Ethylenethiourea: a review of teratogenicity and distribution studies and an assessment of reproduction risk.

Ethylenethiourea (ETU) is a specific neuroteratogen that induces communicating hydrocephalus ex vacuo at oral doses far lower than those that cause any observable toxic sign or 50% death (LD50) in the rat dam. The teratogenic activity appears to be related to ETU itself and not to its metabolites. It is dependent upon the presence of an imidazolidine ring with a specific molecular location of sulfur atom. It is unlikely that ETU-induced alterations in thyroid function or thyroxine levels in the maternal rat are involved in teratogenic activity. The initial target following maternal dosing with ETU is the primitive neuroblast that undergoes necrosis, but the subsequent changes leading to the development of hydrocephalus are not clear. Teratogenicity studies in hamsters, mice, guinea pigs, rabbits, and rats revealed that ETU either required extremely high doses to produce malformations or was ineffective. The results of various distribution studies are summarized. Further, investigations dealing with exposure to ETU in the general population and in exposed workers in the rubber industry as well as those involved in the manufacture and spraying of fungicides are discussed briefly with reference to reducing the exposure levels.