that are potentially reversible but provide clear evidence of 

marked organ dysfunction (e.g., severe fatty change in the liver); and 

(g) Evidence of appreciable cell death (including cell degeneration and reduced cell 

number) in vital organs incapable of regeneration. 

Effects considered not to support classification for Categories 1 and 2

Effects may be seen in humans and/or animals that do not justify classification. Such effects 

include, but are not limited to: 

(a) Clinical observations or small changes in body weight gain, food consumption or 

water intake that may have some toxicological importance but that do not, by themselves, 

indicate “significant” toxicity; 
214

(b) Small changes in clinical biochemistry, hematology or urinalysis parameters and/or 

transient effects, when such changes or effects are of doubtful or of minimal toxicological 

importance; 

(c) Changes in organ weights with no evidence of organ dysfunction; 

(d) Adaptive responses that are not considered toxicologically relevant; and 

(e) Substance-induced species-specific mechanisms of toxicity, i.e., demonstrated with 

reasonable certainty to be not relevant for human health. 

Guidance values to assist with classification based on the results obtained from studies 

conducted in experimental animals for Categories 1 and 2 

In studies conducted in experimental animals, reliance on observation of effects alone, without 

reference to the duration of experimental exposure and dose/concentration, omits a fundamental 

concept of toxicology, i.e., all substances are potentially toxic, and what determines the toxicity 

is a function of the dose/concentration and the duration of exposure. In most studies conducted in 

experimental animals the test guidelines use an upper limit dose value. 

In order to help reach a decision about whether a substance shall be classified or not, and to what 

degree it shall be classified (Category 1 vs. Category 2), dose/concentration “guidance values” 

are provided in the below table for consideration of the dose/concentration which has been 

shown to produce significant health effects. The principal argument for proposing such guidance 

values is that all chemicals are potentially toxic and there has to be a reasonable 

dose/concentration above which a degree of toxic effect is acknowledged. Repeated-dose studies 

conducted in experimental animals are designed to produce toxicity at the highest dose used in 

order to optimize the test objective and so most studies will reveal some toxic effect at least at 

this highest dose. What is therefore to be decided is not only what effects have been produced, 

but also at what dose/concentration they were produced and how relevant is that for humans. 

Thus, in animal studies, when significant toxic effects are observed that indicate classification, 

consideration of the dose/concentration at which these effects were seen, in relation to the 

suggested guidance values, provides useful information to help assess the need to classify (since 

the toxic effects are a consequence of the hazardous property(ies) and also the 

dose/concentration). 

The guidance values refer to effects seen in a standard 90-day toxicity study conducted in rats. 

They can be used as a basis to extrapolate equivalent guidance values for toxicity studies of 

greater or lesser duration, using dose/exposure time extrapolation similar to Haber’s rule for 

inhalation, which states essentially that the effective dose is directly proportional to the exposure 

concentration and the duration of exposure. The assessment should be done on a case-by-case 

basis; for example, for a 28-day study the guidance values below would be increased by a factor 

of three. 
215

Thus, for Category 1 classification, significant toxic effects observed in a 90-day repeated-dose 

study conducted in experimental animals and seen to occur at or below the guidance values (C) 

as indicated in the below table would justify classification. 

For Category 2 classification, significant toxic effects observed in a 90-day repeated-dose study 

conducted in experimental animals and seen to occur within the guidance value ranges as 

indicated below would justify classification. 

Table VII.9.1. Guidance values to assist in Category 1 and 2 classification 

(applicable to a 90-day study)

Route of exposure Units

Guidance values (dose/concentration)

Category 1 Category 2

Oral (rat) mg/kg bw/d C  10 10 < C ≤ 100

Dermal (rat or rabbit) mg/kg bw/d C  20 20 < C ≤ 200

Inhalation (rat) gas ppm/6h/d C  50 50 < C ≤ 250

Inhalation (rat) vapor mg/liter/6h/d C  0.2 0.2 < C ≤ 1.0

Inhalation (rat) 

dust/mist/fume

mg/liter/6h/d C 0.02 0.02 < C ≤ 0.2

Note: “bw” stands for “body weight”, “h” for “hour” and “d” for “day”. 

The guidance values and ranges are intended only for guidance purposes, i.e., to be used as part 

of the weight-of-evidence approach, and to assist with decisions about classification. They are 

not intended as strict demarcation values. 

It is possible that even where a specific profile of toxicity occurs in repeat-dose animal studies at 

a dose/concentration below the guidance value, e.g., < 100 mg/kg body weight/day by the oral 

route, the nature of the effect, e.g., nephrotoxicity seen only in male rats of a particular strain 

known to be susceptible to this effect, may result in the decision not to classify. Conversely, a 

specific profile of toxicity may be seen in animal studies occurring at above a guidance value, 

e.g., ≥ 100 mg/kg body weight/day by the oral route, and in addition there is supplementary 

information from other sources, e.g., other long-term administration studies, or human case 

experience, which supports a conclusion that, in view of the weight of evidence, classification is 

prudent. 

Other considerations when classifying using animal data 

When a substance is characterized only by use of animal data, the classification process must 

include reference to dose/concentration guidance values as one of the elements that contribute to 

the weight-of-evidence approach. 
216

Evidence in humans 

When well-substantiated human data are available showing a specific target organ toxic effect 

that can be reliably attributed to repeated exposure to a substance, the substance shall be 

classified. Positive human data, regardless of probable dose, predominates over animal data. 

Thus, if a substance is unclassified because specific target organ toxicity observed was 

considered not relevant or significant to humans, if subsequent human incident data become 

available showing a specific target organ toxic effect, the substance shall be classified. 

Non-test data 

A substance that has not been tested for specific target organ toxicity shall, where appropriate, be 

classified on the basis of data from a scientifically validated structure activity relationship and 

expert judgment-based extrapolation from a structural analogue that has previously been 

classified together with substantial support from consideration of other important factors such as 

formation of common significant metabolites. 

Classification criteria for mixtures 

Mixtures are classified using the same criteria as for substances, or alternatively as described 

below. As with substances, mixtures may be classified for specific target organ toxicity 

following single exposure, repeated exposure, or both. 

The approach to classifying mixtures for specific target organ toxicity – repeated exposure 

incorporates the tiered approach (i.e., stepwise procedure based on a hierarchy). 

Tier 1: Classification of mixtures when data are available for the complete mixture 

When reliable and good evidence from human experience or appropriate animal studies is 

available for the mixture as a whole, then the mixture can be classified by use of a weight-ofevidence approach using the same criteria as specified for substances. Specifically for mixtures, 

care should be exercised in evaluating data such that the dose, duration of exposure, observation 

or analysis, do not render the results inconclusive. If test data for the mixture is not available 

then the classifier should consider application of the criteria in Tier 2 or Tier 3 below, as 

appropriate. 

Tier 2: Classification of mixtures when data are not available for the complete mixture - 

bridging principles 

Where the mixture itself has not been tested to determine its specific target organ toxicity, but 

there are sufficient data on BOTH the individual ingredients AND similar tested mixtures to 

adequately characterize the hazards of the mixture, these data can be used in accordance with the 

below bridging principles. 
217

All six bridging principles are applicable to the specific target organ toxicity – repeated exposure 

hazard class: 

 Dilution, 

 Batching, 

 Concentration of mixtures,

 Interpolation within one toxicity category, 

 Substantially similar mixtures,

 Aerosols. 

The application of bridging principles ensures that the classification process uses the available 

data to the greatest extent possible in characterizing the potential specific target organ toxicityrepeated exposure hazard. 

Dilution 

If a tested mixture is diluted with a diluent which has the same or a lower toxicity 

classification as the least toxic original ingredient and which is not expected to affect the 

specific target organ toxicity of other ingredients, then the new diluted mixture may be 

classified as equivalent to the original tested mixture. 

Batching 

The specific target organ toxicity of a tested production batch of a mixture can be 

assumed to be substantially equivalent to that of another untested production batch of the 

same commercial product when produced by or under the control of the same 

manufacturer, unless there is reason to believe there is significant variation such that the 

specific target organ toxicity of the untested batch has changed. If the latter occurs, a new 

classification is necessary. 

Concentration of mixtures 

If in a tested mixture of STOT-RE Category 1, the concentration of a specific target 

organ toxic ingredient is increased, the resulting concentrated mixture should be 

classified in STOT-RE Category 1 without additional testing. 

Interpolation within one toxicity category 

For three mixtures (A, B and C) with identical ingredients, where mixtures A and B have 

been tested and are in the same STOT-RE category, and where untested mixture C has 

the same specific target organ toxicologically active ingredients as mixtures A and B but 

has concentrations of specific target organ toxicologically active ingredients intermediate 

to the concentrations in mixtures A and B, then mixture C is assumed to be in the same 

STOT-RE category as A and B. 
218

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

(ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) Data on toxicity for A and C are available and substantially equivalent, i.e., 

they are in the same hazard category and are not expected to affect the specific 

target organ toxicity of B. 

If mixture (i) or (ii) is already classified by testing, then the other mixture can be 

classified in the same hazard category. 

Aerosols 

An aerosol form of a mixture may be classified in the same hazard category as the tested, 

non-aerosolized form of the mixture for oral and dermal specific target organ toxicity 

provided the added propellant does not affect the toxicity of the mixture on spraying. 

Classification of aerosolized mixtures for specific target organ toxicity by the inhalation 

route should be considered separately. 

If appropriate data is not available to apply the above bridging principles then the classifier 

should consider application of the criteria in Tier 3. 

Tier 3: Classification of mixtures when data are available for all ingredients or only for some 

ingredients of the mixture 

The approach to classifying a mixture for specific target organ toxicity in Tier 3 is to use a cutoff/concentration limit.

Where there is no reliable evidence or test data for the specific mixture itself, and the bridging 

principles cannot be used to enable classification, then classification of the mixture is based on 

the classification of the ingredient substances. In this case, the mixture shall be classified as a 

specific target organ toxicant (specific organ specified), following repeated exposure when at 

least one ingredient has been classified as a Category 1 or Category 2 specific target organ 

toxicant and is present at or above the appropriate cut-off value/concentration limit specified in 

the below table for Categories 1 and 2, respectively. 
219

Table VII.9.2. Cut-off values/concentration limits of ingredients of a mixture classified as a 

specific target organ toxicant—repeated exposure that would trigger classification of the 

mixture as Category 1 or 2 

Ingredient Classified as:

Cut-off/concentration limits

triggering classification of a mixture as:

Category 1 Category 2

Category 1

Target organ toxicant

≥ 1.0%

Category 2

Target organ toxicant -

≥ 1.0%

Note that the additivity approach does NOT apply when classifying mixtures for STOT-RE 

categories 1 and 2. 

Care shall be exercised when toxicants affecting more than one organ system are combined that 

the potentiation or synergistic interactions are considered, because certain chemicals can cause 

target organ toxicity at < 1% concentration when other ingredients in the mixture potentiate their 

toxic effect. 

Mixtures containing from 1% to less than 10% of Category 1 STOT-RE ingredients may be 

classified as Category 2 STOT-RE under the limited following circumstances. The criteria allow 

for the classification of mixtures under the criteria as used for substances. Where the 

classification of the ingredients is based on animal data only the use of the guidance values in 

Tables VII.9.1 and VII.9.2 is appropriate as a part of the total weight-of-evidence approach. It 

may be appropriate, in light of the guidance values, to classify a mixture containing from 1% to 

less than 10% of Category 1 STOT-RE substances as a Category 2 STOT-RE hazard, where 

warranted by the weight of evidence. Such a classification must be consistent with all of the 

criteria in 29 CFR 1910.1200 A.9.2 ("Classification Criteria for Substances"), including 

consideration of the severity of the effect observed. However, OSHA would not accept a 

determination not to classify a mixture based on this approach. 

Classification Procedure and Guidance 

Test data 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS requires 

collecting and evaluating the best available existing evidence on the hazards of each chemical. 

Data generated in accordance with internationally recognized scientific principles, are acceptable 

under HCS 2012.
220

Examples of scientifically validated test methods 

There are a number of scientifically validated methods that can provide information to evaluate 

specific target organ toxicity: 

 OECD Test Guideline 407 Repeated dose 28-day oral toxicity study in rodents

 OECD Test Guideline 410 Repeated dose dermal toxicity: 21/28-day study 

 OECD Test Guideline 412 Repeated dose inhalation toxicity: 28-day or 14-day study 

 OECD Test Guideline 408 Repeated dose 90-day oral toxicity study in rodents 

 OECD Test Guideline 411 Subchronic dermal toxicity: 90-day study 

 OECD Test Guideline 452 Chronic toxicity studies 

 OECD Test Guideline 424 Neurotoxicity study in rodents 

The 28-day studies provide information on toxicological effects arising from exposure to the 

chemical during a relatively limited period of the animal’s life span. The 90-day studies provide 

information on general toxicological effects arising from subchronic exposure (a prolonged 

period of the animal’s life span) covering post-weaning maturation and growth well into 

adulthood, on target organs and on potential accumulation of the substance. Chronic toxicity 

studies provide information on toxicological effects arising from repeated exposure over a 

prolonged period of time covering the major part of the animal’s life span. 

The STOT-RE guidance values refer to 90-day toxicity studies conducted in rats. They can be 

extrapolated to develop equivalent guidance values for toxicity studies of greater or lesser 

duration. 

Classification procedure 

Classification for STOT-RE is based on findings of “significant” or “severe” toxic effects. 

Significant effects mean changes which clearly indicate functional disturbance or morphological 

changes which are toxicologically relevant. Severe effects are generally more profound or 

serious than significant effects and are of a considerably adverse nature with substantial impact 

on health. Both factors have to be evaluated by weight of evidence and expert judgment. 

Where the same target organ toxicity of similar severity is observed after single and repeated 

exposure to a similar dose, it may be concluded that the toxicity is essentially an acute (i.e.,

single exposure) effect with no accumulation or exacerbation of the toxicity with repeated 

exposure. In such a case classification with STOT-SE only would be appropriate. 
221

Considerations 

The STOT criteria are applied independently for STOT-SE and STOT-RE. Substances and 

mixtures can be classified into both hazard classes and either Category 1 or Category 2 for each 

hazard class, as well as the additional STOT-SE Category 3 where respiratory tract irritation 

and/or narcotic effects are evaluated separately. 

If the chemical is classified into more than one STOT hazard class and/or category, then all 

relevant classifications should be communicated on the Safety Data Sheet in Section 2 and all 

hazard statements should be communicated along with the specific affected organs on the label. 

The specific target organ(s) should be identified for both substances and mixtures whenever 

known. All known specific target organs should be identified for mixtures classified by any of 

the three tiers. If the mixture is classified on the basis of ingredients, then the target organs 

effects from the ingredients should be identified. This information should be provided on SDSs 

and labels. 

Decision Logic 

Two decision logics for classifying specific target organ toxicity – repeated exposure are

provided. The first decision logic is for substances and tested mixtures. The second decision 

logic is for classifying mixtures not tested as a whole. The decision logics are provided as 

additional guidance. It is strongly recommended that the person responsible for classification 

study the criteria before and during use of the decision logic. 

These decision logics are essentially flowcharts for classifying substances and mixtures 

regarding specific target organ toxicity – repeated exposure. They present questions in a 

sequence that walks you through the classification steps and criteria for classifying specific 

target organ toxicity – repeated exposure. Once you answer the questions provided, you will 

arrive at the appropriate classification. 
222

Decision logic for specific target organ toxicity – repeated exposure 

Substances and tested mixtures 

(Cont’d on next page)

Substance: Does the substance have data and/or information to evaluate 

specific target organ toxicity following repeated exposure?

No

Mixture: Does the mixture as a whole or its ingredients have 

data/information to evaluate specific target organ toxicity 

following repeated exposure?

Yes

Following repeated exposure,

(a) Can the substance or mixture produce significant toxicity in 

humans, or 

(b) Can it be presumed to have the potential to produce significant 

toxicity in humans on the basis of evidence from studies in 

experimental animals? 

See criteria and guidance values. Application of the criteria needs expert 

judgment in a weight of evidence approach.

No

Yes

Category 2

Warning

Not classified

Following repeated exposure, 

Can the substance or mixture be presumed to have the potential to 

be harmful to human health? 

See criteria and guidance values. Application of the criteria needs expert 

judgment in a weight-of-evidence approach.

Yes

No

Classification 

not possible

Classification 

not possible

Category 1

Danger

Does the mixture as a whole have data/information to evaluate 

specific target organ toxicity following repeated exposure?

Yes

Yes

No See next 

decision logic

No
223

Decision logic for specific target organ toxicity – repeated exposure 

Mixtures not tested as a whole

Can bridging principles be applied?

No

Yes

Category 2

Warning 

Does the mixture contain one or more ingredients classified as a 

Category 2 specific target organ toxicant at a concentration of 

 1.0%? 

See Table for explanation of cut-off values.

Yes

Does the mixture contain one or more ingredients classified as a 

Category 1 specific target organ toxicant at a concentration of 

 1.0%? 

See Table for explanation of cut-off values.

No

Not classified

 No

Classify in 

appropriate 

category

Yes

Category 1

Danger
224

Specific Target Organ Toxicity – Repeat Exposure Classification Examples 

The following examples are provided to walk you through specific target organ toxicity – repeat 

exposure classification. 

Example of a substance fulfilling the criteria for classification: 

Substance Example #1

Specific Target Organ Toxicity – Repeated Exposure

Test Data

HCS 2012

Classification Rationale

Human evidence including 

“hemolytic anemia, a decrease in 

white blood cell count” (ACGIH 

(7th, 2001)), and evidence from 

animal studies including “a 

decrease in mean corpuscular 

hemoglobin, hemoglobin 

concentrations, red blood cell 

count and hematocrit levels,” and 

“adrenal degeneration” (MOE 

Risk Assessment Vol. 3 (2004)).

STOT – RE

Category 1

(adrenal, blood 

system)

Fulfills criteria 

 The classification criteria for 

STOT-RE Category 1 are 

fulfilled.

 The effects on experimental 

animals were observed at dosing 

levels within the guidance value 

ranges for Category 1

Example of a mixture fulfilling the criteria for classification: 

Mixture Example #1

Specific Target Organ Toxicity –Repeated Exposure

Data 

HCS 2012

Classification Rationale

Component data:

Component 1: 0.5%

Component 2: 3.5%, Category 1 -

Liver

Component 3: 5%, Category 2 –

Kidney

Component 4: 7%, Category 1 –

Lungs

STOT – RE 

Category 1 (liver, 

lungs ) and STOT 

– RE Category 2 

(kidney )

Fulfills criteria

 Mixture contains 3.5% of a 

STOT Category 1 target organ 

toxicant (Ingredient 2), which is 

≥ 1.0% so the mixture meets the 

Category 1 criteria.

 Mixture contains 5% of a STOT 

Category 2 target organ toxicant 

(Ingredient 3), which is ≥ 1.0% 

so the mixture meets the 

Category 2 criteria.
225

Mixture Example #1

Specific Target Organ Toxicity –Repeated Exposure

Data 

HCS 2012

Classification Rationale

Component 5: 66%  Mixture contains 7% of a STOT 

Category 1 target organ toxicant 

(Ingredient 4), which is ≥ 1.0% 

so the mixture meets the 

Category 1 criteria. 

 In this case the mixture is 

classified into more than one 

category so the most severe

category is used.
226

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.8 Specific Target Organ ToxicityRepeated or Prolonged Exposure 

29 CFR 1910.1200, Hazard Communication, Appendix C Allocation of Label Elements 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 
227

VII.10 Aspiration Hazard 

Introduction

A review of the medical literature on chemical aspiration reveals that some hydrocarbons 

(petroleum distillates) and certain chlorinated hydrocarbons have been shown to pose an 

aspiration hazard in humans.

Aspiration is initiated at the moment of inspiration, in the time required to take one breath, as the 

causative material lodges at the crossroad of the upper respiratory and digestive tracts in the 

throat. Aspiration toxicity includes severe acute effects such as chemical pneumonia, varying 

degrees of pulmonary injury or death following aspiration. 

Aspiration of a substance or mixture can also occur due to vomiting following ingestion. This may 

have consequences for labeling, particularly where, due to acute toxicity, a recommendation may be 

considered to induce vomiting after ingestion. However, if the substance/mixture also presents an 

aspiration toxicity hazard, the recommendation to induce vomiting may need to be modified. 

Definition and General Considerations 

Aspiration means the entry of a liquid or solid chemical directly through the oral or nasal cavity, 

or indirectly from vomiting, into the trachea and lower respiratory system. 

Although the definition of aspiration includes the entry of solids into the respiratory system, 

classification according to the criteria for Category 1 is intended to apply to liquid chemicals only. 

Classification Criteria for Substances 

A substance which is an aspiration hazard shall be classified in a single category based on the 

criteria described below. 

Table VII.10.1. Criteria for Aspiration Toxicity 

Category Criteria

1

Chemicals known 

to cause human 

aspiration toxicity 

hazards or to be 

regarded as if they 

cause human 

aspiration toxicity 

hazard 

A substance shall be classified in Category 1: 

(a) If reliable and good quality human evidence indicates that it 

causes aspiration toxicity (See note); or 

(b) If it is a hydrocarbon and has a kinematic viscosity ≤ 20.5 mm

2

/s, 

measured at 40°C. 

Note: Examples of substances included in Category 1 are certain hydrocarbons, turpentine and 

pine oil. 
228

Classification of aerosol/mist products 

Aerosol and mist products are usually dispensed in containers such as self-pressurized 

containers, trigger and pump sprayers. The key to classifying these products is whether a pool of 

product is formed in the mouth, which then may be aspirated. If the mist or aerosol from a 

pressurized container is fine, a pool may not be formed. On the other hand, if a pressurized 

container dispenses product in a stream, a pool may be formed that may then be aspirated. 

Usually, the mist produced by trigger and pump sprayers is coarse and, therefore, a pool may be 

formed that then may be aspirated. Classification is then to be considered. When the pump 

mechanism may be removed and contents are available to be swallowed, the classification of the 

product should also be considered. 

Classification criteria for mixtures 

The approach to classifying mixtures for the aspiration hazard incorporates the tiered approach 

(i.e., stepwise procedure based on a hierarchy). 

Tier 1: Classification of mixtures when data are available for the complete mixture 

A mixture can be classified into Category 1 based on reliable and good quality human evidence 

using the same criteria used for substances. If test data for the mixture is not available then the 

classifier should consider the application of the criteria in Tier 2 or 3, as appropriate. 

Tier 2: Classification of mixtures when data are not available for the complete mixturebridging principles 

Where the mixture itself has not been tested to determine its aspiration toxicity, but there are 

sufficient data on BOTH the individual ingredients AND similar tested mixtures to adequately 

characterize the hazard of the mixture, these data can be used in accordance with the following 

bridging principles. 

Only the following bridging principles are applicable to Aspiration Category 1 for the Aspiration 

hazard class: 

 Dilution, 

 Batching, 

 Concentration of mixtures,

 Interpolation within one toxicity category, and 

 Substantially similar mixtures.
229

The application of bridging principles ensures that the classification process uses the available 

data to the greatest extent possible in characterizing the potential aspiration hazard. 

Dilution 

If a tested mixture is diluted with a diluent that does not pose an aspiration toxicity 

hazard, and which is not expected to affect the aspiration toxicity of other ingredients or 

the mixture, then the new diluted mixture may be classified as equivalent to the original 

tested mixture. However, the concentration of aspiration toxicant(s) should not drop 

below 10%. 

Batching 

The aspiration toxicity of a tested production batch of a mixture can be assumed to be 

substantially equivalent to that of another untested production batch of the same 

commercial product, when produced by or under the control of the same manufacturer, 

unless there is reason to believe there is significant variation such that the aspiration 

toxicity, reflected by viscosity or concentration, of the untested batch has changed. If the 

latter occurs, a new classification is necessary. 

Concentration of mixtures 

If a tested mixture is classified in Aspiration Category 1, and the concentration of the 

ingredients of the tested mixture that are in Aspiration Category 1 is increased, the 

resulting untested mixture should be classified in Aspiration Category 1 without 

additional testing. 

Interpolation within one toxicity category 

For three mixtures (A, B and C) with identical ingredients, where mixtures A and B have 

been tested and are in Aspiration Category 1, and where untested mixture C has the same 

aspiration toxicologically active ingredients as mixtures A and B but has concentrations 

of aspiration toxicologically active ingredients intermediate to the concentrations in 

mixtures A and B, then mixture C is assumed to be in Aspiration Category 1 like A and 

B.

Substantially similar mixtures 

Given the following: 

(a) Two mixtures: (i) A + B; 

(ii) C + B; 

(b) The concentration of ingredient B is essentially the same in both mixtures; 
230

(c) The concentration of ingredient A in mixture (i) equals that of ingredient C in 

mixture (ii); 

(d) Aspiration toxicity for A and C is substantially equivalent, i.e., they are in 

Aspiration Category 1 and are not expected to affect the aspiration toxicity of B. 

If mixture (i) or (ii) is already classified based on the aspiration hazard substance criteria, 

then the other mixture can be assigned the same hazard category. 

If appropriate data is not available to apply the above bridging principles then the classifier 

should consider application of the criteria in Tier 3. 

Tier 3: Classification of mixtures when data are available for all ingredients or only for some 

ingredients of the mixture 

If there are not sufficient data to apply the bridging principles then the third tier calls for 

classifying the mixture using a summation method. The sum of classified ingredients must be ≥

10% and the mixture’s kinematic viscosity must be less than or equal to 20.5 mm2/s measured at 

40°C. 

Category 1 Criteria 

A mixture will be classified in Category 1 when the sum of the concentration of Category 

1 ingredients ≥ 10% and the mixture has a kinematic viscosity ≤ 20.5 mm2

/s, measured at 

40°C.

Special consideration has been given to mixtures which separate into two or more distinct 

layers. In the case of a mixture which separates into two or more distinct layers, the entire 

mixture is classified as Category 1 if in any distinct layer the sum of the concentration of 

Category 1 ingredients ≥ 10 %, and the layer has a kinematic viscosity ≤ 20.5 mm2

/s, 

measured at 40°C.

The relevant ingredients of a mixture are those which are present in concentrations ≥ 1%. 

Classification Procedure and Guidance 

There is no requirement in the HCS to test a chemical to classify its hazards. The HCS requires 

collecting and evaluating the best available existing evidence on the hazards of each chemical. 

While a methodology for determination of aspiration hazard in animals has been utilized, it has 

not been standardized. Positive experimental evidence with animals can only serve as a guide to 

possible aspiration toxicity in humans. Particular care must be taken in evaluating animal data 

for aspiration hazards. 
231

Classification procedure 

To assess the aspiration hazard of a chemical, identify the data relevant for aspiration. The 

aspiration classification criteria include: 

 reliable and good quality human evidence indicating aspiration toxicity; or 

 the chemical is a hydrocarbon and has a kinematic viscosity ≤ 20.5 mm2/s, measured 

at 40° C.

Data can be found in literature, on SDSs, or be determined by testing, which is not required by 

the HCS. 

In classification the data are compared to the criteria for Aspiration Hazard Category 1. For 

mixtures follow the above three-tier approach. 

The aspiration classification criteria refer to kinematic viscosity. The following provides the 

conversion between dynamic and kinematic viscosity: 

Kinematic /s)(mm viscosity

Density )(g/cm

Dynamic (mPa·s) viscosity 2

3



Decision Logic 

Two decision logics for classifying aspiration toxicity are provided. The first decision logic is for 

substances and mixtures with data on the mixture as a whole. Use the second decision logic for 

classifying mixtures not tested as a whole. 

These decision logics are essentially flowcharts for classifying substances and mixtures 

regarding the aspiration hazard. They present questions in a sequence that walks you through the 

classification steps and criteria for classifying aspiration toxicity. Once you answer the questions 

provided, you will arrive at the appropriate classification. 
232

Decision logic #1 for aspiration toxicity – Substances and tested mixtures

Continued on next page 

 Is there reliable and good quality evidence in humans, or

 Is the substance a hydrocarbon with a kinematic 

viscosity, measured at 40oC, of 20.5 mm2/s or less? 

Substance: Does the substance have aspiration toxicity data? 

Yes

Yes

No

Classification not 

possible

Mixture: Does the mixture as a whole or its 

ingredients have aspiration toxicity data?

Yes

No

Classification not 

possible 

Mixture: Tier 1: Does the mixture as a whole 

show aspiration toxicity based on practical 

experience in humans from reliable and good 

quality evidence?

No

See Decision Logic #2 

for use with ingredients

Category 1

Danger 

Not classified

No

Yes
233

Decision logic #2 for aspiration toxicity – Mixtures not tested as a whole

Tier 3: Does the mixture contain ≥ 10% of an ingredient 

or ingredients classified in Category 1 and have a 

kinematic viscosity ≤ 20.5 mm2/s, measured at 40oC? Yes

No

Tier 2: Can bridging 

principles be applied? 

No

Yes

Classify in 

appropriate 

category 

Category 1

Danger 

Not classified
234

Aspiration Classification Examples 

The following examples are provided to walk you through the aspiration calculation and 

classification processes. 

Example of a substance fulfilling the criteria for classification: 

Substance Example #1

Aspiration Hazard

Test Data

HCS 2012

Classification Rationale

The material is a hydrocarbon 

and has a kinematic viscosity of 

0.74mm2/s at 25°C.

Case reports of human symptoms 

“May cause pulmonary edema if 

inhaled and chemical pneumonia 

if swallowed.” (ATSDR (2001)).

Aspiration 

Category 1 

Fulfills criteria 

 it is a hydrocarbon and has a 

kinematic viscosity ≤ 20.5 

mm2/s, measured at 40°C.

 with hydrocarbons, as the 

temperature increases, the 

kinematic viscosity decreases. 

Therefore, in this example if we 

increase the temperature to 40°C, 

we would expect the viscosity to 

be lower than 0.74mm2/s, which 

would still fulfill the criteria of ≤ 

20.5 mm2/s, measured at 40°C.

Also based on the description in 

reports of human symptoms, the 

Aspiration Category 1 criteria are 

fulfilled

Example of a mixture fulfilling the criteria for classification: 

Mixture Example #1

Aspiration Hazard

Data

HCS 2012

Classification Rationale

Component data:

Component 2: 20%, Aspiration 

Category 1

Aspiration 

Category 1

Material is a hydrocarbon

Fulfills additive threshold criteria 

Aspiration Calculation: 
235

Mixture Example #1

Aspiration Hazard

Data

HCS 2012

Classification Rationale

Component 3: 28%, Aspiration 

Category 1

Mixture data:

Material is a hydrocarbon

Kinematic Viscosity @ 40oC 

(104oF) = 10 mm2/s

 ∑% Category 1 ≥ 10%

 20% + 28% = 48%

Fulfills viscosity criteria

Kinematic viscosity ≤ 20.5 mm2/s @ 

40°C

10 mm2/s < 20.5 mm2/s

Aspiration Category 1 criteria are 

fulfilled

Example of a mixture not fulfilling the criteria for classification: 

Mixture Example #2

Aspiration Hazard

Data

HCS 2012

Classification Rationale

Component data:

Component 1: 8%, Aspiration 

Category 1

Component 4: 7%, Aspiration 

Category 1

Mixture data:

Material is a hydrocarbon

Kinematic Viscosity @ 40oC 

(104oF) = 25 mm2/s

Not classified for 

aspiration hazard

Material is a hydrocarbon

Fulfills additive threshold criteria 

Aspiration Calculation: 

 ∑% Category 1 ≥ 10%

 8% + 7% = 15%

Does not fulfill viscosity criteria

Kinematic viscosity ≤ 20.5 mm2/s @ 

40°C

25 mm2/s > 20.5 mm2/s

Aspiration Category 1 criteria are 

NOT fulfilled
236

References 

29 CFR 1910.1200, Hazard Communication, Appendix A.10 Aspiration Hazard. 

29 CFR 1910.1200, Hazard Communication, Appendix C Allocation of Label Elements. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 
237

VII.11 Simple Asphyxiants

Introduction

An asphyxiant is a vapor or gas that can cause unconsciousness or death by suffocation due to 

lack of oxygen. Asphyxiants can be either chemical asphyxiants or simple asphyxiants. Chemical 

asphyxiants cause suffocation by either preventing the uptake of oxygen in the blood or by 

preventing the normal oxygen transfer from the blood to the tissues or within the cell itself. 

Simple asphyxiants are inert gases or vapors which are harmful to the body when they become so 

concentrated that they reduce oxygen in the air (normally about 21 percent) to dangerous levels 

(19.5 percent or less). When the concentration of a particular gas increases, the fraction of 

inspired oxygen decreases, causing decreased oxygen in the blood. A decrease in the fraction of 

inspired oxygen to less than 19.5% causes inadequate oxygen supply within minutes after 

exposure to a simple asphyxiant, and may result in unconsciousness or death. 

Asphyxiation is a well-known hazard in the workplace. Simple asphyxiants frequently 

contribute to industrial accidents involving loss of life and are of particular concern for those 

who work in confined spaces, as these gases are colorless and odorless and offer no warning 

properties. 

Definition and General Considerations

Simple asphyxiant means a substance or mixture that displaces oxygen in the ambient 

atmosphere, and can thus cause oxygen deprivation in those who are exposed, leading to 

unconsciousness and death. 

Simple asphyxiants are of particular concern in enclosed spaces. Some examples of simple 

asphyxiants include: nitrogen, helium, neon, argon, krypton, and xenon. These gases are wellknown simple asphyxiants from experience in the workplace. Evaluation of other gases as simple 

asphyxiants requires expert judgment to evaluate evidence such as human experience, 

information from similar substances, and other pertinent data. 
238

References 

29 CFR 1910.1200, Hazard Communication, Paragraph C. 

29 CFR 1910.1200, Hazard Communication, Appendix C, Allocation of Label Elements. 
239

VIII. CLASSIFICATION OF PHYSICAL HAZARDS

Introduction

The physical hazards presented by chemicals often cause harm to workers by exposing them to 

fire or explosions. Classification of the physical hazards is based on data found in available 

literature, as a result of a calculation, or through testing using specified test methods. The 

Hazard Communication Standard does not require the testing of chemicals -- only the collection 

and analysis of currently available data. However, if you choose to test the substance or mixture, 

then most chapters specify test methods to be used for the given physical hazard. Each chapter 

also explains the purpose of each test method, as appropriate, should you choose to conduct the 

test or have a recognized testing laboratory conduct the analysis for you. 

Selection of Hazard Classes

Once the chemical manufacturer, importer, or classifier has collected the data, the data and test 

results are compared to the classification criteria. The decision logic included for each physical 

hazard in this guidance document can be used to identify the appropriate hazard class and 

category of the chemical. The decision logic is essentially a flowchart for classifying chemicals 

of the specific hazard. It presents questions in a sequence that considers the classification steps 

and criteria to classify the hazard in the appropriate hazard class and category. 

As mentioned throughout this document, many hazardous chemicals have more than one 

physical hazard and/or health hazard and each hazard must be presented on the label and SDS, as 

specified in HCS Appendix C, Allocation of Label Elements, and HCS Appendix D, Minimum 

Information for an SDS. Note that classification of a chemical for one hazard class does not 

preclude classification of the same chemical for other hazards, unless it is specified otherwise. 

Classification Examples

The United Nations Institute of Training and Research (UNITAR) developed several 

classification examples for physical hazards. These examples are used in each physical hazard 

section to aid in the understanding of how to apply the decision logics for classification. The 

examples in each physical hazard section are specific to the given hazard class. 
240

VIII.1 Explosives 

Introduction

Explosive chemicals are unstable materials which can release enough energy or force to damage 

the surrounding area. Explosive chemicals are separated into two types. One type consists of 

material capable of detonations, that is, reactions that occur at a velocity greater than the speed of 

sound (for example, nitroglycerine and TNT). The other type consists of materials, usually 

mixtures, that burn rapidly but at a velocity that is less than the speed of sound (this is called a 

deflagration). Examples of this second type of explosive include mixtures of natural gas and air, 

liquid propane (LP) gases and air, or gasoline vapors and air black powder or rocket fuels. 

Explosions differ from fire by the rate at which high temperature gases are produced and the 

physical containment of the burning gases. When high temperature gases build up extremely 

quickly, there can be such a sudden release of energy from the gases that it creates a shock wave 

or explosion. Confining the build-up of high-pressure gases to 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. This is the principle behind some munitions that 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 capability, it is 

usually necessary to confirm this hazard through experimental studies. 

Classification of materials in the explosives hazard class and allocation to the appropriate 

division is very complex. The classifier should have the necessary expertise and use Part I of the 

UN Recommendations on the Transport of Dangerous Goods (UN TDG) Manual of Testing and 

Criteria to determine the proper hazard allocation. The HCS classification system almost 

entirely adopted the UN TDG Model Regulations, which is appropriate for transport as well as 

the storage of packaged explosives. 

Definition

An explosive chemical is a solid or liquid chemical, which is in itself capable by chemical 

reaction of producing gas at such a temperature and pressure and at such a speed as to cause 

damage to the surroundings. Pyrotechnic chemicals are included even when they do not evolve 

gases. 

