Title: Organic Pollutants, Children's Health, and Reproductive Health
New Research Direction: Pharmaceuticals and Personal Care Products in the Aquatic Environment
Although these compounds are ubiquitously used and therefore present in our environment, there is little human data on exposure and body burden. Through pilot funding, members of the Organic Core have recently completed a preliminary study that prioritized the risk of these compounds in the aquatic environment. In addition, we held a half-day symposium on personal care products and pharmaceuticals in the environment. The symposium was well-attended and we anticipate that it will foster inter-departmental and inter-Center collaborations on this novel topic area.
Organochlorines and Reproductive Health among Women
We are exploring the relationship of organochlorines with women's reproductive health among Chinese textile workers. Over the past year we have demonstrated a number of important findings. First, we demonstrated a positive, monotonic, exposure-response association between preconception serum DDT levels and the risk of subsequent early (pre-clinical) pregnancy loss (OR=1.17, 95% CI: 1.05, 1.29 for each 10 ng/g increase in serum DDT). This finding is of note given that previous studies have been unable to detect pre-clinical losses; furthermore, previous inconsistencies in findings for DDT-associated risk of clinical miscarriage may be a consequence of more potent DDT-associated increased risk of pre-clinical losses. Second, we demonstrated an inverse association of serum DDT with BMI among these lean, reproductive age women prior to pregnancy, an association consistent with distribution and elimination kinetics characteristic of relatively recent peak DDT exposures. Furthermore, there was evidence of significant secular declines in exposure risk in this population consistent with declining agricultural uses of DDT in China. Lastly, we have demonstrated DDT-associated declines in fetal growth (assessed by birth size measures) among infants born to the textiles workers. The DDT metabolite, p,p'-DDD, was primarily responsible for the observed DDT-fetal growth associations suggesting potential differential toxicity among DDT forms.
Organophosphate Exposure and Semen Quality
We conducted a case control study of OP exposure and semen quality among Chinese men. 367 urine samples with sperm concentration and motility were available for analysis. Motility and concentration distributions were regressed after adjusting for age, alcohol drinking, passive smoking, education, occupational chemical exposures, active smoking, abstinence from sexual activity, and time delay from ejaculation to laboratory analysis of sperm. Cases were defined as those below the median percent motile and median concentration whereas controls were defined as above the median for motility and concentration. 94 and 95 cases and controls were identified respectively and urinalyses were performed to analyze levels of OP metabolites. Covariates in the adjusted model included age, self reported alcohol use, passive smoke exposure, education, occupational exposure to chemicals, current smoking, and abstinence days as well as time from sperm sample collection to lab analysis. After adjustment, men with lower semen quality (cases) had significantly higher levels of dimethylphosphate (DMP) urinary metabolites as compared to men with higher semen quality (controls).
Phthalates and Reproductive Health
An important, but understudied, area in environmental health sciences is the potential adverse human health affects of exposure to modern chemicals. Although modern chemistry and the subsequent birth of synthetic chemicals date back many decades, we continue to have a limited understanding of the potential clinical and public health impact of these ubiquitous chemicals of modern life. Chemicals are widely used in products of everyday life, such as in plastics to make them soft and flexible, in personal care products to hold scent and as a preservative, and in a variety of building products. They are also used in food packaging and processing materials and a variety of toys and products for babies and young children. Among the 80,000 or so chemicals of modern life, there is a subset that is hormonally active, defined as chemicals that alter endocrine signaling at low levels of exposure. As a result of altered endocrine signaling, there may be adverse effects on reproductive health, specifically fertility, as well as on pregnancy and birth outcomes.
The Third National Report on Human Exposure to Environmental Chemicals, conducted by the Centers for Disease Control and Prevention, National Center for Health Statistics, found that a majority of the U.S. general population is exposed to phthalates. This included men and women of reproductive age, as well as children. Evidence of the ability of phthalates to affect reproductive function and pregnancy come from studies in experimental animals and wildlife. More recently, in vitro and in vivo studies have begun to elucidate the molecular mechanisms of adverse action of these chemicals. However, clinical and epidemiologic studies are just beginning to determine the potential health risks of these classes of modern chemicals, particularly in relation to fertility and pregnancy loss.
We were one of the first to determine the relationships of urinary concentrations of phthalate metabolites with traditional measures of semen quality (sperm concentration, motility and morphology) and sperm DNA damage. We recruited 463 male partners of sub-fertile couples who presented to the Massachusetts General Hospital Fertility Center for evaluation of treatment. We found significant dose-response relationships of monobutyl phthalate with low sperm concentration and motility. There was suggestive evidence of an association between the highest MBzP quartile and low sperm concentration. We also recently published data on the relationship between urinary phthalates, specifically mono(2-ethylhexyl) phthalate and sperm DNA damage, measured with the neutral comet assay. Men that were poor metabolizers of phthalates to the oxidative metabolites were found to be at increased risk of sperm DNA damage for a given exposure to di(2-ethylhexyl) phthalate.
Publications:
Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, Calafat AM. DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Human Reprod. 2006; doi: 10.1093/humrep/del428.
Hauser R, Meeker JD, Duty S, Silva M, Calafat A. Altered semen quality in relation to urinary levels of phthalate monoester and oxidative metabolites. Epidemiology. 2006; 17:682-91.
Meeker JD, Barr DB, Hauser R. Thyroid hormones in relation to urinary metabolites of non-persistent insecticides in men of reproductive age. Reprod Toxicol. 2006; 22:437-42.
Perry MJ, Ouyang F, Chen C, Venners S, Korrick S, Xu X, Lasley B, Wang X. A prospective study of serum DDT and progesterone and estrogen levels across the menstrual cycle in nulliparous women of reproductive age. Am J Epidemiol. 2006; 164(11):1056-64.
Sagiv SK, Tolbert PE, Altshul LM, Korrick SA. Organochlorine exposures during pregnancy and infant size at birth. Epidemiology. 2007; 18:120-9.
Weuve J, Sánchez BN, Calafat AM, Schettler T, Green R, Hu H, Hauser R. Exposure to phthalates in neonatal intensive care unit infants: urinary levels of monoesters and oxidative metabolites. Environ Health Perspect. 2006; 114:1424-31.