Toxicoepidemiological insights into PCB metabolism and health outcomes in pregnant African American women

Specific determinants of PCB and DDE serum concentrations in a cohort of pregnant African American women were identified. In-vitro assays elucidated the role of metabolism in determinant-PCB relationships. Using the combined information, metabolism corrected exposure disease outcomes assessments were performed.; Data from the Great Lakes Cohort of Pregnant African American Women (GLCPAAW) (enrollment 1993-1998, n=254) was used. Assessment of exposure to PCBs and DDE through Great lakes sport fish eating was a study goal. Women filled out an extensive questionnaire and blood serum samples were obtained at delivery.; The primary serum PCB congeners found to be present were 101, 118, 138, 153, and 180. Spearman correlation and regression analysis identified the strongest determinants of serum PCB's in the GLCPAAW were age, fish ingestion, serum lipids, race/ethnicity, and smoking. Unlike the higher chlorinated congeners, PCB 101 and PCB 118, were determined by race and smoking.; In-vitro assays showed a loss of both PCB 101 and 118 parent compound when parent PCB congeners were incubated with human liver microsomes. No evidence of PCB 180 metabolism was found. The only PCB congener for which a metabolite was identified was PCB 101 in human liver microsome incubations. Incubations with individual human liver CYP 450 isoforms showed PCB 101 was specifically metabolized by CYP 2A6.; Outcomes investigated were maternal headache in the mothers and low birth weight in the newborns. By using a ratio of PCB 180 over 101, metabolism corrected exposure was assessed. Low birth weight was associated with higher ratios of PCB 180 over 101. Maternal headache was associated with significantly lower levels of PCB 101, 118, and 153. Stratification of low neonatal birth weight and maternal headache by each other showed significant interaction. Logistic regression models showed each natural log unit increase in 180/101 was associated with 4.8 higher odds of having a low birth weight child. Comparatively, women in the cohort with a smoking pack year history greater than 3 pack year had 6.4 higher odds than non-smokers of having a low birth weight child. The 180/101 ratio was not significantly associated with maternal headache. However, the odds of having maternal headache were significantly lower for the fourth (highest) quartile of serum PCB 101 compared to the first quartile. The data indicate that metabolism plays a fundamental role in the exposure disease relationship between PCBs and human health effects.