A hazard evaluation of the reproductive/developmental toxicity of cobalt in medical devices

Abstract

Cobalt (Co) is an essential element with human exposure occurring from the diet, supplement ingestion, occupational sources, and medical devices. The European Chemical Agency (ECHA) recently voted to classify Co metal as a Reproductive Hazard Category 1B; presumed human reproductive toxicant due to adverse testicular effects in male rodents. A weight of evidence evaluation of the preclinical reproductive and developmental toxicity studies and available clinical data was performed to critically evaluate the relevance of this proposed classification for Co in medical devices. Reproductive responses to Co are limited to the male testes and sperm function following high systemic exposure in rodents, only at Co concentrations/doses that result in overt toxicity (i.e., above the maximum tolerable dose (MTD)). The potential mechanisms of Co reproductive/developmental toxicity, including its indirect mode of action in the testes and relevance to humans, are discussed. The available preclinical and clincial evidence suggests that it would be more appropriate to classify Co as a Reproductive Hazard Category 2 compound: suspected human reproductive toxicant and, in the case of Co-containing medical devices, it should not be considered a reproductive hazard.

Keywords: Clinical; Cobalt (Co); European medical device regulation (MDR); Hazard; Preclinical; Reproduction.