Substance-Specific Issues

Classification of Elemental Mercury with respect to Skin Sensitization

Substance:

Mercury, elemental; CAS No. 7439-97-6

Issue:

Does elemental mercury fall within the Controlled Products Regulations (CPR) criteria for skin sensitization?

Background:

Mercury falls within the CPR criteria for D1A Very Toxic Material Causing Immediate and Serious Toxic Effects (LC₅₀ inhalation/4 hours (rat) < 19 mg/m³) [1], D2A Very Toxic Material Causing Other Toxic Effects (chronic toxicity, teratogenicity and embryotoxicity) [2] and WHMIS Class E Corrosive Material (Transportation of Dangerous Goods: class 8) [3].

Despite the known toxicity of mercury and the fact that occupational hygiene control measures are generally in place to minimize or eliminate exposure, there are a number of case reports of skin sensitization following occupational exposure to mercury and mercury salts. Material safety data sheets (MSDSs) from major distributors often include statements to the effect that mercury "may" cause skin sensitization / allergic reactions. However, the inability to deduce from case reports the degree to which potential confounding factors including skin irritation, history of atopy, complications with atopic dermatitis and concomitant sensitization to other agents may have played a role has raised questions as to whether elemental mercury should be considered as falling within the CPR criteria for skin sensitization.

Several authors have reported that allergy to metallic mercury is rare and have raised points to consider when interpreting data on skin sensitization following exposure to mercury:

• The majority of positive patch test reactions to mercury and mercury compounds are related to non-occupational exposure. (Patch testing involves the placement of the test substance against the skin for a specified period.)
• Great care must be used in interpreting patch test reactions to mercury compounds, several of which are irritants.
• For many years, mercuric chloride was used to detect mercury sensitivity. Yet mercuric chloride, 1% aqueous, is corrosive to the skin, and even with a concentration of 0.5%, irritant reactions are common. Consequently, the many false-positive results have caused dermatologists and other physicians to view with skepticism much of the past literature on mercury sensitivity. Patch testing with a concentration of 0.05% in water is more reliable.
• Today it is difficult to know if patch test reactions signify latent sensitivity from some past use of mercury compounds. Mercury-containing medications, especially antiseptics such as Mercurochrome and Thimerosal, were, until recently, present in many medicine cabinets.

Considerations:

The Reference Manual for the WHMIS Requirements of the Hazardous Products Act and Controlled Products Regulations states: In the case of a material (pure substance or tested mixture) which does not meet any of the criteria for Very Toxic Material or Toxic Material, but for which there is valid documented evidence based on established scientific principles that the material causes an adverse effect in humans following occupational exposure, this fact, by itself, is sufficient to include that material within this class. In this context, "adverse effects" mean injury to humans resulting from occupational exposure including any reversible or irreversible material impairment to health or irreversible diminished functional capacity [4].

Where the interpretation of a statute or regulation is unclear or in doubt, the Charter of Rights and Freedoms requires that the statute or regulation be interpreted "restrictively"; that is, to the benefit of the accused. However, when interpreting a law, the court will also look to the purpose of the law and will not interpret it so restrictively as to defeat the purpose of the Act. In other words, if the interpretation that benefits the accused would defeat the purpose of the law, the court will reject the accused's argument. This principle is found at section 12 of the Interpretation Act, which states that:

"Every enactment is deemed remedial, and shall be given such fair, large and liberal construction and interpretation as best ensures the attainment of its objects."

where "remedial" means that a problem was perceived and a law was passed to remedy it.

The objective of WHMIS is to ensure the protection of Canadian workers from the adverse effects of hazardous materials through the provision of relevant information while minimizing the economic impact on industry and the disruption of trade; (reference: Regulatory Impact Analysis Statement, Canada Gazette Part II, Vol. 122, No. 2; January 20, 1988). For greater certainty in ensuring this objective would be met, subsection 12(11) of the CPR requires that

"A material safety data sheet shall disclose, in addition to the information required to be disclosed by subsection (2), any other hazard information with respect to the controlled product of which the supplier is aware or ought reasonably to be aware."

Thus, all relevant toxicological information that is available to the supplier and applicable to the controlled product must be disclosed on the MSDS.

Section 32 of the CPR defines "skin sensitization" as "an immunologically-mediated, cutaneous reaction in a non-atopic person or animal on exposure to a substance to which the person or animal has previously been exposed". Section 61 of the CPR sets out the criteria for the classification of a product in Class D on the basis of skin sensitization:

"A pure substance or tested mixture falls into Subdivision B of Division 2 of Class D - Poisonous and Infectious Material if...

(b) evidence shows that it causes skin sensitization in persons following exposure in a work place."

On the basis of the above definitions, it must be demonstrated that the immunologically-mediated, cutaneous reaction is caused or induced by exposure to a material in order for the material to be classified as a skin sensitizer.

The current GHS definition of a skin sensitizer is "a substance that will lead to an allergic response following skin contact" (Globally Harmonized System of Classification and Labelling of Chemicals, 2nd revised edition, 2007). The GHS definition therefore includes both substances that induce allergic responses and substances that elicit allergic responses.

Conclusions:

In the case reports reviewed, it is unclear whether the skin reactions observed can unequivocally be attributed to elemental mercury exposure due to the inability to ascertain the degree to which potential confounding factors (including prior exposure to mercury salts) may have played a role. While exposure to elemental mercury has elicited reactions, it is less clear that, as set out in paragraph 61(b) of the CPR, it "causes" (induces) skin sensitization; i.e., do patch test reactions signify latent sensitivity from previous exposure to mercury compounds?

Once the GHS is implemented, it may be necessary to revisit the classification of elemental mercury with respect to skin sensitization.

With regard to information to be disclosed on MSDSs, suppliers should, at minimum, continue to disclose that exposure to elemental mercury can elicit a skin sensitization reaction. This statement may be qualifed by indicating that individuals previously exposed to mercury salts may be particularly vulnerable. The MSDS should also disclose information on appropriate precautionary measures, personal protective equipment and first aid. To suggest that a MSDS need not disclose any information advising that precautions be taken because skin sensitization was a consequence of previous exposure to mercury salts would defeat the purpose of the Act and is contrary to the objectives of WHMIS.

References:

1. Livardjani, F., Ledig, M., Kopp, P., et al. 1991. Lung and blood superoxide dismutase activity in mercury vapor exposed rats: Effect of N-acetylcysteine treatment. Toxicology 66(3):289-295.
2. Agency for Toxic Substances and Disease Registry, 1999. Toxicological profile for mercury. Atlanta, Ga. Update. [MO-016599] http://www.atsdr.cdc.gov/toxpro2.html
3. Transport Canada, Transport of Dangerous Goods Regulations. http://www.tc.gc.ca/tdg/menu.htm
4. Health Canada, "Reference Manual for the WHMIS Requirements of the Hazardous Product Act and Controlled Products Regulations".