A pyrotechnic chemical is a chemical designed to produce an effect by heat, light, sound, gas, or 

smoke, or a combination of these, as the result of non-detonative self-sustaining exothermic 

chemical reactions. 
241

An explosive item is an item containing one or more explosive 

chemicals. 

A pyrotechnic item is an item containing one or more 

pyrotechnic chemicals. 

An unstable explosive is an explosive which is thermally 

unstable and/or too sensitive for normal handling, transport, 

or use. 

An intentional explosive is a chemical or item which is manufactured with a view to produce a 

practical explosive or pyrotechnic effect. 

The HCS hazard class of explosives includes: 

(a) Explosive chemicals; 

(b) Explosive items, except devices containing explosive chemicals in such quantity or of such a 

character that their inadvertent or accidental ignition or initiation does not cause any effect 

external to the device either by projection, fire, smoke, heat, or loud noise; and 

(c) Chemicals and items not included under (a) and (b) above, which are manufactured with the 

intent to produce a practical explosive or pyrotechnic effect. 

Classification Criteria 

Chemicals and items of this class are classified as unstable explosives or are assigned to one of 

the following six divisions depending on the type of hazard they present: 

Division 1.1: Chemicals and items which have a mass explosion hazard (a mass explosion is 

one which affects almost the entire quantity present virtually instantaneously). 

Division 1.2: Chemicals and items which have a projection hazard but not a mass explosion 

hazard.

Division 1.3: Chemicals and items which have a fire hazard and either a minor blast hazard or 

a minor projection hazard or both, but not a mass explosion hazard, and: 

i. Combustion which gives rise to considerable radiant heat; or 

ii. Which burn one after another, producing minor blast or projection 

effects or both. 

Division 1.4: Chemicals and items which present no significant hazard: chemicals and items 

which present only a small hazard in the event of ignition or initiation. The 

effects are largely confined to the package and no projection of fragments of 

appreciable size or range is to be expected. An external fire shall not cause 

virtually instantaneous explosion of almost the entire contents of the package. 

The HCS uses the term 

“item,” instead of the term 

“article” in the explosives 

hazard class, because the 

HCS has an existing and 

long-standing definition for 

the term “article.”
242

Division 1.5: Very insensitive chemicals which have a mass explosion hazard: chemicals, 

which have a mass explosion hazard but are so insensitive that there is very little 

probability of initiation or of transition from burning to detonation under normal 

conditions.

Division 1.6: Extremely insensitive items which do not have a mass explosion hazard: items 

which contain only extremely insensitive detonating chemicals and which 

demonstrate a negligible probability of accidental initiation or propagation. 

Unstable explosives are those that are thermally unstable and/or are too sensitive for normal 

handling, transport, and use. Special precautions are necessary.

Classification Procedure and Guidance 

To classify an explosive chemical, data on its explosive behavior, thermal stability, and 

sensitivity are needed. 

Available Literature

The manufacturer, importer, or other responsible party may use available scientific literature and 

other evidence to classify explosives. 

As is the case when classifying other physical hazards, the U.S. Department of Transportation 

(DOT) listings can be used to assist when classifying explosive chemicals (see DOT’s Hazardous 

Materials Table, 49 CFR 172.101). This is especially true if the explosive is transported. In this 

case, the explosive has already been classified and approved for transport by DOT. 

Classification of explosives in the HCS generally corresponds to existing explosives assignments 

that are packaged in authorized DOT transport packaging. Explosives Class 1 is a restricted 

transportation class. There are generic explosive classifications in 49 CFR 172.101 that may be 

used to assist in classification. Refer to the discussion on the interface between the HCS and 

DOT labeling in Chapter V of this document for more information. The decision logics 

presented below also may be used to determine the appropriate hazard classification for 

explosives. 

Test Method 

Most explosives that are approved for transport have already undergone testing and assignment 

to the appropriate explosives hazard class. Testing may be necessary only for those chemicals, 

mixtures, or items that are new and have not been assigned a transport classification. If you 

choose to test the substance or mixture, then use of a testing laboratory specializing in the testing 

of explosives is recommended, as the testing protocol used for explosives is a complex process. 

Also, if you choose to test the substance or mixture, use the methods identified in Appendix B.1 

to 29 CFR 1910.1200, which are described below. 
243

Explosives are either classified as unstable explosives or are assigned to one of the six divisions 

by using the three-step procedure presented in Part I of the of the Fourth Revised Edition of the 

UN TDG Manual of Tests and Criteria. The test method used for classification of explosives 

and appropriate hazard division is a complex, three-step procedure. 

 The first step, the screening procedure, ascertains whether the substance or mixture has 

explosive effects (Test Series 1). 

 The second step provides an acceptance procedure (Test Series 2 to 4). 

 The third step assigns the chemical to a hazard division (Test Series 5 to 7). 

Test Series 8 assesses whether an ammonium nitrate emulsion should be classified as an 

oxidizing liquid (See Appendix B.13 to 29 CFR 1910.1200) or an oxidizing solid (See 

Appendix B.14 to 29 CFR 1910.1200), or whether it is classifiable as an explosive. The results 

of this test series may also be used to evaluate the suitability of the chemical or mixture for 

transport in tanks. Ammonium nitrate emulsions are manufactured precursors for explosives, and 

when manufactured, are not generally in themselves explosive. 

Solid chemicals are classified using tests performed on the chemical as presented and as 

packaged. If, for example, for the purposes of supply or transport, the same chemical is to be 

presented in a physical form different from that in which it was tested, and in a form that is 

considered likely to materially alter the chemical’s performance in a classification test, then 

testing for classification is based the chemical in its new form. 

Refer to the UN TDG Manual of Tests and Criteria for a complete description of the methods, 

the apparatus used, and analysis of the test results. 

Step 1: Screening Procedures 

As with other hazardous chemicals, especially those that may be sensitive to mechanical stimuli 

(such as impact and friction), and to heat and flame, small scale, preliminary tests are suggested 

to protect laboratory personnel. 

Explosive properties are associated with the presence of certain chemical groups in a molecule 

that can react to produce very rapid increases in temperature or pressure. The screening 

procedure is aimed at identifying the presence of such reactive groups and the potential for rapid 

energy release, and is suggested to identify the need for further testing. If the exothermic 

decomposition energy of organic materials is less than 800 J/g, neither a Series 1 type (a) 

propagation of detonation test, nor a Series 2 type (a) test of sensitivity to detonative shock is 

required. If the screening procedure identifies the chemical as a potential explosive or if the 

chemical contains any known explosives, then the acceptance procedure for explosives is 

necessary for assignment to a hazard division. 
244

A chemical is not classified as explosive if any of the following four conditions apply: 

1. There are no chemical groups present in the molecule associated with explosive properties; 

examples of such groups are provided in Table VIII.1.1 below, extracted from the UN TDG 

Manual for Tests and Criteria, Appendix 6. 

Table VIII.1.1. Examples of Chemical Groups Indicating Explosive Properties in 

Organic Material. 

Structural feature Examples

C-C unsaturation Acetylenes, acetylides, 1,2-dienes 

C-Metal, N-Metal Grignard reagents, organo-lithium compounds 

Contiguous nitrogen atoms Azides, aliphatic azo compounds, diazonium 

salts, hydrazines, sulphonylhydrazides 

Contiguous oxygen atoms Peroxides, ozonides 

N-O

Hydroxylamines, nitrates, nitro compounds, 

nitroso compounds, N-oxides, 1,2-oxazoles 

N-halogen Chloroamines, fluoroamines 

O-halogen Chlorates, perchlorates, iodosyl compounds 

or 

2. The substance contains chemical groups associated with explosive properties that include 

oxygen, and the calculated oxygen balance is less than −200. 

The oxygen balance is calculated for the chemical reaction: 

CxH

y

Oz + [x + (y/4)-(z/2)] O2 ↔ x CO2 

+ (y/2) H2O 

using the formula: 

oxygen balance = -1600 [2x +(y/2) -z] / molecular weight; or 

3. The organic substance or a homogenous mixture of organic substances contains chemical 

groups associated with explosive properties, but the exothermic decomposition energy is less 

than 500 J/g and the onset of exothermic decomposition is below 500 °C (932 °F). The 

exothermic decomposition energy may be determined using a suitable calorimetric 

technique; or 
245

4. For mixtures of inorganic oxidizing chemicals with organic material(s), the concentration of 

the inorganic oxidizing chemical is: 

i. less than 15%, by mass, if the oxidizing substance is assigned to Category 1 or 2; 

ii. less than 30%, by mass, if the oxidizing substance is assigned to Category 3. 

Step 2: Acceptance Procedure 

This overview of the explosives test procedures and methods is designed to help classifiers 

understand the intent of the various tests. OSHA urges caution when performing these tests; a 

laboratory specializing in explosives testing always should perform them. 

The acceptance procedure is used to determine whether a 

chemical is a candidate for the explosives hazard class or is an 

unstable explosive. The acceptance procedure should be 

applied to any chemical or mixture of chemicals containing 

any known explosives. Although the acceptance procedure 

includes Test Series 2 through 4, Test Series 1 is included in 

the explanation below. If the chemical is known to be 

designed and intended for use in manufacturing explosives, 

then tests 1 and 2 can be skipped and analysis can begin with Test Series 3. The classification 

criteria originally were designed for transportation and take into account the chemical as 

presented and as packaged. However, as mentioned above, if the same chemical is to be 

presented in a physical form different from that in which it was tested, and in a form that is 

considered likely to materially alter the chemical’s performance (i.e., under normal conditions of 

use or in foreseeable emergencies) in a classification test, then testing for classification must be 

based on the chemical in its new form. 

 Test Series 1 is intended to answer the question “Is it an explosive substance/mixture?” (See 

box 4 of Figure VIII.1.2). This series includes three types of tests to assess possible 

explosive effects. The tests determine the propagation of detonation, the effect of heating 

under confinement, and the effect of ignition under confinement. Although four tests are 

explained in the UN TDG Manual of Tests and Criteria, only three are recommended: the 

UN gap test, the Koenen test, and the time/pressure test. 

 Test Series 2 is intended to answer the question “Is the substance /mixture too insensitive for 

acceptance into this Class?” (See box 6 of Figure VIII.1.2). This series also includes three 

types of tests to assess possible explosive effects. The tests determine the sensitivity to 

shock, the effect of heating under confinement, and the effect of ignition under confinement. 

The three recommended tests are the same as those for Test Series 1. 

 Test Series 3 is intended to answer the questions “Is the substance / mixture thermally 

stable?” and “Is the substance/mixture too dangerous in the form in which it was tested?” 

(See boxes 10 and 11 of Figure VIII.1.2). This test series includes four types of tests to 

determine sensitiveness to impact, sensitiveness to friction (including impacted friction), 

Refer to the UN TDG Manual 

of Tests and Criteria for a 

complete description of the 

methods, the apparatus

used, and analysis of the 

test results.
246

thermal stability of a substance, and response of the substance to fire. Although there are 

eleven tests identified in this test series and explained in the UN TDG Manual of Tests and 

Criteria, only four are recommended: the BAM Fallhammer, BAM friction apparatus, 

thermal stability test at 75 °C, and the small-scale burning tests. 

 Test Series 4 is intended to answer the question “Is the item, packaged item or packaged 

substance too dangerous?” (See box 16 of Figure VIII.1.2). This test series includes two 

types of tests to determine the thermal stability for items, and the danger from dropping. All 

three of the tests in this series explained in the UN TDG Manual of Tests and Criteria are 

recommended: the thermal stability test for unpackaged items and packaged items, steel tube 

drop test for liquids, twelve-meter drop test for items, packaged items and packaged 

substances. 

Step 3: Procedure for Hazard Assignment 

This set of procedures assigns the chemical, mixture, or item to one of the six divisions in this 

hazard class. The assignment depends on the type of hazard presented and applies to all 

chemicals, mixtures, and/or items that are candidates for the explosives hazard class. If testing is 

conducted, then the chemical should be assigned to the division that corresponds to the test 

results to which the chemical, or item as offered for supply and transport, has been subjected 

(that is, the testing and classification includes the chemical, mixture, or item’s packaging). 

The test methods used for assignment to a division are grouped into three test series – numbered 

Test Series 5 to Test Series 7 – designed to provide the information necessary to answer the 

questions in the decision logic presented in Figure VIII.1.3, “Procedure for assignment to a 

division in the class of explosives.” 

 Test Series 5 is intended to answer the question “Is it a very insensitive explosive substance 

with a mass explosion hazard?” The results of this test series also determine if a substance 

may be assigned to Division 1.5. (See box 21 of Figure VIII.1.3) This test series includes 

three types of tests: a shock test to determine the sensitivity to intense mechanical stimulus, 

thermal tests to determine the tendency of transition from deflagration to detonation, and a 

test to determine if a substance, when in large quantities, explodes when subjected to a large 

fire. Although there are five tests identified in test series 5, only three are recommended: the 

cap sensitivity test, USA DDT test, and the external fire test for Division 1.5.

 The results from Test Series 6 tests are used to assign a substance, mixture, or item to 

Division 1.1, 1.2, 1.3 or 1.4 (see boxes 26, 28, 30, 32, and 33 of Figure VIII.1.3). The results 

also are used to determine if the substance, mixture, or item is assigned to Compatibility 

Group S of Division 1.4, and whether the chemical or mixture should be excluded from the 

explosives hazard class (see boxes 35 and 36 of Figure VIII.1.3). This test series includes 

four types of tests on the item as packaged, including tests on: 

o a single package to determine if there is mass explosion of the contents, 
247

o packages of an explosive substance or explosive items, or non-packaged explosive 

items, to determine whether an explosion is propagated from one package to another 

or from a non-packaged item to another, 

o packages of an explosive substance or explosive items, or non-packaged explosive 

items, to determine whether there is a mass explosion or a hazard from dangerous 

projections, radiant heat and/or violent burning or any other dangerous effect when 

involved in a fire, and 

o an unconfined package of explosive items to which special provision 347 of Chapter 

3.3 of the UN TDG Model Regulations applies, to determine if there are hazardous 

effects outside the package arising from accidental ignition or initiation of the 

contents. 

All four of the tests for test series 6 are recommended: the single package test, stack test, 

external fire (bonfire) test, and the unconfined package test. 

 Test Series 7 is intended to answer the question “Is it an extremely insensitive explosive 

item?” (See box 40 of Figure VIII.1.3.) The results of this test series also determine if an 

item is assigned to Division 1.6. There are ten types of tests in this test series; the first six 

tests listed below establish if the chemical is an extremely insensitive detonating substance 

(EIDS), and the last four types of tests determine if an item containing an extremely 

insensitive detonating substance may be assigned to Division 1.6. The tests determine: 

o sensitivity to intense mechanical stimulus, 

o sensitivity to shock, 

o sensitivity of the explosive substance to deterioration under the effect of an impact, 

o the degree of reaction of the explosive substance to impact or penetration resulting 

from a given energy source, 

o the reaction of the explosive substance to an external fire when the material is confined, 

o the reaction of the explosive substance in an environment in which the temperature is 

gradually increased to 365 °C, 

o the reaction to an external fire of an item that is in the condition as presented 

for transport, 

o the reaction of an item in an environment in which the temperature is gradually 

increased to 365 °C, 

o the reaction of an item to impact or penetration resulting from a given energy 

source, and 

o whether a detonation of an item will initiate a detonation in an adjacent, like item. 
248

There are twelve tests in Test Series 7, ten of which are recommended and are listed below. As 

mentioned above, the first six tests are for chemicals, while the last four tests are for items. 

o EIDS cap test

o EIDS gap test

o Friability test

o EIDS bullet impact test

o EIDS external fire test

o EIDS slow cook-off test 

o 1.6 article external fire test

o 1.6 article slow cook-off test

o 1.6 article bullet impact test

o 1.6 article stack test 

Test Series 8 is intended to answer the question “Is the substance a candidate for “ammonium 

nitrate emulsion or suspension or gel, intermediate for blasting explosives (ANE)?”. Three 

types of tests are included in this series to determine the thermal stability, sensitivity to intense 

shock, and the effect of heating under confinement. Three tests are recommended: the thermal 

stability test for ammonium nitrate emulsions (ANE), the ANE gap test, and the Koenen test. 

Compatibility Groups 

For the purposes of transport and storage, compatibility groups are also assigned to explosives. 

These groups identify the necessary controls to prevent hazardous conditions for explosives 

transported or stored together. There are thirteen compatibility groups: A, B, C, D, E, F, G, H, J, 

K, L, N, and S. In the Hazard Communication Standard, there are specific labeling requirements 

for Division 1.4 explosives assigned to compatibility group S (See Appendix C.4.14 to 29 CFR 

1910.1200). Additional information about compatibility groups and their assignment can be 

found in Section 2.1.2 of the UN TDG Model Regulations, and Chapters 49 CFR 177.50 – 52 and 

49 CFR 178.848 of the U.S. DOT regulations. 

Classification Procedure 

Explosives are classified according to the classification principles given in the decision logic and 

the results of test series 1 through 7. 

The explosives classification procedure uses the following four decision logics. Once you have 

collected the data, compare it to the criteria for explosives. Follow the logic paths presented in 

the decision logics (or flowcharts) in Figures VIII.1.1, VIII.1.2, VIII.1.3, and VIII.1.4 to identify 

the appropriate classification for explosives. Figure VIII.1.1 presents the overall scheme of the 

procedure for classifying a chemical, mixture, or item in the explosives hazard class (Class 1 for 

transport). Figure VIII.1.2 presents the overall scheme to answer questions associated with the 

results of Test series 1 through 4. Figure VIII.1.3 presents the logic for assigning a chemical, 

mixture, or item to a division in the explosives hazard class. Figure VIII.1.4 presents the logic 

for classification of an ammonium nitrate emulsion, suspension, or gel. The reference to B.1.1.2 

(b) in Figure VIII.1.3 refers to Appendix B to 29 CFR 1910.1200. 
249

Figure VIII.1.1. Overall scheme of the procedure for classifying a chemical, mixture, or 

item in the class of explosives (Class 1 for transport).

COMPATIBILITY 

GROUP ASSIGNMENT

SUBSTANCE, MIXTURE OR ITEM

FOR CLASSIFICATION

CLASSIFY AS AN 

UNSTABLE 

EXPLOSIVE

REJECT

Not an explosive

explosive

HAZARDOUS DIVISION 

ASSIGNMENT

COMPATIBILITY GROUP 

A, B, C, D, E, F, G, H, J, K, 

L, N or S

CLASSIFICATION CODE

ACCEPTANCE PROCEDURE

PROCEDURE

CLASSIFY AS 

AN EXPLOSIVE

DIVISION

1.1, 1.2, 1.3, 1.4, 1.5 or 1.6
250

No

Yes

Yes

Yes

Yes

Encapsulate and/or package

the substance/mixture 

NOT AN

EXPLOSIVE

TEST SERIES 1*

No

No

No No

TEST SERIES 2

TEST SERIES 4

TEST SERIES 3

Yes

No

Yes

No

Yes

SUBSTANCE/MIXTURE

FOR CLASSIFICATION

ITEM FOR

CLASSIFICATION

Is

the substance/ 

mixture a candidate for 

ammonium nitrate emulsions

suspension or gel, intermediate

for blasting explosive, 

ANE?

Substance/mixture to be 

considered for this Class

Is

the substance/ 

mixture too dangerous 

in the form in which 

it was tested? 

Is the

substance/mixture

thermally stable?

TEST SERIES 8

Go to figure VIII.1.4

Is the

substance/mixture 

too insensitive for 

acceptance into 

this Class? 

Is the

item, packed 

item or packaged 

substance/mixture too 

dangerous? 

Is

the substance/ 

mixture manufactured with 

the view to producing 

a practical explosive 

or pyrotechnic 

effect?

CLASSIFY as an 

unstable explosive 

PROVISIONALLY

ACCEPT INTO 

THIS CLASS 

(go to Figure VIII.1.3)

CLASSIFY as an 

unstable explosive

Figure VIII.1.2. Procedure for provisional acceptance of a substance, mixture, or item in 

the class of explosives (Class 1 for transport). 

* For classification purposes start with test series 2

Is it

an explosive

substance/

mixture?
251

Figure VIII.1.3. Procedure for assignment to a division in the class of explosives 

(Class 1 for transport).

Is

the major 

hazard radiant heat 

and/or violent burning 

but with no dangerous blast or 

projection hazard?

No

No

SUBSTANCE PROVISIONALLY ACCEPTED INTO THIS CLASS 

(from figure VIII.1.2)

Yes

TEST SERIES 5

Yes

Yes

No

No

No

No

Is the

item a candidate 

for Division 1.6? 

24

TEST SERIES 7

39

Is it an

extremely insensitive 

item?

40

Is the

substance a candidate 

for Division 1.5?

19

20

Is it a

very insensitive 

explosive substance with 

a mass explosion 

hazard?

21

Package the 

substance

23

TEST SERIES 6

25

Is the

result a mass 

explosion? 

26

Is the

major hazard that 

from dangerous 

projections?

28

30

32

33

Is the

substance or item 

manufactured with the view of 

 producing a practical explosive 

or pyrotechnic 

effect? 

35

Is the

product an item 

excluded by definition? 

(See B.1.1.2 (b)) 

36

NOT AN 

EXPLOSIVE

38

DIVISION

1.6

41

DIVISION

1.5

22 DIVISION 1.4

Compatibility group 

S 

37

DIVISION 1.4

Compatibility groups other 

than S

34

DIVISION

1.3

31

DIVISION

1.2

29

DIVISION

1.1

27

Yes

Yes

Yes

Yes

Yes

No

No

Yes

Yes

Yes

No

No

No

Would

the hazard hinder 

fire-fighting in the 

immediate 

vicinity?

Are there

hazardous effects 

outside the 

package?
252

Figure VIII.1.4. Procedure for the classification of ammonium nitrate emulsion, 

suspension, or gel (ANE).
253

Explosives Classification Example

The following example is provided to illustrate the classification process and use of the decision 

logic for explosives. Note that the example includes the use and analysis of test data for 

explanatory purposes. 

A solid, hexanitrostilbene, that is manufactured with the intent of producing a practical explosive 

and that has chemical groups associated with explosive properties is tested according to the UN 

tests below to determine if it meets the explosive criteria. 

The test methods for determining the classification and division of explosives are performed 

using the UN Recommendations on the Transport of Dangerous Goods, Manual of Tests and 

Criteria, Part I, Test Series 1 to 8. The tests are designed to provide the information necessary to 

answer the questions in the decision logics for explosives. There is a three-step process for 

determining the classification and division of Explosives: a screening procedure, an acceptance 

procedure, and an assignment to a hazard division. More details on the classification are found 

in the UN Recommendations on the Transport of Dangerous Goods, Manual of Tests and 

Criteria. 

The Explosives Screening Procedure aims to identify the presence of reactive groups and the 

potential for rapid energy release. If the screening procedure identifies the material as a potential 

explosive, the Class 1 Acceptance Procedure should be applied. 

Known data 

 A powder manufactured with the intent of producing a practical explosive and which has 

chemical groups associated with explosive properties. 

 Composition: 96% Hexanitrostilbene 

Test Results 

Test Series 1 and 2 are not conducted because the powder is manufactured to produce a practical 

explosive. These two test series need not be performed, since both tests are designed to 

determine if a material being tested exhibits explosive properties, and whether it is too 

insensitive to be accepted as an explosive. 

Test Series 3: Is the powder thermally stable? 

 For determining the thermal stability of the powder, the thermal stability: 75 °C/48-hour test 

is conducted. 

RESULT: “–”, (or “negative”) indicating the powder is thermally stable. 

 To determine if the powder is too dangerous for transport in the form in which it was tested, 

two tests are conducted. 

o For determining sensitiveness to impact, the BAM Fallhammer test is conducted. 
254

RESULT: Limiting impact energy 5 Joules (J); the result is considered “–” (or 

“negative”), indicating the powder is not too dangerous in the form tested. 

o For determining sensitiveness to friction (including impacted friction), the BAM 

friction test is conducted. 

RESULT: Limiting load > 240 Newtons (N); the result is considered “–” (or 

“negative”), indicating the powder is not too dangerous in the form tested. 

CONCLUSIONS: The powder is provisionally accepted into the Explosives Class. 

Test Series 4 is not conducted when following the decision logic – the powder is not too 

dangerous for transport. 

Test Series 5: Is it a very insensitive explosive substance with a mass explosion hazard? 

 To determine if the powder, in large quantities, explodes when subjected to a large fire 

[External fire test for Division 1.5] 

RESULT: The powder explodes; the result is considered “+” (or “positive”), indicating the 

powder is not classified as Division 1.5. 

 Based on the results above, neither the shock test (to determine the sensitivity to intense 

mechanical stimulus), nor the thermal test (to determine the tendency for transition from 

deflagration to detonation) is performed. The need for testing is waived. 

CONCLUSIONS: No, the powder is NOT a very insensitive explosive substance with a mass 

explosion hazard. 

Test Series 6: Is the result a mass explosion? 

 To determine the effect of initiation in the package, a test is conducted on a single package to 

determine if there is mass explosion of the contents. 

RESULT: detonation, crater 

 To determine the effect of propagation, a test is conducted on packages of an explosive 

substance to determine whether an explosion is propagated from one package to another. 

RESULT: detonation of the whole stack of packages, crater 

 Based on the results above, the test to determine whether there is a mass explosion or a 

hazard from dangerous projections, radiant heat and/or violent burning or any other 

dangerous effect when involved in a fire is not conducted. The need for testing is waived. 

CONCLUSIONS: Yes, there is a mass explosion hazard. The powder is assigned to Explosives, 

Division 1.1. 

Test Series 7 is not conducted as the powder is not an item. 
255

Test Series 8 is not conducted as the powder is not a candidate for ammonium nitrate emulsions 

suspension or gel, intermediate for blasting explosive. 

Decision/Rationale 

To classify an explosive, the classifier would screen the substance, mixture or item for 

classification as an explosive, use the information gathered from the test data, and follow the 

decision logics for explosives, answering the questions and following the flowchart as illustrated 

in Figures VIII.1.2 and VIII.1.3 above. 

1. To screen an explosive: Does the powder have reactive groups and/or the potential for rapid 

energy release? 

ANSWER: Yes, this powder contains a nitro group which is a chemical group (associated 

with explosive properties. 

2. To classify an explosive, the classifier follows the decision logics for explosives, answering 

the questions and following the logic presented in the flowcharts. Beginning with the logic 

presented in Figure VIII.1.2, Procedure for Provisional Acceptance, and starting with Box 2. 

3. Is the powder manufactured with the intent to produce a practical explosive or 

pyrotechnic effect? 

ANSWER: Yes; go to Box 8 of Figure VIII.1.2, because the powder is to be considered for 

classification in the Explosives hazard class (that is, Transportation Class 1).

4. Go to Box 9, Test Series 3 

5. Go to Box 10, Test Series 3: Is Powder thermally stable? 

RESULT: Using the results from Test series 3: Yes.

6. Go to Box 11, Test Series 3: Is Powder too dangerous in the form in which it was tested? 

RESULT: Using the results from Test series 3: No.

7. Go to Box 18, the powder is Provisionally Accepted into the Explosives hazard class. 

8. Exit Figure VIII.1.2, Acceptance Procedure. Go to Figure VIII.1.3, Procedure for 

Assignment to a Division in the Class of Explosives, and start with Box 24. 

9. Is Powder a candidate for Division 1.6? 

ANSWER: No; the powder is not an item. Go to Box 19. 

10. Is the powder a candidate for Division 1.5? 

ANSWER: Uncertain, so go to Test Series 5 (Box 20). 

11. In Box 21, Test Series 5: Is powder a very insensitive explosive substance with a mass 

explosion hazard? 

RESULT: No; go to Box 23 (Package the substance), and then to Box 25, Test Series 6. 
256

12. Is the result a mass explosion? 

RESULT: Yes; detonation of a single package with crater and detonation of the whole stack 

of packages with crater. 

13. Go to Box 27 and classify the powder as Explosive, Division 1.1. 

Test Series 1, 2, 4, 7 and 8 are not required for this powder if the classifier follows the test logic. 

Resulting Classification 

The powder is classified as an Explosive, Division 1.1 because it has a mass explosion hazard (a 

mass explosion is one that affects almost the entire quantity present, virtually instantaneously). 
257

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.1, Explosives. 

29 CFR 1910.1200, Hazard Communication, Appendix C, Allocation of Label Elements.

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
258

VIII.2 Flammable Gases 

Introduction

Gases that ignite pose a serious safety hazard, especially since most gases are stored in cylinders 

or other containers. Many of these gases have no odor and their presence cannot be detected 

without the use of a specific detector. Should a leak occur, the gas often accumulates, forming a 

pocket of gas. These pockets can accumulate at ground level or towards the room’s ceiling, 

depending on the gas’ density. Pockets of certain gases can, in turn, lead to fires or explosions. 

The gas’ container may provide another hazard because, should it explode, the container may 

become a missile/projectile or send parts of the container in all directions. 

Definitions

Flammable gas means a gas having a flammable range with air at 20 °C (68 °F) and a standard 

pressure of 101.3 kPa (14.7 psi). 

Flammable range (often referred to as the explosive range) is the range between the lower and 

upper flammable limit, expressed in terms of percentage of vapor or gas in air by volume. 

The flammable range includes all concentrations of flammable vapor or gas in air, in which a 

flash will occur or a flame will travel if the mixture is ignited and includes rapid combustion or 

an explosion. 

Classification Criteria 

A flammable gas is classified in one of two categories, as shown in Table VIII.2.1. 

Table VIII.2.1. Classification criteria for flammable gases. 

Category Criteria

1 Gases, which at 20 °C (68 °F) and a standard pressure of 101.3 kPa (14.7 psi): 

a) are ignitable when in a mixture of 13% or less by volume in air; or 

b) have a flammable range with air of at least 12 percentage points regardless 

of the lower flammable limit.

2 Gases, other than those of Category 1, which, at 20 °C (68 °F) and a standard 

pressure of 101.3 kPa (14.7 psi), have a flammable range while mixed in air. 

Note: Aerosols should not be classified as flammable gases.

Classification Procedure and Guidance 

To classify a flammable gas, data are necessary on the flammable range and the percentage of 

the mixture that ignites in air. 
259

Available Literature

The classifier may use available scientific literature and other evidence to identify the flammable 

range or the percentage of the mixture that ignites in air for many flammable gases. Appendix B

of this document provides a listing of information sources that may prove useful during hazard 

classification. 

In addition, many substances presenting flammable gas hazards have already been classified. 

The Hazardous Materials Regulations table from the U.S. Department of Transportation can be 

used to assist in flammable gas classifications (see 49 CFR 172.101). The classification of 

flammable gases in the HCS corresponds to DOT’s classification of flammable gases. 

As explained in the introduction to Classification of Physical Hazards in this guidance document, 

the information needed to classify a flammable gas (flammable range and percentage of a 

mixture that ignites) is the same as that required to assign the chemical to the appropriate hazard 

class under DOT regulations. When a gas is classified under the DOT regulations as a Class 2, 

Division 2.1 flammable gas, it is classified under the HCS, as a flammable gas, category 1. 

However, DOT does not cover HCS Category 2 flammable gases. Therefore, to classify 

chemicals as Category 2 flammable gases, the necessary information and data must be gathered 

elsewhere. Refer to the discussion of the interface between the HCS and DOT labeling in 

Chapter V of this document.

The decision logic presented below should be used to determine the appropriate hazard 

classification category for a flammable gas under the HCS.

Test Method 

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

should you choose to test the substance or mixture, use the test methods identified in Appendix 

B.2 to 29 CFR 1910.1200, which are described below. 

The test method presented in ISO 10156:1996, Gases and Gas mixtures – Determination of fire 

potential and oxidizing ability for the selection of cylinder valve outlets is used for determining 

whether or not a gas is flammable in air and whether a gas is more or less oxidizing than air. 

This ISO standard provides both the test method (complete with procedure and necessary testing 

equipment) and the calculation method. 

In most cases, however, the classifier will use a calculation to determine if the gas mixture is 

flammable or not. As noted above, the calculation to determine flammability of gas mixtures is 

provided by ISO 10156:1996. Where insufficient data are available to use this method, 

equivalent validated methods may be used. 
260

The ISO 10156:1996 calculation determines only if the mixture is flammable or not. The 

calculation does not determine a flammable range, nor does it determine if the mixture is 

classified as a flammable gas Category 1 or Category 2. Therefore, in the absence of additional 

information, mixtures determined to be flammable according the calculation method should be 

classified as a Category 1 flammable gas. When there is a need to distinguish between 

Category 1 and 2, the lower and the upper explosion limits must be determined by using a 

suitable test method (e.g., ASTM E 681). 

ISO Calculation 

The calculation in ISO 10156:1996 uses the criterion that a gas mixture is considered nonflammable in air if: 

Criterion: 

1

%

 

n

i ci

i

T

V

 

Formula: 

cn

n

cc

n

i ci

i

T

V

T

V

T

V

T

V

 .... 

%

2

2

1

1

Where 

Vi% the equivalent flammable gas content 

Tci the maximum concentration of a flammable gas in nitrogen at which the mixture 

is still not flammable in air 

i the first gas in the mixture

n the nth gas in the mixture 

Ki the equivalence factor for an inert gas versus nitrogen 

In the above equation, both the Tci and Ki values are constants. The Tci values are provided in 

ISO 10156:1996 Table 2, Maximum content Tci of flammable gas which, when mixed with 

nitrogen, is not flammable in air. The Ki values are a coefficient of equivalency which expresses 

the terms of an equivalent composition in which all the inert-gas fractions are converted into 

their nitrogen equivalent. Where a gas mixture contains an inert diluent other than nitrogen, the 

volume of this diluent is adjusted to the equivalent volume of nitrogen using the equivalency 

factor for the inert gas Ki. The Ki values are provided in ISO 10156:1996 Table 1, Coefficients 

of equivalency, Ki, for inert gases relative to nitrogen. 
261

Classification Procedure 

The necessary data to classify flammable gases includes the following: 

 the flammable range and 

 the percentage of the mixture that ignites in air 

Classification follows the assessment of data on the flammable range and the percentage of the 

mixture that ignites in air. Once you have collected the data, compare it to the criteria for 

flammable gases Category 1 and Category 2, presented in Table VIII.2.1. Follow the logic paths 

presented in the decision logic (or flowchart) in Figure VIII.2.1, to identify the appropriate 

classification categories for flammable gases. 

Decision logic for classifying flammable gases 

The decision logic for classifying flammable gases is provided below. 
262

Figure VIII.2.1. Decision logic for classifying flammable gases. 

Flammable Gas Classification Examples 

The following examples are provided to illustrate the classification process when data is 

available for the given chemical. 

Example #1: Classification by Calculation According to ISO 10156:1996 

When the composition of a material is known, a calculation in ISO 10156:1996, “Gases and gas 

mixtures – Determination of fire potential and oxidizing ability for the selection of cylinder valve 

outlets,” can be used to determine whether a gas mixture that is suspected of being flammable 

should be classified as a flammable gas. The following example presents the steps to perform 

this calculation. For the purpose of this example the following gas mixture is used: 

2% (H2) + 6% (CH4) + 27% (Ar) + 65% (He) 

Does it have a flammable range with air at 20 °C 

(68 °F) and a standard pressure of 101.3 kPa 

(14.7 psi)?

At 20 °C (68 °F) and a standard pressure of 101.3 kPa

(14.7 psi), does it:

(a) ignite when in a mixture of 13% or less by 

volume in air?; or 

(b) have a flammable range with air of at least 12 

percentage points regardless of the lower 

flammable limit?

Not classified

Category 1

Danger Yes

Yes

No

Gaseous substance or mixture of gases

Category 2

No symbol 

Warning 

No
263

1. Look up the values of Tci and Ki in ISO 10156: 

Ki (Ar) = 0.5 

Ki (He) = 0.5 

Tci H2 = 5.7% 

Tci CH4 = 14.3% 

2. Calculate the equivalent mixture with nitrogen as balance gas using the Ki figures for the 

inert gases: 

2%(H2) + 6%(CH4) + [27% × Ki (Ar) + 65% × Ki (He)](N2) = 

2%(H2) + 6%(CH4) + [27% × 0.5 + 65% × 0.5](N2) = 2%(H2) + 6%(CH4) + 46%(N2) = 54% 

3. Adjust the sum of the contents to 100%. The results provide the equivalent flammable gas 

content (Vi%) values for hydrogen and methane: 

54

100

x [2%(H2) + 6%(CH4) + 46%(N2)] = 3.7%(H2) + 11.1%(CH4) + 85.2%(N2) 

4. Calculate the flammability of the equivalent mixture using the formula in ISO 10156:2010 

(shown above) and the Vi% and Tci values for H2 and CH4: 

.1 42

14 3.

11 1.

7.5

% 7.3

 

n

i ci

i

T

V

5. Compare the answer to the criterion: 



n

i Tci

Vi%

> 1 Since 1.42 > 1, the mixture is flammable in air. Without additional 

information, the chemical is classified as a Flammable Gas, Category 1. 

Example #2: Classification with Known Data 

When the flammability range is known, the classification of the substance can be obtained 

according to the HCS Flammable Gas Decision Logic. 

