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POLYCHLORINATED BIPHENYL AND POLYCHLORINATED DIBENZOFURAN BIOMARKERS OF RISK ASSESSMENT IN ADOLESCENT CHILDREN AND THEIR MOTHERS
Description:
This is two cohort comparison study of endocrine and cytochrome P450 family 1 biomarkers for risk assessment of polychlorinalted biphenyls (PCBs)/polychlorinated dibenzofurans (PCDFs) induced developmental toxicities in the human. The subjects will be sexually mature adolescents exposed to high levels of PCBs/PCDFs since conception and their mothers. One cohort exposed to PCBs and PCDFs during childhood experienced diminished neurobehavioral function, birth defects, and abnormal sexual maturation; while the other cohort was not so severely affected during childhood. Each exposed subject and their mothers will be compared to their previously identified matched control subjects.
The cytochrome P450 family 1 biomarkers include in vivo activity of cytochrome P4501A2 as determined by the [13 C] caffeine breath test, Ah receptor levels in blood lymphocytes, cytochrome P43501A1 inducibility as well as the polymorphism of the CYP1A1 gene. The endocrine biomarkers included serum T4, T3, TSH, estrogen, testosterone, FSH & LH levels. The adverse human health effects that will be examined for or are already documented in these subjects are, abnormal or delayed sexual maturation including penis size and areolar width, sperm counts, abnormal ectodermal tissue development (chloracne, hyperpigmentation, dentition), growth, tympanic membrane perforations and scarring, medical history of recurrent illnesses including respiratory illnesses and otitis media, menstrual abnormalities, and abnormal neurobehavioral development.
The data will be analyzed to determine the relationship between the biomarkers and health effects, and the congener specific PCB/PCDF serum levels and biomarker level or human health outcome. Also, the effects of time of life when the exposure occurred (in utero or adult) and/or gender on biomarker level and human health outcome will be determined.
This study should assess the capacity of these most promising biomarkers to be predictive of human health risk and thereby help to reduce the uncertainty of risk assessment in some of the most sensitive organ systems (endocrine and liver) and in the most precious and sensitive population, the developing human.