Teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the love canal.

The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6-15 of gestation to C57BL/6J mice (Ahb/Ahb) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg-1 day-1 and to DBA/2J (Ahd/Ahd) females, which were mated with either DBA/2J or C57BL/6J males, at 0, 0.5, 1, and 2.0 g kg-1 day-1. In C57BL/6J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg-1 day-1, respectively. Maternal mortality was 5% at the highest dose. In DBA/2J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg-1 day-1 but the ED50 for hydronephrosis was 0.76 g OPL kg-1 day-1. TCDD was similarly administered to pregnant C57BL/6J mice at 0, 0.5, 1, 2, and 4 micrograms kg-1 day-1 and to DBA/2J mice at 0, 0.5, 2, 4, and 8 micrograms kg-1 day-1. In C57BL/6J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 microgram TCDD kg-1 day-1, respectively. In DBA/2J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 micrograms TCDD kg-1 day-1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL/6J fetal weights. OPL decreased the number of fetuses per C57BL/6J dam at the two highest doses but there were no other reproductive effects in any of the groups. It was concluded that the OPL is teratogenic and that hydronephrosis is a sensitive measure of TCDD toxicity in a complex organic mixture. Based on the ED50's of OPL- and TCDD-induced cleft palate and hydronephrosis in the C57BL/6J strain, the OPL had TCDD equivalence of 6.6 and 10.5 ppm, respectively. These values compare closely with the chemical analysis of 3 ppm.(ABSTRACT TRUNCATED AT 400 WORDS)

Toxicity of chloroform and bromodichloromethane when administered over a lifetime in rats.

Chloroform (CHCl3) and bromodichloromethane (CHBrCl2) are the two most common haloorganic contaminants of chlorinated drinking water. A significantly increased incidence of hepatic neoplastic nodules was found in female rats when either of these compounds was administered in drinking water to Wistar rats throughout their life-span. Hepatic adenofibrosis was also produced by chronic ingestion of these two halomethanes.

The effects of Love Canal soil extracts on maternal health and fetal development in rats.

The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

Lifetime toxicity of chloroform and bromodichloromethane when administered over a lifetime in rats.

Chloroform (CHCl3) and bromodichloromethane (CHBrCl2) are the two most common haloorganic contaminants of chlorinated drinking water. A significantly increased incidence of hepatic neoplastic nodules was found in female rats when each of these compounds was administered in drinking water to Wistar rats throughout their life span. Hepatic adenofibrosis was also produced by chronic ingestion of these two halomethanes.

Toxicity and persistence of low-level PCB in adult wistar rats, fetuses, and young.

Aroclor 1254 was fed to female and male rats daily for 9 weeks at a dose of 6.4 mg/kg in their drinking water. Control animals received plain tap water plus the emulsified (0.15% Tween 80). Elevated mixed function oxidase (MFO) activity appeared to be due to 2,4,5,2',4',5'- and 2,4,5,2'3'4'-hexachlorobiphenyls, since only these compounds were present to any degree in the tissues of the animals when MFO activity persisted after termination of exposure. The placenta apparently is an effective barrier to PCB transfer.