Information Bulletin

June 1997

Guidelines for the Disclosure of Toxicological Information
on a Material Safety Data Sheet

This guideline is targeted primarily to those tasked with the preparation of material safety data sheets (MSDSs). Employers, suppliers, workers and regulators may also wish to make use of this document. The purpose of the guideline is to clarify the Hazardous Products Act (HPA) and the Controlled Products Regulations (CPR) requirements for the MSDS disclosure of toxicological information for a WHMIS "controlled product".

A product, material or substance is a controlled product if it meets any of the hazard criteria specified in Part IV of the CPR. A controlled product may be a "pure" substance, a tested mixture or an untested mixture. Section 33 of the CPR sets out the procedures for a supplier to establish whether or not a substance is a controlled product and does not apply to the determination of the information that must be disclosed on the MSDS.

Note: Although the classification criteria specified in sections 34-66 of the CPR may provide a useful guideline for certain MSDS information, it is section 12 and Schedule I to the CPR which set out what information must be disclosed on a MSDS; paragraph 13(a) of the HPA sets out what ingredients are subject to disclosure on the MSDS; section 4 of the CPR specifies the concentration above which those ingredients must be disclosed.

All relevant toxicological information available to the supplier and applicable to the controlled product must be disclosed on the MSDS. The results of animal testing which yield positive results and on which classification is based must be disclosed. The specific categories of information which must be addressed are listed under the heading "Toxicological Properties" (see item 7, Schedule I to the CPR). These categories require the disclosure of information on: the routes of entry including skin contact, skin absorption, eye contact, inhalation and ingestion; the effects of acute exposure; the effects of chronic exposure, i.e., irritancy, sensitization, carcinogenicity, reproductive toxicity, embryotoxicity, teratogenicity, fetotoxicity, mutagenicity; and any toxicologically synergistic interactions. In addition, subsection 12(11) of the CPR requires the disclosure of "any other hazard information with respect to the controlled product [which includes information relating to its toxicological properties] of which the supplier is aware or ought reasonably to be aware."

Professional judgement will generally be required to determine the extent and nature of hazard disclosure, particularly where the data are extensive, conflicting or contradictory. In order to be understandable by the intended user, the preparer of the MSDS should summarize the hazard and should make an effort to minimize the disclosure of extraneous scientific or technical jargon.

Mixtures: Most products are mixtures as opposed to being "pure" substances. Any toxicological information resulting from tests on a mixture must be disclosed if available and applicable to the mixture. In the absence of scientific evidence to the contrary, it should be assumed that, taking into account possible synergistic interactions, the toxicological properties to be disclosed for an untested mixture are the same as those of the mixture's ingredients which are subject to disclosure. Information relating to ingredients subject to disclosure must be disclosed if this information is applicable to the mixture. The information disclosed on the MSDS should correlate the toxicological information to the ingredient with which the adverse effect is associated.

Example: Where an untested mixture contains 5% of ingredient "X" and this ingredient has been shown to be neurotoxic, the mixture will also fall within the same classification as the pure ingredient by virtue of paragraph 58(b) of the CPR. In the absence of evidence demonstrating that this adverse effect is not applicable to the mixture, the MSDS must disclose that an ingredient in the product has been shown to be neurotoxic and should specify which ingredient is associated with this adverse effect.

"Applicable" information: As suppliers cannot anticipate all possible uses of their products, thorough information on toxicological properties should be provided without limiting such information to the hazards based on presumed use.

Results of any studies conducted according to the WHMIS classification criteria (sections 33, 46 to 62 of the CPR) and other studies conducted according to established scientific principles, which report statistically significant adverse effects, must be disclosed on the MSDS if this information is available to the supplier and applicable to the controlled product. Where more than one study has similar results, the information may be summarized. If available, the MSDS must disclose significant human health effects reported in epidemiological studies, and case reports in the literature, relevant to occupational exposure.

Since evidence of health effects to humans is typically not available, it is reasonable to disclose information, considered statistically significant, based on "relevant" animal testing. Relevant testing relates to the normal routes of occupational exposure such as inhalation, ingestion, skin and eye contact, and skin absorption as opposed to routes such as intraperitoneal, intramuscular, subcutaneous etc. Negative information may also be disclosed if it aids significantly in assessing the potential health risks of downstream use of the product. Where it is appropriate to extrapolate data from a similar product to an untested mixture for classification purposes, the supplier should disclose the relevant test data, indicate that the data relate to a similar substance and identify the substance.

