Abstract  A potential endpoint for female reproductive toxicants is fertilizability of the oocytes. This endpoint has not been adequately examined for mammalian females. The objective of these studies was to evaluate fertilizability of rat oocytes following in vivo exposure to known male reproductive toxicants that exert effects via pathways that do not include endocrine disruption and to 4-vinylcyclohexene diepoxide, known to interfere with early follicular development. Oocytes were obtained from females following exposure and quality assessed by in vitro fertilization rate. One study evaluated fertilizability following 2 weeks exposure of females to inhaled tetrachloroethylene (2h/day, 5 days/week). The remaining studies evaluated fertilizability immediately following 2 weeks exposure via drinking water to tetrachloroethylene, trichloroethylene, the fuel oxidants methyl tertiary butyl ether (MTBE), ethyl tertiary butyl ether (ETBE), tertiary amyl methyl ether (TAME), and a metabolite of the first two ethers 2-methyl-1,2-propanediol (2M2P), and to 4-vinylcyclohexene diepoxide. The percentage of oocytes fertilized was reduced following inhalation exposure to tetrachloroethylene, or consumption of trichloroethylene or TAME. Fertilizability was not altered by exposures to the other reproductive toxicants or to the other fuel oxidants. Consistent with the reduced oocyte fertilizability following exposure to trichloroethylene, oocytes from exposed females had a reduced ability to bind sperm plasma membrane proteins. Female reproductive capability assessed by the endpoint, oocyte fertilizability, was reduced by exposure to trichloroethylene and inhaled tetrachloroethylene.

Abstract  The potential for immunotoxicological effects of ethyl tertiary butyl ether (ETBE, CAS RN 637-92-3) was studied in young adult female Crl:CD(SD) rats following subchronic oral exposures. Rats were exposed by gavage once daily for 28 consecutive days to 0, 250, 500, or 1000 mg ETBE/kg body weight (BW)/day; a concurrent positive control group received four intraperitoneal injections of at 50 mg cyclophosphamide monohydrate (CPS)/kg/day on study Days 24-27. Immunotoxicity was evaluated using a splenic antibody-forming cell (AFC) assay to assess T-cell-dependent antibody responses in rats sensitized with sheep red blood cells (SRBC). All rats survived to the scheduled necropsy. There were no effects on clinical observations, body weights, feed or water consumption, or macroscopic pathology findings in the ETBE-treated rats. No ETBE-related effects were observed on absolute or relative (to final body weight) spleen or thymus weights, spleen cellularity, or on the specific (AFC/10(6) spleen cells) or total activity (AFC/spleen) of splenic IgM AFC to the T-cell-dependent antigen SRBC. CPS produced expected effects consistent with its known immunosuppressive properties and validated the appropriateness of the AFC assay. Based on the results of this study, ETBE did not suppress the humoral component of the immune system in female rats. The no-observed-effect level for immunotoxicity was the highest dosage tested at 1000 mg/kg/day.

Abstract  Abstract A subchronic (180-day) toxicity study was conducted to evaluate the effects of ethyl tertiary-butyl ether (ETBE), a biomass fuel, in male and female rats. ETBE was administered at dose levels of 0, 5, 25, 100 and 400 mg/kg/body weight (b.w.)/day by gavage. No treatment-related adverse effects were observed at 5, 25 or 100 mg/kg. Centrilobular hypertrophy of hepatocytes was observed in males and females and their relative liver weights were increased, suggesting enhanced metabolic activity. From these results, we concluded that the no observed adverse effect level of ETBE was 100 mg/kg b.w./day under the conditions tested.