A two-generational reproductive toxicity study of zinc in rats.
A two-generation reproductive toxicity study of zinc chloride (ZnCl(2)) was conducted in rats. F(o) male and female rats were administered 0.00 (control), 7.50 (low), 15.00 (mid) and 30.00 (high) mg/kg/day of ZnCl(2). Selected F(1) male and female rats were exposed to the same doses received by their parents (F(o)). Exposure of F(0) parental rats to ZnCl(2) showed significant reduction in fertility, viability (days 0 and 4), and the body weight of F(1) pups from the high-dose group but caused no effects on litter size, weaning index, and sex ratio. Similarly, the continued exposure of F(1) parental rats to ZnCl(2) also reduced fertility, liter size, viability (day 0), and the body weight of F(2) pups within the high-dose group but caused no effects on weaning index and sex ratio. Exposure of ZnCl(2) to F(0) and F(1) parental males resulted in a significant reduction in their body weights, and the F(0) and F(1) parental females did not show any significant difference in their body weights compared to their control groups. However, the postpartum dam weights of both F(0) and F(1) female rats were significantly reduced compared to their controls. Exposure of ZnCl(2) to F(o) and F(1) generation parental rats did not produce any significant change of their clinical signs as well as their clinical pathology parameters, except the alkaline phosphotase (ALK) level, which showed an upward trend in both sexes of both generations. Exposure of ZnCl(2) to F(0) rats resulted in a reduction of brain, liver, kidney, spleen and seminal vesicles weights of males and in the spleen and uterus of females. Similarly, exposure of F(1) rats to ZnCl(2) also resulted in reduction of brain, liver, kidney, adrenal, spleen, prostate and seminal vesicles weights of males and in spleen and uterus of females. ZnCl(2) exposure resulted in grossly observed gastro-intestianla (GI) tract, lymphoreticular/hematopoietic, and reproductive tract lesions in parental rats in both generations. Reduced body fat was also recorded in F(1) parental rats.
Khan
Abu T
AT
College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL, USA. abu.khan@fda.hhs.gov
Graham
Thomas C
TC
Ogden
L
L
Ali
S
S
Salwa
Thompson
Sherylee J
SJ
Shireen
Kaniz F
KF
Mahboob
Mohd
M
D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D002712:Chlorides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005298:Fertility / Q000187:drug effects* / Q000502:physiology; D008098:Litter Size / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D012737:Sex Factors; D016019:Survival Analysis; D018675:Toxicity Tests; D017967:Zinc Compounds / Q000633:toxicity*
D002712:Chlorides; D017967:Zinc Compounds; C016837:zinc chloride