ASSESSMENT OF THE REPRODUCTIVE TOXICITY OF A COMPLEX MIXTURE OF 25 GROUNDWATER CONTAMINANTS IN MICE AND RATS

The potential reproductive toxicity of a mixture of 25 chemicals (MIX) formulated to simulate contaminated groundwater supplies near hazardo us waste dumps was evaluated in CD-1 Swiss mice and Sprague-Dawley rat s using the reproductive assessment by continuous breeding protocol. M ale and female mice and rats were exposed to MIX in the drinking water at concentrations of 1, 5, and 10% of a technically achievable stock solution. For mice, body weight and feed consumption were not affected by MIX but water consumption was decreased for both the 5 and 10% MIX groups in both F-0 and F-1 animals. For F-0 mice, the number of live pups/litter was decreased at 10% MIX and the number of females/litter was decreased 10 and 17% at the mid and high MIX dose, respectively. V aginal cytology was normal, as were testis weight and testicular sperm atid head count. For F-1 mice, fertility was unaffected, but there was a decreased number of female pups/litter (19%) and a decreased adjust ed live pup weight at 10% MIX. At necropsy, cauda epididymal sperm con centration and spermatid head count were reduced (20%) in the presence of normal testis, epididymis, prostate, seminal vesicle, liver, and k idney/adrenal weight. Female estrous cyclicity was altered at 5 and 10 % MIX with normal kidney/adrenal, uterus, and ovary/oviduct weight. Fo r rats, F-0 body weight and feed consumption were not affected by MIX but water consumption was decreased 10, 30, and 40% in the low-, mediu m-, and high-dose MIX groups, respectively, and 39% in the high-dose M IX F-1 animals. Rat fertility was normal but there was a decreased num ber of male pups/litter (11%) and a decreased live pup weight (6%) at 10% MIX. Male and female (F-1) pup weights were decreased on Postnatal Days 0, 4, 7, 14, and 21 (10% MIX) and remained lower through necrops y on Day 120 +/- 10. F-1 fertility was normal but F-2 pup weights were decreased (10% MIX). At necropsy, F-1 (10% MIX) male body weight was decreased 16% and relative kidney, testis, epididymis, and prostate we ights were increased in the presence of normal sperm concentration per centage motile sperm and percentage abnormal sperm. Estrous cyclicity was normal as were kidney/adrenal and ovary weight while female liver weight was reduced 14%. In summary, a ''cocktail'' of 25 chemicals com monly found in contaminated groundwater at or near hazardous waste sit es was administered in drinking water at doses which resulted in sever ely decreased water consumption in both mice and rats. Despite the pre sence, albeit at relatively low concentrations, of many known reproduc tive toxicants including cadmium, mercury, lead, chloroform, di(2-ethy lhexyl)phthalate, and methylene chloride, only minimal reproductive ef fects were observed in F-0 and F-1 mice and rats. (C) 1995 society of Toxicology.