Effect of Dosing Vehicle on the Developmental Toxicity of Bromodichloromethane and Carbon Tetrachloride in Rats

Several halocarbons have been shown to cause full-litter resorption(FLR) in Fischer-344 rats when administered orally in corn oil.Since halocarbons often occur as contaminants of drinking water,we sought to determine the influence of the vehicle, aqueousversus lipid, on the developmental toxicity of two of theseagents. In separate assays, bromodichloromethane (BDCM) andcarbon tetrachloride (CCl₄. were administered by gavage to Fischer-344rats on gestation days (GD) 6–15 at 0, 25, 50, or 75 mg/kg/dayin either corn oil or an aqueous vehicle containing 10% EmulphorEL-620. Dams were allowed to deliver and the litters were examinedpostnatally. Uteri of females that did not deliver were stainedwith 10% aminonium sulfide to detect FLR. Effects of both agentson maternal weight gain were slightly more pronounced in theaqueous vehicle at lower doses, but at the highest dose, CCl₄was more maternally toxic in corn oil. Developmentally, bothagents caused FLR at 50 and 75 mg/kg in both vehicles. At 75mg/kg, dams receiving corn oil had significantly higher ratesof FLR (83% for BDCM, 67% for CCl₄) compared to their aqueous-vehiclecounterparts (21% for BDCM, 8% for CCl₄). Blood concentrationsof BDCM following GD-6 gavage revealed a shorter eliminationhalflife in the aqueous dosing vehicle (2.7 h) compared to theoil vehicle (3.6 h). Benchmark doses of CCl₄ were similar forthe oil (18.9 mg/kg) and aqueous (14.0 mg/kg) vehicles. ForBDCM, the corn oil vehicle yielded a less conservative (i.e.,higher) value (39.3 mg/kg) than the aqueous vehicle (11.3 mg/kg),reflecting different confidence intervals around the estimated5%-effect dose levels.