The rate of 2,5-hexanedione intoxication, not total dose, determines the extent of testicular injury and altered microtubule assembly in the rat.
Toxicol Appl Pharmacol 1988 Jun; 94(1):76-83
The effect of dose rate on the testicular toxicity of 2,5- hexanedione (110134) (25HD) was studied in rats. Male CD-rats were administered 1.0, 0.5, or 0.25 percent 25HD in their drinking water for 21, 35, or 69 days, respectively. This yielded the same cumulative dose, 131 millimoles per kilogram (mmol/kg), but varying dose rates of 1.9, 3.8, and 6.1mmol/kg/day. The rats were killed 4 weeks after exposure ended and weighed. The testes were removed, weighed, and examined for histopathological changes. Rats were dosed with 0, 0.25, 0.5, or 1.0 percent 25HD for 3 weeks. They were then killed and the testes were removed. Testis pyrrole reactivity and purified tubulin assembly behavior were evaluated. Rats given 6.1mmol/kg/day 25HD had significantly reduced body and testicular weights. The other dose rates did not affect body or testicular weight. Virtually complete germ cell depletion was seen in the testes of rats given 6.1mmol/kg/day 25HD. Rats given 3.8mmol/kg/day 25HD showed either near total germ cell depletion or essentially normal seminiferous tubule morphology. The 1.9mmol/kg/day dose rate caused no significant histological changes. Testis pyrrole reactivity was increased and microtubule nucleation time was decreased by 25HD. The decrease in nucleation time correlated with increasing dose rate. The authors conclude that 25HD induced testicular toxicity depends on the rate of intoxication and not the total dose.
NIOSH-Publication; NIOSH-Grant; In-vivo-studies; Laboratory-animals; Histopathology; Toxic-effects; Reproductive-hazards; Physiological-chemistry; Hydrocarbons; Ketones
Pathology and Lab Medicine Div. of Biology and Medicine Brown University, Box G Providence, RI 02912
Toxicology and Applied Pharmacology
Brown University, Providence, Rhode Island