A gaseous substance that has a known flammability range is suspected of being a flammable gas. 
264

Known data

 Gaseous substance. 

 Boiling Point: -42 °C 

 Flammable range: 2.2 – 11 % in air at ambient temperature (20 °C) and standard pressure 

(101.3 kPa) 

Decision/Rationale 

1. Does the chemical have a flammable range with air at 20 °C and a standard pressure of 

101.3 kPa?

ANSWER: Yes. The chemical has a flammable range of 2.2 – 11% in air. 

2. At 20 °C and a standard pressure of 101.3 kPa, does it: 

a) ignite when in a mixture of 13% or less by volume in air?; or 

b) have a flammable range with air of at least 12 percentage points regardless of the lower 

flammable limit? 

ANSWER: Yes. The chemical is a gaseous substance and ignites at a concentration of <13% 

at ambient temperature and standard pressure. 

Resulting Classification 

Since the chemical fulfills the criteria for Flammable Gas, Category 1, it is classified as such. 
265

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.2, Flammable Gases. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 

International Standards Organization (ISO) 10156:1996 (E), Gases and Gas Mixtures - 

Determination of Fire Potential and Oxidizing Ability for the Selection of Cylinder Valve 

Outlets, Second Edition, Feb. 15, 1996. 
266

VIII.3 Flammable Aerosols 

Introduction

The analysis as to whether a chemical is a flammable aerosol is usually 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 and should be used with caution. 

Definition

Aerosol means any non-refillable receptacle containing a 

gas compressed, liquefied or dissolved under pressure, and 

fitted with a release device allowing the contents to be 

ejected as particles in suspension in a gas, or as a foam, 

paste, powder, liquid or gas.

Classification Criteria 

Aerosols are considered for classification as flammable if they contain any component that is 

classified as flammable in accordance with the HCS, Appendix B, i.e.: 

Flammable gases (See Appendix B.2 to 29 CFR 1910.1200) 

Flammable liquids (See Appendix B.6 to 29 CFR 1910.1200) 

Flammable solids (See Appendix B.7 to 29 CFR 1910.1200) 

Flammable components do not include pyrophoric, self-heating or water-reactive chemicals 

because such components are never used as aerosol contents. Flammable aerosols do not fall 

additionally within the scope of flammable gases, flammable liquids, or flammable solids. That 

is, if a chemical is classified as a flammable aerosol, then it would not be classified additionally 

as a flammable gas, flammable liquid or flammable solid. However, depending on their 

contents, flammable aerosols may fall additionally within the scope of other hazard classes (e.g., 

health hazard or physical hazard classes), and be subject to additional labeling elements.

A flammable aerosol is classified in one of two categories on the basis of its flammable 

components (see Table VIII.3.1), its chemical heat of combustion and, if applicable, the results 

of the foam test (for foam aerosols) and the ignition distance test and enclosed space test (for 

spray aerosols) in the test procedure described below. 

Receptacle means a containment 

vessel for receiving and holding 

substances or articles, including 

any means of closing. (Definition 

from UN TDG Model Regulations, 

Rev. 16)
267

Table VIII.3.1. Classification criteria for flammable aerosols. 

Category Criteria

1 Contains ≥ 85% flammable components and the chemical heat of combustion 

is ≥ 30 kilojoules/gram (kJ/g); 

OR 

a) For spray aerosols, in the ignition distance test, ignition occurs at a 

distance ≥ 75 cm (29.5 in), 

OR 

b) For foam aerosols, in the aerosol foam flammability test 

i. The flame height is ≥ 20 cm (7.87 in) and the flame duration ≥ 2 

seconds; 

OR 

ii. The flame height is ≥ 4 cm (1.57 in) and the flame duration ≥ 7

seconds 

2 Contains > 1% flammable components, or the heat of combustion is ≥ 20 kJ/g; 

AND 

a) For spray aerosols, in the ignition distance test, ignition occurs at a 

distance ≥ 15 cm (5.9 in), 

OR 

In the enclosed space ignition test, the 

i. Time equivalent is ≤ 300 seconds/m

3

; 

OR 

ii. Deflagration density is ≤ 300 gram/m

3 

b) For foam aerosols, in the aerosol foam flammability test, the flame height 

is ≥ 4 cm and the flame duration is ≥ 2 seconds 

AND it does not meet the criteria for Category 1.

Note: Aerosols not submitted to the flammability classification procedures found in 29 CFR 

1910.1200, Appendix B are classified as extremely flammable (Category 1). 

Classification Procedure and Guidance 

To classify a flammable aerosol, the following are necessary: data on its flammable components, 

on its chemical heat of combustion and, if applicable, the results of the aerosol foam 

flammability test (for foam aerosols) and the results of the ignition distance test and enclosed 

space test (for spray aerosols). 

Available Literature

The classifier may use available literature and other evidence to identify flammable components, 

the chemical heat of combustion and, if applicable, the results of the aerosol foam flammability 
268

test (for foam aerosols) and the results of the ignition distance test and enclosed space test (for 

spray aerosols). Appendix B of this document lists information sources that may prove useful 

during hazard classification. 

In addition, many substances presenting flammable aerosol hazards have already been classified. 

The Hazardous Materials Regulations table from the U.S. Department of Transportation can be 

used to assist in flammable aerosol classifications (see 49 CFR 172.101). Refer to the discussion 

of the interface between the HCS and DOT labeling presented in Chapter V of this document. 

The decision logic presented below should be used to determine the appropriate hazard 

classification category for flammable aerosols. 

Chemical Heat of Combustion (ΔHc) 

The chemical heat of combustion (ΔHc), in kilojoules per gram (kJ/g), is the product of the 

theoretical heat of combustion (ΔHcomb), and a combustion efficiency, usually less than 1.0 (a 

typical combustion efficiency is 0.95 or 95%). 

For a composite aerosol formulation, the chemical heat of combustion is the summation of the 

weighted heats of combustion for the individual components, as follows: 

Hc (product) = 



n

i

[ wi% x Hc(i)] 

where: 

Hc = chemical heat of combustion (kJ/g) 

wi% = mass fraction of component i in the product 

Hc(i) = specific heat of combustion (kJ/g) of component i in the product 

The chemical heats of combustion are found in literature, calculated or determined by tests 

identified in Appendix B.3 to 29 CFR 1910.1200; these are ASTM D240-02; ISO 13943: 2000 

(E/F), Sections 86.1 to 86.3; and NFPA 30B. 

Test Methods 

As mentioned throughout this guidance document, the Hazard Communication Standard does not 

require the testing of chemicals – only the collection and analysis of currently available data. 

However, in the case of spray or foam aerosols, information needed for classification may not be 

readily available and it may be necessary to conduct certain tests. Should you choose to test the 

substance or mixture, use the test methods identified in Appendix B.3 to 29 CFR 1910.1200, and 

described below. 

Classification Based on Test Methods in the UN TDG Manual of Tests and Criteria 

The criteria for flammable aerosols are based on tests described in Part III of the Fourth Revised 

Edition of the United Nations Recommendations on the Transport of Dangerous Goods (UN 

TDG) – Manual of Tests and Criteria., The Ignition Distance Test, Enclosed Space Ignition Test, 
269

and Aerosol Foam Flammability Test are performed in accordance with sub-sections 31.4, 31.5, 

and 31.6 of this manual, respectively. Refer to the UN TDG Manual of Tests and Criteria for a 

complete description of the method, the apparatus used, and analysis of the test results. The 

purpose of each test is presented below. 

 Ignition Distance Test for Spray Aerosols (UN TDG Manual of Tests and Criteria, subsection 31.4) 

The ignition distance test is the method used to determine the ignition distance of an 

aerosol spray in order to assess the associated flame risk. This test is applicable to 

aerosol products that can spray a distance of 15 cm or more. 

Aerosol products with a spray distance of less than 15 cm, such as dispensing foams, 

mousses, gels and pastes or fitted with a metering valve, are excluded from this test. 

Aerosol products that dispense foams, mousses, gels or pastes are subject to testing under 

the aerosol foam flammability test. 

 Enclosed Space Ignition Test (UN TDG Manual of Tests and Criteria, sub-section 31.5) 

The enclosed space ignition test is the method used to assess the flammability of products 

emerging from aerosol dispensers due to their propensity to ignite in an enclosed or 

confined space. 

 Aerosol Foam Flammability Test (UN TDG Manual of Tests and Criteria, subsection 31.6) 

The aerosol foam flammability test is the method to determine the flammability of an 

aerosol spray emitted in the form of a foam, mousse, gel or paste. 

Classification Procedure 

The necessary data to classify flammable aerosols includes: 

 Amount of flammable components, 

 Chemical heat of combustion, and 

 Testing results, if applicable, for the aerosol foam flammability test, ignition distance test, 

and enclosed space test. 

Classification follows the assessment of data on the flammable components, on chemical heat of 

combustion and, if applicable, the results of any testing performed. Once you have collected the 

data, compare it to the criteria for flammable aerosol category 1 and category 2, presented in Table 

VIII.3.1. Follow the logic paths presented in the decision logics (or flow charts) in Figures VIII.3.1, 

VIII.3.2, and VIII.3.3 to identify the appropriate classification categories for flammable aerosols. 
270

Figure VIII.3.1. Decision logic for classifying flammable aerosols. 

 

 

For the decision logic for spray aerosols, proceed to Figure VIII.3.2. 

For the decision logic for foam aerosols, proceed to Figure VIII.3.3. 

No

Does it contain  1% flammable components and

does it have a heat of combustion

< 20 kJ/g?

Does it contain  85% flammable components and

does it have a heat of combustion 

 30 kJ/g?

Aerosol

Not classified

Category 1

Danger 

Yes

Yes

No
271

Figure VIII.3.2. Decision logic for spray aerosols. 

Does it have a heat of combustion < 20 kJ/g?

In the ignition distance test, does ignition 

occur at a distance  75 cm?

Spray aerosol

Category 1

Danger

Yes

Category 2

Warning

In the ignition distance test, does ignition 

occur at a distance  15 cm?

In the enclosed space ignition test, is the 

(a) time equivalent  300 s/m3; or 

(b) deflagration density  300 g/m3?

Yes

Yes

Category 2

Warning

No

No

Not classified as 

flammable aerosol

No

Yes

Category 2

Warning

No
272

Figure VIII.3.3. Decision logic for foam aerosols. 

In the foam test, is the

(a) flame height  20 cm and the flame duration  2 s; or

(b) flame height  4 cm and the flame duration  7 s?

Foam aerosol

Category 1

Danger Yes

Category 2

Warning

In the foam test, is the flame height  4 cm and 

the flame duration  2 s?

Not classified as 

flammable 

aerosol

No

Yes

No
273

Flammable Aerosol Classification Examples 

Example #1 

The following example illustrates the classification process for a chemical suspected of being a 

flammable aerosol when data on flammable components and on the chemical heat of combustion 

are known. The classification of the chemical can be determined according to the HCS 

Flammable Aerosol Decision Logics. 

Known data

 The chemical is an aerosol product 

 Flammable components: 

Butane/propane = 70% (by mass) 

Ethanol = 25% 

 Non-flammable components: 5% 

 The chemical heats of combustion 18 (ΔHc) for gases in the mixture: 

ΔHc (Butane/propane) = 43.5 kJ/g 

ΔHc (Ethanol) = 24.7 kJ/g 

ΔHc (other non-flammable components) = 0 kJ/g 

1. Calculate the chemical heat of combustion (ΔHc) using the formula presented above: 

  

n

i

Hc product wi Hc(%[)( i)]

where 

ΔHc is the chemical heat of combustion [kJ/g] 

wi% is the mass fraction of component i in the product 

ΔHc(i) is the specific heat of combustion [kJ/g] of component i in the product 

For this example, the chemical heat of combustion calculation (the summation of the weighted 

heats of combustion for the individual components) is: 

ΔHc (product) = [wi% x ΔHc(i) for butane/propane] + [wi% x ΔHc(i) for ethanol] + [wi% x ΔHc(i) 

for the non-flammable components ] 

ΔHc (product) = [0.70 x 43.5] + [0.25 x 24.7] + [0.5 x 0] = 30.45 + 6.175 + 0 = 36.6 

 

18 The chemical heats of combustion can be found in literature, or be calculated or determined by 

tests (see ASTM D 240, ISO/FDIS 13943:1999 (E/F) 86.l to 86.3 and NFPA 30B). 
274

Decision/Rationale 

Using the information gathered, answer the questions posed in the decision logic VIII.3.1, above. 

1. Does the chemical contain ≤ 1% flammable components and does it have a heat of 

combustion < 20 kJ/g? 

ANSWER: No. It has 95% flammable components and the heat of combustion is 36.6 kJ/g. 

2. Does the chemical contain ≥ 85% flammable components and does it have a heat of 

combustion ≥ 30 kJ/g? 

ANSWER: Yes. It has 95% flammable components and the heat of combustion is 36.6 kJ/g. 

Resulting Classification 

The chemical is classified as a Flammable Aerosol, Category 1, because it contains  85% 

flammable components and a heat of combustion  30 kJ/g. 

Example #2

In this example, data on flammable components, the chemical heats of combustion and the 

results of the ignition distance test and enclosed space test (for spray aerosols) are known. The 

resulting classification is determined using the HCS Flammable Aerosol Decision Logic VIII.3.1 

for aerosols and VIII.3.2 for spray aerosols. 

Tests for Flammable Aerosols are located in the UN Recommendations on the Transport of 

Dangerous Goods, Manual of Tests and Criteria, Part III, Sub-sections 31.4 and 31.5, Ignition 

distance test and Enclosed space ignition test. 

Known data

 Chemical FA2 is a spray aerosol product. 

 Flammable components in Chemical FA2: 

Butane/propane: 30% 

 Non-flammable components in Chemical FA2: 70% 

 The chemical heats of combustion1

(ΔHc) for gases in the mixture: 

ΔHc (Butane/propane) = 43.5 kJ/g 

ΔHc (other non-flammable components) = 0 kJ/g 
275 

Test data/results

Results of the ignition distance test: Ignition occurs at less than 75 cm but more than 15 cm. 

Results of enclosed space ignition test: Not conducted 

Calculate the chemical heat of combustion1(ΔHc) using the formula presented above: 

  

n

i

Hc product wi Hc(%[)( i)]

where 

ΔHc is the chemical heat of combustion [kJ/g] 

wi% is the mass fraction of component i in the product 

ΔHc(i) is the specific heat of combustion [kJ/g] of component i in the product 

For Chemical FA2, the chemical heat of combustion calculation (the summation of the weighted 

heats of combustion for the individual components) is: 

ΔHc (Chemical FA2) = [wi% x ΔHc(i) for butane/propane] + [wi% x ΔHc(i) for the nonflammable components] 

ΔHc (Chemical FA2) = [0.30 x 43.5] + [0.7 x 0] = 13.05 + 0 = 13.1 kJ/g 

Decision/Rationale

1. Does Chemical FA2 contain ≤ 1% flammable components and does it have a heat of 

combustion < 20 kJ/g? 

ANSWER: No. Chemical FA2 has 30% flammable components and the heat of combustion 

is 13.1 kJ/g. 

2. Does Chemical FA2 contain ≥ 85% flammable components and does it have a heat of 

combustion ≥ 30 kJ/g? 

ANSWER: No. Chemical FA2 has 30% flammable components and the heat of combustion 

is 13.1 kJ/g. 

3. For spray aerosols, go to decision logic VIII.3.2. 

4. In the ignition distance test, does ignition occur at a distance ≥ 75 cm? 

ANSWER: No. Ignition occurs between 75 and 15 cm. 

5. Does Chemical FA2 have a heat of combustion < 20 kJ/g? 

ANSWER: Yes. The heat of combustion is 13.1 kJ/g. 

6. In the ignition distance test, does ignition occur at a distance ≥ 15 cm? 

ANSWER: Yes. The ignition occurs at less than 75 cm but more than 15 cm. 
276

Resulting Classification 

Chemical FA2 is classified as a Flammable Aerosol, Category 2 because it contains < 85% 

flammable components and has a heat of combustion of 13.1 kJ/g, which is < 20 kJ/g. In the 

ignition distance test, the ignition occurs at less than 75 cm but more than 15 cm. 

Example #3

In this example, data on flammable components, the chemical heats of combustion and the 

results of the foam test (for foam aerosols) are known. The resulting classification is determined 

using the HCS Flammable Aerosol Decision Logic VIII.3.1 for aerosols and VIII.3.3 for foam 

aerosols. 

Tests for Flammable Aerosols are in the UN Recommendations on the Transport of Dangerous 

Goods, Manual of Tests and Criteria, Part III, Sub-section 31.6, Aerosol foam flammability test. 

Known data

 Chemical FA3 is a foaming aerosol product. 

 Flammable components in Chemical FA3: Butane/propane: 4%; 

 Non-flammable components in Chemical FA3: 96% 

 The chemical heats of combustion1 (ΔHc) for gases in the mixture: 

ΔHc (Butane/propane) = 43.5 kJ/g 

ΔHc (other non-flammable components) = 0 kJ/g 

Test data/results

Chemical FA3 foam test results: the flame height is less than 4 cm and the flame duration is less 

than 2 seconds. 

Calculate the chemical heat of combustion1

(ΔHc) using the formula presented above: 

  

n

i

Hc product wi Hc(%[)( i)]

where 

ΔHc is the chemical heat of combustion [kJ/g] 

wi% is the mass fraction of component i in the product 

ΔHc(i) is the specific heat of combustion [kJ/g] of component i in the product 

For Chemical FA3, the chemical heat of combustion calculation (the summation of the weighted 

heats of combustion for the individual components) is: 

ΔHc (Chemical FA3) = [wi% x ΔHc(i) for butane/propane] + [wi% x ΔHc(i) for the nonflammable components] 

ΔHc (Chemical FA3) = [0.04 x 43.5] + [0.96 x 0] = 1.74 + 0 = 1.7 kJ/g 
277

Decision/Rationale

1. Does Chemical FA3 contain ≤ 1% flammable components and does it have a heat of 

combustion < 20 kJ/g? 

ANSWER: No. Chemical FA3 has 4% flammable components and the heat of combustion is 

1.7 kJ/g. 

2. Does Chemical FA3 contain ≥ 85% flammable components and does it have a heat of 

combustion ≥ 30 kJ/g? 

ANSWER: No. Chemical FA3 has 4% flammable components and the heat of combustion is 

1.7 kJ/g. 

3. For foam aerosols, go to HCS decision logic VIII.3.3. 

4. In the foam test, is 

(a) the flame height ≥ 20 cm and the flame duration ≥ 2 seconds; or 

(b) the flame height ≥ 4 cm and the flame duration ≥ 7 seconds? 

ANSWER: No. In the foam test, the flame height is less than 4 cm and the flame duration 

less than 2 seconds. 

5. In the foam test, is the flame height ≥ 4 cm and the flame duration ≥ 2 seconds? 

ANSWER: No. In the foam test, the flame height is less than 4 cm and the flame duration 

less than 2 seconds. 

Resulting Classification 

Chemical FA3 is not classified as a Flammable Aerosol because this foam aerosol contains 4% 

of flammable components and its chemical heat of combustion equals 1.7 kJ/g. In the foam test, 

the flame height is less than 4 cm and the flame duration less than 2 seconds. It is not 

flammable. 
278

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.3, Flammable Aerosols. 

29 CFR 1910.1200, Hazard Communication, Appendix C, Allocation of Label Elements. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
279

VIII.4 Oxidizing Gases 

Introduction

An oxidizer is a chemical that brings about an oxidation reaction. In an oxidation reaction, the 

oxidizer may provide oxygen to the substance being oxidized (in which case the oxidizer 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 oxidizer for electron-transfer purposes, even 

though it contains no oxygen). 

Oxidizers can initiate or greatly accelerate the burning of fuels. The most common oxidizer is 

atmospheric oxygen. Oxygen-containing chemicals (e.g., 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 ability that they are classified as explosives or blasting 

agents, rather than oxidizers. 

Definition

Oxidizing gas means any gas which may, generally by providing oxygen, cause or contribute to 

the combustion of other material more than air does. 

Gases which cause or contribute to the combustion of other material more than air does means 

pure gases or gas mixtures with an oxidizing power greater than 23.5% (as determined by a 

method specified in ISO 10156:1996 or 10156-2:2005, or an equivalent testing method).

Classification Criteria 

An oxidizing gas is classified in a single category, as shown in Table VIII.4.1. 

Table VIII.4.1. Classification criteria for oxidizing gases. 

Category Criteria

1 Any gas which may, generally by providing oxygen, cause or contribute to 

the combustion of other material more than air does. 

Classification Procedure and Guidance 

To classify an oxidizing gas, data on the oxidizing potential of the gas are needed. As mentioned 

throughout this guidance document, the Hazard Communication Standard does not require the 

testing of chemicals – only the collection and analysis of currently available data. 
280

Available Literature 

The classifier may use available scientific literature and other evidence to classify a chemical as 

an oxidizing gas. Appendix B of this document provides a listing of information sources that 

may prove useful during hazard classification. 

In addition, many substances presenting oxidizing gas hazards have already been classified. The 

Hazardous Materials Regulations table from the U.S. Department of Transportation can be used 

to assist in oxidizing gas classifications (see 49 CFR 172.101). The HCS criteria for classifying 

oxidizing gases correspond to the DOT Class 5.1, Oxidizer. Refer to the discussion of the 

interface between the HCS and DOT labeling presented in Chapter V of this document.

The decision logic presented below should be used to determine the appropriate hazard 

classification category for an oxidizing gas. 

Test Method 

Although the HCS does not require testing, the oxidizing ability of a gas or gas mixture may be 

determined by tests or by calculation using the methods identified in Appendix B.4 to 29 CFR 

1910.1200, which are: 

 ISO 10156:1996, “Gases and gas mixtures – Determination of fire potential and oxidizing 

ability for the selection of cylinder valve outlets” and 

 ISO 10156-2:2005, “Gas cylinders, Gases and gas mixtures. Part 2: Determination of 

oxidizing ability of toxic and corrosive gases and gas mixtures.” 

 An equivalent validated method to either of the above. 

In most cases, the classifier will use a calculation method to determine if the gas or gas mixture 

is oxidizing or not. The calculation to determine the oxidizing potential of gas mixtures either 

may be determined in accordance with ISO 10156:1996, “Gases and gas mixtures –

Determination of fire potential and oxidizing ability for the selection of cylinder valves outlets,” 

or through the use of ISO 10156-2:2005, “Gas cylinders, Gases and gas mixtures. Part 2: 

Determination of oxidizing ability of toxic and corrosive gases and gas mixtures.” 

However, if the classifier decides to test the gas or gas mixture, use of the test method presented 

in ISO 10156-2 “Gas cylinders, Gases and gas mixtures. Part 2: Determination of oxidizing 

ability of toxic and corrosive gases and gas mixtures” is recommended.19 

The calculation methods are presented and summarized in this guidance document. Should 

testing be decided on, refer to the ISO methods for details of the procedure and necessary testing 

apparatus. 

 

19 ISO does not recommend the testing of a gas mixture by use of the test method presented in ISO 10156:1996, 

“Gases and gas mixtures – Determination of fire potential and oxidizing ability for the selection of cylinder valves 

outlets” in certain situations (explained in the scope of this method). 
281

ISO Calculation 

The calculation provided in ISO 10156 and ISO 10156-2 uses the criterion that a gas mixture is 

considered as more oxidizing than air if the oxygen equivalency of the gas mixture is 21% or 

higher. 

Since air contains 20.95% oxygen, oxidizing gases or gas mixtures are considered to contribute 

to the combustion of other material more than air, if the oxygen equivalency of the gas mixture is 

greater than or equal to 21%. 

Criterion:

 %)(  21

n

i

mixtureC Vi Ci

Formula to calculate the oxidation ability of a gas mixture: 

 

n

i

mixtureC Vi%)( Ci

Where 

C(mixture) the oxidation ability of the mixture 

Vi% the volume percentage of a gas 

Ci the coefficient of oxygen equivalency 

i the first gas in the mixture 

n the nth gas in the mixture 

Note: Balance gas (i.e., non-oxidizing gas) is not taken into consideration 

 Only the oxidizing gas is considered 

 The degree of combustibility in air is considered. 

For mixtures containing both flammable and oxidizing components, special calculation methods 

are described in ISO 10156-2. In the above equation, the value Ci is a constant. The Ci value is 

found in ISO 10156-2:2005 Table 1, Coefficients of oxygen equivalency (Ci) of toxic and 

corrosive gases. 

A decision logic, Figure VIII.4.1, for classifying oxidizing gases is provided below. 
282

Figure VIII.4.1. Decision logic for classifying oxidizing gases. 

Does the gas contribute to the combustion 

of other material more than air does?

Gaseous substance or mixture of 

gases

Yes

No

Not classified

Category 1

Danger
283

Oxidizing Gas Classification Example 

This example uses the calculation provided in ISO 10156 and ISO 10156-2. The calculation uses 

the criterion that a gas mixture is considered to be more oxidizing than air if the oxygen 

equivalency of the gas mixture is 21% or higher. 

Criterion:

 %)(  21

n

i

mixtureC Vi Ci

Formula to calculate the oxidation ability of a gas mixture 

 

n

i

mixtureC Vi%)( Ci

Where 

C(mixture) the oxidation ability of the mixture 

Vi% the volume percentage of a gas 

Ci the coefficient of oxygen equivalency (See ISO 10156-2:2005 Table 1, 

Coefficients of oxygen equivalency (Ci) of toxic and corrosive gases) 

i the first gas in the mixture 

n the nth gas in the mixture 

Known data 

 The chemical is a gas 

 Oxidizing components: 

1.5% fluorine 

 Non-oxidizing components: 

98.5 % nitrogen 

1. Ascertain the coefficient of oxygen equivalency (Ci) for the oxidizing gases in the mixture, 

i.e., fluorine, found in ISO 10156-2:2005 Table 1, Coefficients of oxygen equivalency (Ci) of 

toxic and corrosive gases 

Ci (F2) = 40

2. Calculate if the gas mixture is oxidizing using the coefficient of oxygen equivalency figures 

for the oxidizing gases 

Formula: 

 

n

i

mixtureC Vi%)( Ci

C(mixture) = 1.5%(F2) + 98.5%(N2) = 40 x 1.5 + 98.5 x 0 = 60 

Note: The coefficient of oxygen equivalency (Ci) for non-oxidizing components in a mixture 

is zero. 
284

Decision/Rationale 

Using the information gathered, answer the question posed in the decision logic VIII.4.1, above. 

1. Does the gas contribute to combustion of other material more than air does? 

ANSWER: Yes; the oxidation ability of the gas mixture is 60, which is greater than 21. 

Resulting Classification 

The gas mixture is classified as Oxidizing Gas, Category 1. According to the criterion, the gas 

mixture is considered more oxidizing than air [60 > 21]. 
285

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.4, Oxidizing Gases. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 

International Standards Organization (ISO) 10156:1996 (E), Gases and Gas mixtures –

Determination of fire potential and oxidizing ability for the selection of cylinder valve outlets, 

February 15, 1996. 

International Standards Organization (ISO) 10156-2: 2005(E), Gas cylinders, Gases and gas 

mixtures. Part 2: Determination of oxidizing ability of toxic and corrosive gases and gas 

mixtures, August 1, 2005. 
286

VIII.5 Gases under Pressure 

Introduction

All gases under pressure are potentially hazardous since they are under great pressure inside 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. Therefore, the hazard from some gases under pressure may be 

strictly mechanical (e.g., compressed air); others may present other types of hazards, such as 

being flammable (e.g., methane and propane) or toxic 

(e.g., ammonia and chlorine). 

Definition

Gases under pressure are gases which are contained in a 

receptacle at a pressure of 200 kPa (29 psi) (gauge) or 

more20, or which are liquefied or liquefied and 

refrigerated. They comprise compressed gases, liquefied 

gases, dissolved gases and refrigerated liquefied gases. 

In practice, this definition means that gases that are 

packaged at a pressure less than 200 kPa (29 psi) are not 

classified as gases under pressure. Being under pressure 

is not an intrinsic property of the substance. 

Classification Criteria

Gases under pressure are classified, according to their physical state when packaged, in one of 

four groups, as shown in Table VIII.5.1. 

 

20 The pressure of these gases is normally measured at 20 °C (68 oF). 

Receptacle means a containment 

vessel for receiving and holding 

substances or articles, including 

any means of closing. (Definition 

from UN TDG Model Regulations, 

Rev.16)

Pressure receptacle is a collective 

term that includes cylinders, 

tubes, pressure drums, closed 

cryogenic receptacles and bundles 

of cylinders. (Definition from UN 

TDG Model Regulations, Rev.16)
287

Table VIII.5.1. Classification criteria for Gases under pressure. 

Category Criteria

Compressed gas A gas which when under pressure is entirely gaseous at -50 °C (-58 °F), 

including all gases with a critical temperature*≤ -50 °C (-58 °F).

Liquefied gas A gas which when under pressure is partially liquid at temperatures above -

50 °C (-58 °F). A distinction is made between: 

(a) High pressure liquefied gas: a gas with a critical temperature* between -

50 °C (-58 °F) and +65 °C (149 °F); 

and 

(b) Low pressure liquefied gas: a gas with a critical temperature* above +

65 °C (149 °F). 

Refrigerated 

liquefied gas 

A gas which is made partially liquid because of its low temperature.

Dissolved gas A gas which when under pressure is dissolved in a liquid phase solvent.

*

 The critical temperature is the temperature above which a pure gas cannot be liquefied, regardless of the degree 

of compression.

Classification Procedure and Guidance 

The Hazard Communication Standard does not require the testing of chemicals - only the 

collection and analysis of currently available data. 

To classify a gas under pressure, data on its vapor pressure, critical temperature, and its physical 

state are necessary. 

Available Literature

The manufacturer, importer, or other responsible party may use available scientific literature and 

other evidence to identify the vapor pressure, physical state and critical temperature for many 

gases under pressure. Appendix B of this document lists information sources that may prove 

useful during hazard classification. 

In addition, most pure gases under pressure presenting compressed gas, liquefied gas, 

refrigerated liquefied gas, and dissolved gas hazards have already been classified. The 

Hazardous Materials Regulations table from the U.S. Department of Transportation can be used 

to assist in classifications of gases under pressure (see 49 CFR 172.101). Refer to the discussion 

of the interface between the HCS and DOT labeling presented in Chapter V of this document. 

The decision logic presented below should be used to determine the appropriate hazard 

classification category for gases under pressure. 
288

Test Method 

No test methods are specified for gases under pressure. 

Classification Procedure 

To classify gases under pressure, the data listed below are needed: 

(a) The vapor pressure at 50 °C (122 oF); 

(b) The physical state at 20 °C (68 oF) at standard pressure; 

(c) The critical temperature. 

Once you have collected the data, compare the data to the criteria for compressed gases, 

liquefied gases, dissolved gases, and refrigerated liquefied gases, presented in Table VIII.5.1. 

Follow the logic paths presented in the decision logics (or flowcharts) in Figure VIII.5.1 to 

identify the appropriate classification for gases under pressure. 

Gases under pressure also need to be considered for classification in other hazard classes, such as 

flammable gases, flammable aerosols, and oxidizing gases, where relevant. In addition, gases 

considered to be simple asphyxiants should be considered for classification as gases under 

pressure if they meet the criteria. Simple asphyxiants are those chemicals which displace oxygen 

in the ambient atmosphere, and can thus cause oxygen deprivation in those who are exposed, 

leading to unconsciousness and death. Chapter VII.11 of this document presents information on 

simple asphyxiants). 
289

Figure VIII.5.1. Decision logic for classifying gases under pressure. 

* The pressure of these gases is normally measured at 20 °C (68 oF). 

Dissolved gas

Warning

No

Is its critical temperature above +65 °C? 

Is the gas partially liquid because of its low temperature?

No

Is the gas entirely in gaseous state at –50 C?

No

(Low pressure)

Liquefied gas 

Warning

Refrigerated 

liquefied gas 

Warning

Compressed gas

Warning

Is its critical temperature between –50 °C and 

+65 C?

Is the gas dissolved in a liquid phase solvent?

The substance or mixture is a gas

No

Is the gas contained in a receptacle at a pressure of 200 kPa (gauge)*, 

or is the gas liquefied or liquefied and refrigerated?

Not classified as a 

gas under pressure

No

Yes

Yes

Yes

Is the gas partially liquid 

at temperatures above – 50 °C?

Yes

(High pressure)

Liquefied gas 

Warning

Yes

Yes

Yes
290

Gases Under Pressure Classification Examples 

Compressed Gas Example 

The following examples are provided to illustrate the gases under pressure classification process 

and use of the decision logic. 

When the vapor pressure at 50 °C (122 oF), critical temperature, and physical state at 20 °C 

(68 oF) and at standard pressure are known, the classification of the gas can be obtained 

according to the gases under pressure decision logic. 

Known data 

 The substance is a gas 

 The gas is contained in a receptacle at a pressure of > 200 kPa at 20 °C 

 Vapor pressure at 50 °C (122 oF) is > 410 kPa (4.1 bar) 

 Substance when packaged under pressure is entirely gaseous at -50 °C (-58 °F) 

 Critical temperature: -240.1 °C 

Decision/Rationale 

Using the known data, answer the questions posed in the gases under pressure decision logic, 

Figure VIII.5.1, above. 

The substance is a gas (Vapor pressure of the substance at 50 °C is > 410 kPa (4.1 bar).) 

1. Is the gas contained in a receptacle at a pressure of 200kPa (psi)21, or is the gas liquefied or 

liquefied and refrigerated? 

ANSWER: Yes. The gas is contained in a receptacle at a pressure of ≥200 kPa at 20 °C 

2. Is the gas dissolved in a liquid solvent under pressure? 

ANSWER: No. 

3. Is the gas partially liquid because of its low temperature? 

ANSWER: No. The substance when packaged is entirely gaseous at -50 oC 

4. Is the gas partially liquid at temperatures above -50 oC.

ANSWER: No. The substance when packaged is entirely gaseous at -50 oC 

5. Is the gas entirely in gaseous state at -50 °C? 

ANSWER: Yes. 

 

21 The pressure of these gases is normally measured at 20 °C (68 oF). 
291

Resulting Classification 

The gas is classified as a compressed gas. A compressed gas is a gas which when packaged 

under pressure is entirely gaseous at -50 °C; including all gases with a critical temperature 

≤ -50 °C. 

Liquefied Gas Example 

Known data 

 Vapor pressure at 50 °C is 290 kPa (2.9 bar) 

 Substance is completely gaseous at 20 °C and standard pressure (101.3 kPa) 

 Critical temperature: 75.3 °C 

 The substance is a gas and contained in a receptacle at a pressure of 200kPa (psi)22

Decision/Rationale 

Using the known data, answer the questions posed in the gases under pressure decision logic, 

Figure VIII.5.1, above. 

The substance is a gas (completely gaseous at 20 °C and 101.3 kPa) 

1. (a) Is the gas contained in a receptacle at a pressure of 200kPa (psi)5, or is the gas liquefied 

or liquefied and refrigerated? 

ANSWER: Yes 

(b) Is the substance or mixture completely gaseous at 20 °C and 101.3 kPa? 

ANSWER: Yes. 

2. Is the gas dissolved in a liquid solvent under pressure? 

ANSWER: No. 

3. Is the gas partially liquid because of its low temperature? 

ANSWER: No 

4. Is the critical temperature above +65 °C? 

ANSWER: Yes. 

This ends the classification and the decision logic is exited. 

 

22 The pressure of these gases is normally measured at 20 °C (68 oF). 
292

Resulting Classification 

The gas is classified as liquefied gas and fulfills the low pressure liquefied gas criteria. 

The criteria for a low pressure liquefied gas are: A gas which when packaged under pressure is 

partially liquid at temperatures above -50 °C, and has a critical temperature above +65 °C. 

Example for a Substance that is Not Classified 

Known data 

 Vapor pressure at 50 °C is 200 kPa (2 bar) 

 Substance is not completely gaseous at 20 °C and standard pressure (101.3 kPa) 

Decision/Rationale 

Using the known data, answer the questions posed in the gases under pressure decision logic 

VIII.5.1, above. 

1. (a) Is the vapor pressure at 50 °C greater than 300 kPa (3 bar)? 

ANSWER: No. Vapor pressure at 50 °C is not greater than 300 kPa (3 bar) 

(b) Is the substance or mixture completely gaseous23 at 101.3 kPa? 

ANSWER: No. 

Resulting Classification 

The substance is not a gas and therefore is not classified as a gas under pressure. 

 

23 The pressure of these gases is normally measured at 20 °C (68 oF). 
293

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.5, Gases Under Pressure. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
294

VIII.6 Flammable Liquids 

Introduction

The ability of a chemical to either burn or support burning is a potentially dangerous physical 

hazard. The two primary measures of the ease with which a liquid will burn are the flash point 

and auto-ignition temperature. The flash point is the lowest temperature at which a liquid will 

emit sufficient vapors to form an ignitable mixture with air. In contrast, auto-ignition 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 chemicals 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 flash point. 

For this reason, the HCS uses flash point in classifying the fire hazard of a chemical liquid. 

