Infertility in rats induced by 2,5-hexanedione in combination with acetone.
The morphological changes as well as the functional consequences for the reproduction of the testis-injuring effect of 2,5-hexanedione (2,5-HD) were evaluated in rats. The potentiation by acetone and the reversibility of the effects was also studied. Male rats were dosed for 6 weeks with 0, 0.13%, 0.25% or 0.50% 2,5-HD alone or in combination with 0.50% acetone in the drinking water. During the last week of treatment the fertility of half of the treated males was studied by introducing each of them to a non-treated female rat, after which the number of matings, pregnancies and foetuses was examined. In order to evaluate the degree of reversibility of the effect on testis the same examination was made in the other half of the males after a 10 weeks dose-free period. The weight and morphology of testis from all the males was studied. The weight of testis, testis tubuli diameter and fertility was reduced by 2,5-HD and further reduced in groups dosed with 2,5-HD, 0.25% and 0.50% plus acetone 0.50%. Combined administration of acetone and 2,5-HD caused a potentiation comparable to the effect of the double dose of 2,5-HD. Minor changes were reversible within the 10 weeks dose-free period, whereas infertility and other severe changes in the highest combined group were non-reversible within this period. The number of matings was unaffected. It is concluded that 2,5-HD has a testis-injuring effect, which in high doses and combined with acetone causes non-reversible infertility and that testis is more sensitive than the nerve tissue to 2,5-HD.(ABSTRACT TRUNCATED AT 250 WORDS)
Larsen
J J
JJ
Institute of Toxicology, National Food Agency, Ministry of Health, Søborg, Denmark.
Lykkegaard
M
M
Ladefoged
O
O
D000096:Acetone / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D005260:Female; D006588:Hexanones / Q000633:toxicity*; D007248:Infertility, Male / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000187:drug effects / Q000473:pathology
D006588:Hexanones; D000096:Acetone; C011269:2,5-hexanedione