Section 13 of the CPR requires that, where contradictory or ambiguous toxicological information is disclosed, sufficient information be disclosed so that a proper judgement as to the nature or extent of the hazards posed by the controlled product can be made.

Information sources: Preparers of MSDSs must exercise professional judgement when determining the source and extent of information to be reviewed and disclosed. For example, often only article abstracts are obtained through literature searches; i.e., literature searches may not provide all of the information subject to disclosure on the MSDS. Information sources which should be considered include:

• company information on toxicity tests or illness experience;
• supplier MSDSs for ingredients used in untested mixtures;
• the latest edition of the sources listed in the Appendix to this guideline;
• information made available by regulatory agencies, trade associations and labour organizations.

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Specific guidelines for MSDS disclosure in respect of subitems 1(3), 1(4) and 7(1) to 7(11) of Schedule I to the Controlled Products Regulations:

Subitems 1(3) and 1(4) - LD₅₀ (species and route) and LC₅₀ (species and duration of exposure): Sections 46, 48, 49, and 51 of the CPR specify the classification criteria for acute lethality. Formulae for determining "equivalent" LD₅₀ and LC₅₀ are described in sections 44 and 45 of the CPR.

1. For LD₅₀ data, the supplier must disclose the species of the animal used in the test [e.g. rat, mouse]; the unit of measurement [e.g. milligrams of test substance per kilogram of body weight of the test animal (mg/kg)]; and route of exposure [e.g. oral, dermal]; for example: LD₅₀ (rat, oral): 100 mg/kg.
   
   For LC₅₀data, the supplier must disclose the species of the animal used in the test [e.g. rat, mouse]; the unit of measurement [e.g. the concentration of the test substance in air (i.e., ppm or mg/m³ for gases and vapours, and mg/m³ or mg/L for dusts, mists and fumes)]; and the duration of the exposure [e.g. 4 hours]; for example: LC₅₀ (rat, 4 hours): 600 ppm.
   
   
2. For untested mixtures, relevant and available LD₅₀ and LC₅₀ values must be disclosed for each ingredient subject to disclosure.
   
   
3. For tested mixtures, as per subsection 12(10) of the CPR, "where the LD₅₀ or LC₅₀ of a controlled product that is a mixture is determined by testing the mixture", the supplier need not disclose the LD₅₀ or LC₅₀ of the ingredients of the mixture (regardless of whether the LD₅₀ or LC₅₀ determined through testing the product is a range or a "greater than" value as opposed to a "single (i.e., specific) dose" in the case of an LD₅₀ or a specific concentration in the case of an LC₅₀).
   
   If the LD₅₀ and LC₅₀ values are known for each ingredient present at a concentration of at least 1% in the mixture, the supplier may disclose the LD₅₀ and/or LC₅₀ value calculated in accordance with subsection 45(1) of the CPR. Each value used in the formula must be related to the same route of exposure, animal species and sex.
   
   
4. When more than one LD₅₀ and/or LC₅₀ value for a tested mixture or an ingredient is available, it is recommended that the supplier disclose:
   
   
   1. the value established in accordance with the referenced Organization for Economic Cooperation and Development (OECD) Guideline or, if this is not available, values established using other protocols carried out in accordance with generally accepted standards of good scientific practice;
   2. the rat value where values are available for more than one species, and other mammalian species values if different hazard classifications are indicated;
   3. where more than one LD₅₀ or LC₅₀ value is available for the same species and using the same protocol, the supplier should disclose the lowest appropriate value reported or a range that encompasses the values.

Example: A controlled product which is an untested mixture is composed of five hazardous ingredients all five of which are subject to disclosure. The following acute toxicity data is available:

Using guidelines (a) to (c) above, the MSDS should disclose the following data for LD₅₀/LC₅₀ of the hazardous ingredients:

(Footnote 1: The CPR will be amended to more explicitly state that all subheadings which appear on an MSDS be addressed by disclosing the relevant information or by declaring that the information in "not available" or "not applicable".)

NOTE: Where the results of the new Fixed Dose Method (OECD Test Guideline 420) are used to determine the classification of the product, the MSDS should disclose the mortality and evident toxicity data (under subitem 7(2) of Schedule I to the CPR) used to make that determination.

Subitem 7(1) - Routes of entry, including skin contact, skin absorption, eye contact, inhalation and ingestion: Of these five potential routes of entry, those routes which can present health risks to workers during reasonable foreseeable use must be specified. These routes of entry will relate to the nature and properties of the substance under consideration as well as its uses; for example:

Subitem 7(2) - Effects of acute exposure to product: Acute toxicity relates to toxic effects provided by a single or multiple exposure to a substance by any route for a short period of time. The MSDS must disclose both immediate and delayed effects resulting from short-term exposure; for example, skin corrosion (immediate) or pulmonary edema (delayed) from exposure to nitric acid. The information that must be disclosed on the MSDS is not limited to the results of tests for acute lethality specified in the classification section of the CPR.

Subitem 7(3) - Effects of chronic exposure to product: Chronic toxic effects include any target organ effects from prolonged, repeated or seasonal exposures. The MSDS must disclose significant human health effects reported in epidemiological studies and case reports in the literature. Since human evidence of health effects is typically not available, it is reasonable to disclose information based on mammalian animal testing which is judged to report significant information on toxicological properties. It is important to include the route of exposure when disclosing the effects of chronic exposure.

For chronic toxicity animal studies, the exposure time is considered to be approximately 80 percent of the lifespan; for subchronic toxicity, the exposure time is approximately 10 percent of the lifespan. In the absence of data on chronic or subchronic exposure, the results of studies of shorter duration (i.e., "subacute" studies) should be evaluated.

Subitem 7(4) - Exposure Limits: Exposure limits are recommended by bodies such as the American Conference of Governmental Industrial Hygienists (ACGIH) and the National Institute for Occupational Safety and Health (NIOSH) or are legislated by federal, provincial and territorial agencies responsible for occupational safety and health. Various types of exposure limits, short-term and long-term, may be applicable depending on the working conditions. The MSDS must disclose appropriate values for the controlled product. The MSDS should also disclose values for ingredients of a mixture if this information is applicable to the mixture. The MSDS must specify which type of exposure limit is being disclosed; for example, time weighted average (TWA), short-term exposure limit (STEL) or ceiling (C).

If exposure limits are not available from the ACGIH or other jurisdictional authorities but are recommended by the supplier, the appropriate bodies recommending those limits should be disclosed on the MSDS. Up to the present time, no source, North American or other, has been identified as publishing unacceptable exposure limits. The CPR will be amended to require that whatever exposure limit is used, the limit is to be qualified by indicating the source of the exposure limit and that a statement to the effect "consult local authorities for acceptable exposure limits" appears on the MSDS. Disclosure of the term: "TLV (TWA) - 10ppm" would suffice as all "TLVs" are issued by the ACGIH, and consequently the ACGIH is the source of all TLVs. (The term "TLV" is a registered trade mark of the ACGIH). In the case of other exposure limits, the MSDS should disclose the source.

Where it is known that the use of the product could give rise to potentially lethal conditions, such as high airborne concentrations of solvent vapours from use of degreasers or furniture strippers, the supplier should disclose an IDLH limit if available. IDLH is the acronym for Immediately Dangerous to Life and Health. The IDLH is the concentration at which, in the event of respirator failure, a worker could evacuate within 30 minutes without experiencing any escape-impairing or irreversible health effects.

Subitem 7(5) - Irritancy of product: Sections 33(3) and 60 of the CPR specify the criteria to be used when determining whether a substance falls within the WHMIS criteria for skin or eye irritation. The information disclosed on the MSDS must indicate the severity of the irritant effect, i.e., whether the effect is slight/mild, moderate or severe. A product will fall within the classification criteria for eye or skin irritation if the irritant effect is greater than "slight". The effect relates only to chemical reaction, not to the effect of mechanical abrasion.

Numerical irritation scores, such as those obtained through testing in accordance with OECD Test Guidelines 404 (Acute Dermal Irritation/Corrosion) and 405 (Acute Eye Irritation/ Corrosion) or the Draize test, may be disclosed but this information is not generally comprehensible to the majority of MSDS users.