There are four flammable liquid categories ranging from category 1 extremely flammable liquids 

and vapors to category 4 combustible liquids. Although the flash point is the criterion used for 

classification for all hazard categories in this hazard class, the initial boiling point also is used to 

identify hazard categories 1 and 2. The difference between the flammable liquid categories is the 

relative ease (temperature) with which the chemical burns or supports burning. 

When a chemical 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 

Category 1 is potentially more hazardous than a flammable liquid Category 4. A flammable 

liquid Category 1 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. For a 

flammable liquid Category 4 to present a fire hazard, it must be above normal room temperature. 

Definitions

Flammable liquid is a liquid having a flash point of not more than 93 °C (199.4 °F). 

Flash point is the minimum temperature at which a liquid gives off vapor in sufficient 

concentration to form an ignitable mixture with air near the surface of the liquid, as determined 

by a specified test method. 

Initial boiling point is the temperature of a liquid at which its vapor pressure is equal to the 

standard pressure (101.3 kPa24; 14.7 psi), i.e., the first gas bubble appears. (Definition from 

GHS, Rev. 3) 

 

24 Pascal [Pa] is the SI Unit (International System of Units) for pressure. 

1 Pa = 1 N/m2 = 10-5 bar = 0.75 10-2 torr 

The letter “k” stands for “kilo”: 1 kPa = 1,000 Pa. 
295

Classification Criteria

A flammable liquid is classified in one of four categories on the basis of its flash point and initial 

boiling point, as presented in Table VIII.6.1. 

Table VIII.6.1. Classification criteria for flammable liquids.

Category Criteria

1 Flash point < 23 °C (73.4 °F) and initial boiling point ≤ 35 °C (95 °F) 

2 Flash point < 23 °C (73.4 °F) and initial boiling point > 35 °C (95 °F)

3 Flash point ≥ 23 °C (73.4 °F) and ≤ 60 °C (140 °F) 

4 Flash point > 60 °C (140 °F) and ≤ 93 °C (199.4 °F) 

Note: Aerosols should not be classified as flammable liquids. 

Classification Procedure and Guidance 

To classify a flammable liquid, data on its flash point and initial boiling point are necessary. 

Available Literature

The classifier may use available scientific literature and other evidence to identify the flash point 

and initial boiling point for many flammable liquids. The required information may already exist 

and be well-documented for many flammable liquids. 

In addition, many substances presenting flammable liquid hazards have already been classified. 

The information in the U.S. Department of Transportation’s Hazardous Materials Table can be 

used to assist in flammable liquid classifications (See 49 CFR 172.101). The classification of 

flammable liquids in the HCS corresponds to DOT’s classification of flammable liquids. Refer 

to the discussion on the interface between the HCS and DOT labeling in Chapter V of this 

document for more information.

Under DOT regulations, flammable liquids are considered Class 3, hazardous materials and are 

assigned to three packing groups, corresponding to categories 1, 2, and 3 of the HCS. DOT 

regulations do not include those liquids with a flash point between 60 °C (140 °F) and 93 °C 

(199.4 °F) in an assigned packing group for Class 3 hazardous materials. Therefore, to classify 

chemicals as HCS Category 4 flammable gases, the necessary information and data must be 

gathered elsewhere. The decision logic presented below should be used to determine the 

appropriate hazard classification category for a flammable liquid. 

Test Method 

As mentioned throughout this guidance, the HCS does not require the testing of chemicals – only 

the collection and analysis of currently available data. However, if you decide to test the 
296

substance or mixture, use the methods identified in Appendix B.6 to 29 CFR 1910.1200 and 

presented below. 

Flash Point 

To determine the flash point experimentally, information on the viscosity of the liquid is needed 

to select a suitable method. 

The HCS requires that the flash point be determined using any of the following test methods. 

 ASTM D56-05, Standard Test Method for Flash Point by Tag Closed Cup Tester 

 ASTM D3278-96 (2004) E1, Standard Test Methods for Flash Point of Liquids by Small 

Scale Closed Cup Apparatus 

 ASTM D3828-07a, Standard Test Methods for Flash Point by Small Scale Closed Cup Tester 

 ASTM D93-08, Standard Test Methods for Flash Point by Pensky-Martens Closed Cup 

Tester, or 

 Any other method specified in GHS Revision 3, Chapter 2.6. 

The GHS Rev. 3 lists the following additional methods for determining the flash point of 

flammable liquids. 

 International standards 

ISO 1516 

ISO 1523 

ISO 2719 

ISO 13736 

ISO 3679 

ISO 3680 

 National standards: 

 Association française de normalisation, AFNOR, 11, rue de Pressensé. 93571 La Plaine 

Saint-Denis Cedex 

o French Standard NF M 07 - 019

o French Standards NF M 07 - 011 / NF T 30 - 050 / NF T 66 - 009 

o French Standard NF M 07 – 036

 Deutsches Institut für Normung, Burggrafenstr. 6, D-10787 Berlin 

o Standard DIN 51755 (flash points below 65 °C) 

 State Committee of the Council of Ministers for Standardization, 113813, GSP, Moscow, 

M-49 Leninsky Prospect, 9 

o GOST 12.1.044-84
297

Initial Boiling Point 

The HCS requires that the initial boiling point be determined using either of the following methods. 

 ASTM D86-07a, “Standard Test Method for Distillation of Petroleum Products at 

Atmospheric Pressure” 

 ASTM D1078-05, “Standard Test Method for Distillation Range of Volatile Organic 

Liquids” 

Classification procedure 

Once information on the chemical’s flash point and initial boiling point (either from available 

scientific literature or the test results) is gathered, the information is compared to the 

classification criteria. Follow the logic paths presented in the decision logics in Figure VIII.6.1, 

to identify the appropriate classification categories for flammable liquids. 
298

Figure VIII.6.1. Decision logic for classifying flammable liquids. 

Category 4

No symbol

Yes Warning

Yes

No

Does it have an initial boiling point > 35 °C (95 °F)?

Not classified No

Does it have a flash point  23 C (73.4 °F)?

Does it have a flash point > 60 °C (140 °F)?

Does it have a flash point  93 C (199.4 °F)?

The substance/mixture is a liquid

Category 3

Warning

Yes

No

Category 2

Danger

Yes

Category 1

Danger 

No
299

Flammable Liquid Classification Examples

Example 

The following example is provided to illustrate the classification process when data are available 

for the chemical in question. In this case, a liquid is suspected of being a flammable liquid, and 

has a known flash point and a known initial boiling point. With this information, the 

classification of the chemical can be determined using the Decision Logic for flammable liquids. 

Known data

 Physical state: liquid 

 Melting point: -95 oC 

 Initial boiling point: 56 oC, at standard pressure 

 Flash point: -18 oC (closed cup test) 

Decision/Rationale

1. Does the chemical have a flash point ≤ 93 C?

ANSWER: Yes. The chemical has a flash point of -18 oC. 

2. Does the chemical have a flash point > 60 °C? 

ANSWER: No. The chemical has a flash point of -18 oC. 

3. Does the chemical have a flash point ≥ 23 °C? 

ANSWER: No. The chemical has a flash point of -18 oC. 

4. Does the chemical have an initial boiling point > 35 °C? 

ANSWER: Yes. The chemical has an initial boiling point of 56 oC. 

Resulting Classification

The chemical fulfills the requirements of a Flammable Liquid, Category 2, because it has a flash 

point < 23 C and a boiling point > 35 °C. 
300

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.6, Flammable Liquids. 

29 CFR 1910.1200, Hazard Communication, Appendix C, Allocation of Label Elements.

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
301

VIII.7 Flammable Solids 

Introduction

The ability of a solid chemical to ignite, to burn rapidly, or for the flame to spread quickly is a 

potentially dangerous physical hazard. These chemicals can burn so vigorously or persistently 

that they create a serious fire hazard. 

Classification as a flammable solid differentiates between solid chemicals that can be ignited and 

those that burn rapidly, or whose burning behavior is particularly dangerous. Only solid 

chemicals whose burning rate exceeds a certain value are classified as flammable solids.

Various solid organic chemicals meet the criteria to be classified as flammable solids. For 

inorganic solids, classification as a flammable solid is less frequent. 

Definition

Flammable solid means a solid which is a readily combustible solid, or which may cause or 

contribute to fire through friction. 

Readily combustible solids are powdered, granular, or pasty chemicals which are dangerous if 

they can be easily ignited by brief contact with an ignition source, such as a burning match, and 

if the flame spreads rapidly.

Classification Criteria

A flammable solid is classified in one of two categories based on its burning behavior in the test 

procedure described below (see Table VIII.7.1). 

Table VIII.7.1. Classification criteria for flammable solids. 

Category Criteria

1 Burning rate test:

Chemicals other than metal powders:

(a) wetted zone does not stop fire; and

(b) burning time < 45 seconds or burning rate > 2.2 mm/second

Metal powders:

Burning time ≤ 5 minutes

2 Burning rate test:

Chemicals other than metal powders:

(a) wetted zone stops the fire for at least 4 minutes; and

(b) burning time < 45 seconds or burning rate > 2.2 mm/second

Metal powders:

Burning time > 5 minutes and ≤ 10 minutes
302

Note: Classification of solid chemicals is based on tests performed on the chemical as presented. 

If, for example, for the purposes of supply or transport, the same chemical is to be presented in a 

physical form different from that which was tested and which is considered likely to materially 

alter its performance in a classification test, classification must be based on testing of the 

chemical in the new form. 

Aerosols should not be classified as flammable solids. 

Classification Procedure and Guidance 

To classify a flammable solid, data on the burning behavior of the chemical is necessary. 

Available Literature

The classifier may use available scientific literature and other evidence to identify the burning 

behavior for many flammable liquids. The required information may already exist and be welldocumented for many flammable solids. Many sources, such as those listed in Appendix B, 

Information Sources to Assist with Hazard Classification, provide chemical data and other 

information on chemicals. 

In addition, many substances presenting flammable solid hazards have already been classified. 

The information in the U.S. Department of Transportation’s Hazardous Materials Table can be 

used to assist in flammable solid classifications (See 49 CFR 172.101). Under DOT regulations, 

flammable solids are considered Class 4, Division 4.1 hazardous materials, and are assigned to 

two packing groups. Flammable solid categories 1 and 2 of the HCS correspond to DOT’s Class 

4, Division 4.1, Packing Groups II and III. Refer to the discussion on the interface between the 

HCS and DOT labeling in Chapter V of this document for more information.

The decision logic presented below should be used to determine the appropriate hazard 

classification category for a flammable solid. 

Test Method

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance, use the methods identified in Appendix B. 7 to 29 CFR 

1910.1200, which are described below. 
303

Classification based on Test Methods in the UN TDG Manual of Tests and Criteria

The classification of flammable solids is based on tests described in Part III of the Fourth 

Revised Edition of the United Nations Recommendations on the Transport of Dangerous 

Goods(UN TDG) – Manual of Tests and Criteria, Sub-section 33.2.1, “Test N.1: Test method 

for readily combustible solids.” A summary of this test is presented below. 

Refer to the UN TDG Manual of Tests and Criteria for a complete description of the method, the 

apparatus used, and analysis of the test results. 

This test method includes a preliminary screening test and a burning rate test. The method 

evaluates the ability of a substance to propagate combustion by igniting it to determine the 

burning time and whether a wetted zone stops the propagation. These tests should only be 

applied to granular, paste-like, or powdery substances. If in the screening test, the substance 

does not ignite and propagate combustion by either burning with flame or smoldering, it is not 

necessary to perform the complete burning rate test, because the substance is not a readily 

combustible solid as defined in the HCS. However, if propagation occurs and the burning time is 

less than the time specified in the test, then the full burning rate test should be performed. 

Classification Procedure 

When using the N.1 test results to determine classification, information from both the 

preliminary screening test and burning rate test is needed. The following information is needed: 

 Whether or not the chemical ignites and propagates combustion (Preliminary Screening 

Test)

 Burning time [seconds] or burning rate [mm/second] (Burning Rate Test) 

 Other than metal powders, does the wetted zone stop the propagation of the fire? 

Classification is based upon the fastest burning rate and shortest burning time obtained in six test 

runs, unless a positive result is observed earlier. For substances and mixtures other than metal 

powders, the category is assigned depending on whether the wetted zone is able to stop the 

flame. 

The results and observation from the Test N.1 are compared to the criteria for flammable solids 

Category 1 and Category 2 using the decision logic for classifying flammable solids provided in 

Figure VIII.7.1, below. 
304

Figure VIII.7.1. Decision logic for classifying flammable solids based on Test N.1. 

Screening test

Burning rate test:

(a) For substances or mixtures other than metal powders:

Burning time < 45 s or burning rate > 2.2 mm/s? 

(b) Metal powders: Burning time 10 min.? 

Not classified

Category 1

Danger

Positive

The substance/mixture is a solid

(a) For substances or mixtures other than metal powders:

Does the wetted zone stop propagation of the flame at 

least 4 min? 

(b) Metal powders: Burning time > 5 min.?

Yes

No Not classified

No

Category 2

Warning

Negative

Yes
305

Flammable Solids Classification Example 

The following example illustrates the classification process for a chemical suspected of being a 

flammable solid when there is no existing data, and information from the required test procedure 

is gathered. An organic solid material is suspected of being a flammable solid, but has no other 

information to help with the classification process. In this case, the chemical is tested using the 

UN Recommendations on the Transport of Dangerous Goods, Manual of Tests and Criteria, 

Part III, Sub-section 33.2.1.4, Test N.1: Test method for readily combustible solids. The 

procedure consists of two tests: a preliminary screening test and a burning rate test. 

Once the test is complete, classification of the chemical can be determined according to the HCS 

Flammable Solids decision logic. 

Known data

Organic solid material, not a metal 

Test data results

1. Preliminary screening test results: Burns with an open flame in less than 2 minutes, which is 

a positive result. 

2. Burning rate test results: Burning times for a distance of 100 mm (6 runs): 44 seconds (s); 

40 s; 49 s; 45 s; 37 s; 41 s. 

3. Wetted zone stops the fire, no re-ignition. 

Decision/Rationale

1. Preliminary screening test is performed to determine whether the chemical is a candidate for 

classification as a flammable solid. The chemical burns with an open flame in less than 2 

minutes, so the result is positive. 

2. Since the preliminary screening test is positive, a burning rate test is performed. 

3. Is the shortest burning time less than 45 s? 

ANSWER: Yes, the shortest burning time was 37 s, indicating the substance is a flammable 

solid. 

4. Does the wetted zone stop the fire? 

ANSWER: Yes, and the chemical does not reignite. 

Resulting Classification 

The organic solid is classified as a flammable solid, Category 2, based on the outcome of UN

TDG Manual of Tests and Criteria, Method N.1.
306

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.7, Flammable Solids. 

29 CFR 1910.1200, Hazard Communication, Appendix C, Allocation of Label Elements. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009.

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
307

VIII.8 Self-Reactive Chemicals 

Introduction

Self-reactive chemicals display a very wide range of properties. While the most hazardous type 

of self-reactive chemicals are too dangerous to transport commercially, they can be stored safely 

with appropriate precautions. The self-reactive classification also includes substances that only 

decompose slowly at temperatures well above normal storage and transport temperatures [e.g., 

75 °C (167 oF)]. 

The decomposition of self-reactive chemicals can be initiated by heat, contact with catalytic 

impurities (e.g., acids, heavy metal compounds, or bases), friction, or impact. The rate of 

decomposition increases with temperature and varies with the chemical. Decomposition, 

particularly if no ignition occurs, may result in the evolution of toxic gases or vapors. For 

certain self-reactive chemicals, the temperature must be controlled, while others may decompose 

explosively, particularly if confined. This characteristic may be modified by the addition of 

diluents or by the use of appropriate packagings. Some self-reactive chemicals burn vigorously. 

Examples of self-reactive chemicals include some compounds of the types listed below: 

 Aliphatic azo compounds (-C-N=N-C-);

 Organic azides (-C-N3); 

 Diazonium salts (-CN2+Z-);

 N-nitroso compounds (-N-N=O); and 

 Aromatic sulphohydrazides (-SO2-NH-NH2). 

This list is not exhaustive and chemicals with other reactive groups and some mixtures may have 

similar properties. 

Definition

Self-reactive chemicals are thermally unstable liquid or 

solid chemicals liable to undergo a strongly exothermic 

decomposition even without participation of oxygen 

(air). This definition excludes chemicals classified as 

explosives, organic peroxides, oxidizing liquids, or 

oxidizing solids. 

A self-reactive chemical is regarded as possessing 

explosive properties when in laboratory testing the 

formulation detonates, deflagrates rapidly, or shows a 

violent effect when heated under confinement. 

Deflagration. Propagation of a 

reaction zone at a velocity that is 

less than the speed of sound in the 

unreacted medium (Definition 

from NFPA 68).

Detonation. Propagation of a 

combustion zone at a velocity that 

is greater than the speed of sound 

in the unreacted medium 

(Definition from NFPA 68).
308

Classification Criteria 

Self-reactive chemicals are assigned to one of the seven types, A to G, according to the degree of 

danger they present. Table VIII.8.1 presents the classification criteria for self-reactive 

chemicals. 

Table VIII.8.1. Classification criteria for self-reactive chemicals. 

Self-Reactive 

Type Criteria

A Any self-reactive chemical that can detonate or deflagrate rapidly, as 

packaged. 

B Any self-reactive chemical possessing explosive properties and which, as 

packaged, neither detonates nor deflagrates rapidly, but is liable to undergo 

a thermal explosion in that package.

C Any self-reactive chemical possessing explosive properties when the 

chemical as packaged cannot detonate or deflagrate rapidly or undergo a 

thermal explosion.

D Any self-reactive chemical which, in laboratory testing, meets the criteria in 

i, ii, or iii presented below: 

i. Detonates partially, does not deflagrate rapidly, and shows no 

violent effect when heated under confinement; or 

ii. Does not detonate at all, deflagrates slowly, and shows no violent 

effect when heated under confinement; or 

iii. Does not detonate or deflagrate at all, and shows a medium effect 

when heated under confinement.

E Any self-reactive chemical which, in laboratory testing, neither detonates 

nor deflagrates at all and shows low or no effect when heated under 

confinement.

F Any self-reactive chemical which, in laboratory testing, neither detonates in 

the cavitated state nor deflagrates at all and shows only a low or no effect 

when heated under confinement as well as low or no explosive power.
309

Self-Reactive 

Type Criteria

G Any self-reactive chemical which, in laboratory testing, neither detonates in 

the cavitated state nor deflagrates at all, and shows no effect when heated 

under confinement nor any explosive power, provided that it is thermally 

stable (self-accelerating decomposition temperature is 60 °C (140 °F) to 75 

°C (167 °F) for a 50 kg (110 lb.) package), and, for liquid mixtures, a 

diluent having a boiling point greater than or equal to 150 °C (302 °F) is 

used for desensitization.

If the mixture is not thermally stable or a diluent having a boiling point less 

than 150 °C (302 °F) is used for desensitization, the mixture is defined as 

self-reactive chemical TYPE F.

Note: Type G has no hazard communication elements assigned but should be considered for 

properties belonging to other hazard classes. 

Classification Procedure and Guidance 

To classify a self-reactive chemical, data on its ability to detonate, deflagrate, and the effect of 

heating under confinement are needed. 

A self-reactive chemical is considered for classification in this class unless: 

a) It is classified as an explosive according to Appendix B.1 to 29 CFR 1910.1200; 

b) It is classified as an oxidizing liquid or an oxidizing solid according to Appendix B.13 or 

B.14 to 29 CFR 1910.1200, except that a mixture of oxidizing chemicals which contains 5% 

or more of combustible organic substances is classified as a 

self-reactive chemical according to the procedure defined in 

B.8.2.2 to 29 CFR 1910.1200 (explained below); 

c) It is classified as an organic peroxide according to Appendix 

B.15 to 29 CFR 1910.1200; 

d) Its heat of decomposition is less than 300 Joules/gram; or 

e) Its self-accelerating decomposition temperature (SADT) is 

greater than 75 °C (167 °F) for a 50 kg (110 lb.) package. 

Paragraph B.8.2.2 to 29 CFR 1910.1200 explains that mixtures of 

oxidizing substances, meeting the criteria for classification as 

oxidizing liquids or oxidizing solids, containing 5% or more of combustible organic substances 

and which do not meet the criteria explained in (a), (c), (d) or (e), above, are subjected to the 

self-reactive chemicals classification. Mixtures showing the properties of a self-reactive 

chemical type B to F are classified as a self-reactive chemical. 

Self-accelerating 

decomposition 

temperature (SADT) 

means the lowest 

temperature at which 

self-accelerating 

decomposition may 

occur with a substance 

as packaged. (Definition 

from GHS, Rev. 3)
310

The classification procedures for self-reactive chemicals need not be applied if they meet either 

of the following two criteria: 

1. There are no chemical groups present in the molecule associated with explosive or selfreactive properties; examples of such groups are provided in Tables VIII.8.2 and VIII.8.3 

below, extracted from the UN Recommendations on the Transport of Dangerous Goods (UN 

TDG) Manual for Tests and Criteria, Appendix 6. 

Table VIII.8.2. Examples of Chemical Groups Indicating Explosive Properties in 

Organic Material. 

Structural feature Examples

C-C unsaturation Acetylenes, acetylides, 1,2-dienes 

C-Metal, N-Metal Grignard reagents, organo-lithium compounds 

Contiguous nitrogen atoms Azides, aliphatic azo compounds, diazonium 

salts, hydrazines, sulphonylhydrazides 

Contiguous oxygen atoms Peroxides, ozonides 

N-O

Hydroxylamines, nitrates, nitro compounds, 

nitroso compounds, N-oxides, 1,2-oxazoles 

N-halogen Chloroamines, fluoroamines 

O-halogen Chlorates, perchlorates, iodosyl compounds 

Table VIII.8.3. Examples of Chemical Groups Indicating Self-Reactive Properties in 

Organic Material. 

Structural feature Examples

Mutually reactive groups Aminonitriles, haloanilines, organic salts of 

oxidizing acids

S=O Sulphonyl halides, sulphonyl cyanides, 

sulphonyl hydrozines

P-O Phosphites

Strained rings Epoxides, aziridines

Unsaturation Olefines, cyanates

or 
311

2. For a single organic substance or a homogeneous mixture of organic substances, the 

estimated SADT is greater than 75 °C (167 °F) or the exothermic decomposition energy is 

less than 300 Joules/gram. The onset temperature and decomposition energy may be 

estimated using a suitable calorimetric technique (See 20.3.3.3 in Part II of the UN TDG 

Manual of Tests and Criteria).

Available Literature

The classifier may use available scientific literature and other evidence to classify self-reactive 

chemicals. The information needed to classify the chemicals may be found in available literature 

or through laboratory testing. Should data from laboratory testing be used, the chemical must be 

tested together with their packages. 

In addition, many substances presenting self-reactive chemical hazards have already been 

classified. The information in the U.S. Department of Transportation’s Hazardous Materials 

Table can be used to assist when classifying self-reactive chemicals (See 49 CFR 172.101). The 

DOT regulations also provide a list of self-reactive substances in 49 CFR 173.224. Under DOT 

regulations, the majority of self-reactive chemicals are considered Hazard Class 4 Division 4.1, 

self-reactive materials. Self-reactive chemicals classified in accordance with the HCS 

correspond to self-reactive materials classified for transport. Therefore, the labeling 

requirements for self-reactive materials in the HCS correspond to DOT’s Hazard Class 4, 

Division 4.1, self-reactive materials. Refer to the discussion on the interface between the HCS 

and DOT labeling in Chapter V of this document for more information. 

Test Method

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals - only the collection and analysis of currently available data. 

However, if you choose to test the substance or mixture, then use methods identified in 

Appendix B.8 to 29 CFR 1910.1200 and described below. 

The classification of self-reactive chemicals is based on tests described in Part II of the Fourth 

Revised Edition of the UN TDG Manual of Tests and Criteria, Sub-sections 20 to 28, Test Series 

A to H. The methods are designed for testing both self-reactive chemicals and organic 

peroxides. The decision logic presented below should be used to determine the appropriate 

hazard classification category for self-reactive chemicals if testing is performed to gather the 

necessary information. 

Self-reactive chemicals are classified into seven types according to the hazard. The tests are 

performed in two stages. The first stage uses preliminary small scale tests to ascertain the 

stability and sensitivity of the chemicals and ensure the safety of laboratory workers. During the 

second stage, classification tests are performed. Note that explosive properties are associated 

with the presence of certain chemical groups in a molecule that can react to produce very rapid 

increases in temperature or pressure. The preliminary procedure is aimed at identifying the 

presence of such reactive groups and the potential for rapid energy release. 
312

A brief summary of these tests is presented below. Refer to the UN TDG Manual of Tests 

and Criteria for a complete description of the method, the apparatus used, and analysis of the 

test results. 

Preliminary procedure 

Performing small-scale preliminary tests before attempting to handle larger quantities is essential 

for ensuring the safety of laboratory workers. The preliminary tests determine the sensitiveness 

of the chemical to mechanical stimuli (impact and friction), and to heat and flame. Four types of 

small-scale tests are used to make the preliminary assessment: 

(a) A falling weight test to determine sensitiveness to impact; 

(b) A friction or impacted friction test to determine the sensitiveness to friction; 

(c) A test to assess thermal stability and the exothermic decomposition energy; and 

(d) A test to assess the effect of ignition. 

The details of these preliminary tests can be found in Part I of the Fourth Revised Edition of the 

UN TDG Manual of Tests and Criteria, Sub-section 13, Test Series 3. Appendix 6 of the UN 

TDG Manual of Tests and Criteria provides additional guidance on screening procedures. 

Classification test 

The classification of a self-reactive chemical in one of the seven categories, Types A to G, is 

dependent on its detonation, explosive thermal explosion and deflagrating properties, its 

response to heating, the concentration and the type of diluent added to desensitize the substance. 

The classification of a self-reactive chemical as Type A, B or C is also dependent on the type of 

packaging in which the chemical is tested, as the package affects the degree of confinement to 

which the chemical is subjected. 

Should testing be performed on the chemical, data from self-reactive chemical test series A to H 

is needed. A brief description of the tests described in the UN TDG Manual of Tests and 

Criteria is presented below. 

Test Series A answers the question, “Does the chemical propagate a detonation?” The tests 

measure the ability of a substance to propagate a detonation by subjecting it to a detonating 

booster charge under confinement in a steel tube. The test methods include: 

 BAM 50/60 steel tube test 

 TNO 50/70 steel tube test 

 UN gap test 

 UN detonation test (the recommended test) 
313

Test Series B answers the question “Can the chemical detonate as packaged for transport?” The 

tests measure the ability of a chemical to propagate a detonation when packaged for transport by 

subjecting it to the shock from a detonating booster charge. The test is required only for 

substances that propagate detonation. 

Test Series C answers the question, “Does the chemical propagate a deflagration?” This test 

series consists of two tests – the time/pressure test, and the deflagration test. Both tests are 

recommended. The time and pressure test measures the ability of a substance under confinement 

to propagate a deflagration. The deflagration test measures the ability of a chemical to propagate 

a deflagration. 

Test Series D answers the question, “Does the chemical deflagrate rapidly in package?” The test 

measures the ability of a chemical to rapidly propagate a deflagration when packaged for 

transport. The test is required for substances that deflagrate rapidly in a Test Series C test. 

Test Series E answers the question, “What is the effect of heating the chemical under defined 

confinement?” This test series consists of three test methods – the Koenen test, the Dutch 

pressure test, and the USA pressure test. For self-reactive chemicals, the Koenen test is 

recommended in combination with one of the other tests. The three tests are described below. 

The Koenen test determines the sensitivity of substances to the effect of intense heat under high 

confinement. The Dutch pressure vessel test and the USA pressure test determine the sensitivity 

of substances to the effect of intense heat under defined confinement. 

Test Series F answers the question, “What is the chemical’s explosive power?” Several tests are 

described in the UN TDG Manual of Tests and Criteria, including the Ballistic mortar Mk. IIId 

test, the Ballistic mortar test, the BAM Trauzl test, the Modified Trauzl test, and the Highpressure autoclave. The Modified Trauzl test is the recommended test, measures the explosive 

power of a chemical, and is used for chemicals being considered for transport in intermediate 

bulk containers (IBCs) or tank-containers. 

Test Series G answers the question, “Can the chemical explode as packaged for transport?” The 

test series uses two test methods – the thermal explosion test in package, and the accelerating 

decomposition test in package. The test is needed only for chemicals that show a violent effect 

in tests involving heating under defined confinement (Test Series E). The thermal explosion test 

in package is the recommended test and is used to determine the potential for thermal explosion 

in a package. 

Temperature control 

In addition to the classification tests, the thermal stability of the self-reactive substances is 

needed to determine the Self-Accelerating Decomposition Temperature (SADT). There is no 

relation between the SADT of a self-reactive substance and its classification in one of the seven 

categories Types A to G. However, the SADT is used to derive safe handling, storage and 
314

transport temperatures (control temperature), and alarm temperature (emergency temperature). 

Self-reactive substances need to be subjected to temperature control if their SADT is less than or 

equal to 55 °C (131 oF). 

The UN TDG Manual of Tests and Criteria, Part II, Sub-section 

28, Test Series H, describes several test methods for determining 

the SADT, including the United States SADT test, the Adiabatic 

storage test, the Isothermal storage test, and the heat accumulation 

storage test. Since there are several test methods presented, the 

test selected and conducted should be representative of the 

package, both in size and material. Each test involves either 

storage at a fixed external temperature and observation of any 

reaction initiated or storage under near adiabatic conditions and 

measurement of the rate of heat generation versus temperature. 

Classification Procedure 

Self-reactive chemicals are classified according to the classification principles given in the 

decision logic and the results of test series A to H. In addition, classification may be determined 

using information provided in available scientific literature. As one can see from the 

explanations above, the test series are designed to provide the information necessary to answer 

the questions in the decision logic for self-reactive chemicals, presented in Figure VIII.8.1. 

 Test series A includes laboratory tests and criteria concerning propagation of detonation as 

requested in box 1 of the flowchart. 

 Test series B includes a test and criteria concerning the propagation of detonation of the 

substance as packaged for transport, as requested in box 2 of the flowchart. 

 Test series C includes laboratory tests and criteria concerning propagation of deflagration as 

requested in boxes 3, 4, and 5 of the flowchart. 

 Test series D includes a test and criteria concerning the propagation of a rapid deflagration of 

the substance as packaged for transport, as requested in box 6 of the flowchart. 

 Test series E includes laboratory tests and criteria concerning the determination of the effect 

of heating under defined confinement, as requested in boxes 7, 8, 9, and 13 of the flowchart. 

 Test series F includes laboratory tests and criteria concerning the explosive power of 

substances that are considered for transport in Intermediate Bulk Containers (IBCs) or tanks, 

or for exemption (see box 11 of the flowchart), as requested in box 12 of the flowchart. 

 Test series G includes tests and criteria concerning the determination of the effect of a 

thermal explosion of the substance as packaged for transport, as requested in box 10 of the 

flowchart. 

Self-accelerating 

decomposition 

temperature (SADT) 

means the lowest 

temperature at which 

self-accelerating 

decomposition may 

occur with a substance 

as packaged. (Definition 

from GHS, Rev. 3)
315

 Test series H includes tests and criteria concerning the determination of the self-accelerating 

decomposition temperature of self-reactive or potentially self-reactive substances. 

The decision logic for classifying self-reactive chemicals is provided in Figure VIII.8.1. To 

answer the questions in the decision logic the following information is needed: 

 Propagation of detonation 

 Propagation of deflagration 

 Effect on heating in confinement 

 Thermal stability: Self-accelerating decomposition temperature (SADT) 

Data from additional tests may also be needed (for example, explosive power, or explosivity as 

packaged) depending on the circumstances and/or the results of the foregoing tests. 

Classification follows the assessment of available data and, if applicable, the results of any 

testing performed. Once you have collected the data, the data and test results are compared to 

the classification criteria for self-reactive chemicals types A through G presented in 

Table VIII.8.1. Follow the logic paths presented in the decision logic (or flowchart) in 

Figure VIII.8.1 to identify the appropriate classification for self-reactive chemicals. 
316

Figure VIII.8.1. Decision logic for classifying self-reactive chemicals. 

6.1 Yes

Box 6

Test D

6.2 No

7.2 Medium

7.3 Low

7.4 None

Box 7

Test E

7.1 

Violent

10.1 Yes

Box 10

Test G

10.2 No

3.2 Yes, slowly

3.3 No

3.1 

Yes, rapidly

2.1 Yes 2.2 No

1.1 Yes

1.2 Partial

1.3 No

4.1 

Yes, rapidly

SUBSTANCE/MIXTURE

11.2 No

12.1

Not low

12.2 Low

12.3 None

13.1 Low

13.2 None

Box 13

Test E

5.1 

Yes, rapidly

5.2 Yes, slowly

5.3 No

Box 8

Test E

8.1 

Violent

8.2 Medium

8.3 Low

8.4 None

?

4.2 Yes, slowly

4.3 No

9.2 Medium

Box 9

Test E

9.1 

Violent

9.3 Low

9.4 None

11.1 Yes

Box 11

Box 12

Test F

Type A Type B Type C Type D Type E Type F Type G

Does it propagate 

a detonation 

? 

Can it 

detonate as 

packaged 

? 

Can it 

propagate a 

deflagration 

? 

Box 2

Test B

Box 3

Test C

Can it 

propagate a 

deflagration 

? 

Can it 

propagate a 

deflagration 

Box 4

Test C

Box 5

Test C

Does it

deflagrate rapidly

in package 

? 

What is

the effect of heating

under confinement

? 

What is

the effect of heating

under confinement

? 

What is

the effect of heating

under confinement

? 

Can it 

detonate as 

packaged 

? 

Packaged

in packages of more

than 400 kg/450 l or to 

be considered for 

exemption 

?

What is

the effect of heating

under confinement

? 

What is

its explosive 

power 

? 
317

Self-Reactive Chemical Classification Example 

The following example is provided to illustrate the self-reactive chemicals classification process 

and use of the decision logic. 

A white solid is suspected of being a self-reactive chemical and is tested according to the 

appropriate UN tests. 

The test methods for determining the type of self-reactive chemical are performed using the UN 

TDG Manual of Tests and Criteria, Part II, Test Series A to H. The tests are designed to provide 

the information necessary to answer the questions in the decision logic for self-reactive 

chemicals and to apply the principles for classification. In the following example, the results of 

the tests are assessed in alphanumeric order; however, the tests are performed in the order given 

in section 20.4.5 of the UN TDG Manual of Tests and Criteria.

Known data 

 White solid 

 Composition: 96% Azodicarbonamide 

 Molecular formula: C2H4N4O2

 Apparent density: 945 kg/m3

 Particle size: < 400 μm 

Test results

Test Name Observation Result

Test series A - Detonation 

propagation [BAM 50/60 steel 

tube test]

30 cm of tube fragmented, 

unreacted substance remained 

in the tube

Partial propagation of detonation 

(Exit 1.2 of Box 1/Test Decision 

Logic flowchart)

Test series B - Detonation as 

packaged 

Not applicable

Test series C - Deflagration 

propagation [Time/pressure test]

Test conducted on 5 g of 

sample three times and the time 

it took for the pressure to rise 

from 690 kPa to 2,070 kPA 

was noted (3.0 s, 2.5 s, 2.7 s). 

Shortest recorded time (2.5 s) 

is used for result.

Test result/criteria: Yes, slowly, 

because the time for pressure to 

rise from 690 kPa to 2,070 kPA 

is greater than or equal to 30 ms.
318

Test Name Observation Result

Test series C - Deflagration 

propagation [Deflagration test]

Test conducted two times on 

265 cm3of sample at 50 °C, 

and the reaction rate noted for 

each (0.71 mm/s, 0.65 mm/s). 

Shortest recorded rate (0.65 

mm/s) is used for result.

Test result/criteria: Yes, slowly, 

because the deflagration rate is 

less than or equal to 5.0 mm/s 

and greater than or equal to 0.35 

mm/s. 

Overall result: Yes, slowly (Exit 

4.2 of Box 4/Test C Decision 

Logic flowchart)

Test series D - Deflagration as 

packaged 

Not applicable

Test series E - Effect of heating 

under confinement [Koenen test]

Tested 26.0 g of sample. 

Limiting diameter of 3.5 mm 

(time to reaction 19.0 s, 

duration of reaction 22 s)

Test result/criteria: Violent, 

because the limiting diameter is 

greater than or equal to 2.0 mm.

Test series E - Effect of heating 

under confinement [Dutch 

Pressure Vessel test]

Tested 10.0 g of sample. 

Limiting diameter of 10.0 mm 

(time to reaction 110 s, 

duration of reaction 4 s)

Test result/criteria: Violent, 

because rupture of the disc with 

an orifice of 9.0 mm or greater 

and a sample mass of 10.0 g.

Overall result: Violent (Exit 8.1 

of Box 8/Test E Decision Logic 

flowchart)

Test series F - Explosive Power Not applicable

Test series G - Detonation as 

packaged [Thermal explosion test 

in the package]

Tested 25 kg of substance in 

packaging type 6HG2. 

