Hepato- and neuro-toxicity by ethylenthiourea.
Thyrotoxicity of Ethylenthiourea (2-imidazolidinethione) (ETU) is well known: this paper examines the extent to which ETU alone may damage certain non-thyroid tissues, and the possible enhancement of its effects through synergism when it is taken with substances employed for medical or alimentary reasons. It was found that the lethality of ETU is augmented by accumulation of fractionated doses, particularly in male as opposed to female rats. When accompanied by ethanol, its harmfulness is increased, whereas phenobarbital provides a certain degree of protection. Liver secretion of triglycerides is greatly impaired (delta % = -31) by acute administration, which results in steatosis. This is not observed during subacute administration. Liver microsomal cytochrome P450 is significantly reduced (delta % = -32) after a long term administration. The 30 week treatment leads to a form of "selection". Some animals die (28.6%), whereas others survive despite: i) prolonged failure to put on weight, ii) alopecia (80% loss of hair), iii) severe conjuntivitis, iv) blepharitis, v) peripheral nervous system distress. These findings underscore the importance of investigating the relation between hazardous compounds and possible potentiating factors, on the one hand, and inclusion of organs not yet recognized as targets, on the other hand, when setting tolerance limits for ambient pollution.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005031:Ethylenethiourea / Q000633:toxicity*; D005260:Female; D007093:Imidazoles / Q000633:toxicity*; D007928:Lethal Dose 50; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010525:Peripheral Nerves / Q000187:drug effects*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D007093:Imidazoles; D005031:Ethylenethiourea; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital