Review: Risk assessment implications of variation in susceptibility to perchloroethylene due to genetic diversity,ethnicity, age,gender, diet and pharmaceuticals

Current cancer risk assessments do not adequately consider impacts of human inter-individual variability on susceptibility to environmental pollutants like perchloroethylene (PCE). PCE is metabolized through both oxidative and glutathione (GSH) conjugation pathways. Toxicity criteria derived using both pathways are 23-fold more stringent than those calculated using only oxidative metabolism. While toxicokinetic modeling of PCE metabolism predicted very high variability through the GSH conjugation pathway, it is unclear if the range in estimates is due to human variability or uncertainty. Thus, the variation in the GSH conjugation pathway of PCE metabolism due to genetics, ethnicity, age, gender, diet, and pharmaceutical co-exposures is examined. Genetic polymorphisms were found at several loci including, GSTT1, GSTM1, CCBL1, AGXT2, NAT8, ACY3, MRP2, OAT1/3, FMO3, and CYP3A that code for enzymes/transporters in the GSH conjugation pathway. Genetic diversity in GSTT1, GSTM1, and CCBL1 between ethnic populations, as well as age, gender, diet, and pharmaceutical co-exposures influences toxic and mutagenic metabolites produced through this pathway. Given this diversity, large differences in PCE metabolism through the GSH conjugation pathway are expected. To be health protective for diverse ethnic populations and lifestyles, both the oxidative and GSH conjugation pathways need to be considered in developing PCE toxicity criteria.     

Gas phase photocatalytic degradation on TIO2 pellets of volatile chlorinated organic compounds from a soil vapor extraction well

The degradation of trichloroethylene (TCE, Cl₂C=CHCl) and tetrachloroethylene (PCE, Cl₂C=CCI₂) in a gas stream from a soil vapor extraction (SVE) well was demonstrated with an annular photocatalytic reactor packed with porous TiO₂ pellets in a field trial at the Savannah River Site in Aiken, SC. The TiO₂ pellets were prepared using a sol‐gel method. The experiments were performed at 55 to 60°C using space times of 10⁸ to 10¹⁰ g ? s ? mol^‐1 for TCE and PCE. Chloroform (CHCl₃) and carbon tetrachloride (CCl₄) were detected as minor products from side reactions. On a molar basis, the amounts CCl₄ and CHCl₃ produced were about 2 and 0.2% of the reactants, respectively.     

Developmental toxicity studies in Crl:CD (SD) rats following inhalation exposure to trichloroethylene and perchloroethylene

The potential for trichloroethylene (TCE) and perchloroethylene (PERC) to induce developmental toxicity was investigated in Crl:CD (SD) rats whole-body exposed to target concentrations of 0, 50, 150 or 600 ppm TCE or 0, 75, 250 or 600 ppm PERC for six hours/day, seven days/week on gestation day (GD) 6-20 and 6-19, respectively. Actual chamber concentrations were essentially identical to target with the exception of the low PERC exposure level, which was 65 ppm. The highest exposure levels exceeded the limit concentration (2 mg/L) specified in the applicable test guidelines. Maternal necropsies were performed the day following the last exposure. Dams exposed to 600 ppm TCE exhibited maternal toxicity, as evidenced by decreased body weight gain (22% less than control) during GD 6-9. There were no maternal effects at 50 or 150 ppm TCE and no indications of developmental toxicity (including heart defects or other terata) at any exposure level tested. Therefore, the TCE NOEC for maternal toxicity was 150 ppm, whereas the embryo/fetal NOEC was 600 ppm. Maternal responses to PERC were limited to slight, but statistically significant reductions in body weight gain and feed consumption during the first 3 days of exposure to 600 ppm, resulting in a maternal NOEC of 250 ppm. Developmental effects at 600 ppm consisted of reduced gravid uterus, placental and fetal body weights, and decreased ossification of thoracic vertebral centra. Developmental effects at 250 ppm were of minimal toxicological significance, being limited to minor decreases in fetal and placental weight. There were no developmental effects at 65 ppm.     

In vivo effect of vitamin E on serum and tissue glycoprotein levels in perchloroethylene induced cytotoxicity

The antioxidant efficacy of vitamin E on Perchloroethylene (PER) induced cytotoxicity has been studied in rats. Feeding PER to rats for 42 days using sesame oil as vehicle alters total protein and protein bound carbohydrate components in liver and kidney of experimental animals. Supplementation of vitamin E prevented the changes observed in total protein and protein bound carbohydrate components of PER administered rats. Histopathological studies also show the effectiveness of vitamin E on PER administered rats in protecting the cellular architecture of liver and kidney from PER induced cytotoxicity.     

四氯乙烯和镉对草鱼的单一与联合毒性效应

以静水生物测试法研究了四氯乙烯和重金属镉对草鱼的单一与联合毒性,同时采用Marking相加指数法对二者的联合毒性进行了评价.单一毒性试验表明:四氯乙烯对草鱼24、48、72和96 h的半数致死浓度(LC₅₀)分别为49.12、41.68、36.37和34.30 mg·L^-1;镉对草鱼24、48、72和96h的LC₅₀分别为45.58、34.81、28.63和24.05mg·L^-1;二者对草鱼均有毒性,而且为高毒,镉的毒性大于四氯乙烯.联合毒性试验表明:二者毒性比为1∶1,暴露时间为24、48、72和96 h时四氯乙烯和镉的LC₅₀分别为24.63、12.54、9.88和7.08 mg·L^-1以及17.11、8.71、6.87和4.92 mg·L^-1,相加指数AI(additive index)分别为0.14、0.81、0.95和1.43,联合作用结果为协同效应,并且随着时间的增加,协同作用增强;二者浓度比为1∶1, 暴露时间为24、48 、72和96 h时四氯乙烯和镉的LC₅₀分别为17.00、11.18、10.61和9.19 mg·L^-1,AI分别为0.39、0.70、0.51和0.54,联合作用为协同作用.     

Field trials of a TiO2 pellet‐based photocatalytic reactor for off‐gas treatment at a soil vapor extraction well

A field trial of a pilot‐scale TiO₂ photocatalytic reactor for treatment of off‐gases from a soil vapor extraction (SVE) well at a chlorinated solvent spill site at the Savannah River Site near Aiken, SC, is described. Trichloroethylene (TCE), perchloroethylene (PCE), 1,1‐dichloroethylene (1,1 ‐DCE), and 1,1,1 ‐trichloroethane (1,1,1 ‐TCA) were treated at flow rates up to 6 1/min and space times of 5.1 x 10⁷ to 1.2 x 10⁹ g/mol. The TiO₂ used was in the form of porous pellets with a surface area of 150 m²/g. Operation of the reactor with the undiluted waste stream (5000 ppmv) at 80, 100, and 110°C yielded many undesirable byproducts, such as phosgene, chloroform, carbon tetrachloride, and penta‐ and hexachloroethane, even though the conversion of PCE and TCE approached 100%. After diluting the waste stream with ambient air to below 1000 ppmv and maintaining space times around 5 x 10⁸ g/mol, a conversion >99.5% was achieved with the production of only small amounts (<10 ppmv) of hexachloroethane. The reactor was Operated continuously for 8 d, with no noticeable deterioration in catalyst activity. In a subsequent laboratory study to determine the mass balance, CO₂ determined in the reactor effluent accounted for 80% of the influent carbon.