Observed fumes only, no 

fragmentation of the package.

Test result/criteria: No 

explosion: No fragmentation or 

a fragmentation into no more 

than three pieces shows that the 

substance does not explode in the 

package.

Exit 10.2 of Box 10/Test G 

Decision Logic flowchart.

Chemical is classified as a selfreactive Type C.
319

Test Name Observation Result

Test series H - Thermal stability 

[United States SADT test]

Tested 20 liters of substance in 

packaging type 6HG2 in a test 

chamber with a capacity of 25 

liters. Observed autoaccelerating decomposition at 

63°C (145.4oF) and no autoaccelerating decomposition at 

58°C (136.4oF). The selfaccelerating decomposition 

temperature was identified as 

63°C (145.4oF). 

Self-reactive chemicals need to 

be subjected to temperature 

control if their SADT is less than 

or equal to 55 °C (131oF). This 

chemical has a SADT of 63°C 

(145.4oF).

No temperature control is 

required for this package.

Chemical is classified as a selfreactive Type C.

Decision/Rationale 

To classify a self-reactive chemical, the classifier follows the decision logic for self-reactive 

chemicals, answering the questions and following the flowchart: 

Box 1, Test Series A 

1. Does Substance 15 propagate a detonation? 

RESULT (Test series A): 1.2 Partial 

Box 4, Test C 

2. Can Substance 15 propagate a deflagration? 

RESULT (Tests series C): 4.2 Yes, slowly 

Box 8, Test E 

3. What is the effect of heating under confinement? 

RESULT (Tests series E): 8.1 Violent 

Box 10, Test G 

4. Can it detonate as packaged? 

RESULT (Tests series G): 10.2 No 

Tests B, D, F are not required for this chemical, if the classifier follows the test logic. 

5. Test H is performed to determine whether the substance requires temperature control 

measures. 

RESULT (Tests series H): this chemical has a SADT of 63°C (145.4oF). 
320

Resulting Classification 

This chemical is classified as Self-Reactive, Type C: Any self-reactive substance or mixture 

possessing explosive properties when the chemical as packaged cannot detonate or deflagrate 

rapidly or undergo a thermal explosion will be defined as self-reactive substance Type C.

This chemical has a SADT of 63 °C (145.4 oF). No temperature control is required for this 

package. 
321

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.8, Self-Reactive Chemicals. 

29 CFR 1910.1200, Hazard Communication, Appendix C, Allocation of Label Elements.

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

NFPA 68, Standard on Explosion Protection by Deflagration Venting, 2013. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009.

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
322

VIII.9 Pyrophoric Chemicals 

Introduction

Pyrophoric chemicals ignite spontaneously in air without a supplied spark, flame, heat or other 

ignition source. There are only a few chemicals that have the ability to catch fire without an 

ignition source when exposed to air. Examples of potential pyrophoric chemicals include alkali 

metals in elemental form (e.g., lithium, powdered aluminum, magnesium), organometallic 

compounds (such as lithium hydride, diethyl zinc), or gases (such as diborane, phosphine, and 

silane). Tests should be performed on the substance or mixture as presented, including how it 

can reasonably be expected to be used. 

This chapter covers all pyrophoric hazard classes, that is, pyrophoric liquids, solids, and gases. 

Pyrophoric Liquids 

Definition 

A pyrophoric liquid is a liquid which, even in small quantities, is liable to ignite within five 

minutes after coming in contact with air. 

Classification Criteria 

A pyrophoric liquid is classified in a single category, as shown in Table VIII.9.1. 

Table VIII.9.1. Classification criteria for pyrophoric liquids. 

Category Criteria

1

The liquid ignites within 5 min. when added to an inert carrier and exposed 

to air, or it ignites or chars a filter paper on contact with air within 5 min. 

Classification Procedure and Guidance 

To classify pyrophoric liquids, data on ignition is necessary. The classification procedure for 

pyrophoric liquids need not be applied when experience in production or handling shows that the 

chemical does not ignite spontaneously when it comes in contact with air at normal temperatures, 

i.e., the substance is known to be stable at room temperature for prolonged periods of time 

(days). 

Available Literature

The classifier may use available scientific literature and other evidence to identify the ignition 

information necessary to classify pyrophoric liquids. 

In addition, many substances presenting pyrophoric liquid hazards have already been classified. 

The information in the U.S. Department of Transportation’s Hazardous Materials Table can be 

used to assist in pyrophoric liquid classifications (See 49 CFR 172.101). The classification of 
323

pyrophoric liquids in the HCS corresponds to DOT’s classification for spontaneously 

combustible materials. Under DOT regulations, pyrophoric liquids are considered Class 4, 

Division 4.2, hazardous materials and assigned to Packing Group I. Refer to the discussion of 

the interface between the HCS and DOT labeling in Chapter V of this document for more 

information. 

The decision logic presented below should be used to determine the appropriate hazard 

classification category for pyrophoric liquids. 

Test Methods 

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance or mixture, use the methods identified in Appendix B.9 to 29 

CFR 1910.1200, which are discussed below. 

Classification Based on Test Methods in the UN TDG Manual of Tests and Criteria

The classification of pyrophoric liquids is based on Test N.3, “Test method for pyrophoric 

liquids,” described in Part III, sub-section 33.3.1.5, of the United Nations Recommendations on 

the Transport of Dangerous Goods (UN TDG) Manual of Tests and Criteria, Fourth Revised 

Edition. The decision logic presented below should be used to determine the appropriate hazard 

classification for a pyrophoric liquid using the test data. Refer to the UN TDG Manual of Tests 

and Criteria for a complete description of the method, the apparatus used, and analysis of the test 

results. 

The test method for pyrophoric liquids uses a two-part procedure and determines the ability of 

the liquid a) to ignite when added to an inert carrier and exposed to air, or (b) to char or ignite a 

filter paper on contact with air. 

Classification Procedure 

The classification procedure is based on the following test data: 

 Result of the Test N.3, Procedure (a): ignition in porcelain cup when exposed to air 

occurs within 5 minutes, or 

 Result of the Test N.3, Procedure (b): ignition or charring of a filter paper when in 

contact to air occurs within 5 minutes 

Classification follows the assessment of the ignition or charring data. Once you have collected 

the data, compare it to the criteria for pyrophoric liquids category 1 presented in Table VIII.9.1. 

Follow the logic paths presented in the decision logics in Figure VIII.9.1 to identify the 

appropriate classification categories for pyrophoric liquids. 
324

Figure VIII.9.1. Decision logic for classifying pyrophoric liquids. 

Pyrophoric Solids 

Definition 

A pyrophoric solid is a solid which, even at small quantities, is liable to ignite within five 

minutes after coming into contact with air.

Classification Criteria 

A pyrophoric solid is classified in a single category, as shown in Table VIII.9.2. 

Table VIII.9.2. Classification criteria for pyrophoric solids. 

Category Criterion

1 The solid ignites within 5 minutes of coming into contact with air.

Classification of solid chemicals is based on tests performed on the chemical as presented. If, for 

example, for the purposes of supply or transport, the same chemical is to be presented in a 

physical form different from that which was tested and which is considered likely to materially 

alter its performance in a classification test, classification must be based on testing of the 

chemical in the new form. Note that particle size can influence the ability of the chemical to 

spontaneously ignite. 

Does it ignite within 5 min when poured into a porcelain cup 

filled with diatomaceous earth or silica gel?

The substance/mixture is a liquid

Category 1

Danger

Yes

Does it ignite or char a filter paper within 5 min.? Yes

Not classified

No

Category 1

Danger

No
325

Classification Procedure and Guidance 

To classify pyrophoric solids, data on ignition is necessary. As for pyrophoric liquids, the 

classification procedure for pyrophoric solids need not be applied when experience in production 

or handling shows that the chemical does not ignite spontaneously when it comes in contact with 

air at normal temperatures, i.e., the substance is known to be stable at room temperature for 

prolonged periods of time (days). 

Available Literature

The classifier may use available scientific literature and other evidence to identify the ignition 

information necessary to classify pyrophoric solids. 

In addition, many substances presenting pyrophoric solid hazards have already been classified. 

The information in the U.S. Department of Transportation’s Hazardous Materials Table can be 

used to assist in pyrophoric solid classifications (See 49 CFR 172.101). The classification of 

pyrophoric solids in the HCS corresponds to DOT’s classification for spontaneously combustible 

materials. Under DOT regulations, pyrophoric solids are considered Class 4, Division 4.2, 

hazardous materials and assigned to Packing Group I. Refer to the discussion of the interface 

between the HCS and DOT labeling in Chapter V of this document for more information. 

The decision logic presented below should be used to determine the appropriate hazard 

classification category for pyrophoric solids. 

Test Methods 

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance or mixture, use the methods identified in Appendix B.10 to 29 

CFR 1910.1200 and described below. 

Classification Based on Test Methods in the UN TDG Manual of Tests and Criteria

The classification of pyrophoric solids is based on Test N.2, Test method for pyrophoric solids, 

described in described in Part III, sub-section 33.3.1.4, of the United Nations Recommendations 

on the Transport of Dangerous Goods (UN TDG), Manual of Tests and Criteria, Fourth Revised 

Edition. The test determines the ability of a solid to ignite on contact with air and determines the 

time of ignition. The decision logic presented below should be used to determine the appropriate 

hazard classification for a pyrophoric solid using the test data. Refer to the UN TDG Manual of 

Tests and Criteria for a complete description of the method, the apparatus used, and analysis of 

the test results. 
326

Classification Procedure 

Classification follows the assessment of the ignition data. Once you have collected the data, 

compare it to the criteria for pyrophoric solids category 1 presented in Table VIII.9.2. Follow 

the logic paths presented in the decision logics (or flowcharts) in Figure VIII.9.2 to identify the 

appropriate classification categories for pyrophoric solids. 

Figure VIII.9.2. Decision logic for classifying pyrophoric solids. 

Pyrophoric Gases 

Definition 

A pyrophoric gas is a chemical in a gaseous state that will ignite spontaneously in air at a 

temperature of 130 oF (54.4 oC) or below. 

Classification Criteria 

A pyrophoric gas is classified in a single category, as shown in Table VIII.9.3. 

Table VIII.9.3. Classification criteria for pyrophoric gases. 

Category Criteria

Pyrophoric 

Gas

A gas which ignites spontaneously in air at a temperature of 130 oF (54.4 oC)

or below. 

Does it ignite within 5 min after exposure to air?

The substance/mixture is a solid

Category 1

Danger

Yes

Not classified 

No
327

Classification Procedure and Guidance 

To classify pyrophoric gases, data on ignition is necessary. The classification procedure for 

pyrophoric gases need not be applied when experience in production or handling shows that the 

chemical does not ignite spontaneously when it comes in contact with air at normal temperatures, 

i.e., the substance is known to be stable at room temperature for prolonged periods of time 

(days). 

Available literature

The classifier may use available scientific literature and other evidence to identify the ignition 

information necessary to classify pyrophoric gases. 

In addition, many substances presenting pyrophoric gas hazards have already been classified. 

Information in the U.S. Department of Transportation’s Hazardous Materials Table can be used 

to assist in pyrophoric gas classifications (See 49 CFR 172.101). The classification of 

pyrophoric gases in the HCS corresponds to DOT’s classification for flammable gases. Under 

DOT regulations, pyrophoric gases are considered Class 2, Division 2.1, hazardous materials. 

The UN special packing instruction P200 is also used by transport for this hazard. Refer to the 

discussion of the interface between the HCS and DOT labeling in Chapter V of this document for 

more information. 

Test Methods 

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance or mixture, then use of the following test methods is

suggested. 

Pyrophoric gases are a new hazard class in the United Nations Globally Harmonized System of 

Classification and Labelling of Chemicals (GHS). The test methods listed below may be used 

when data is not available. 

Please refer to these test methods for a complete description of the necessary apparatus and 

analytical procedure needed to classify a gas as pyrophoric. 

 IEC 60079-20-1 ed 1.0 (2010-01)): Explosive atmospheres - Part 20-1: Material 

characteristics for gas and vapour classification - Test methods and data 

 DIN 51794: Determining the ignition temperature of petroleum products 
328

Classification Criteria 

Classification follows the assessment of ignition data. Once you have collected the data, 

compare it to the criteria for pyrophoric gases presented in Table VIII.9.3. Follow the logic 

paths presented in the decision logic in Figure VIII.9.3 to identify the appropriate classification 

categories for pyrophoric gases. 

However, the classification procedure for pyrophoric gases need not be applied when experience 

in production or handling shows that the substance does not ignite spontaneously on coming into 

contact with air at a temperature of 130 oF (54 oC) or below. Flammable gas mixtures, that

contain more than one percent pyrophoric components, should be classified as a pyrophoric gas 

unless test data or other evidence supports non-classification. 

Expert judgment in the properties and physical hazards of pyrophoric gases and their mixtures 

should be used in assessing the need for classification of flammable gas mixtures containing one 

percent or less pyrophoric components. In this case, testing may be considered if expert 

judgment indicates a need for additional data to support the classification process. 

Figure VIII.9.3. Decision logic for classifying pyrophoric gases.

Pyrophoric Chemical Classification Examples 

Example #1

The following example illustrates the classification process for a chemical that is suspected of 

being a pyrophoric liquid, when no information is available and it must be tested. Tests are 

performed using the UN Recommendations on the Transport of Dangerous Goods, Manual of 

Tests and Criteria, Part III, Sub-section 33.3.1.5, Test Method N.3: Test method for pyrophoric 

liquids. This procedure consists of two steps: the inert carrier test, and the filter paper test. 

Once the test data is gathered, the classification of the chemical can be determined using the 

HCS Pyrophoric Liquids Decision Logic. 

Does the flammable gas or gas mixture ignite 

spontaneously in air at a temperature of 130 oF 

(54.4 oC) or below?

Flammable gas or gas mixture

Pyrophoric 

gas 

Danger

Yes
329

Test data

Using UN Test N.3, Part III, subsection 33.3.1.5 of the UN TDG Manual of Tests and Criteria: 

Test method for pyrophoric liquids, the liquid is tested.

Step 1: Inert carrier test results: 

Liquid is tested six times on silica gel at room temperature and exposed to air for five 

minutes. No ignition occurred after six trials. Because of the negative result, and according 

to the test procedure, the second part of the N.3 test is conducted. 

Step 2: Filter paper test results: 

This procedure is performed two times on the liquid. The filter paper is charred in the first 

test after 5 minutes 15 seconds and in the second test after 4 minutes 45 seconds. 

Decision/Rationale 

Using the information gathered, answer the questions posed in the pyrophoric liquids 

decision logic. 

1. Does the liquid ignite within 5 minutes when it is poured into a porcelain cup filled with 

diatomaceous earth or silica gel? 

ANSWER: No. The liquid does not ignite within 5 minutes when poured into a porcelain 

cup filled with silica gel. 

2. Does the liquid ignite or char a filter paper within 5 min? 

ANSWER: Yes. In the second trial, the liquid chars the filter paper within 5 min. 

Resulting Classification 

The chemical is classified as a Pyrophoric Liquid, Category 1. 

Example #2

The following example illustrates the classification process for a chemical that is suspected of 

being a pyrophoric solid, but no information is available and it must be tested. Tests are 

performed using the UN TDG Manual of Tests and Criteria, Part III, Sub-section 33.3.1.4, Test 

method N.2: Test method for pyrophoric solids. 

Once the test data is gathered, the classification of the chemical can be determined using the 

HCS Pyrophoric Solids Decision Logic. 
330

Test data

A powder is suspected of being a pyrophoric solid and is tested to determine if the solid ignites 

when poured from a height of about one meter onto a non-combustible surface. It is observed 

whether the chemical ignites during dropping or within 5 minutes of settling. This procedure was 

performed five times with the following results: 

The chemical did not ignite within 5 minutes on the first 4 droppings. However, on the fifth 

dropping the powder ignited at 4 minutes, 45 seconds after settling. 

Decision/Rationale 

Using the information gathered, answer the questions posed in the Pyrophoric Solids decision 

logic. 

1. Does the solid chemical ignite within 5 minutes after exposure to air? 

ANSWER: Yes. The solid ignites within 5 minutes of coming into contact with air. 

Resulting Classification 

The chemical is classified as a Pyrophoric Solid, Category 1, because the solid ignited within 

5 minutes of coming into contact with air. 
331

References 

29 CFR 1910.1200, Hazard Communication.

29 CFR 1910.1200, Hazard Communication, Appendix B.9, Pyrophoric Liquids. 

29 CFR 1910.1200, Hazard Communication, Appendix B.10, Pyrophoric Solids. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
332

VIII.10 Self-Heating Chemicals 

Introduction

A chemical that self-heats undergoes a gradual reaction with oxygen (in air) and generates heat. 

The reaction is not initiated by an outside source. If the rate of heat production exceeds the rate 

of heat loss, then the temperature of the chemical will rise which, after an induction time, may 

lead to self-ignition and combustion. 

Definition

A self-heating chemical is a solid or liquid chemical, other than a pyrophoric liquid or solid, 

which, by reaction with air and without energy supply, is liable to self-heat; this chemical differs 

from a pyrophoric liquid or solid in that it will ignite only when in large amounts (kilograms) 

and after long periods of time (hours or days). 

Classification Criteria

A self-heating chemical is classified in one of two categories, as shown in Table VIII.10.1. 

Table VIII.10.1. Classification criteria for self-heating chemicals. 

Category Criteria

1 A positive result is obtained in a test using a 25 mm sample cube at 140 °C 

(284 °F).

2 A negative result is obtained in a test using a 25 mm cube sample at 140 °C 

(284 °F), a positive result is obtained in a test using a 100 mm sample cube 

at 140 °C (284 °F), and: 

a) The unit volume of the chemical is more than 3 m3; or 

b) A positive result is obtained in a test using a 100 mm cube sample at 

120 °C (248 °F) and the unit volume of the chemical is more than 

450 liters; or 

c) A positive result is obtained in a test using a 100 mm cube sample at 

100 °C (212 °F). 

Note: Although the HCS does not require testing, should testing be performed, then classification 

of solid chemicals is based on tests performed on the chemical as presented. If, for example, for 

the purposes of supply or transport, the same chemical is to be presented in a physical form 

different from that which was tested and which is considered likely to materially alter its 

performance in a classification test, classification must be based on testing of the chemical in the 

new form. 

Chemicals with a temperature of spontaneous combustion higher than 50 °C (122 °F) for a 

volume of 27 m3

are not classified as self-heating chemicals. 
333

Chemicals with a spontaneous ignition temperature higher than 50 °C (122 °F) for a volume of 

450 liters (~118.88 gallons) are not classified in Category 1. 

Classification Procedure and Guidance 

To classify a self-heating chemical, data on how it reacts with air at specified temperatures is 

necessary. 

Even though the definition of this hazard class includes liquids, in general, liquids are not 

classified as self-heating and the test method is not applicable to liquids. 

Available Literature

The classifier may use available scientific literature and other evidence to classify self-heating 

chemicals. Appendix B of this document provides a listing of information sources that may 

prove useful during hazard classification. 

In addition, some chemicals presenting self-heating chemical hazards have already been 

classified. The Hazardous Materials Regulations table from the U.S. Department of 

Transportation can be used to assist in classifying self-heating chemicals (See 49 CFR 172.101). 

The HCS self-heating chemicals category 1 corresponds to DOT Class 4, Division 4.2, 

Substances Liable to Spontaneous Combustion Packing Group II. HCS self-heating chemicals 

category 2 corresponds to DOT Class 4, Division 4.2, Substances Liable to Spontaneous 

Combustion Packing Group III. Refer to the discussion on the interface between the HCS and 

DOT labeling in Chapter V of this document for more information. 

The decision logic presented below should be used to determine the appropriate hazard 

classification category for a self-heating chemical. 

Test Method

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance or mixture, use the methods identified in Appendix B.11 to 29 

CFR 1910.1200 and described below. 

The classification procedure for self-heating chemicals need not be applied if the results of a 

screening test can be adequately correlated with the classification test and an appropriate safety 

margin is applied. 

Examples of screening tests are: 

a) The Grewer Oven test (VDI guideline 2263, part 1, 1990, Test methods for the 

Determination of the Safety Characteristics of Dusts) with an onset temperature 80° Kelvin

(K) above the reference temperature for a volume of 1 liter; and 
334

b) The Bulk Powder Screening Test (Gibson, N. Harper, D. J. Rogers, R. Evaluation of the fire 

and explosion risks in drying powders, Plant Operations Progress, 4 (3), 181-189, 1985) with 

an onset temperature 60° Kelvin (K) above the reference temperature for a volume of 1 liter. 

Classification Based on Test Methods in the UN TDG Manual of Tests 

and Criteria 

The classification of self-heating chemicals is based on tests described in Part III, Sub-section 

33.3.1.6 of the United Nations Recommendations on the Transport of Dangerous Goods (TDG), 

Manual of Tests and Criteria, Test N.4 “Test method for self-heating substances.” The test 

determines the ability of a chemical to undergo oxidative self-heating by exposure to air at 

temperatures of 100 °C (212 °F), 120 °C (248 °F), or 140 °C (284 °F) in a 25 mm or 100 mm 

wire mesh cube sample container. Spontaneous ignition or dangerous self-heating are indicated 

by a 60 °C rise in the oven temperature within 24 hours. 

Refer to the UN TDG Manual of Tests and Criteria for a complete description of the method, the 

apparatus used, and analysis of the test results. 

Classification Procedure 

Classification of self-heating chemicals is based on information from available literature or the 

results of the N.4 test. If the N.4 test is performed, then classification is as follows: 

Category 1 is assigned to a chemical providing a positive test result using a 25 mm sample cube 

at an oven temperature of 140 °C (284 °F). 

Category 2 is assigned to a chemical providing a positive result using a 100 mm sample cube at 

140°C (284°F), providing a negative test result using a 25 mm cube sample at 140 °C (284 °F), 

and: 

a) The volume of the chemical is more than 3 m3; or 

b) A positive result is obtained in a test using a 100 mm cube sample at 120°C (248°F) 

and the volume of the chemical is more than 450 liters; or 

c) A positive result is obtained in a test using a 100 mm cube sample at 100°C (212°F). 

Once the data has been collected, compare the data and test results to the classification criteria 

for self-heating chemicals presented in Table VIII.10.1. Follow the logic path presented in the 

decision logic (or flowchart) in Figure VIII.10.1 to identify the appropriate classification 

categories for self-heating chemicals. 
335

Figure VIII.10.1. Decision logic for classifying self-heating chemicals based on Test N.4. 

Not classified

Category 1

Danger

Yes

No

Yes

No

Is it packaged in more than 3 m3?

Is it packaged in more than 450 litres volume?

Does it undergo self-heating (positive test result) when 

tested in a 100 mm sample cube at 100 C?

Yes

No

Yes

Yes

Does it undergo self-heating (positive test result) when 

tested in a 100 mm sample cube at 120 C?

Does it undergo self-heating (positive test result) when 

tested in a 25 mm sample cube at 140 C?

Does it undergo self-heating (positive test result) when 

tested in a 100 mm sample cube at 140 C?

Substance/mixture

Not classified

Not classified

Category 2

Warning No

Category 2

Warning

Yes

No

Category 2

Warning

No
336

Self-Heating Chemicals Classification Example 

The following example is provided to illustrate the self-heating chemicals decision logic. 

Tests are performed using the UN TDG Manual of Tests and Criteria, Part III, Sub-section 

33.3.1.6, Test method N.4: Test method for self-heating substances. 

An inorganic black powder is suspected of being a self-heating substance and is tested according 

to the above UN test. 

Known data 

 Inorganic black powder, transported in packages of 400 liters.

 Tested per UN Test method N.4 with the following results: 

o A positive result using a 100 mm sample cube at 140 °C (284 °F).

o A negative result using a 25 mm sample cube at 140 °C (284 °F). 

According to the procedure, if a positive result is obtained at 140 °C (284 °F) in a 100 mm 

sample cube, but not in a 25 mm sample cube, then an additional test with the substance in a 

100 mm sample cube should be performed based on the packaging and quantity being 

transported. Below are the results of this addition test: 

o A positive result using a 100 mm sample cube at 120 °C (248 °F). 

o A positive result using a 100 mm sample cube at 100 °C (212 °F). 

Decision/Rationale 

Using the test data, answer the questions posed in the oxidizing liquid decision logic Figure 

VIII.10.1, above. 

The substance is a powder. 

1. Does a 100 mm sample cube undergo self-heating when tested at 140 °C (284 °F)? 

ANSWER: Yes. A positive result was obtained. 

2. Does a 25 mm sample cube undergo self-heating when tested at 140 °C (284 °F)? 

ANSWER: No. A negative result was obtained. 

3. Is it packaged in more than 3 m3? 

ANSWER: No. it is transported in packages of 400 liters. 

4. Does a 100 mm sample cube undergo self-heating when tested at 120 °C (248 °F)? 

ANSWER: Yes. A positive result was obtained. 
337

5. Is it packaged in more than 450 liters? 

ANSWER: No. it is transported in packages of 400 liters. 

6. Does a 100 mm sample cube undergo self-heating when tested at 100 °C (212 °F)? 

ANSWER: Yes. A positive result is obtained using a 100 mm sample cube at 100 °C 

(212 °F). 

Resulting Classification 

The chemical is classified as Self-Heating Substance, Category 2. 

A positive result is obtained in a test using a 100 mm sample cube at 140 °C, and a negative 

result is obtained in a test using a 25 mm sample cube at 140 °C, and a positive result is obtained 

using a 100 mm sample cube at 100 °C. The chemical fulfills the Category 2(c) criteria. 
338

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.11, Self-Heating Chemicals. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
339

VIII.11 Chemicals Which, in Contact with Water, Emit 

Flammable Gases 

Introduction

Some chemicals, when in contact with water, may emit flammable gases that can form explosive 

mixtures with air. Such mixtures are easily ignited by ordinary sources of ignition, for example 

sparking tools or light bulbs. The resulting blast wave and flames may be hazardous to people 

and the environment. Sometimes these chemicals are referred to as water-reactive substances. 

Definition

Chemicals which, in contact with water, emit flammable gases are solid or liquid chemicals 

which, by interaction with water, are liable to become spontaneously flammable or to give off 

flammable gases in dangerous quantities. 

Classification Criteria

A chemical which, in contact with water, emits flammable gases is classified in one of three 

hazard categories on the basis of information in available literature or though testing that 

measures gas evolution and speed of evolution, as described in Table VIII.11.1, below. 

Table VIII.11.1. Classification criteria for chemicals which, in contact with water, emit 

flammable gases. 

Category Criteria

1

Any chemical which reacts vigorously with water at ambient temperatures and 

demonstrates generally a tendency for the gas produced to ignite spontaneously, 

or which reacts readily with water at ambient temperatures such that the rate of 

evolution of flammable gas is equal to or greater than 10 liters per kilogram of 

chemical over any one minute.

2

Any chemical which reacts readily with water at ambient temperatures such that 

the maximum rate of evolution of flammable gas is equal to or greater than 20 

liters per kilogram of chemical per hour, and which does not meet the criteria 

for Category 1. 

3

Any chemical which reacts slowly with water at ambient temperatures such that 

the maximum rate of evolution of flammable gas is equal to or greater than 1 

liter per kilogram of chemical per hour, and which does not meet the criteria for 

Categories 1 and 2. 

Note: Although the HCS does not require testing, should testing be performed, then classification of 

solid chemicals is based on tests performed on the chemical as presented. If, for example, for the 

purposes of supply or transport, the same chemical is to be presented in a physical form different 

from that which was tested and which is considered likely to materially alter its performance in a 

classification test, classification must be based on testing of the chemical in the new form. 
340

Classification Procedure and Guidance 

To classify a chemical which, in contact with water, emits flammable gases, data on how it reacts 

with water and the evolution rate of the flammable gas is necessary. 

Available Literature

The manufacturer, importer, or other responsible party may use available scientific literature and 

other evidence to classify chemicals which, in contact with water, emit flammable gases. 

Appendix B of this document provides a listing of information sources that may prove useful 

during hazard classification. 

In addition, some substances presenting the hazards from chemicals which, in contact with water, 

emit flammable gases have already been classified. The Hazardous Materials Regulations table 

from the U.S. Department of Transportation can be used to assist in classifying chemicals which, 

in contact with water, emit flammable gases (See 49 CFR 172.101). DOT Hazard Class 4, 

Division 4.3 substances which in contact with water emit flammable gases, Packing Groups I, II 

and III correspond directly to the HCS hazard categories 1, 2 and 3, respectively. Refer to the 

discussion on the interface between the HCS and DOT labeling in Chapter V of this document 

for more information.

The decision logic presented below may also be used to determine the appropriate hazard 

classification category for a chemical which, in contact with water, emits flammable gases. 

Test Method 

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance, then use the method identified in Appendix B.12 to 29 CFR 

1910.1200 and described below.

The test method for this physical hazard class is used to determine whether the reaction of a 

chemical with water leads to the development and evolution of a dangerous amount of gases that 

may be flammable. 

The classification procedure for this class need not be applied if: 

(a) The chemical structure of the chemical does not contain metals or metalloids; 

(b) Experience in production or handling shows that the chemical does not react with water, 

(e.g., the chemical is manufactured with water or washed with water); or 

(c) The chemical is known to be soluble in water to form a stable mixture. 
341

Classification Based on Test Methods in the UN TDG Manual of Tests 

and Criteria 

The classification of a chemical which, in contact with water, emits flammable gases is based on 

tests described in Part III of the Fourth Revised Edition of the United Nations Recommendations 

on the Transport of Dangerous Goods (UN TDG) - Manual of Tests and Criteria. Test Method 

N.5, “Test method for substances which in contact with water emit flammable gases” is found in 

Sub-section 33.4.1.4 of the manual. Test method N.5 does not prescribe a specific test apparatus. 

The test is performed in three steps (each involving contact with water under a different 

condition). If the chemical identity of the evolved gas is unknown, the gas should be tested for 

flammability. Refer to the UN TDG Manual of Tests and Criteria for a complete description of 

the method and analysis of the test results. 

Classification Procedure 

Classification for the physical hazard chemicals which, in contact with water, emit flammable 

gases is based on the maximum rate of evolved flammable gas [Liters flammable gas/kilogram 

chemical and time]. 

Should testing be performed, a chemical is assigned to the hazard class chemicals which, in 

contact with water, emit flammable gases when, during testing, contact with water causes the 

chemical to 

 spontaneously ignite in any step of the test procedure; or 

 evolution of a flammable gas occurs at a rate ≥1 liter per kilogram of chemical per hour. 

Once the data is collected, compare the data and/or test results to the criteria for Category 1, 

Category 2, and Category 3, presented in Table VIII.11.1. Follow the logic path presented in the 

decision logic in Figure VIII.11.1 to identify the appropriate classification categories for 

chemicals which, in contact with water, emit flammable gases. 
342

Figure VIII.11.1. Decision logic for classifying chemicals which, in contact with water, emit 

flammable gases. 

In contact with water, does it react slowly at ambient temperatures such 

that the maximum rate of evolution of flammable gas is ≥ 1 liter per kg 

of chemical per hour?

In contact with water, does the chemical react vigorously with water at 

ambient temperatures and demonstrate generally a tendency for the gas 

produced to ignite spontaneously, or does it react readily with water at 

ambient temperatures such that the rate of evolution of flammable gas is 

≥ 10 liters per kg of chemical over any one minute?

Not classified

Category 1

Danger

No

Substance/mixture

In contact with water, does it react readily with water at ambient 

temperatures such that the maximum rate of evolution of flammable gas 

is ≥ 20 liters per kg of chemical per hour?

Yes

Yes

No

Yes

Category 2

Danger

Category 3

Warning

No
343

Chemicals Which, in Contact with Water, Emit Flammable Gases 

Classification Example

The following example is provided to illustrate the classification process and decision logic for 

chemicals which, in contact with water, emit flammable gases. 

A liquid is suspected of being a chemical which, in contact with water, emits flammable gas. 

The liquid is tested to determine whether any gas is evolved, if spontaneous ignition of the gas 

occurs, and if there is evolution of flammable gas at a rate greater than 1 liter per kilogram of the 

chemical per hour. 

Tests are performed using the UN Recommendations on the Transport of Dangerous Goods, 

Manual of Tests and Criteria, Part III, Sub-section 33.3.1.4, Test method N.5: “Test method for 

substances which in contact with water emit flammable gases.” 

Known data

 Liquid contains an organometallic.

 The chemical reacts slowly with water and emits a gas known to be flammable. 

 Chemical was tested for seven hours at ambient temperature per UN Test N.5 “Test method 

for substances which, in contact with water, emit flammable gases.” Test results showed 

o A maximum rate of evolution of 15 liters per kilogram (L/kg) substance per hour of 

flammable gas. 

o The gas did not spontaneously ignite. 

Decision/Rationale 

1. When contacted with water, does the chemical react slowly, such that the maximum rate of 

evolution of flammable gas is ≥ 1 L/kg of chemical per hour? 

ANSWER: Yes 

2. When contacted with water, does the chemical react vigorously with water at ambient 

temperatures and demonstrate generally a tendency for the gas produced to ignite 

spontaneously, or does it react readily with water at ambient temperatures such that the rate 

of evolution of flammable gas is ≥ 10 L/kg of chemical over any one minute? 

ANSWER: No 

3. When contacted with water, does the chemical react readily at ambient temperatures such 

that the maximum rate of evolution is ≥ 20 L/kg of substance per hour? 

ANSWER: No. This chemical reacts slowly with water at ambient temperatures such that the 

maximum rate of evolution of flammable gas is ≥ 1L/kg/hr, and ≤ 20 L/kg/hr and there is no 

spontaneous ignition. 
344

Resulting Classification 

Liquid is classified as a chemical which, in contact with water, emits flammable gases, 

Category 3. 

The liquid fulfills the Category 3 criteria: Any chemical which reacts slowly with water at 

ambient temperatures such that the maximum rate of evolution of flammable gas is equal to or 

greater than 1 liter per kilogram of chemical per hour, and which does not meet the criteria for 

Categories 1 and 2. 
345

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.12 Chemicals which, in Contact with 

Water, Emit Flammable Gases. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
346

VIII.12 Oxidizing Liquids and Solids 

Introduction 

An oxidizer is a chemical that brings about an oxidation reaction that can promote combustion of 

other materials due to the release of oxygen. Although widely known as “oxidizing materials,” 

their hazards and behavior may be better understood by considering them as “fire enhancing 

substances.” For example, an unclassified solid in contact with an oxidizing material may, upon 

ignition, behave like a flammable solid. 

In an oxidation reaction the oxidizer may provide oxygen to the substance being oxidized (in 

which case the oxidizer has to be oxygen or contain oxygen), or it may receive electrons being 

transferred from the substance undergoing oxidation. For example, chlorine is a good oxidizer 

for electron-transfer purposes, even though it contains no oxygen. 

Oxidizers can initiate or greatly accelerate the burning of fuels. The most common oxidizer is 

atmospheric oxygen. Oxygen-containing chemicals (e.g., hydrogen peroxide) and halogens (e.g., 

bromine, chlorine, and fluorine) can also be strong oxidizers. Some chemicals may be oxidizers 

with such an extremely fast burning ability that they are classified as explosives or blasting 

agents rather than oxidizers. Often the fact that a chemical possesses oxidizing ability 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-), nitrate (NO3-), nitrite (NO2-), dichromate (Cr2O7), 

persulfate (S2O8), and permanganate (MnO4).

Because of the similarities of liquid and solid oxidizing chemicals, this chapter provides 

classification guidance on both. There is a separate chapter on oxidizing gases. 

Oxidizing Liquids

Definition 

Oxidizing liquid means a liquid which, while in itself not necessarily combustible, may, 

generally by yielding oxygen, cause, or contribute to, the combustion of other material.

Classification Criteria 

To classify a liquid chemical as an oxidizing liquid, information is needed about its ability to 

increase the burning rate or burning intensity of a combustible substance (fibrous cellulose) 

when the two are thoroughly mixed. 

Oxidizing liquids are assigned to one of three hazard categories based on test results that

measure ignition or pressure rise time compared to that of defined (or control) mixtures, as 

shown in Table VIII.12.1. Pressure rise time is the length of time that it takes the pressure to rise 

from 690 kilopascals (kPa) to 2,070 kPa. 
347

Table VIII.12.1. Classification criteria for oxidizing liquids. 

Category Criteria

1

Any chemical which, in the 1:1 mixture, by mass, of chemical and cellulose tested, 

spontaneously ignites; or the mean pressure rise time of a 1:1 mixture, by mass, of 

chemical and cellulose is less than that of a 1:1 mixture, by mass, of 50% 

perchloric acid and cellulose.

2

Any chemical which, in the 1:1 mixture, by mass, of chemical and cellulose tested, 

exhibits a mean pressure rise time less than or equal to the mean pressure rise time 

of a 1:1 mixture, by mass, of 40% aqueous sodium chlorate solution and cellulose; 

and the criteria for Category 1 are not met.

