Module 3 - Strategic case studies in practice

ICH Q3D(R1) Guideline

PDE = 50 µg/d / 10 = 5.0 µg/day

PDE – Inhalation Exposure

Cobalt sulfate and other soluble Co(2+) salts are possible human carcinogens (Group 2B) that can induce lung tumors. Pneumoconiosis, asthma and contact dermatitis were the principal non-carcinogenic effects in humans after chronic inhalation. The MRL approach was considered acceptable for cobalt as the data are considered more reliable and the lack of human data for carcinogenicity cobalt sulfate. The best estimate of human cancer risk is approximately the same as the PDE derived using the MRL (WHO, 2006). For the calculation of the inhalation PDE, the chronic inhalation MRL of 0.1 µg/ m 3 was used (ATSDR, 2004).

PDE = 0.0001 mg/ m 3 /1000 m 3 /L x 28800 L/d = 2.9 µg/day

No modifying factors were applied because they are incorporated into the derivation of the MRL.

R EFERENCES

ATSDR. Toxicological profile for cobalt. Agency for Toxic Substances and Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 2004. IARC. Cobalt in hard metals and cobalt sulfate, gallium arsenide, indium phosphide and vanadium pentoxide. International Agency for Research on Cancer, World Health Organization, Lyon. 2003;86, updated in 2006. NAS.IOM. Food and Nutrition Board. Dietary Reference Intakes: RDA and AI for vitamins and elemnets. Institute of Medicine National Academies. Summary Tables, 2010. (available online at http://fnic.nal.usda.gov/dietary-guidance/dietary-reference- intakes/dri-tables; accessed May 27, 2014) NTP. Technical report on the toxicology studies of cobalt metal (CAS No. 7440-48-4) in F344/N rats and B6C3F1/N mice and toxicology and carcinogenesis studies of cobalt metal in F344/NTac rats and B6C3F1/N mice (inhalation studies). National Toxicology Program, Public Health Service, U.S. Department of Health and Human Services, Research Triangle Park, NC. 2013;NTP TR 581. Tvermoes BE, Unice KM, Paustenbach DJ, Finley BL, Otani JM, Galbraith DA. Effects and blood concentrations of cobalt after ingestion of 1 mg/day by human volunteers for 90 d. Am J Clin Nutr 2014;99:632-646. US EPA. Cobalt compounds: technology transfer network air toxics web site: Hazard summary. 2000 (http://www.epa.gov/ttn/atw/hlthef/cobalt.html; accessed April 23, 2014). WHO. Cobalt and inorganic cobalt compounds. Concise International Chemical Assessment Document. Inter-Organization Programme for the Sound Management of Chemicals (IOMC). World Health Organization. 2006;69.

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