Hazardous Chemical Information System (HCIS)

Cadmium and compounds (as Cd)

Carcinogen Category first adopted in 1990

Review notice: Cadmium as respirable particulate mass - reason for review:establishment of exposure standard.

Carcinogen category notice:

Category 1B: Presumed to have carcinogenic potential for humans; the placing of this substance is largely based on animal evidence. See section 3.6 of the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Third revised edition.

Based on strength of evidence together with additional 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). Alternatively, evidence may be derived from animal experiments for which there is sufficient evidence to demonstrate animal carcinogenicity (presumed human carcinogen). In addition, on a case by case basis, scientific judgement may warrant a decision of presumed human carcinogenicity derived from studies showing limited evidence or carcinogenicity in humans together with limited evidence of carcinogenicity in experimental animals.

No standard should be applied without reference to Guidance on the interpretation of Workplace exposure standards for airborne contaminants.

Documentation notice:

Carcinogen Category 2 (Probable Human Carcinogen)

Note: This exposure standard is adopted from the 1994-1995 ACGIH Adopted TLVslist. Readers should refer to the relevant ACGIH documentation

⁽¹⁾ for substantiation for this value. Moreover,after detailed review of the relevant literature, the Exposure Standards Working Group has recommended thatcadmium and compounds be classified as a Carcinogen Category 2. This documentation provides a summary of thecarcinogenicity review and substantiates the Working Group's classification.

1. CARCINOGENICITY

1.1 Animal Studies

Reviews by the International Agency for Research on Cancer (IARC)

^(2,3) indicated that subcutaneous injections of cadmium compounds (cadmium chloride, sulphate, sulphide and oxide) caused the development of local sarcomas in rats, and intramuscular injection of cadmium powder and cadmium sulphide also produced local sarcomas in rats.

The subcutaneous administration of soluble cadmium salts (cadmium chloride and sulphate) in mice and rats resulted in interstitial-cell tumours of the testes following testicular atrophy

^(4,5) .

In the animal inhalation study of Takenaka et al

⁽⁶⁾ , exposure for 18 months to 12.5, 25 and 50ug/m³ of cadmium chloride produced lung carcinomas in white rats. The incidence rates were 15.4%, 52.6% and 71.4% respectively. The increase was dose-dependent. In another follow-up study

⁽⁷⁾ , rats exposed for 3.4-18 months to aerosols of cadmium chloride, oxide, sulphate and sulphide, developed lung cancer at concentrations ranging from 30ug/m³ CdO and CdCl₂ to 90ug/m³ for CdSO₄ and CdS.

1.2 Human Studies

The IARC has reviewed

^(2,3) the carcinogenicity of cadmium compounds to humans. However, with confounding factors in most studies, such as smoking and exposure to nickel and arsenic, the information has not demonstrated a clear, statistically significant dose-response relationship.

A study

⁽⁸⁾ in the United Kingdom of a cohort of 3025 nickel-cadmium battery workers showed an excess of lung cancer in groups exposed for 18 years or more. However, these workers were also exposed to nickel which is likely to be a human carcinogen. (Note: the carcinogenicity of nickel and compounds is under review by the Exposure Standards Working Group.)

In a study of 602 cadmium smelter workers

⁽⁹⁾ in the United States, 20 respiratory cancer deaths were observed, as compared to 12.2 expected. A significant trend was noted for cumulative exposure and lung cancer mortality. However, data on patterns of workers' smoking habits were inadequate and workers were also exposed to low levels of arsenic.

2. CONCLUSION

There is sufficient evidence for carcinogenicity of cadmium and compounds (especially cadmium oxide) in animals.

There is also limited evidence for carcinogenicity in humans, based upon some retrospective human mortality studies. However in these studies, other possible contributing factors to carcinogenesis had not been ruled out.

3. RECOMMENDATION FOR CARCINOGEN CATEGORY

After reviewing the relevant data, the Exposure Standards Working Group is of the view that there is sufficient evidence to provide a strong presumption that human exposure to cadmium and compounds may result in the development of lung cancer, based on animal studies and limited epidemiological evidence. The Working Group recommends that these compounds be classified as Carcinogen Category 2 (Probable Human Carcinogen). The reader is encouraged to review the section on Carcinogens in the Guidance Note on the Interpretation of Exposure Standards for Atmospheric Contaminants in the Occupational Environment, for guidance on the classification system of carcinogens.

REFERENCES

1. American Conference of Governmental Industrial Hygienists (ACGIH), Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th edition, Ohio, 1991.

2. International Agency for Research on Cancer (IARC), IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, 11:39-74, Lyon, 1976.

3. International Agency for Research on Cancer (IARC), IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Supplement 7, p.139-141, Lyon, 1987.

4. Reddy J et al, "Cadmium-induced Leydig cell tumors of rat testis: morphologic and cytochemical study", J Natl Cancer Inst, 51:891-903, 1975.

5. Poirier L A et al, "Effects of calcium and magnesium acetates on the carcinogenicity of cadmium chloride in Wistar rats", Cancer Res, 43: 4575-4581, 1983.

6. Takenaka S et al, "Carcinogenicity of cadmium chloride aerosols in W rats", J Natl Cancer Inst, 70: 367-373, 1983.

7. Oldgies H et al, "Low level inhalation experiments with four different cadmium compounds in rats", Presented at the VIth International Congress of Toxicology, July 27-31, 1986, Kitakyushu City, Japan.

8. Sorahan T, "A further mortality study of nickel-cadmium battery workers", In: Wilson D & Volpe R A (ed), Proceedings of the Fourth International Cadmium Conference, Munich, 1982, London, Cadmium Association, pp. 143-148, 1983.

9. Thun M J et al, "Mortality among a cohort of US cadmium production workers - an update", J Natl Cancer Inst, 74: 325-333, 1985.

Footnotes:

Review notice:

A review notice indicates that the substance requires further review by the Exposure Standards Expert Working Group. In most cases the ACGIH documentation should be consulted for these substances.

Documentation notice:

The major part of the adopted exposure standard is supported by the documentation of the ACGIH but the adopted natioanl standard differs from that recommended by the ACGIH in one or more details.