3

Any chemical which, in the 1:1 mixture, by mass, of chemical and cellulose tested, 

exhibits a mean pressure rise time less than or equal to the mean pressure rise time 

of a 1:1 mixture, by mass, of 65% aqueous nitric acid and cellulose; and the 

criteria for Categories 1 and 2 are not met. 

Classification Procedure and Guidance 

To classify a chemical as an oxidizing liquid , data is necessary on how it reacts with air at 

specified temperatures. 

For this hazard class, organic and inorganic chemicals are treated differently. When classifying 

chemicals suspected of being oxidizing liquids, pre-test evaluations are necessary. For organic 

chemicals, the classification procedure for oxidizing liquids does not need to be applied if: 

(a) the chemical does not contain oxygen, fluorine or chlorine; or 

(b) the chemical contains oxygen, fluorine or chlorine and these elements are chemically bonded 

only to carbon or hydrogen. 

For inorganic chemicals, the classification procedure for oxidizing liquids does not need to be 

applied if the chemical does not contain oxygen or halogen atoms. 

Available Literature

The classifier may use available scientific literature and other evidence to classify chemicals as 

oxidizing liquids. Appendix B of this document provides a listing of sources that may prove 

useful during hazard classification. 

Many chemicals that present oxidizing liquid hazards have already been classified. The 

Hazardous Materials Regulations table from the U.S. Department of Transportation can be used 

to assist in oxidizing liquid classifications (see 49 CFR 172.101). The HCS criteria for oxidizing 

liquids category 1, 2 or 3 corresponds to DOT Class 5.1, Oxidizing Substances Packing Group I, 

II, or III, respectively. Refer to the discussion on the interface between the HCS and DOT 

labeling in Chapter V of this document for more information. 
348

Test Method 

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance or mixture, use methods identified in Appendix B.13 to 29 

CFR 1910.1200, described below.

Classification Based on Test Methods in the UN TDG Manual of Tests 

and Criteria 

The classification of oxidizing liquids is based on tests described in Part III of the Fourth 

Revised Edition of the United Nations Recommendations on the Transport of Dangerous Goods 

(UN TDG) - Manual of Tests and Criteria. Test O.2, “Test for oxidizing liquids,” is performed 

in accordance with sub-section 34.4.2 of the manual. The test measures the time it takes for the 

pressure to rise from 690 kilopascals (kPa) to 2,070 kPa, and compares this period with the time 

taken for the pressure of a similar mixture containing the reference substance and cellulose to 

rise the same amount. 

Refer to the UN TDG Manual of Tests and Criteria for a complete description of the method, the 

apparatus used, and analysis of the test results. 

Classification Procedure 

Classification of oxidizing liquids is based on the results of Test O.2. You may also find 

information available from assigned transport packing groups under the DOT regulations to be 

helpful. The transport packing group assignments coincide with the hazard category assignments 

for oxidizing liquids. 

When test results diverge from known experience in the handling and use of a chemical shows 

the chemical to be an oxidizing hazard, then professional judgment, based on known experience, 

takes precedence over test results. When professional judgment is relied upon for classification, 

the classifier must be able to explain why professional judgment was used instead of the test 

results. 

Figure VIII.12.1 provides a decision logic for classifying oxidizing liquids based on the results 

from Test O.2 or from available literature. 
349

Figure VIII.12.1. Decision logic for classifying oxidizing liquids. 

Does it, in the 1:1 mixture, by mass, of substance (or mixture) 

and cellulose tested, exhibit a pressure rise  2070 kPa (gauge)?

Does it, in the 1:1 mixture, by mass, of substance (or mixture) 

and cellulose tested, exhibit a mean pressure rise time less than 

or equal to the mean pressure rise time of a 1:1 mixture, by 

mass, of 65% aqueous nitric acid and cellulose?

Category 1

Danger

Category 3

Warning

The substance/mixture is a liquid

Does it, in the 1:1 mixture, by mass, of substance (or mixture) 

and cellulose tested, spontaneously ignite or exhibit a mean 

pressure rise time less than that of a 1:1 mixture, by mass, of 

50% perchloric acid and cellulose?

Yes

Category 2

Danger

Does it, in the 1:1 mixture, by mass, of substance (or mixture) 

and cellulose tested, exhibit a mean pressure rise time less than 

or equal to the mean pressure rise time of a 1:1 mixture, by 

mass, of 40% aqueous sodium chlorate and cellulose?

Not classified 

Not classified 

Yes

Yes

No

No

No

No

Yes
350

Oxidizing Solids

Definition 

Oxidizing solid means a solid which, while in itself is not necessarily combustible, may, 

generally by yielding oxygen, cause, or contribute to, the combustion of other material.

Classification Criteria 

To classify a solid as oxidizing, data are needed on the potential for a solid chemical to increase 

the burning rate or burning intensity of a combustible substance (in general, fibrous cellulose) 

when the two are thoroughly mixed. 

Oxidizing solids are assigned to one of three hazard categories on the basis of information from 

available literature or from test results that measure mean burning time compared to defined 

mixtures, as shown in Table VIII.12.2. 

Table VIII.12.2. Classification criteria for oxidizing solids. 

Category Criteria

1

Any chemical which, in the 4:1 or 1:1 sample-to-cellulose ratio (by mass) tested, 

exhibits a mean burning time less than the mean burning time of a 3:2 mixture (by 

mass) of potassium bromate and cellulose.

2

Any chemical which, in the 4:1 or 1:1 sample-to-cellulose ratio (by mass) tested, 

exhibits a mean burning time equal to or less than the mean burning time of a 2:3 

mixture (by mass) of potassium bromate and cellulose and the criteria for 

Category 1 are not met.

3

Any chemical which, in the 4:1 or 1:1 sample-to-cellulose ratio (by mass) tested, 

exhibits a mean burning time equal to or less than the mean burning time of a 3:7 

mixture (by mass) of potassium bromate and cellulose and the criteria for 

Categories 1 and 2 are not met.

Note 1: Some oxidizing solids may present explosion hazards under certain conditions (e.g., 

when stored in large quantities). For example, some types of ammonium nitrate may give rise to 

an explosion hazard under extreme conditions. The “Resistance to detonation test” (IMO: Code 

of Safe Practice for Solid Bulk Cargoes, 2005, Annex 3, Test 5) may be used to assess this 

hazard. When information indicates that an oxidizing solid may present an explosion hazard, the 

explosive hazard must be indicated on the Safety Data Sheet. 

Note 2: Classification of solid chemicals should be based on tests performed on the chemical as 

presented. If, for example, for the purposes of supply or transport, the same chemical is to be 

presented in a physical form different from that which was tested and which is considered likely 

to materially alter its performance in a classification test, then classification is based on testing of 

the chemical in the new form. 
351

Classification Procedure and Guidance 

To classify an oxidizing solid, data is needed on its potential to increase the burning rate or 

burning intensity of a combustible substance. 

Organic and inorganic chemicals are treated differently during classification; that is, an organic 

chemical should not be classified as an oxidizing solid if: 

(a) the chemical does not contain oxygen, fluorine or chlorine; or 

(b) the chemical contains oxygen, fluorine or chlorine and these elements are chemically bonded 

only to carbon or hydrogen. 

In addition, inorganic chemicals that do not contain oxygen or halogen atoms are not oxidizing 

solids, and should not be classified as such. 

Available Literature

The classifier may use available scientific literature and other evidence. Appendix B of this 

document provides a list of sources that may prove useful during hazard classification. 

In addition, many substances presenting oxidizing solid hazards have already been classified. 

The Hazardous Materials Regulations table from the U.S. Department of Transportation can be 

used to assist in oxidizing solid classifications (see 49 CFR 172.101). The HCS criteria for 

oxidizing solids category 1, 2, or 3 corresponds to DOT’s Class 5.1 Oxidizing Substances 

Packing Group I, II, or III, respectively. Refer to the discussion on the interface between the 

HCS and DOT labeling in Chapter V of this document for more information.

Test Method 

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance or mixture, use the test methods identified in Appendix B.14 

to 29 CFR 1910.1200, and described below. 

Classification Based on Test Methods in the UN TDG Manual of Tests 

and Criteria

The classification of oxidizing solids is based on tests described in Part III of the Fourth Revised 

Edition of the United Nations Recommendations on the Transport of Dangerous Goods (UN 

TDG) - Manual of Tests and Criteria. Test O.1, “Test for oxidizing solids,” is performed in 

accordance with sub-section 34.4.1 of the manual. The test method measures the potential for a 

solid chemical to increase the burning rate or burning intensity of a combustible substance when 

the two are thoroughly mixed. 

Refer to the UN TDG Manual of Tests and Criteria for a complete description of the methods, 

the apparatus used, and analysis of the test results. 
352

Classification Procedure 

Classification of oxidizing solids is based on the results of Test O.1. You may also find that 

information provided by DOT-assigned transport packing groups to be helpful. The transport 

packing group assignments coincide with the hazard category assignments for oxidizing solids. 

If the test results diverge from known experience in the handling and use of a chemical shown to 

be oxidizing, then professional judgment, based on known experience, takes precedence over the 

test results. When professional judgment is relied upon for classification, the classifier must be 

able to explain why professional judgment was used over the test results. 

Figure VIII.12.2 presents the decision logic for classifying oxidizing solids based on available 

information or from the results of Test O.1. 
353

Figure VIII.12.2. Decision logic for classifying oxidizing solids. 

Does it, in the 4:1 or 1:1 sample-to-cellulose ratio, by mass, 

tested ignite or burn?

Does it, in the 4:1 or 1:1 sample-to-cellulose ratio, by mass, 

tested, exhibit a mean burning time ≤ the mean burning time of 

a 3:7 mixture, by mass, of potassium bromate and cellulose?

Category 1

Danger

Category 3

Warning

The substance/mixture is a solid

Does it, in the 4:1 or 1:1 sample-to-cellulose ratio, by mass, 

tested, exhibit a mean burning time < the mean burning time of 

a 3:2 mixture, by mass, of potassium bromate and cellulose?

No

Yes

Category 2

Danger

Not classified 

Does it, in the 4:1 or 1:1 sample-to-cellulose ratio, by mass, 

tested, exhibit a mean burning time ≤ the mean burning time of 

a 2:3 mixture, by mass, of potassium bromate and cellulose?

Not classified 

No

No

No

Yes

Yes

Yes
354

Oxidizing Liquid Classification Example

The following example illustrates the classification process and decision logic for oxidizing 

liquids when data are available for the given chemical. 

Tests are performed using the UN TDG, Manual of Tests and Criteria, Part III, Sub-section 

34.4.2, Test Method O.2: “Test for oxidizing liquids.” 

A liquid suspected of being an oxidizing liquid is tested to determine whether a mixture of the 

substance and cellulose spontaneously ignites. The mean time taken for the pressure to rise from 

690 kPa to 2,070 kPa is compared with those of the reference substances. The reference 

substances are: 50% perchloric acid, 40% aqueous sodium chlorate solution and 65 % aqueous 

nitric acid. Five trials are performed with the mixture and each of the reference substances. The 

time taken for the pressure rise from 690 kPa to 2,070 kPa is noted. The mean time interval is 

used for classification. 

Known data

A liquid substance is tested per UN TDG Manual of Tests and Criteria, Test Method O.2: “Test 

method for oxidizing liquids.” 

Test data/results

 2.5 g of the liquid to be tested is mixed with 2.5 g of dried cellulose. The mixture did not 

spontaneously ignite. 

 The mixture is heated, and the time taken for the pressure rise from 690 kPa to 2,070 kPa is 

measured. The mean pressure rise time for 5 trials is 4,210 seconds (s). 

o The test sample exhibited a pressure rise ≥ 2,070 kPa gauge. 

o The mean pressure rise time for the reference substance containing 65% aqueous nitric 

acid and cellulose is 4,767 s. 

o The mean pressure rise time for the reference substance containing 40% aqueous sodium 

chlorate and cellulose is 4,050 s. 

o The mean pressure rise time for the reference substance containing 50% perchloric acid 

and cellulose is 3,085 s. 

Decision/Rationale 

Using the test data, answer the questions posed in the oxidizing liquid decision logic, Figure 

VIII.12.1, above. 

The substance is a liquid. 
355

1. Does a 1:1 mixture, by mass, of substance and cellulose tested, exhibit a pressure rise ≥ 2,070 

kPa gauge? 

ANSWER: Yes. The test sample exhibited a pressure rise of ≥ 2,070 kPa gauge. 

2. Does a 1:1 mixture, by mass, of substance and cellulose tested, exhibit a mean pressure rise 

time less than or equal to the mean pressure rise time of a 1:1 mixture, by mass, of 65% 

aqueous nitric acid and cellulose? 

ANSWER: Yes. The mean pressure rise time for the liquid test substance is 4,210 s, which is 

less than 4,767 s for 65% aqueous nitric acid. 

3. Does a 1:1 mixture, by mass, of substance and cellulose tested, exhibit a mean pressure rise 

time less than or equal to the mean pressure rise time of a 1:1 mixture, by mass, of 40% 

aqueous sodium chlorate and cellulose? 

ANSWER: No. The mean pressure rise time for the liquid test substance is 4,210 s, which is 

greater than 4,050 s for 40% aqueous sodium chlorate. The decision logic is exited and the 

substance is classified. 

According to UN Test O.2, the classification criteria, and decision logic VIII.12.1, the liquid test 

substance fulfils the criteria for Oxidizing Liquids Category 3 and does not meet the criteria for 

Categories 1 and 2. 

Resulting Classification 

The chemical is classified as Oxidizing Liquids, Category 3. 

Oxidizing Solid Classification Example

The following example illustrates the classification process and decision logic for oxidizing 

solids when data are available for the given chemical. 

Tests are performed using the UN TDG Manual of Tests and Criteria, Part III, Sub-section 

34.4.1, Test Method O.1: “Test for oxidizing solids.” 

A chemical suspected of being an oxidizing solid is tested to determine whether a mixture of 

substance and cellulose ignites and burns, and to compare the mean burning time with those of 

reference mixtures. 

Tests require that the substance in question be mixed with dry fibrous cellulose in ratios of 1:1 

and 4:1, by mass, of sample to cellulose. 

The burning characteristics of these mixtures are compared with the standard reference mixtures, 

3:7, 3:2 and 2:3 ratios, by mass, of potassium bromate to cellulose. Five trials are performed on 

the test substance in each of the sample to cellulose ratios. Five trials are performed with each 

reference mixture. 
356

Known data

The solid powder substance was tested using the UN TDG, Manual of Tests and Criteria, Test 

Method O.1: “Test for oxidizing solids.” 

Test data/results

 The chemical in the particle size in which it will be transported and cellulose are prepared in 

ratios of 4:1 and 1:1, by mass.

 The reference substance (potassium bromate) and cellulose are prepared in the ratios 3:7, 2:3 

and 3:2, by mass. 

 The test is initiated. The solid substance samples are ignited and burned. 

 The mean burning time is measured in five trials for the different sample ratios. 

 The data for the 4:1 and 1:1 ratio of the test mixtures are 

o The mean burn time for the 4:1 ratio of the test mixture to cellulose is 105 s 

o The mean burn time for the 1:1 ratio of the test mixture to cellulose is 340 s 

 The data for the standard reference mixtures, 3:7, 3:2 and 2:3 ratios of potassium bromate to 

cellulose are 

o The mean burn time for the 3.7 ratio of potassium bromate to cellulose is 100 s 

o The mean burn time for the 2.3 ratio of potassium bromate to cellulose is 54 s 

o The mean burn time for the 3.2 ratio of potassium bromate to cellulose is 4 s 

Decision/Rationale

Using the test data, answer the questions posed in the oxidizing solid decision logic, Figure 

VIII.12.2, above. 

The substance is a solid 

1. Does a 4:1 or 1:1 sample-to-cellulose ratio, by mass, tested ignite or burn? 

ANSWER: Yes. The 4:1 and 1:1 solid substance samples ignited and burned. 

2. Does a 4:1 or 1:1 sample-to-cellulose ratio, by mass, tested, exhibit a mean burning time less 

than or equal to the mean burning time of a 3:7 mixture, by mass, of potassium bromate and 

cellulose? 

ANSWER: No. The mean burn times for both the 4:1 and 1:1 solid substance sample-tocellulose ratios (105 s, 340 s) are greater than the mean burning time of the 3:7 mixture, by 

mass, of potassium bromate and cellulose (100 s). The solid substance is not classified as an 

oxidizing solid. Exit the decision logic. 

Resulting Classification 

Since the solid substance does not fulfil the criteria for oxidizing solids, it is not classified as an 

oxidizing solid.
357

References

29 CFR 1910.1200, Hazard Communication, Appendix B.13, Oxidizing Liquids. 

29 CFR 1910.1200, Hazard Communication, Appendix B.14, Oxidizing Solids. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
358

VIII.13 Organic Peroxides 

Introduction

The Organic Peroxides hazard class is the only hazard to which chemicals are assigned based on 

their chemical structure. 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 normal 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 because of 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. 

Organic peroxides are liable to exothermic decomposition at normal or elevated temperatures. 

The decomposition can be initiated by heat, contact with impurities (e.g., acids, heavy-metal 

compounds, and amines), friction or impact. Decomposition may result in the evolution of 

harmful, or flammable, gases or vapors. The rate of decomposition increases with temperature 

and varies with the organic peroxide formulation. For certain organic peroxides, the temperature 

is controlled during transport. Some organic peroxides may decompose explosively, particularly 

if confined. This characteristic may be modified by the addition of diluents or by the use of 

appropriate packagings. Many organic peroxides also burn vigorously. 

Contact of organic peroxides with the eyes should be avoided. Some organic peroxides will 

cause serious injury to the cornea, even after brief contact, or will be corrosive to the skin. 

Definition

Organic peroxide means a liquid or solid organic chemical, which contains the bivalent -O-Ostructure, and as such, is considered a derivative of hydrogen peroxide, where one or both of the 

hydrogen atoms have been replaced by organic radicals. The term organic peroxide includes 

mixtures containing at least one organic peroxide. Organic peroxides are thermally unstable 

chemicals, which may undergo exothermic self-accelerating decomposition. In addition, they 

may have one or more of the following properties: 

(a) be liable to explosive decomposition; 

(b) burn rapidly; 

(c) be sensitive to impact or friction; 

(d) react dangerously with other substances. 

An organic peroxide is regarded as possessing explosive 

properties when in laboratory testing the formulation 

detonates, deflagrates rapidly, or shows a violent effect 

when heated under confinement. 

Deflagration. Propagation of a 

reaction zone at a velocity that is 

less than the speed of sound in the 

unreacted medium (Definition 

from NFPA 68).

Detonation. Propagation of a 

combustion zone at a velocity that 

is greater than the speed of sound 

in the unreacted medium 

(Definition from NFPA 68).
359

Classification Criteria

Like self-reactive chemicals, organic peroxides are assigned to one of seven types, A to G,

according to the degree of danger that they present. Table VIII.13.1 presents the classification 

criteria for organic peroxides. 

Table VIII.13.1. Classification criteria for organic peroxides. 

Organic 

Peroxide Type Criteria

A Any organic peroxide, which, as packaged, can detonate or deflagrate rapidly.

B Any organic peroxide possessing explosive properties and which, as 

packaged, neither detonates nor deflagrates rapidly, but is liable to undergo 

a thermal explosion in that package.

C Any organic peroxide possessing explosive properties when the chemical as 

packaged cannot detonate or deflagrate rapidly or undergo a thermal 

explosion.

D Any organic peroxide which in laboratory testing meets the criteria in i, ii, 

or iii below: 

i. Detonates partially, does not deflagrate rapidly and shows no violent 

effect when heated under confinement; or 

ii. Does not detonate at all, deflagrates slowly and shows no violent 

effect when heated under confinement; or

iii. Does not detonate or deflagrate at all and shows a medium effect 

when heated under confinement;

E Any organic peroxide which, in laboratory testing, neither detonates nor 

deflagrates at all and shows low or no effect when heated under confinement.

F Any organic peroxide which, in laboratory testing, neither detonates in the 

cavitated state nor deflagrates at all and shows only a low or no effect when 

heated under confinement as well as low or no explosive power.
360

Organic 

Peroxide Type Criteria

G Any organic peroxide which, in laboratory testing, neither detonates in the 

cavitated state nor deflagrates at all and shows no effect when heated under 

confinement nor any explosive power, provided that it is thermally stable 

(self-accelerating decomposition temperature is 60 °C (140 °F) or higher for 

a 50 kg (110 lb.) package), and, for liquid mixtures, a diluent having a 

boiling point of not less than 150 °C (302 °F) is used for desensitization. 

If the organic peroxide is not thermally stable or a diluent having a boiling 

point less than 150 °C (302 °F) is used for desensitization, it is defined as 

organic peroxide TYPE F.

Note: Type G has no hazard communication elements assigned but should be considered for 

properties belonging to other hazard classes. 

Classification Procedure and Guidance 

Organic peroxides are classified by definition based on their chemical structure and on the available 

oxygen and hydrogen peroxide contents of the mixture. In addition, data are needed on the ability 

of the chemical to detonate and deflagrate, and on the effects of heating under confinement. 

Any organic peroxide is considered for classification in this class, unless it contains: 

a) not more than 1.0% available oxygen from the organic peroxides when containing not 

more than 1.0% hydrogen peroxide; or 

b) not more than 0.5% available oxygen from the organic peroxides when containing more 

than 1.0% but not more than 7.0% hydrogen peroxide. 

The available oxygen content (in percent [%]) of an organic peroxide mixture is given by 

the formula: 

  













 



n

i i

ii

m

cn

16

where 

ni = number of peroxygen groups per molecule of organic peroxide i 

ci = concentration (mass %) of organic peroxide i 

mi = molecular mass of organic peroxide i 
361

Available Literature

The classifier may use available scientific literature and other evidence to classify organic 

peroxides. The information needed to classify the chemicals may be found in available literature 

or through laboratory testing. Should data from laboratory testing be used, a chemical must be 

tested together with its package. 

In addition, many substances presenting organic peroxide hazards have already been classified. 

The information in the U.S. Department of Transportation Hazardous Materials table can be used 

to assist in organic peroxide classification (See 49 CFR 172.101). Under DOT regulations, 

organic peroxides are considered Hazard Class 5 Division 5.2, organic peroxides. Organic 

peroxide chemicals, classified in accordance with the HCS, correspond to organic peroxide 

materials classified under DOT regulations. Therefore, the labeling requirements for organic 

peroxides in the HCS correspond to DOT’s Hazard Class Division 5.2, organic peroxides. Refer 

to the discussion on the interface between the HCS and DOT labeling in Chapter V of this 

document for more information.

Test Methods

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance or mixture, use the test methods identified in Appendix B.15 

to 29 CFR 1910.1200, described below. The decision logic presented below should be used to 

determine the appropriate hazard classification category for organic peroxide chemicals if testing 

is performed to gather the necessary information. 

The classification of organic peroxide chemicals is based on tests described in Part II of the 

Fourth Revised Edition of the United Nations Recommendations on the Transport of Dangerous 

Goods (UN TDG) – Manual of Tests and Criteria, Sub-sections 20 to 28, Test Series A to H. 

The methods are designed for testing both organic peroxides and self-reactive chemicals. 

Organic peroxide chemicals are classified into seven types. The tests are performed in two 

stages. The first stage uses preliminary small-scale tests to ascertain the stability and sensitivity 

of the chemicals and to ensure the safety of laboratory workers. During the second stage, 

classification tests are performed. A brief summary of the purpose of these tests is presented 

below. Refer to the UN TDG Manual of Tests and Criteria for a complete description of the 

method, the apparatus used, and analysis of the test results. 

Preliminary procedure 

Performing small-scale preliminary tests before attempting to handle larger quantities is essential 

to ensure the safety of laboratory workers. The preliminary tests determine the sensitivity of the 

chemical to mechanical stimuli (impact and friction), and to heat and flame. Four types of smallscale tests are used to make the preliminary assessment: 
362

(e) A falling weight test to determine sensitivity to impact; 

(f) A friction or impacted friction test to determine the sensitivity to friction; 

(g) A test to assess thermal stability and the exothermic decomposition energy; and 

(h) A test to assess the effect of ignition. 

The details of these preliminary tests can be found in Part I of the Fourth Revised Edition of the 

UN TDG Manual of Tests and Criteria, Sub-section 13, Test Series 3. Appendix 6 of the UN 

TDG Manual for Tests and Criteria provides additional guidance on screening procedures. 

Classification test 

The classification of an organic peroxide chemical in one of the seven categories, Types A to G,

is dependent on its detonation, explosive thermal explosion and deflagrating properties, its 

response to heating, the concentration and the type of diluent added to desensitize the substance. 

The classification of an organic peroxide chemical as Type A, B, or C is also dependent on the 

type of packaging in which the chemical is tested, as the package affects the degree of 

confinement to which the chemical is subjected. 

Should testing be performed on the chemical, data from organic peroxide chemical test series A 

to H is needed. A brief description of the purpose of each of the tests described in the UN TDG

Manual for Tests and Criteria is presented below. 

Test Series A answers the question, “Does the chemical propagate a detonation?” Several tests 

are identified in the UN TDG Manual for Tests and Criteria and each measures the ability of a 

chemical to propagate a detonation by subjecting it to a detonating booster charge under 

confinement in a steel tube. The test methods include: 

 BAM 50/60 steel tube test 

 TNO 50/70 steel tube test 

 UN gap test 

 UN detonation test (the recommended test) 

Test Series B answers the question “Can the chemical detonate as packaged for transport?” The 

tests measure the ability of a chemical to propagate a detonation when packaged for transport by 

subjecting it to the shock from a detonating booster charge. The test is required only for 

substances that propagate detonation. 

Test Series C answers the question, “Does the chemical propagate a deflagration?” This series 

consists of two recommended tests – the time/pressure test, and the deflagration test. The time 

and pressure test measures the ability of a substance under confinement to propagate a 

deflagration. The deflagration test measures the ability of a chemical to propagate a deflagration. 
363

Test Series D answers the question, “Does the chemical deflagrate rapidly in package?” The test 

measures the ability of a chemical to rapidly propagate a deflagration when packaged for 

transport. The test is required for substances that deflagrate rapidly in a Test Series C test. 

Test Series E answers the question, “What is the effect of heating the chemical under defined 

confinement?” This test series consists of three test methods – the Koenen test, the Dutch 

pressure test, and the USA pressure test. For organic peroxide chemicals, the Dutch pressure test 

is recommended in combination with one of the other tests. The purpose of these three tests is 

described below. 

The Koenen test determines the sensitivity of substances to the effect of intense heat under high 

confinement. The Dutch pressure vessel test and the USA pressure test determine the sensitivity 

of substances to the effect of intense heat under defined confinement. 

Test Series F answers the question, “What is the chemical’s explosive power?” Several tests are 

described in the UN TDG Manual of Tests and Criteria for use when testing for organic 

peroxides, including the Ballistic mortar Mk. IIId test, the Ballistic mortar test, the BAM Trauzl 

test, and the Modified Trauzl test. The Modified Trauzl test is the recommended test, measures 

the explosive power of a chemical, and is used for chemicals being considered for transport in 

intermediate bulk containers (IBCs) or tank-containers. 

Test Series G answers the question, “Can the chemical explode as packaged for transport?” The 

test series uses two test methods – the thermal explosion test in package, and the accelerating 

decomposition test in package. The test is needed only for chemicals that show a violent effect 

in tests involving heating under defined confinement (Test Series E). The thermal explosion test 

in package is the recommended test and is used to determine the potential for thermal explosion 

in a package. 

Temperature control 

In addition to the classification tests, the thermal stability of the 

organic peroxide is needed to determine the Self-Accelerating 

Decomposition Temperature (SADT). The SADT is used to 

derive safe handling, storage and transport temperatures 

(control temperature), and alarm temperature (emergency 

temperature). 

To protect those exposed to organic peroxides under normal 

conditions of use and foreseeable emergencies, including 

emergency responders, organic peroxides should be subjected to temperature control if their 

SADT is less than or equal to 55 °C (131 oF), including the following organic peroxides: 

a) organic peroxide types B and C with an SADT ≤ 50 °C (122 oF); 

Self-accelerating 

decomposition 

temperature (SADT) means 

the lowest temperature at 

which self-accelerating 

decomposition may occur 

with a substance as 

packaged. (Definition from 

GHS, Rev. 3)
364

b) organic peroxide type D showing a medium effect when heated under confinement with 

an SADT ≤ 50 °C (122 oF), or showing a low or no effect when heated under 

confinement with an SADT ≤ 45 °C (113 oF); and 

c) organic peroxide types E and F with an SADT ≤ 45 °C (113 oF). 

The UN TDG Manual of Tests and Criteria, Part II, Sub-section 28, Test Series H, describes 

several test methods for determining the SADT, including the United States SADT test, the 

adiabatic storage test, the isothermal storage test, and the heat accumulation storage test. Since 

there are several test methods presented, the test selected and conducted should be representative 

of the package, both in size and material. Each test involves either storage at a fixed external 

temperature and observation of any reaction initiated or storage under near adiabatic conditions 

and measurement of the rate of heat generation versus temperature. The recommended tests are 

described below. 

The United States SADT test determines the minimum constant temperature air environment at 

which auto-accelerative decomposition occurs for a substance in a specific package (up to 220 

liters). The adiabatic storage test determines the rate of heat generation produced by a reacting 

substance as a function of temperature. The heat generation parameters obtained are used with 

the heat loss data relating to the package to determine the SADT of a substance in its packaging, 

including IBCs and tanks. The heat accumulation storage test determines the minimum constant 

air environment temperature at which thermally unstable substances undergo exothermic 

decomposition at conditions representative of the substance when packaged for transport. The 

test method can be used for the determination of the SADT of a substance in its packaging, 

including IBCs and small tanks (up to 2 m3).

Classification Procedure 

Organic peroxides are classified according to the classification principles given in the decision 

logic and the results of test series A to H. Classification also may be determined using 

information provided in available scientific literature. As the explanations above indicate, the

tests are designed to provide the information necessary to answer the questions in the decision 

logic for organic peroxides, presented in Figure VIII.13.1. 

 Test series A includes laboratory tests and criteria concerning propagation of detonation, as 

requested in box 1 of the flowchart. 

 Test series B includes a test and criteria concerning the propagation of detonation of the 

chemical as packaged for transport, as requested in box 2 of the flowchart. 

 Test series C includes laboratory tests and criteria concerning propagation of deflagration, as 

requested in boxes 3, 4, and 5 of the flowchart. 

 Test series D includes a test and criteria concerning the propagation of a rapid deflagration of 

the substance as packaged for transport, as requested in box 6 of the flowchart. 
365

 Test series E includes laboratory tests and criteria concerning the determination of the effect 

of heating under defined confinement, as requested in boxes 7, 8, 9, and 13 of the flowchart. 

 Test series F includes laboratory tests and criteria concerning the explosive power of 

substances that are considered for transport in Intermediate Bulk Containers (IBCs) or tanks, 

or for exemption (see box 11 of the flowchart), as requested in box 12 of the flowchart. 

 Test series G includes tests and criteria concerning the determination of the effect of a 

thermal explosion of the substance as packaged for transport, as requested in box 10 of the 

flowchart. 

 Test series H includes tests and criteria concerning the determination of the SADT of organic 

peroxides. 

Mixtures that include organic peroxides may be classified as the same type of organic peroxide as 

that of the most dangerous ingredient. However, since two stable ingredients can form a thermally 

less stable mixture, information on the SADT of the mixture is needed for classification. 

The decision logic for classifying organic peroxides is provided in Figure VIII.13.1. To answer 

the questions in the decision logic the following information is needed: 

 propagation of detonation; 

 propagation of deflagration; 

 effect on heating in confinement; and 

 thermal stability: SADT. 

Data from additional tests may also be needed (for example, explosive power, or explosivity as 

packaged) depending on the circumstances and/or the results of the foregoing tests. 

Classification follows the assessment of available data and, if applicable, the results of any 

testing performed. Once you have collected the data, compare it to the classification criteria for 

organic peroxide chemicals types A through G, presented in Table VIII.13.1. Follow the logic 

paths presented in the decision logic (or flowchart) in Figure VIII.13.1 to identify the appropriate 

classification for organic peroxide chemicals. 
366

Figure VIII.13.1. Decision logic for classifying organic peroxides. 

6.1 Yes

Box 6

Test D

6.2 No

7.2 Medium

7.3 Low

7.4 None

Box 7

Test E

7.1 

Violent

10.1 Yes

Box 10

Test G

10.2 No

3.2 Yes, slowly

3.3 No

3.1 

Yes, rapidly

2.1 Yes 2.2 No

1.1 Yes

1.2 Partial

1.3 No

4.1 

Yes, rapidly

SUBSTANCE/MIXTURE

11.2 No

12.1

Not low

12.2 Low

12.3 None

13.1 Low

13.2 None

Box 13

Test E

5.1 

Yes, rapidly

5.2 Yes, slowly

5.3 No

Box 8

Test E

8.1 

Violent

8.2 Medium

8.3 Low

8.4 None

?

4.2 Yes, slowly

4.3 No

9.2 Medium

Box 9

Test E

9.1 

Violent

9.3 Low

9.4 None

11.1 Yes

Box 11

Box 12

Test F

Type A Type B Type C Type D Type E Type F Type G

Does it propagate 

a detonation 

? 

Can it 

detonate as 

packaged 

? 

Can it 

propagate a 

deflagration 

? 

Box 2

Test B

Box 3

Test C

Can it 

propagate a 

deflagration 

? 

Can it 

propagate a 

deflagration 

? 

Box 4

Test C

Box 5

Test C

Does it

deflagrate rapidly

in package 

? 

What is

the effect of heating

under confinement

? 

What is

the effect of heating

under confinement

? 

What is

the effect of heating

under confinement

? 

Can it 

detonate as 

packaged 

? 

Packaged

in packages of more

than 400 kg/450 l or to 

be considered for 

exemption 

?

What is

the effect of heating

under confinement

? 

What is

its explosive 

power 

? 
367

Organic Peroxide Classification Example 

The following example illustrates the classification process and application of the decision logic

for organic peroxides. The example was developed using information from the ECHA Guidance 

on the Application of Regulation (EC) No. 1272/2008. 

A colorless liquid is suspected of being an organic peroxide and is tested according to the tests 

presented in the UN TDG Manual of Tests and Criteria. Organic peroxides, by definition, must 

contain the molecular structure -O-O-, and must contain a certain level of available oxygen and 

hydrogen peroxide content. 

The UN TDG Manual of Tests and Criteria provides several cautionary notes and preliminary 

test procedures that must be followed before embarking on the classification test procedure. The 

tests are designed to provide the information necessary to answer the questions in the decision 

logic for organic peroxides and to apply the principles for classification. In the following 

example, the results of the tests are assessed in alphanumeric order; however, the tests are 

performed in the order given in section 20.4.5 of the UN TDG Manual of Tests and Criteria.

Known data 

 Colorless liquid. 

 Composition: technically pure (97%) 

 Molecular formula: not available 

 Apparent density: 900 kg/m3

 Available oxygen content: 7.18% 

Test results 

Test Name Observation Result

Test series A - Detonation 

propagation [BAM 50/60 steel 

tube test]

Sample conditions: peroxide 

assay 97%

Observations: fragmented part of 

the tube: 18 cm 

Test result/criteria: No 

propagation of detonation (Exit 

1.3 of Box 1/Test A 3 Decision 

Logic flowchart)

Test series B - Detonation as 

packaged 

Not applicable

Test series C - Deflagration 

propagation [Time/pressure test]

Test conducted on 5 g of sample 

three times; the time it took for 

the pressure to rise from 690 kPa 

to 2,070 kPA was noted. 

Shortest recorded time (4000 ms) 

is used for result.

Test result/criteria: Yes, slowly, 

because the time for pressure to 

rise from 690 kPa to 2,070 kPA 

is greater than or equal to 30 ms.
368

Test Name Observation Result

Test series C - Deflagration 

propagation [Deflagration test]

Test conducted two times on 

265 cm3of sample at 25 °C, and 

the reaction rate noted for each. 

Shortest recorded rate (0.74 

mm/s) is used for result.

Test result/criteria: Yes, slowly, 

because the deflagration rate is 

less than or equal to 5.0 mm/s 

and greater than or equal to 0.35 

mm/s. 

Overall result: Yes, slowly (Exit 

5.2 of Box 5/Test C Decision 

Logic flowchart)

Test series D - Deflagration as 

packaged 

Not applicable

Test series E - Effect of heating 

under confinement [Koenen test]

Tested 60 mm of sample. 

Limiting diameter: 2.0 mm 

fragmentation type “F,” 

evaluated as “explosion.”

Test result/criteria: Violent, 

because the limiting diameter is 

greater than or equal to 2.0 mm.

Test series E - Effect of heating 

under confinement [Dutch 

Pressure Vessel test]

Tested 10.0 g of sample. 

Limiting diameter: 6.0 mm (with 

10 g)

Test result/criteria: Medium, 

because rupture of the disc with 

an orifice of 6.0 mm and a 

sample mass of 10.0 g.

Overall result: Violent (Exit 8.1 

of Box 8/Test E Decision Logic 

flowchart)

Test series F - Explosive Power Not applicable

Test series G - Detonation as 

packaged [Thermal explosion 

test in the package]

Tested 30-liter packaging.