Subitem 7(6) - Sensitization [Respiratory or Skin] to product: A statement summarizing the results from the tests specified in sections 56 and 61 of the CPR (or from other relevant animal tests) must be disclosed on the MSDS if available. Positive human experience data must also be disclosed on the MSDS. It is important that the disclosed information identify the sensitizing agent. Non-occupational situations may be included if considered relevant.

Subitem 7(7) - Carcinogenicity: Section 54 of the CPR describes the classification criteria for carcinogens under WHMIS:

1. Group 1 or 2 in the International Agency for Research on Cancer (IARC) "Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans" published by the World Health Organization; or
2. Section A1, A2 or A3² of Appendix A of the Threshold Limit Values for Chemical Substances and Physical Agents in the Work Environment published by the ACGIH, as amended from time to time.

(Footnote 2: as agreed to through the WHMIS Current Issues Comittee Policy Issue Sheet No 72(b).)

Information to be disclosed on the MSDS is not limited to the above classification criteria. Other sources which are considered applicable include:

• lists of carcinogens from other countries;
• the U.S. National Toxicology Program list and related studies;
• academic studies;
• unpublished studies.

Information from these other sources must be disclosed on the MSDS if it is available to the supplier and applicable to the controlled product.

Subitem 7(8) - Reproductive toxicity & Subitem 7(9) - Teratogenicity: The classification criteria for developmental and reproductive toxins described in sections 33, 53 and 55 of the CPR may serve as a starting point for the evaluation of relevant hazard information to be disclosed on the MSDS. In contrast to the classification criteria, the information that must be disclosed on the MSDS is not limited to the results of tests which demonstrate that there was "no adverse effect on the pregnant female".

Reproductive toxicity relates to effects on the parents such as sterility or other impairment of reproductive capability in either males or females. Developmental toxicity relates to toxicity and abnormalities in offspring, e.g., teratogenicity (malformations), embryotoxicity and fetotoxicity.

In animal bioassays, adverse effects on fetal development or parental reproductive functions may occur at doses above or below those producing signs of toxicity in the parent animals. The handling, storage or use of controlled products may occasionally produce exposures resulting in mild parental toxicity thereby resulting in potential developmental or reproductive toxicity hazards. For the purpose of MSDS disclosure, any indication of an adverse effect on fetal development or reproductive parameters must be disclosed on the MSDS irrespective of whether or not there is an adverse effect on the pregnant female. Any relevant epidemiological evidence must also be disclosed.

Subitem 7(10) - Mutagenicity: The classification criteria for mutagenicity are described in sections 33, 57, and 62 of the CPR. These criteria are limited to:

1. epidemiology results for human populations, or
2. in vivo tests carried out on living mammals.

Positive results from studies that meet the above criteria must be disclosed. Results of tests on bacteria (e.g. Ames Salmonella Mutation Test), insects (e.g. Drosophila) or cells studied in cultures outside the living animals, must also be disclosed on the MSDS if this information is available to the supplier and applicable to the controlled product.

Subitem 7(11) - Name of toxicologically synergistic products: A synergistic effect occurs when the combined toxicological effect of two chemicals is greater than the sum of the effect caused by each agent alone. For example, both carbon tetrachloride and ethanol are hepatotoxic compounds. Together they produce much more liver injury than the sum of their individual effects on the liver would suggest. Available relevant information regarding toxicological interactions between the product, including its ingredients, and other chemicals must be disclosed if applicable to the controlled product. Exposure to two or more chemical agents may result in various types of toxicological interaction other than synergism, including additivity, antagonism and potentiation:

Additivity: An additive effect occurs when the combined toxicological effect of two chemicals is equal to the sum of the effect caused by each agent alone. For example, when two organic phosphate insecticides are given together, the cholinesterase inhibition is usually additive.

Antagonism (or Inhibition): Antagonism occurs when two chemicals interfere with each other's actions or when one chemical interferes with the action of the other chemical, the net effect being a reduction in toxicity. For example, the prevention of absorption of a toxicant by ipecac or charcoal.

Potentiation: A potentiator is a substance which produces no toxic effects itself but when administered in conjunction with another substance which does cause toxic effects, it makes the latter much more toxic. For example, isopropanol is not hepatotoxic but when isopropanol is administered in addition to carbon tetrachloride, the hepatotoxicity of carbon tetrachloride is much greater than when administered in isolation.