Testicular toxicity of DEHP, but not DEHA, is elevated under conditions of thioacetamide-induced liver damage.
As part of an investigation of possible enhancement by liver disease of testicular toxicity caused by phthalates, we tested the effects of di(2-ethylhexyl)phthalate (DEHP) and di(2-ethylhexyl)adipate (DEHA) in a thioacetamide (TAA)-induced rat liver damage model. Male, 6-week-old, F344 rats (n=60) were divided into ten groups. Animals of groups 1-5 received TAA (200 mg/kg, intraperitoneal, three times per week) for 4 weeks, and groups 6-10 served as controls without TAA. After a 1 week interval, at week 5, powder diet containing DEHP or DEHA was provided to the animals of groups 1 and 6 (DEHP 25000 ppm), groups 2 and 7 (DEHP 6000 ppm), groups 3 and 8 (DEHA 25000 ppm) and groups 4 and 9 (DEHA 6000 ppm), while groups 5 and 10 received basal diet. All animals were sacrificed at week 9. Significant decrease in sperm numbers and motility and increase in morphology abnormalities were evident in group 1 as compared to groups 5 and 6 (p<0.01). However, DEHA treatment was not associated with any apparent testicular toxicity in either TAA- or vehicle-treated animals. Histopathological examination of the testes revealed severe atrophy and degeneration of testicular tubules in all animals given TAA and DEHP at high dose, only mild to moderate lesions being found with DEHP alone. We conclude that liver toxicity induced by TAA is associated with the enhancement of testicular toxicity of DEHP, but not DEHA, in rats.
Kang
Jin Seok
JS
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Morimura
Keiichirou
K
Toda
Chitose
C
Wanibuchi
Hideki
H
Wei
Min
M
Kojima
Nakao
N
Fukushima
Shoji
S
D000272:Adipates / Q000633:toxicity; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004822:Epididymis / Q000187:drug effects* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010968:Plasticizers / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013091:Spermatogenesis; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013853:Thioacetamide
D000272:Adipates; D010968:Plasticizers; D013853:Thioacetamide; C013966:dioctyl adipate; D004051:Diethylhexyl Phthalate