Observations: no fragmentation 

of the package (N.F.)

Test result/criteria: No 

fragmentation or a fragmentation 

into no more than three pieces 

shows that the Substance 23 does 

not explode in the package.

Exit 10.2 of Box 10/Test G 

Decision Logic flowchart. Liquid 

is classified as an organic 

peroxide Type C.
369

Test Name Observation Result

Test series H - Thermal stability 

[Heat accumulation storage test; 

the recommended test for 

substances transported in 

packagings, IBCs, or small 

tanks.]

Tested 380 g of liquid. 

Half life time of cooling of 

Dewar vessel with 400 ml DMP: 

10.0 hrs (representing substance 

in package)

Observed: 

Self-accelerating decomposition 

at 35 °C (95 oF), no selfaccelerating decomposition at 

30 °C (86 oF). The selfaccelerating decomposition 

temperature (SADT) is 35 °C 

(95 oF).

Liquid has a SADT of 35 °C 

(95 oF).

Liquid is classified as an 

Organic Peroxide Type C 

because the substance does 

not detonate, but does exhibit 

violent effects when heated 

under confinement, and 

slowly deflagrates. In 

addition, the UN 

Recommendations on the 

Transport of Dangerous 

Good, Model Regulations and 

the UN Manual of Tests and 

Criteria recommend the use of 

temperature control for this 

substance since the selfaccelerating decomposition 

temperature (SADT) is less 

than or equal to 50 °C 

(122 oF).

Decision/Rationale 

The liquid has 7.18% available oxygen. As required by Appendix B.15.2.1 of 29 CFR 

1910.1200, the liquid is considered for classification as an organic peroxide since the available 

oxygen is greater than 1%. 

To classify an organic peroxide, the classifier follows the decision logic for organic peroxides, 

answering the questions and following the flowchart: 

Box 1, Test Series A 

1. Does the chemical in question propagate a detonation? 

RESULT (Test series A): No, Exit 1.3 

Box 5, Test C 

2. Can the chemical in question propagate a deflagration? 

RESULT (Tests series C): Yes, slowly, Exit 5.2 
370

Box 8, Test E 

3. What is the effect of heating under confinement? 

RESULT (Tests series E): Violent, Exit 8.1 

Box 10, Test G 

4. Can it detonate as packaged? 

RESULT (Tests series G): No, Exit 10.2 

By following the test logic, the classifier determines that Tests B, D, and F are not required for 

this chemical. 

5. Test H is performed to determine whether the chemical in question requires temperature 

control measures. 

RESULT: Liquid has a SADT of 35 °C (95 oF). Temperature control is required for this 

package. 

Resulting Classification 

The chemical is classified as an organic peroxide, Type C: Any organic peroxide possessing 

explosive properties when the substance or mixture as packaged cannot detonate or deflagrate 

rapidly or undergo a thermal explosion. 
371

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.15, Organic Peroxides. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

NFPA 68, Standard on Explosion Protection by Deflagration Venting, 2013. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods (UN TDG) – Manual of 

Tests and Criteria, Fourth Revised Edition, 2003. 
372

VIII.14 Corrosive to Metals 

Introduction

This corrosive to metals hazard class does not cover all chemicals that might corrode metals. 

Classification as corrosive to metals refers only to chemicals that corrode steel and/or aluminum 

and does not provide information about the corrosivity potential to other metals. 

Two types of corrosion phenomena are considered when classifying chemicals as corrosive to 

metals: – the uniform corrosion attack and the localized corrosion (e.g., pitting corrosion, 

shallow pit corrosion). 

Definition

A chemical which is corrosive to metals means a chemical which by chemical action will 

materially damage, or even destroy, metals. 

Classification Criteria

A chemical which is corrosive to metals is classified in a single category when corrosion is 

observed in steel or aluminum surfaces (See Table VIII.14.1). 

Table VIII.14.1. Classification criteria for corrosive to metals. 

Category Criteria

1 Corrosion rate on steel or aluminum surfaces exceeding 6.25 mm per year at a 

test temperature of 55 °C (131 °F) when tested on both materials.

Note: Where an initial test on either steel or aluminum indicates that the chemical being tested is 

corrosive, the follow-up test on the other metal is not necessary. 

Classification Procedure and Guidance 

To classify a chemical as corrosive to metal, data are necessary on its corrosion rate on steel 

and/or aluminum. 

Available Literature

The classifier may use available scientific literature and other evidence to identify the corrosion 

rate on steel or aluminum for chemicals that are corrosive to metals. The required information 

may already exist and may be well-documented for many of these chemicals. 

In addition, many substances presenting corrosive to metals hazards have already been classified. 

The information provided in the U.S. Department of Transportation Hazardous Material table 

can be used to assist in corrosive to metals classifications (See 49 CFR 172.101). Under DOT 

regulations, materials corrosive to metals are considered Class 8 hazardous materials. The HCS 

corrosive to metals category 1 corresponds to DOT Hazard Class 8, Packing Group III, corrosive 
373

substances. Refer to the discussion on the interface between the HCS and DOT labeling in 

Chapter V of this document for more information.

Test Method 

As mentioned throughout this guidance, the Hazard Communication Standard does not require 

the testing of chemicals – only the collection and analysis of currently available data. However, 

if you choose to test the substance or mixture, use the methods identified in Appendix B.16 to 29 

CFR 1910.1200, described below. For mixtures, test data are required from the mixture as a 

whole. 

The corrosion rate can be measured according to the test method of Part III, sub-section 37.4 of 

the UN Recommendations on the Transport of Dangerous Goods (UN TDG), Manual of Tests 

and Criteria, Test C.1, “Test for determining the corrosive properties of liquids and solids that 

may become liquid during transport.”25

 This test method is designed to determine the corrosive 

capabilities of chemicals with metals; it is not applicable for determining corrosivity exposures 

to skin. 

A brief summary of this test is presented below. Refer to the UN TDG Manual of Tests and 

Criteria for a complete description of the method, the apparatus used, and analysis of the test 

results. 

Two types of metals are specified in the test method – carbon steel and aluminum, as follows: 

a) For the purposes of testing steel: 

Steel types S235JR+CR (1.0037 resp. St 37-2), S275J2G3+CR (1.0144 resp. St 44-3), 

ISO 3574, Unified Numbering System (UNS) G 10200, or SAE 1020; 

b) For the purposes of testing aluminum: 

Non-clad types 7075-T6 or AZ5GU-T6. 

Test C.1 obtains two types of data: 

 Uniform corrosion measured by mass loss in [percent], (UN TDG Manual of Tests and 

Criteria Table 37.4.1.4.1, reproduced in Table VIII.14.2 below) and 

 Localized corrosion measured by intrusion depth in [micrometers] (UN TDG Manual of 

Tests and Criteria Table 37.4.1.4.2, reproduced in Table VIII.14.3 below). 

 

25 Note the method explains that chemicals that cannot be tested must be classified by comparing them with similar 

entries in the United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations. 
374

Classification Procedure 

Data from available information may be used to classify the chemical. However, if testing is 

performed, use the data from Test C.1 described above to determine the corrosion rates. 

 For uniform corrosion, the measured loss of mass [in percent] within a given time 

extrapolated to one year, or 

 For localized corrosion, the measured minimum intrusion depth [in μm] (depth of the 

deepest hole) within a given time. 

In the case of uniform corrosion attack, the mass loss of the most corroded sample is used. The 

C.1 test is considered positive when, for any test specimen, the mass loss on the metal specimen 

is more than the amount stated in the following table (Table VIII.14.2). In Table VIII.14.2, the 

first column gives the exposure time in days and the second column gives the percent mass loss. 

Table VIII.14.2. Minimum Mass Loss of Specimens after different Exposure Times. 

[from UN Manual of Tests and Criteria Table 37.4.1.4.1]

Exposure Time Mass Loss

7 days 13.5 %

14 days 26.5 %

21 days 39.2 %

28 days 51.5 %

The equation below is used to calculate rate of corrosion in mm/year using the minimum mass 

loss at the appropriate exposure time from the above table and the measured mass loss. 

mm y

mm y

 measured % mass loss change amount of /in corrosion 

 exposureat time

 tablefrom

 (%) loss mass min.

.6 25 /

 

The mass loss of corrosion for the tested sample is determined as a percentage value as follows. 

Obtain the percent minimum mass loss at the appropriate exposure time from the Minimum 

Mass Loss of Specimens after different Exposure Times table (Table VIII.14.2). Use this 

value as shown in the above equation with the measured mass loss to calculate the corrosion rate 

for the tested sample in mm/year. If this value is greater than 6.25 mm/year, then the chemical is 

corrosive to metal. 

When localized corrosion occurs besides or instead of uniform corrosion of the surface, the depth 

of the deepest hole is used to determine the intrusion. When the deepest intrusion exceeds the 

values shown in the following table (Table VIII.14.3), the C.1 test result is considered positive. 
375

In Table VIII.14.3, the first column gives the exposure time in days and the second column gives 

the values for intrusion/depth of hole in micrometers (μm). 

Table VIII.14.3. Minimum Intrusion Depths after Exposure Time. 

[from UN Manual of Tests and Criteria Table 37.4.1.4.2]

Exposure Time Min. Intrusion Depth 

7 days 120 μm

14 days 240 μm

21 days 360 μm

28 days 480 μm

The equation below is used to calculate rate of corrosion in mm/year using the minimum 

intrusion depth at the appropriate exposure time from the above table and the measured intrusion 

depth. 

mm y

mm y

 depth intrusion measured amount of corrosion in / 

 exposureat time

 tablefrom

 [μm] depth

 intrusion min.

.6 25 /

 

Obtain the minimum intrusion depth at the appropriate exposure time from the Minimum 

Intrusion Depths after different Exposure Times table (Table VIII.14.3). Use this value as 

shown in the above equation with the measured intrusion depth to calculate the corrosion rate for 

the tested sample in mm/year. If this value is greater than 6.25 mm/year, the chemical is 

corrosive to metal. 

The values in the Tables VIII.14.2 and VIII.14.3 are calculated based upon a 6.25 mm/year 

corrosion rate. 

Once you have collected the data and made the calculation(s) described above, compare it to the 

criteria for corrosive to metals category 1 presented in Table VIII.14.1. The chemical is 

classified as corrosive to metals if it corrodes either steel or aluminum surfaces at a rate 

exceeding 6.25 mm/year at a test temperature of 55 °C (131 °F). Follow the logic path presented 

in the decision logic (or flowchart) in Figure VIII.14.1 to identify the appropriate classification 

for corrosive to metals. 
376

Figure VIII.14.1. Decision logic for classifying substances and mixtures corrosive to metals. 

No Not classified

Does it corrode on either steel or aluminum surfaces at 

a rate exceeding 6.25 mm/year at a test temperature of 

55 °C when tested on both materials?

Substance/mixture

Category 1

Warning 

Yes
377

Corrosive to Metals Classification Example 

The following example is provided to illustrate the corrosive to metals calculation and decision 

logic. 

A liquid is suspected of being classified as corrosive to metals and is tested to determine if at 

55 °C the liquid corrodes either steel or aluminum surfaces at a rate exceeding 6.25 mm/year. 

Known data 

 The substance is a liquid 

 UN Test method C.1 test results showed after 21 days that the mass loss of corrosion to 

aluminum was 41.2 %. 

Calculation 

1. Calculate the corrosion rate in mm/year by referring to Table VIII.14.2. Use the below 

formula. 

mm y

mm y

 measured % mass loss change amount of /in corrosion 

 exposureat time

 tablefrom

 (%) loss mass min.

.6 25 /

 

For this example 

where 41.2 % is the measured mass loss after 21 days expressed as a percentage 

where 39.2% is the minimum mass loss from Table 37.4.1.4.1 for 21 days 

where 6.25 mm/year is the corrosion rate basis for 39.2% and the corrosion rate threshold 

for the corrosive to metals criteria 

mm y

mm y

41 .6%2. 569 /

39 %2.

.6 25 /



The corrosion rate on aluminum is calculated to be 6.569 mm/year. 

41 %2.

/

39 %2.

.6 25 mm/ Xy mm y


378

Decision/Rationale 

Using the information from the test results and calculation, answer the question posed in the 

decision logic VIII.14.1, above. 

1. Does the substance corrode either steel or aluminum surfaces at a rate exceeding 6.25 mm 

per year at a test temperature of 55 °C when tested on both materials? 

ANSWER: Yes. The corrosion rate on aluminum is calculated to be 6.569 mm/year. 

Resulting Classification 

The chemical is classified as a corrosive to metals, category 1, based on the outcome of UN Test 

Method C.1. 
379

References 

29 CFR 1910.1200, Hazard Communication, Appendix B.16, Corrosive to Metals. 

49 CFR Parts 100-185, Other Regulations Relating to Transportation, Pipeline and Hazardous 

Materials Safety Administration, U.S. Department of Transportation. 

United Nations Globally Harmonized System of Classification and Labelling of Chemicals, 

Third Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Model Regulations, 

Sixteenth Revised Edition, 2009. 

United Nations Recommendations on the Transport of Dangerous Goods – Manual of Tests and 

Criteria, Fourth Revised Edition, 2003. 
380

VIII.15 Combustible Dust 

Introduction

Combustible dust hazards involve dusts or other small particles that present a fire or deflagration 

hazard when suspended at a sufficient concentration in air or some other oxidizing medium. 

Combustible dusts present an explosion hazard when they are contained in an enclosure (e.g., 

enclosed building, sand blasting chamber). 

A small dust explosion can stir up dust that has settled on surfaces nearby, which in turn ignites, 

creating a secondary and often larger explosion. This secondary explosion can then force more 

dust in the air, creating a chain of explosions. This series of cascading explosions is generally 

more hazardous than the initial one. 

Refer to OSHA’s Hazard Communication Guidance on Combustible Dust for more information 

on combustible dusts, including a discussion on understanding and controlling the potential for 

dust explosions. This guidance is located on the combustible dust safety and health topics page, 

located at: www.osha.gov/dsg/combustibledust.

The ease of ignition and the severity of a combustible dust explosion are typically influenced by 

particle size. Other factors that influence the explosiveness of dusts include moisture content, 

ambient humidity, oxygen available for combustion, the shape of dust particles, and the 

concentration of dust in the air. Physical properties used to measure combustible dusts include: 

 Minimum ignition energy (MIE), which predicts the ease and likelihood of ignition of a 

dispersed dust cloud. 

 Minimum explosible concentration (MEC), which measures the minimum amount of dust 

dispersed in air required to spread an explosion. (The MEC is analogous to the Lower 

Flammable Limit (LFL) or Lower Explosive Limit (LEL) for gases and vapors in air.) 

 Dust deflagration index (Kst), which measures the relative explosion severity compared to 

other dusts. The larger the value for Kst, the more severe the explosion (See Table VIII.15.1, 

below.) Kst provides the best “single number” estimate of the anticipated behavior of a dust 

deflagration. 

Different dusts of the same chemical material can have different ignitability and explosibility 

characteristics, depending upon physical characteristics such as particle size, shape, and moisture 

content. These physical characteristics can change during manufacturing, use or while the 

material is being processed. Any combustible dust with a Kst value greater than zero can be 

subject to dust deflagration. Even weak explosions can cause significant damage, injury and 

death. For example, sugar has a relatively low Kst, but it fueled an explosion in 2008 that killed 

14 workers at a refinery.
381

Not all materials present a combustible dust hazard, even when reduced to fine particles. For 

example, silicates, sulphates, nitrates, carbonates, phosphates, cement, salt, gypsum, sand, and 

limestone do not present fire or deflagration hazards. However, many materials do present dust 

explosion hazards. Many organic materials, plastics, and metals are explosible in dust form. 

Definition

The HCS does not contain a definition of the term combustible dust. However, OSHA has 

provided a definition in the Agency’s Combustible Dust National Emphasis Program (NEP).

Combustible dust is defined in OSHA’s Combustible Dust NEP as a solid combustible material, 

composed of distinct pieces or particles that presents “a fire or deflagration hazard when 

suspended in air or some other oxidizing medium over a range of concentrations, regardless of 

particle size or shape.” 

Classification Procedure and Guidance 

The National Fire Protection Association (NFPA), FM-Global, and the American Society for 

Testing and Materials (ASTM) International suggest various tests, data, and criteria that may be 

used to determine whether a material presents a combustible dust hazard. The classifier must 

consider not only the hazards of the chemical in the form in which it is shipped, but also any 

hazards posed by the product in normal conditions of use and foreseeable emergencies. The 

classifier also must consider the full range of available information about those hazards. 

For combustible dusts, often the best information is actual experience with the product. If the 

classifier knows that the product has been involved in a deflagration or dust explosion event, the 

classifier should classify the product as a combustible dust, unless the classifier can show that the 

conditions surrounding the event are not expected in normal conditions of use or foreseeable 

emergencies. In the absence of information on a deflagration or dust explosion event, classifiers 

may use one or more of the following approaches in determining whether such hazards exist, 

depending on the information that is available. 

Laboratory Testing 

If published test results are not available, then the use of test data is recommended. Voluntary 

consensus standards recognize that reliable test data for a material, based on scientifically validated 

tests, is strong evidence for determining whether a material presents a combustible dust hazard and 

should be used for classification if available. The Hazard Communication Standard does not 

require the testing of chemicals – only the collection and analysis of currently available data. 

Reliable screening tests, such as that described in ASTM E1226, showing a positive normalized 

rate of pressure rise or dust deflagration index (Kst), and tests for Class II dusts may be used to 

determine whether a material presents a combustible dust hazard, and classification should be 

based on such data if it is available. Many voluntary standards recognize the ASTM E1226 

(Standard Test Method for Explosibility of Dust Clouds) and ASTM E1515 (Standard Test 

Method for Minimum Explosible Concentration of Combustible Dusts) methods as reliable 

means to establish a combustible dust hazard. 
382

OSHA’s combustible dust NEP describes the Agency’s own test method for determining the Kst, 

and the NEP treats a dust as presenting the hazard when the Kst is greater than zero. In addition, 

the NEP describes OSHA’s method for determining whether a dust is a Class II dust for purposes 

of the electrical standard, which is also an indication that a dust presents a combustible dust hazard. 

Published Test Results

Several NFPA standards publish lists of test results for various materials, including: 

 NFPA 61 (Standard for the Prevention of Fires and Dust Explosions in Agricultural and 

Food Processing Facilities), 

 NFPA 68 (Standard on Explosion Protection by Deflagration Venting), 

 NFPA 484 (Standard for Combustible Metals), and 

 NFPA 499 (Recommended Practice for the Classification of Combustible Dusts and of 

Hazardous (Classified) Locations for Electrical Installations in Chemical Process Areas) 

Although the NFPA documents caution care in the use of these results because the extent of 

explosibility can vary even for different dusts of the same solid material, they nonetheless can 

“aid in the determination of the potential for a dust hazard to be present in [an] enclosure.” 

(NFPA 61, A.6.2.1 (2013)). 

As a part of a poster about combustible dust hazards, OSHA has published a list of combustible 

materials based on the information provided in the NFPA standards (www.osha.gov/

Publications/combustibledustposter.pdf). In addition, there are public databases of dust 

explosibility characteristics that may be consulted, such as the “Gestis-Dust-EX” database 

maintained by the Institute for Occupational Safety and Health of the German Social Accident 

Insurance (www.dguv.de/ifa/GESTIS/GESTIS-STAUB-EX/index-2.jsp).

Dust Particle Size

For many years, NFPA 654 (Standard for the Prevention of Fire and Dust Explosions from the 

Manufacturing, Processing, and Handling of Combustible Particulate Solids) defined 

combustible dust as a “finely divided solid material 420 microns or smaller in diameter (material 

passing a U.S. No. 40 Standard Sieve) that presents a fire or explosion hazard when dispersed 

and ignited in air.” 

OSHA used this definition in earlier combustible dust guidance, such as its 2005 Safety and 

Health Information Bulletin, and uses a similar criterion in defining “fugitive grain dust” in its 

Grain Handling Facilities standard (see 29 CFR 1910.272(c)). Some NFPA standards still use a 

size criterion in defining combustible dust, such as NFPA 61 (2013) and NFPA 704 (2012) 

(Standard System for the Identification of Hazardous Materials for Emergency Response). 

Other NFPA standards, however, have changed their combustible dust definition to remove the 

size criterion, but discuss size in their explanatory notes. In general, the notes concerning 

particle size state that dusts of combustible material with a particle size of less than 420 microns 
383

can be presumed to be combustible dusts. However, certain particles, such as fibers, flakes, and 

agglomerations of smaller particles, may not pass a No. 40 sieve but still have a surface-area-tovolume ratio sufficient to pose a deflagration hazard. In the most recent revisions, the 

explanatory notes in many of the NFPA standards have moved from a 420 to 500 micron size 

threshold. See NFPA 484 (2013), NFPA 654 (2013), NFPA 664 (2012) and FM Global Data 

Sheet 7-76 (2014).26

 

Where there are no test data, or if the testing is inconclusive, classification may be based on 

particle size, if particle size information is available. If the material will burn and contains a 

sufficient concentration of particles 420 microns or smaller to create a fire or deflagration 

hazard, then it should be classified as a combustible dust. A classifier may, if desired, instead 

use the 500 micron particle size (U.S. Sieve No. 35) threshold contained in more recent NFPA 

standards. Care must be used with this approach where the particles are fibers or flakes, or 

where agglomerations of smaller particles may be held together by static charges or by other 

means that would prevent the dust from passing through respective sieves No. 40 and 35, but 

would still present a fire or deflagration hazard. 

 

26 NFPA 664 is NFPA’s Standard for the Prevention of Fires and Explosions in Wood Processing and Woodworking 

Facilities. FM Global Data Sheet 7-76 is a Property Loss Prevention Data Sheet on the Prevention and Mitigation of 

Combustible Dust Explosion and Fire. 
384

References 

29 CFR 1910.1200, Hazard Communication 

29 CFR 1910.272, Grain Handling Facilities 

Many informational materials are available on OSHA’s Combustible Dust Safety and Health 

Topics Page (www.osha.gov/dsg/combustibledust), including: 

Occupational Safety and Health Administration (2013). Classification of Combustible Dusts 

under the Revised Hazard Communication Standard. Washington, D.C. Retrieved from: 

www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=INTERPRETATIONS&p_id

=28880#5

Occupational Safety and Health Administration (2009). Hazard Communication Guidance 

for Combustible Dusts, Washington DC. Retrieved from: 

www.osha.gov/Publications/3371combustible-dust.html

Combustible Dust National Emphasis Program Instruction, OSHA Directive CPL 03-00-008 

(2008). www.osha.gov/OshDoc/Directive_pdf/CPL_03-00-008.pdf

OSHA Poster (2008), Combustible Dust. 

www.osha.gov/Publications/combustibledustposter.pdf

Consensus Standards related to combustible dust include:

ASTM E1226 (Standard Test Method for Explosibility of Dust Clouds) 

ASTM E1515 (Standard Test Method for Minimum Explosible Concentration of 

Combustible Dusts)

NFPA 61, Standard for the Prevention of Fires and Dust Explosions in Agricultural and Food 

Processing Facilities 

NFPA 68, Standard on Explosion Protection by Deflagration Venting 

NFPA 484, Standard for Combustible Metals 

NFPA 499, Recommended Practice for the Classification of Combustible Dusts and of 

Hazardous (Classified) Locations for Electrical Installations in Chemical Process Areas 

NFPA 654, Standard for the Prevention of Fire and Dust Explosions from the Manufacturing, 

Processing, and Handling of Combustible Particulate Solids 

NFPA 664, Standard for the Prevention of Fires and Explosions in Wood Processing and 

Woodworking Facilities 

FM 7-76, "Prevention and Mitigation of Combustible Dust Explosions and Fires," Loss 

Prevention Data Sheet 7-76. FM Global, April 2014.
385

IX. HAZARDS NOT OTHERWISE CLASSIFIED

Introduction

Workers need to be informed of every health and physical hazard present in the workplace. 

Thus, the Hazard Communication Standard (HCS), like the GHS, includes a mechanism for 

informing workers of hazards other than the physical and health hazards specifically identified in 

the HCS classification criteria. These hazards are called “hazards not otherwise classified.” 

Definition

A hazard not otherwise classified (HNOC) means an adverse physical or health effect identified 

through evaluation of scientific evidence during the classification process that does not meet the 

specified criteria for the physical and health hazard classes addressed in this section. This does 

not extend coverage to adverse physical and health effects for which there is a hazard class 

addressed in the HCS, but the effect either falls below the cut-off value/concentration limit of the 

hazard class or is under a GHS hazard category that has not been adopted by OSHA (e.g., acute 

toxicity Category 5). 

Classification Guidance27

During the classification of hazards not otherwise classified, consider the following: 

a) An adverse physical or health effect is a material impairment of health or functional capacity, 

as that phrase is used in section 6(b)(5) of the OSH Act, 29 U.S.C. § 655(b)(5), resulting 

from workplace exposure to a chemical. 

b) A health effect is determined in accordance with the weight-of-evidence criteria presented in 

Appendix A.0.3 of the HCS. 

c) The term physical effect generally refers to a material impairment of health or functional 

capacity caused by the intrinsic hazard(s) of a particular chemical in normal conditions of use 

or foreseeable emergencies. Scalds caused by exposure to chemicals at high temperatures, 

and slips and falls caused by treading on a solid chemical shaped in a rounded form or spilled 

liquids are not covered physical effects under the HNOC definition. By way of example, 

water is not classified as an HNOC merely because an employee might be scalded by contact 

with boiling water or because an employee might contract hypothermia by being immersed in 

cold water for a long period of time. Similarly, water is not classified as an HNOC by virtue 

of the fact that an employee might be injured when slipping and falling on a wet surface or 

when sprayed by water at high pressure. The foregoing examples of adverse physical effects 

that are outside the scope of HNOC are designed to assist in better understanding the concept 

of HNOC. They are not intended to be exhaustive or limited to chemicals, such as water, 

which are not hazardous chemicals. 

 

27 Hazards not otherwise classified must be identified in Section 2 of the Safety Data Sheet. Although HNOCs are 

not required to be provided on the label, they may be included on the label as supplemental information. 
386

APPENDIX A. 

Glossary of Terms and Definitions

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

guidance.

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. Those adverse effects occurring following oral or dermal administration of a 

single dose of a substance, or multiple doses given within 24 hours, or an inhalation exposure of 

4 hours.

Aerosol. Any non-refillable receptacle containing a gas compressed, liquefied or dissolved under 

pressure, and fitted with a release device allowing the contents to be ejected as particles in 

suspension in a gas, or as a foam, paste, powder, liquid or gas.

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 between 7 

and 14. They are bitter in a water solution. Alkalis with pH values between 12 and 14 are 

considered to be corrosive (caustic) and will cause severe damage to the skin, eyes and mucous 

membranes. Common strong alkalis are the substance sodium and mixture 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.
387

Aspiration. The entry of a liquid or solid chemical directly through the oral or nasal cavity, or 

indirectly from vomiting, into the trachea and lower respiratory system. 

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 lower temperatures as the concentration of oxygen increases 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.

 Initial boiling point is the temperature of a liquid at which its vapor pressure is equal 

to the standard pressure (101.3 kPa28; 14.7 psi), i.e., the first gas bubble appears.

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.

Carcinogen. A substance or a mixture of substances which induce cancer or increase its 

incidence. Substances and mixtures which have induced benign and malignant tumors in wellperformed experimental studies on animals are considered also to be presumed or suspected 

human carcinogens unless there is strong evidence that the mechanism of tumor formation is not 

relevant for humans.

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.

 

28 Pascal [Pa] is the SI Unit (International System of Units) for pressure. 

1 Pa = 1 N/m2= 10-5 bar = 0.75 10-2 torr 

The letter “k” stands for “kilo”: 1 kPa = 1,000 Pa. 
388

Chemical. The name assigned to any substance, or mixture of substances.

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 that will clearly identify the chemical for hazard classification purposes.

Chemicals which, in contact with water, emit flammable gases. Solid or liquid chemicals 

which, by interaction with water, are liable to become spontaneously flammable or to give off 

flammable gases in dangerous quantities.

Chemical which is corrosive to metals. A chemical which by chemical action will materially 

damage, or even destroy, metals.

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 an explosion can occur if an ignition source is present. Also see Flammable 

Limits, LEL, and UEL.
389

Explosive chemical. A solid or liquid chemical which is in itself capable by chemical reaction of 

producing gas at such a temperature and pressure and at such a speed as to cause damage to the 

surroundings. Pyrotechnic chemicals are included even when they do not evolve gases. 

 Pyrotechnic chemical. A chemical designed to produce an effect by heat, light, sound, 

gas or smoke or a combination of these as the result of non-detonative self-sustaining 

exothermic chemical reactions. 

 Explosive item. An item containing one or more explosive chemicals. 

 Pyrotechnic item. An item containing one or more pyrotechnic chemicals. 

 Unstable explosive. An explosive which is thermally unstable and/or too sensitive for 

normal handling, transport, or use. 

 Intentional explosive. A chemical or item which is manufactured with a view to produce 

a practical explosive or pyrotechnic effect. 

Eye irritation. The production of changes in the eye following the application of a test substance 

to the anterior surface of the eye, which are fully reversible within 21 days of application. 

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 Gas, Flammable Liquid, and Flammable Solid.

Flammable gas. A gas having a flammable range with air at 20°C (68°F) and a standard 

pressure of 101.3 kPa (14.7 psi). 

Flammable liquid. A liquid having a flashpoint of not more than 93°C (199.4°F). 

Flammable solid. A solid which is a readily combustible solid, or which may cause or 

contribute to fire through friction. 

 Readily combustible solids. Powdered, granular, or pasty chemicals which are 

dangerous if they can be easily ignited by brief contact with an ignition source, such as a 

burning match, and if the flame spreads rapidly. 

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 vapor in sufficient 

concentration to form an ignitable mixture with air near the surface of the liquid, as determined 

by a method identified in Appendix B.6.3 of 29 CFR 1910.1200. 

Gases under pressure. Gases which are contained in a receptacle at a pressure of 200 kPa 

(29 psi) (gauge) or more, or which are liquefied or liquefied and refrigerated. They comprise 

compressed gases, liquefied gases, dissolved gases and refrigerated liquefied gases. 
390

Genetic. Pertaining to or carried by genes; hereditary.

Genotoxic and genotoxicity. These apply to agents or processes which alter the structure, 

information content, or segregation of DNA, including those which cause DNA damage by 

interfering with normal replication processes, or which in a non-physiological manner 

(temporarily) alter its replication. Positive genotoxicity test results are usually taken as 

indicators for mutagenic effects.

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

Hazard category. The division of criteria within each hazard class, e.g., oral acute toxicity and 

flammable liquids include four hazard categories. These categories compare hazard severity 

within a hazard class and should not be taken as a comparison of hazard categories more 

generally. 

Hazard class. The nature of the physical or health hazards, e.g., flammable solid, carcinogen, 

acute toxicity. 

Hazard not otherwise classified (HNOC). An adverse physical or health effect identified 

through evaluation of scientific evidence during the classification process that does not meet the 

specified criteria for the physical and health hazard classes addressed in this section. This does 

not extend coverage to adverse physical and health effects for which there is a hazard class 

addressed in this section, but the effect either falls below the cut-off value/concentration limit of 

the hazard class or is under a GHS hazard category that has not been adopted by OSHA (e.g., 

acute toxicity Category 5).

Hazardous chemical. Any chemical which is classified as a physical hazard or a health hazard, 

a simple asphyxiant, combustible dust, pyrophoric gas, or hazard not otherwise classified. 

Health hazard. A chemical which is classified as posing one of the following hazardous effects: 

acute toxicity (any route of exposure); skin corrosion or irritation; serious eye damage or eye 

irritation; respiratory or skin sensitization; germ cell mutagenicity; carcinogenicity; reproductive 

toxicity; specific target organ toxicity (single or repeated exposure); or aspiration hazard. The 

criteria for determining whether a chemical is classified as a health hazard are detailed in 

Appendix A to 29 CFR 1910.1200 -- Health Hazard Criteria. 

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.

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

In Vitro. Outside a living organism (e.g., in a test tube).
391

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

or illness.

LC50 - Lethal Concentration 50, 50% Lethal Concentration. The concentration of a chemical 

in air or of a chemical in water which causes the death of 50% (one half) of a group of test 

animals. The LC50 can be expressed in several ways: 

 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. The amount of a chemical, given all at once, which causes the death of 

50% (one half) of a group of test animals. 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 a 

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.

m

3

. 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 (1x10-3g).

Mixture. a combination or a solution composed of two or more substances in which they do 

not react.

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

milliliters.
392

Mutation. A permanent change in the amount or structure of the genetic material in a cell. The 

term “mutation” applies both to heritable genetic changes that may be manifested at the 

phenotypic level and to the underlying DNA modifications when known (including, for example, 

specific base pair changes and chromosomal translocations). The terms “mutagenic” and 

“mutagen” are used for agents giving rise to an increased occurrence of mutations in populations 

of cells and/or organisms. 

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.

Organic peroxide. A liquid or solid organic chemical which contains the bivalent -0-0- structure 

and as such is considered a derivative of hydrogen peroxide, where one or both of the hydrogen 

atoms have been replaced by organic radicals. The term organic peroxide includes mixtures 

containing at least one organic peroxide. Organic peroxides are thermally unstable chemicals, 

which may undergo exothermic self-accelerating decomposition. In addition, they may have one 

or more of the following properties: 

a) Be liable to explosive decomposition; 

b) Burn rapidly; 

c) Be sensitive to impact or friction; 

d) React dangerously with other substances.

Oxidation. A change in a chemical characterized by the loss of electrons. Oxidation is a reaction 

in which a substance combines with oxygen.

Oxidizing gas. Any gas which may, generally by providing oxygen, cause or contribute to the 

combustion of other material more than air does. 

 “Gases which cause or contribute to the combustion of other material more than air does” 

means pure gases or gas mixtures with an oxidizing power greater than 23.5% (as 

determined by a method specified in ISO 10156 or 10156-2; see Appendix B.4 of 29 CFR 

1910.1200). 

Oxidizing liquid. A liquid which, while in itself not necessarily combustible, may, generally by 

yielding oxygen, cause, or contribute to, the combustion of other material.
393

Oxidizing solid. A solid which, while in itself is not necessarily combustible, may, generally by 

yielding oxygen, cause, or contribute to, the combustion of other material.

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.

Physical hazard. A chemical that is classified as posing one of the following hazardous effects: 

explosive; flammable (gases, aerosols, liquids, or solids); oxidizer (liquid, solid or gas); selfreactive; pyrophoric (liquid or solid); self-heating; organic peroxide; corrosive to metal; gas 

under pressure; or in contact with water emits flammable gas. The criteria for determining 

whether a chemical is classified as a physical hazard are detailed in Appendix B to 29 CFR 

1910.1200 -- Physical Hazard Criteria. 

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.

Pyrophoric gas. A chemical in a gaseous state that will ignite spontaneously in air at a 

temperature of 130oF (54.4oC) or below.

Pyrophoric liquid. A liquid which, even in small quantities, is liable to ignite within five 

minutes after coming into contact with air.

Pyrophoric solid. A solid which, even in small quantities, is liable to ignite within five minutes 

after coming into contact with air.

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.

Reproductive toxicity. This hazard includes adverse effects on sexual function and fertility in 

adult males and females, as well as adverse effects on development of the offspring. Some 

reproductive toxic effects cannot be clearly assigned to either impairment of sexual function and 

fertility or to developmental toxicity. Nonetheless, chemicals with these effects shall be 

classified as reproductive toxicants. 

For classification purposes, the known induction of genetically based inheritable effects in the 

offspring is addressed in Germ cell mutagenicity (See Appendix A.5 of 29 CFR 1910.1200). 

 Adverse effects on sexual function and fertility. Any effect of chemicals that interferes 

with reproductive ability or sexual capacity. This includes, but is not limited to, alterations 

to the female and male reproductive system, adverse effects on onset of puberty, gamete 

production and transport, reproductive cycle normality, sexual behavior, fertility, 

parturition, pregnancy outcomes, premature reproductive senescence, or modifications in 

other functions that are dependent on the integrity of the reproductive systems. 
394

 Adverse effects on development of the offspring. Any effect of chemicals which 

interferes with normal development of the conceptus either before or after birth, which is 

induced during pregnancy or results from parental exposure. These effects can be 

manifested at any point in the life span of the organism. The major manifestations of 

developmental toxicity include death of the developing organism, structural abnormality, 

altered growth and functional deficiency. 

Respiratory sensitizer. A chemical that will lead to hypersensitivity of the airways following 

inhalation of the chemical. 

Risk. The probability that an adverse effect will occur.

Self-accelerating decomposition temperature (SADT). The lowest temperature at which selfaccelerating decomposition may occur with a substance as packaged. 

Self-heating chemical. A solid or liquid chemical, other than a pyrophoric liquid or solid, which, 

by reaction with air and without energy supply, is liable to self-heat; this chemical differs from a 

pyrophoric liquid or solid in that it will ignite only when in large amounts (kilograms) and after 

long periods of time (hours or days). 

 Self-heating of a substance or mixture is a process where the gradual reaction of that 

substance or mixture with oxygen (in air) generates heat. If the rate of heat production 

exceeds the rate of heat loss, then the temperature of the substance or mixture will rise 

which, after an induction time, may lead to self-ignition and combustion. 

Self-reactive chemicals. Thermally unstable liquid or solid chemicals liable to undergo a 

strongly exothermic decomposition even without participation of oxygen (air). This definition 

excludes chemicals classified under 29 CFR 1910.1200 as explosives, organic peroxides, 

oxidizing liquids or oxidizing solids. 

Serious eye damage. The production of tissue damage in the eye, or serious physical decay of 

vision, following application of a test substance to the anterior surface of the eye, which is not 

fully reversible within 21 days of application. 

Simple asphyxiant. A substance or mixture that displaces oxygen in the ambient atmosphere, and 

can thus cause oxygen deprivation in those who are exposed, leading to unconsciousness and death.

Skin corrosion. The production of irreversible damage to the skin; namely, visible necrosis 

through the epidermis and into the dermis, following the application of a test substance for up to 

4 hours. Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of 

observation at 14 days, by discoloration due to blanching of the skin, complete areas of alopecia 

(baldness), and scars. Histopathology should be considered to evaluate questionable lesions. 

Skin irritation. The production of reversible damage to the skin following the application of a 

test substance for up to 4 hours. 
395

Skin sensitizer. A chemical that will lead to an allergic response following skin contact. 

Specific target organ toxicity - single exposure (STOT-SE). Specific, non-lethal target organ 

toxicity arising from a single exposure to a chemical. All significant health effects that can 

impair function, both reversible and irreversible, immediate and/or delayed and not specifically 

addressed in Appendices A.1 to A.7 and A.10 of 29 CFR 1910.1200 are included. 

Specific target organ toxicity - repeated exposure (STOT-RE). Specific target organ toxicity 

arising from repeated exposure to a substance or mixture. All significant health effects that can 

impair function, both reversible and irreversible, immediate and/or delayed and not specifically 

addressed in Appendices A.1 to A.7 and A.10 of 29 CFR 1910.1200 are included. 

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.

Substance. Chemical elements and their compounds in the natural state or obtained by any 

production process, including any additive necessary to preserve the stability of the product and 

any impurities deriving from the process used, but excluding any solvent which may be 

separated without affecting the stability of the substance or changing its composition.

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. 
396

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 to 12 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. Decomposing readily or another 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 100° F will always be higher than the vapor pressure of 

the substance at 68° F (20° C), 

 Vapor pressures reported on SDSs in millimeters of mercury (mmHg) are usually very 

low pressures; 760 mmHg is equivalent to 14.7 pounds 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 gas at ordinary 

temperatures. Liquids such as alcohol and gasoline, because of their tendency to evaporate 

rapidly, are called volatile liquids.
397

APPENDIX B. 

Information Sources to Assist with Hazard Classification

This compilation is not intended to be a complete listing of the many literature sources and 

computerized databases that include information on the physical 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, 3rd 

Edition. Pradyot Patnaik. Wiley & Sons, New York. 2007.

 ATSDR’s Toxicological Profiles. U.S. Public Health Service, Atlanta, Georgia, USA. 

Available on CD-ROM and online at: www.atsdr.cdc.gov/toxprofiles/index.asp 

 Bretherick’s Handbook of Reactive Chemicals Hazards: An Indexed Guide to 

Published Data, 7th Edition. 2 volume set. L. Bretherick, P. L. Urben, and M. Pitt. 

Butterworth-Heinemann, Boston. 2006. Also on CD-ROM.

 Chemical Reaction Hazards, 2nd Edition. John Barton and Richard Rogers. Gulf 

Professional Publishing. 1997.

 Chemical Safety Manual for Small Business. 3rd Edition. American Chemical 

Society, Washington, D.C. 2007. Available online. 

 Chemically Induced Birth Defects, 3rd Edition. James L. Schardein. Marcel Dekker, 

Inc., New York. 2000.

 The Chemistry of Explosives. Jacqueline Akhavan. Royal Society of Chemistry. 2011.

 Chemistry of Hazardous Materials. 6th Edition. Eugene Meyer. Prentice-Hall, Inc., 

Englewood Cliffs, NJ. 2013.

 Clinical Toxicology of Commercial Products. Gleason, Gosselin, and Hodge. The 

Williams and Wilkins Co., Baltimore. 1984.

 The Comprehensive Handbook of Hazardous Materials: Regulations, Handling, 

Monitoring, and Safety. H. L. A. Sacarello. Lewis Publishers, Inc., Boca Raton, Florida. 

1994.

 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, 94th Edition. David R. Lide, editor. CRC 

Press, Boca Raton, Florida. 2013. Also on CD-ROM.

 CRC Handbook of Toxicology. Michael J. Derlanko and Mannfred A. Hollinger. CRC 

Press. 1995.

 Dangerous Properties of Industrial and Consumer Chemicals. Nicholas P. 

Cheremisinoff. Marcel Dekker, Inc., New York. 1994.
398

 Dictionary of Chemical Names and Synonyms. Philip H. Howard and Michael Neal. 

ACGIH Publication 9422. ACGIH, Cincinnati. 1992. Also available on CD-ROM. 1998. 

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

Florida. 1998. 

 Emergency Responder Training Manual for the Hazardous Material Technician. 

Wiley –Interscience, 2nd edition. Hoboken, NJ. 2004.

 Emergency Response to Chemical Spills. W. Brock Neely. Lewis Publishers, Inc., 

Boca Raton, Florida. 1992.

 Emergency Response Guidebook. A guidebook for first responders during the initial 

phase of a hazardous materials/dangerous goods incident. DOT, Washington, D.C. 

2012. Available online. 

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

 Encyclopedia of Toxicology. 3rd Edition. Philip Wexler, editor-in-chief. Elsevier 

Academic Press, San Diego. 2014.

 Environmental and Occupational Medicine, 4th Edition. William N. Rom, editor. 

Little, Brown and Co., Boston. 2006.

 EPA’s Integrated Risk Information System (IRIS). United States Environmental 

Protection Agency. http://www.epa.gov/iris

 Ethel Browning’s Toxicity and Metabolism of Industrial Solvents. Volume 3. 2nd

edition. Elsevier Science Publishing Co., New York. 1992.

 Explosives Identification Guide. 2nd edition. Mike Pickett. Delmar Learning. 2004.

 Fire Protection Guide to Hazardous Materials. National Fire Protection Association 

(NFPA), Quincy, Massachusetts. 2010.

 Fundamentals of Occupational Safety and Health. Mark A. Friend and James P. 

Kohn. Bernan Press, London. 2014.

 General and Applied Toxicology, 3rd edition. Volume 1. Bryan Ballantyne, Timothy 

Marrs and Tore Syverson, editors. McMillan References, Ltd., London. 2009.

 2013 Guide to Occupational Exposure Values. ACGIH, Cincinnati. 2013.

 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 Hazardous Chemical Properties. Nicholas P. Cheremisinoff. 

Butterworth-Heinemann. 1999.

 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.
399

 Handbook of Industrial Toxicology, 3rd Edition. E.R. Plunkett, editor. Chemical 

Publishing Co., Inc., New York. 1987.

 Handbook of Industrial Toxicology and Hazardous Materials. Nicholas P. 

Cheremisinoff. CRC Press. 1999. 

 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. 1996.

 Handbook of Toxic and Hazardous Chemicals and Carcinogens, 6th Edition. 

Marshall Sittig. Noyes Data Corp., Park Ridge, New Jersey. 2011.

 Handbook of Toxicology, 3rd Edition. Michael J. Derelanko and Mannfred A. 

Hollinger. CRC Press, Taylor and Francis Group, Florida. 2014.

 Hawley’s Condensed Chemical Dictionary, 15th Edition. Richard J. Lewis, editor. 

Van Nostrand Reinhold, New York. 2007.

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

Fawcett. 1988.

 Hazardous Chemicals: Safety Management and Global Regulations. T. S. S. 

Dikshith. CRC Press, Taylor and Francis Group, Florida. 2013.

 Hazardous Chemicals Desk Reference, 6th Edition. Richard J. Lewis, Jr., John Wiley 

& Sons/Van Nostrand Reinhold, New York. 2008.

 Hazardous Chemicals Handbook, 2nd Edition. P. Carson and C. J. Mumford. 

Butterworth-Heinemann. 2002.

 Hazardous Industrial Chemicals - Material Safety Data Sheets - Preparation. ANSI 

Standard Z400.1. 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: 3rd Edition. Robert 

Burke. CRC Press. 2013.

 Hazardous Materials Handbook. Richard P. Pohanish and Stanley A. Greene. John 

Wiley & Sons. 1996.

 Hazardous Materials Response Handbook, 3rd Edition. National Fire Protection 

Association. Quincy, Massachusetts. 1997.

 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. Prentice Hall, 

Englewood Cliffs, New Jersey. 1992.

 IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to 

Humans. International Agency for Research on Cancer, WHO, Lyon, France and 

available online. 
400

 Improving Reactive Hazard Management. U.S. Chemical Safety and Hazard 

Investigation Board, Report No. 2001-01-H. 2002. 

 Industrial Organic Chemicals, 3rd edition. Harold A. Wittcoff, Bryan Reuben, and 

Jeffery Plotkin. 2012.

 Kirk Othmer Encyclopedia of Chemical Technology, Fifth edition. 15 volumes. 

Wiley-Interscience. 2004.

 The Merck Index: An Encyclopedia of Chemicals, Drugs and Biologicals, 15th 

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. 2013.

 MERCK Index. Full text of the printed edition. Gives concise information on over 

10,000 chemicals and available online at: https://www.rsc.org/merck-index. 

 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. 

 NTP’s Annual Report on Carcinogens. National Toxicology Program. Research 

Triangle Park, NC. Available online. 

 Occupational Health and Safety, 3rd Edition. Marci Balge and Gary Krieger, editors. 

National Safety Council, Chicago, Illinois. 2000.

 Occupational Health Guidelines for Chemical Hazards. NIOSH/OSHA. NIOSH Pub. 

No. 81-123. 1981. Available online. 

 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, 6th Edition, 13 Volume Set. Eula Bingham, Barbara 

Cohrssen, and Charles H. Powell. John Wiley & Sons, New York. 2010.

 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, 6th edition (6 volume set). Eula Bingham, Barbara Cohrssen, and 

Charles H. Powell. 2012.

 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. 

1993.

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

1997.
401

 Rapid Guide to Hazardous Chemicals in the Workplace, 4th Edition. Richard J. 

Lewis, Sr., Van Nostrand Reinhold. 2000.

 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. 1991.

 Sax’s Dangerous Properties of Industrial Materials, 12th edition. 5 volume set. 

Richard J. Lewis. Wiley-Interscience. 2004.

 Sittig’s Handbook of Toxic and Hazardous Chemicals and Carcinogens, 4th edition. 

Two Volume Set. Richard P. Pohanish, editor. Noyes Publications. 2012.

 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. 

 Threshold Limit Values and Biological Exposure Indices. ACGIH, Cincinnati. 2013.

Available online.

 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. 1995.

 Wiley Guide to Chemical Incompatibilities, 3rd Edition. Richard P. Pohanish and 

Stanley A. Greene. John Wiley & Sons. 2009.

II. Useful References on Principles and Procedures:

 A Textbook of Modern Toxicology, 4th Edition. Ernest Hodgson and Patricia E. Levi. 

McGraw-Hill Professional. 2010.

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

 Basic Environmental Toxicology. Lorris G. Cockerham and Barbara S. Shane. CRC 

Press, Boca Raton, Florida. 1993.

 Basic Toxicology: Fundamentals, Target Organs, and Risk Assessment, 5th Edition. 

Frank C. Lu. Taylor and Francis, Washington, D.C. 2009.

 Casarett and Doull’s Toxicology: The Basic Science of Poisons, 8th Edition. Louis J. 

Casarett, Curtis D. Klaasen, and John Doull, editors. McGraw-Hill Professional, New 

York. 2013.

 Chemical Hazard Communication Guidebook, 2nd Edition. Andrew B. Waldo and 

Richard deC. Hinds. McGraw Hill Book Company, Highstown, New Jersey. 1995.

 Comprehensive Review in Toxicology, 3rd Edition. Peter D. Bryson. Aspen 

Publishers, Rockville, Maryland. 1996.

 Comprehensive Toxicology. 2nd Edition. I. Glenn Sipes, A. Jay Gaddolfi, and 

Charlene A. McQueen, Elsevier Science. 2010.

 Dictionary of Toxicology, 2nd edition. Ernest Hodgson, Richard Mailman, and Robert 

Dow. McMillan References, Ltd. London. 1998.
402

 Essentials of Environmental Toxicology. W. William Hughes. Taylor and Francis, 

Washington, D.C. 1996.

 Fundamentals of Industrial Hygiene. 6th Edition. Barbara A. Plog and Patricia J. 

Quinlan, National Safety Council. 2012.

 Industrial Toxicology: Safety and Health Applications in the Workplace. Phillip L. 

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

 Information Resources in Toxicology, 4th edition. P. J. Hakkinen, Gerald Kennedy, 

Frederick Stoss, and Philip Wexler, editors. Academic Press. 2009.

 International Directory of Testing Laboratories, ASTM, West Conshohocken, 

Pennsylvania. Available online. 

 Loomis’s Essentials of Toxicology, 4th Edition. Ted A. Loomis. Academic Press, San 

Diego, California. 1996.

 The Occupational Environment: Its Evaluation and Control. Second Edition. 

Salvatore R. Dinardi, editor. AIHA. 2003.

 Principles and Methods of Toxicology, 5th Edition. A. Wallace Hayes, editor. Raven 

Press, New York. 2007.

 Principles of Toxicology: Environmental and Industrial Applications, 2nd Edition. 

Phillip L. Williams, Robert C. James and Stephen M. Roberts, editors. 2000.

 Toxicology: A Primer on Toxicology Principles and Applications. Michael A. 

Kamrin. Lewis Publishers, Inc., Boca Raton, Florida. 1988.

Comprehensive Bibliographic and Factual Databases:

 Chemical Hazard Response Information System (CHRIS). This 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. 

Available online. The link is to the Manual. 

 Chemical Information Systems (CIS). CIS is a collection of 33 databases from various 

sources like EPA, NIOSH, and 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. 

 eChem Portal. Developed by the Organisation for Economic Co-operation and 

Development (OECD), this is a global portal to information on chemical substances, 

designed to improve the availability of hazard data on chemicals. 

 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. 
403

 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 workplaces. The ICSC 

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. 

 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. 

 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 subject to federal 

occupational safety and health regulations. 

 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. 

 Toxic Substances Control Act Test Submissions (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: This service contains a links to a number of databases, including those 

listed below. 

o 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.

o ChemIDplus. This is an online data file that contains names, synonyms, CAS 

registry numbers, and a locator for other databases that contain information for 

thousands of chemicals.

o CHEMID/SUPERLIST. This file serves as a locator for NLM databases containing 

information for over 180,000 compounds. It also lists chemicals regulated by other 

government agencies.

o DART. A bibliographic database covering teratology and other aspects of 

developmental and reproductive toxicology. Serves as a continuation of ETIC, below.

o DERMAL. Contains toxic effects, absorption, distribution, metabolism, and 

excretion data related to dermal absorption of 650+ chemicals.

o DIRLINE. A database containing information about information resource centers, 

primarily health and biomedical organizations.
404

o EMIC. A bibliographic database on chemical agents that have been tested for 

mutagenic activity.

o ETIC. A bibliographic database on chemical agents that have been tested for 

mutagenic activity.

o GENETOX. Peer-reviewed mutagenicity test data from the Environmental 

Protection Agency (EPA).

o 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.

o 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.

o HSDB. Hazardous Substances Data Bank. This is a peer-reviewed database which 

contains chemical and physical properties for over 4,200 chemicals.

o 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.

o 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).

o 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.

o TERIS. Produced by the University of Washington and deals with the risks of 

prenatal exposure to hazardous substances.

o Toxicology Tutorials. Three college-level tutorials covering principles of toxicology, 

toxicokinetics, and cellular toxicology.

o TOXLINE. Contains comprehensive bibliographic coverage of toxicology 

information in published literature.

o TRI. Toxics Release Inventory, an annual report of the EPA that estimates releases of 

toxic chemicals to the environment. 

Internet Addresses for Information or Publications Related to Chemical Hazards and 

Hazard Communication: 

 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

 Health Canada

 Center for Chemical Process Safety

 Department of Transportation, Pipeline and Hazardous Materials Administration
405

 Environmental Protection Agency (EPA) 

 European Chemicals Agency (ECHA) 

 MSDSOnline.com

 MSDS.com

 National Institute for Occupational Safety and Health (NIOSH) 

 National Library of Medicine (NLM) Data Bases

 Occupational Safety and Health Administration (OSHA) 

 United Nations Globally Harmonized System of Classification and Labelling of 

Chemicals (GHS) 

 United Nations Transport of Dangerous Goods (TDG) 
406

APPENDIX C. 

List of Substances Deemed Toxic or Hazardous by an 

Authoritative Process

The following sources were consulted to develop this list:

 29 CFR 1910, Subpart Z - Toxic and Hazardous Substances

 American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit 

Values (TLVs)

 International Agency for Research on Cancer (IARC) “Monographs on the Evaluation of 

Carcinogenic Risks to Humans”

 National Toxicology Program (NTP) “Report on Carcinogens” 

Note: These sources may be periodically updated, 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

Acrolein

Acrylamide

Acrylic acid

Aldrin

Allyl alcohol

Allyl chloride

Allyl glycidyl ether

Allyl propyl disulfide

alpha-Alumina

Aluminum metal

Aluminum, soluble salts

Aluminum, welding fumes

2-Aminopyridine

Amitrole

Ammonia

Ammonium sulfamate
407

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 (Sedoped)

Bismuth telluride, undoped

Borates, tetra, sodium salts, anhydrous

Borates, tetra, sodium salts, decahydrate

Borates, tetra, sodium salts, pentahydrate

Boron oxide

Boron tribromide

Boron trifluoride

Bromine

Bromine pentafluoride

Bromoform

Butadiene (1,3-Butadiene)

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
408

n-Butyl glycidyl ether (BGE)

n-Butyl lactate

Butyl mercaptan

Butylamine (n-)

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)

Carbon black

Carbon dioxide

Carbon disulfide

Carbon monoxide

Carbon tetrachloride

Catechol (pyrocatechol)

Cellulose

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)

Chlorobenzene

o-Chlorobenzylidene malonitrile

Chlorobromomethane

Chlorodifluoromethane

Chlorodiphenyl (42% chlorine) (PCB)

Chlorodiphenyl (54% chlorine) (PCB)

Chloroform (Trichloromethane)
409

Chloropicrin

Chloropicrin/methyl chloride

beta-Chloroprene

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)-

Cumene

Cyanides (as CN)

Cyanogen

Cyclohexane

Cyclohexanol

Cyclohexanone

Cyclohexene

Cyclopentadiene

Cyclopentane

Cyhexatin

Decaborane

Demeton (Systox)

Di-sec octyl phthalate (Di-2-ethylhexyl-phthalate)

Diacetone alcohol (4-Hydroxy-4-methyl-2-pentanone)

Diazomethane

Diborane

Dibutyl phosphate

Dibutyl phthalate

Dichloro diphenyl trichloroethane (DDT)

1,1-Dichloro-1-nitroethane

1,3-Dichloro-5,5-dimethyl hydantoin
410

Dichloroacetylene

o-Dichlorobenzene

p-Dichlorobenzene

Dichlorodifluoromethane

1,1-Dichloroethane

Dichloroethyl ether

1,2-Dichloroethylene

Dichlorofluoromethane

1,3-Dichloropropene

1,2-Dichlorotetrafluoroethane

Dichlorvos (DDVP)

Dicyclopentadienyl iron

Dieldrin

Diethanolamine

Diethylamine

2-Diethylaminoethanol

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

Dinitro-o-cresol

Dinitrobenzene (alpha-)

Dinitrobenzene (meta-)

Dinitrobenzene (para-)

Dinitrobenzene, all isomers

Dinitrotoluene

Dioxane (Diethylene dioxide)

Diphenyl (Biphenyl)

Diphenylamine

Dipropylene glycol, methyl ether

Disulfiram

Emery

Endosulfan

Endrin
411

Epichlorohydrin

EPN

Ethanolamine

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

N-Ethylmorpholine

Fenaminphos

Ferbam

Ferrovanadium dust

Fluorides

Fluorine

Fluorotrichloromethane (Trichlorofluoromethane)

Formaldehyde

Formamide

Formic acid

Furfural

Furfuryl alcohol

Gasoline

Glycerin mist

Glycidol

Grain dust (oat, wheat, barley)

Graphite, natural

Graphite, synthetic
412

Gypsum

Hafnium

Heptachlor

Heptane (n-Heptane)

Hexachlorobutadiene

Hexachloroethane

Hexachloronaphthalene

Hexafluoroacetone

n-Hexane

2-Hexanone (Methyl n-butyl ketone)

Hexone (Methyl isobutyl ketone)

sec-Hexyl acetate

Hydrazine

Hydrogen bromide

Hydrogen chloride

Hydrogen cyanide

Hydrogen fluoride

Hydrogen peroxide

Hydrogen selenide

Hydrogen sulfide

Hydroquinone

Indium

Indium compounds, n.o.s.

Iodine

Iodoform

Iron oxide fume

Isoamyl acetate

Isoamyl alcohol (primary and secondary)

Isobutyl acetate

Isobutyl alcohol

Isooctyl alcohol

Isophorone

Isopropyl acetate

Isopropyl alcohol

Isopropyl ether

Isopropyl glycidyl ether (IGE)

Isopropylamine

N-Isopropylaniline

Kaolin

Ketene

L.P.G. (liquified petroleum gas)
413

Lead

Lindane

Lithium hydride

Magnesite

Magnesium oxide fume

Malathion

Maleic anhydride

Manganese compounds (as Mn)

Manganese fume (as Mn)

Mercury

Mercury (organo) alkyl compounds

Mesityl oxide

Methanol

Methoxychlor

Methyl acetate

Methyl acetylene (Propyne)

Methyl acetylene - Propadiene mixture (MAPP)

Methyl acrylate

Methyl alcohol

Methyl bromide (Bromomethane)

Methyl cellosolve (2-methoxyethanol)

Methyl cellosolve acetate (2-Methoxyethyl acetate)

Methyl chloride

Methyl chloroform (1,1,1-Trichloroethane)

Methyl formate

Methyl hydrazine (Monomethyl hydrazine)

Methyl iodide

Methyl isoamyl ketone

Methyl isobutyl ketone

Methyl isocyanate

Methyl methacrylate

Methyl n-amyl ketone

Methyl parathion

alpha-Methyl styrene

Methylal (Dimethoxymethane)

Methylamine

Methylcyclohexane

Methylcyclohexanol

o-Methylcyclohexanone

Methylene bisphenol isocyanate (MDI)

Methylene chloride
414

4,4'-Methylenebis (2-chloroaniline) (MBOCA)

Methylisobutyl carbinol

Methylmercaptan

Mica

Molybdenum

Molybdenum insoluble compounds

Molybdenum soluble compounds

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

Octachloronaphthalene

Octane

Oil mist, mineral

Organo (alkyl) mercury

Osmium tetroxide

Oxalic acid

Oxygen difluoride

Ozone

Paraquat

Paraquat methosulfate
415

Parathion

Particulates not otherwise regulated

Phenol

Pentaborane

Pentachloronaphthalene

Pentachlorophenol

Pentaerythritol

Pentane

2-Pentanone (Methyl propyl ketone)

Perchloroethylene (Tetrachloroethylene)

Perchloryl fluoride

Petroleum distillates (naphtha) (rubber solvent)

Phenol

Phenyl ether

Phenyl ether-Biphenyl mixture vapor

Phenyl glycidyl ether (PGE)

Phenyl mercaptan

p-Phenylene diamine

Phenylhydrazine

Phosdrin (Mevinphos)

Phosgene (Carbonyl chloride)

Phosphine

Phosphoric acid

Phosphorus (yellow)

Phosphorus pentachloride

Phosphorus pentasulfide

Phosphorus trichloride

Phthalic anhydride

m-Phthalodinitrile

Picloram

Picric acid

Pindone (2-pivalyl-1,3-indandione)

Plaster of paris

Platinum

Platinum soluble salts

Portland cement

Propane

n-Propyl acetate

n-Propyl alcohol

n-Propyl nitrate

Propylene dichloride
416

Propylene imine

Propylene oxide

Pyrethrum

Pyridine

Quinone

Resorcinol

Rhodium

Rhodium soluble compounds

Rhodium, insoluble compounds

Ronnel

Rosin core solder pyrolysis products, as formaldehydeRotenone

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 fluoroacetate

Sodium hydroxide

Starch

Stibine

Stoddard solvent

Strychnine

Styrene

Subtilisins (proteolytic enzymes)

Sucrose

Sulfur dioxide

Sulfur hexafluoride

Sulfur monochloride

Sulfur pentafluoride

Sulfuric acid
417

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

Tetrachloroethylene

Tetrachloronaphthalene

Tetraethyllead

Tetrahydrofuran

Tetramethyl lead

Tetramethyl succinonitrile

Tetranitromethane

Tetryl (2,4,6-Trinitro-phenylmethylnitramine)

Thallium soluble compounds

Thallium soluble compounds

4,4'-Thiobis (6-tert-butyl-m-cresol)

Thioglycolic acid

Thiram

Tin

Tin inorganic compounds

Tin organic compounds

Titanium dioxide

Toluene

Toluene 2,4-diisocyanate (TDI)

o-Toluidine

Tributyl phosphate

1,1,2-Trichloro-1,2,2-trifluoroethane

Trichloroacetic acid

1,2,4-Trichlorobenzene

1,1,2-Trichloroethane

Trichloroethylene
418

Trichloronaphthalene

1,2,3-Trichloropropane

Triethylamine

Trifluorobromomethane

Trimethyl benzene

2,4,6-Trinitrotoluene (TNT)

Triorthocresyl phosphate

Triphenyl phosphate

Tungsten

Tungsten, insoluble compounds

Tungsten, soluble compounds

Turpentine

Uranium

Uranium insoluble compounds

Uranium soluble compounds

Vanadium

Vanadium pentoxide

Vegetable oil mist

Vinyl acetate

Vinyl bromide

Vinyl toluene

Vinylidene chloride (1,1-Dichloroethylene)

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 oxide

Zinc stearate

Zirconium

Zirconium compounds, n.o.s.
419

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 

Lead 

Methyl chloromethyl ether 

Methylene chloride 

Methylenedianiline 

N-Nitrosodimethylamine 

Vinyl chloride 
420

Workers’ Rights

Workers have the right to: 

 Working conditions that do not pose a risk of serious harm. 

 Receive information and training (in a language and vocabulary the worker understands) 

about workplace hazards, methods to prevent them, and the OSHA standards that apply 

to their workplace. 

 Review records of work-related injuries and illnesses. 

 File a complaint asking OSHA to inspect their workplace if they believe there is a serious 

hazard or that their employer is not following OSHA’s rules. OSHA will keep all 

identities confidential. 

 Exercise their rights under the law without retaliation, including reporting an injury or 

raising health and safety concerns with their employer or OSHA. If a worker has been 

retaliated against for using their rights, they must file a complaint with OSHA as soon as 

possible, but no later than 30 days. 

For more information, see OSHA’s Workers page. 

OSHA Assistance, Services and Programs

OSHA has a great deal of information to assist employers in complying with their 

responsibilities under OSHA law. Several OSHA programs and services can help employers 

identify and correct job hazards, as well as improve their injury and illness prevention program. 

Establishing an Injury and Illness Prevention Program 

The key to a safe and healthful work environment is a comprehensive injury and illness 

prevention program. 

Injury and illness prevention programs are systems that can substantially reduce the number and 

severity of workplace injuries and illnesses, while reducing costs to employers. Thousands of 

employers across the United States already manage safety using injury and illness prevention 

programs, and OSHA believes that all employers can and should do the same. Thirty-four states 

have requirements or voluntary guidelines for workplace injury and illness prevention programs. 

Most successful injury and illness prevention programs are based on a common set of key elements. 

These include management leadership, worker participation, hazard identification, hazard 

prevention and control, education and training, and program evaluation and improvement. Visit 

OSHA’s Injury and Illness Prevention Programs web page at www.osha.gov/dsg/topics/safetyhealth

for more information. 
421

Compliance Assistance Specialists 

OSHA has compliance assistance specialists throughout the nation located in most OSHA 

offices. Compliance assistance specialists can provide information to employers and workers 

about OSHA standards, short educational programs on specific hazards or OSHA rights and 

responsibilities, and information on additional compliance assistance resources. For more details, 

visit www.osha.gov/dcsp/compliance_assistance/cas.html or call 1-800-321-OSHA (6742) to 

contact your local OSHA office. 

Free On-site Safety and Health Consultation Services for Small 

Business 

OSHA’s On-site Consultation Program offers free and confidential advice to small and mediumsized businesses in all states across the country, with priority given to high-hazard worksites. 

Each year, responding to requests from small employers looking to create or improve their safety 

and health management programs, OSHA’s On-site Consultation Program conducts over 29,000 

visits to small business worksites covering over 1.5 million workers across the nation. 

On-site consultation services are separate from enforcement and do not result in penalties or 

citations. Consultants from state agencies or universities work with employers to identify 

workplace hazards, provide advice on compliance with OSHA standards, and assist in 

establishing safety and health management programs. 

For more information, to find the local On-site Consultation office in your state, or to request a 

brochure on Consultation Services, visit www.osha.gov/consultation, or call 1-800-321-OSHA (6742). 

Under the consultation program, certain exemplary employers may request participation in OSHA’s 

Safety and Health Achievement Recognition Program (SHARP). Eligibility for participation 

includes, but is not limited to, receiving a full-service, comprehensive consultation visit, 

correcting all identified hazards and developing an effective safety and health management 

program. Worksites that receive SHARP recognition are exempt from programmed inspections 

during the period that the SHARP certification is valid. 

Cooperative Programs 

OSHA offers cooperative programs under which businesses, labor groups and other 

organizations can work cooperatively with OSHA. To find out more about any of the following 

programs, visit www.osha.gov/cooperativeprograms. 

Strategic Partnerships and Alliances

The OSHA Strategic Partnerships (OSP) provide the opportunity for OSHA to partner with 

employers, workers, professional or trade associations, labor organizations, and/or other 

interested stakeholders. OSHA Partnerships are formalized through unique agreements designed 

to encourage, assist, and recognize partner efforts to eliminate serious hazards and achieve model 

workplace safety and health practices. Through the Alliance Program, OSHA works with groups 
422

committed to worker safety and health to prevent workplace fatalities, injuries and illnesses by 

developing compliance assistance tools and resources to share with workers and employers, and 

educate workers and employers about their rights and responsibilities. 

Voluntary Protection Programs (VPP)

The VPP recognize employers and workers in private industry and federal agencies who have 

implemented effective safety and health management programs and maintain injury and illness 

rates below the national average for their respective industries. In VPP, management, labor, and 

OSHA work cooperatively and proactively to prevent fatalities, injuries, and illnesses through a 

system focused on: hazard prevention and control, worksite analysis, training, and management 

commitment and worker involvement. 

Occupational Safety and Health Training 

The OSHA Training Institute partners with 27 OSHA Training Institute Education Centers at 42 

locations throughout the United States to deliver courses on OSHA standards and occupational 

safety and health topics to thousands of students a year. For more information on training 

courses, visit www.osha.gov/otiec. 

OSHA Educational Materials 

OSHA has many types of educational materials in English, Spanish, Vietnamese and other 

languages available in print or online. These include: 

 Brochures/booklets; 

 Fact Sheets; 

 Guidance documents that provide detailed examinations of specific safety and health issues; 

 Online Safety and Health Topics pages; 

 Posters; 

 Small, laminated QuickCardsTM that provide brief safety and health information; and 

 QuickTakes, OSHA’s free, twice-monthly online newsletter with the latest news about 

OSHA initiatives and products to assist employers and workers in finding and preventing 

workplace hazards. To sign up for QuickTakes visit www.osha.gov/quicktakes.

To view materials available online or for a listing of free publications, visit 

www.osha.gov/publications. You can also call 1-800-321-OSHA (6742) to order publications. 

Select OSHA publications are available in e-Book format. OSHA e-Books are designed to 

increase readability on smartphones, tablets and other mobile devices. For access, go to 

www.osha.gov/ebooks. 

OSHA’s web site also has information on job hazards and injury and illness prevention for 

employers and workers. To learn more about OSHA’s safety and health resources online, 

visit www.osha.gov or www.osha.gov/html/a‐z‐index.html. 
423

NIOSH Health Hazard Evaluation Program

Getting Help with Health Hazards 

The National Institute for Occupational Safety and Health (NIOSH) is a federal agency that 

conducts scientific and medical research on workers’ safety and health. At no cost to employers 

or workers, NIOSH can help identify health hazards and recommend ways to reduce or eliminate 

those hazards in the workplace through its Health Hazard Evaluation (HHE) Program. 

Workers, union representatives and employers can request a NIOSH HHE. An HHE is often 

requested when there is a higher than expected rate of a disease or injury in a group of workers. 

These situations may be the result of an unknown cause, a new hazard, or a mixture of sources. To 

request a NIOSH Health Hazard Evaluation go to www.cdc.gov/niosh/hhe/request.html. To find 

out more, in English or Spanish, about the Health Hazard Evaluation Program: 

E-mail HHERequestHelp@cdc.gov or call 800-CDC-INFO (800-232-4636).

OSHA Regional Offices

Region I 

Boston Regional Office 

(CT*, ME*, MA, NH, RI, VT*) 

JFK Federal Building, Room E340 

Boston, MA 02203 

(617) 565-9860 (617) 565-9827 Fax 

Region II 

New York Regional Office 

(NJ*, NY*, PR*, VI*) 

201 Varick Street, Room 670 

New York, NY 10014 

(212) 337-2378 (212) 337-2371 Fax 

Region III 

Philadelphia Regional Office 

(DE, DC, MD*, PA, VA*, WV) 

The Curtis Center 

170 S. Independence Mall West 

Suite 740 West 

Philadelphia, PA 19106-3309 

(215) 861-4900 (215) 861-4904 Fax 

Region IV 

Atlanta Regional Office 

(AL, FL, GA, KY*, MS, NC*, SC*, TN*) 

61 Forsyth Street, SW, Room 6T50 

Atlanta, GA 30303 

(678) 237-0400 (678) 237-0447 Fax 

Region V 

Chicago Regional Office 

(IL*, IN*, MI*, MN*, OH, WI) 

230 South Dearborn Street 

Room 3244 

Chicago, IL 60604 

(312) 353-2220 (312) 353-7774 Fax 

Region VI 

Dallas Regional Office 

(AR, LA, NM*, OK, TX) 

525 Griffin Street, Room 602 

Dallas, TX 75202 

(972) 850-4145 (972) 850-4149 Fax 

(972) 850-4150 FSO Fax 
424

Region VII 

Kansas City Regional Office 

(IA*, KS, MO, NE) 

Two Pershing Square Building 

2300 Main Street, Suite 1010 

Kansas City, MO 64108-2416 

(816) 283-8745 (816) 283-0547 Fax 

Region VIII 

Denver Regional Office 

(CO, MT, ND, SD, UT*, WY*) 

Cesar Chavez Memorial Building 

1244 Speer Boulevard, Suite 551 

Denver, CO 80204 

(720) 264-6550 (720) 264-6585 Fax 

Region IX 

San Francisco Regional Office 

(AZ*, CA*, HI*, NV*, and 

American Samoa, 

Guam and the Northern Mariana Islands) 

90 7th Street, Suite 18100 

San Francisco, CA 94103 

(415) 625-2547 (415) 625-2534 Fax 

Region X 

Seattle Regional Office 

(AK*, ID, OR*, WA*) 

300 Fifth Avenue, Suite 1280 

Seattle, WA 98104 

(206) 757-6700 (206) 757-6705 Fax 

*These states and territories operate their own OSHA-approved job safety and health plans and 

cover state and local government employees as well as private sector employees. The 

Connecticut, Illinois, Maine, New Jersey, New York and Virgin Islands programs cover public 

employees only. (Private sector workers in these states are covered by Federal OSHA). States 

with approved programs must have standards that are identical to, or at least as effective as, the 

Federal OSHA standards. 

Note: To get contact information for OSHA area offices, OSHA-approved state plans and OSHA 

consultation projects, please visit us online at www.osha.gov or call us at 1-800-321-OSHA (6742). 

How to Contact OSHA

For questions or to get information or advice, to report an emergency, fatality, inpatient 

hospitalization, amputation, or loss of an eye, or to file a confidential complaint, contact your 

nearest OSHA office, visit www.osha.gov or call OSHA at 1-800-321-OSHA (6742), TTY 

1-877-889-5627. 

For assistance, contact us. 

We are OSHA. We can help. 

For more information:

Occupational

Safety and Health

Administration

www.osha.gov (800) 321-OSHA (6742)

U.S. Department of Labor