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Extramural Papers of the Month

By Jerry Phelps
May 2010

Flame Retardants Linked to Reduced Human Fertility

Women exposed to high levels of flame retardants take longer to become pregnant, according to an NIEHS funded study at the University of California Berkeley. This is the first study to show decreases in human fertility related to the chemicals.

Polybrominated diphenyl ethers, or PBDEs, are a class of flame retardants found in many consumer products such as foam cushions in furniture, carpet padding, clothing, and electronics. The compounds are essentially ubiquitous in the environment and some consumer products contain as much as 90 percent PBDEs by weight.

In the current study, more than 97 percent of the women participating in the study had measureable levels of PBDEs in their blood. The analysis was limited to four congeners detected in more than 75 percent of the population. Increased levels of the compounds were associated with longer time to pregnancy. With each 10-fold increase in the blood level, the odds of becoming pregnant dropped by 30 percent. None of the women in the study were infertile, and on average they took about 3 months to become pregnant. However, PBDEs may be pushing some women into a sub-fertile zone making it more difficult for them to conceive. About 15 percent of the women in the study took longer than 12 months to conceive.

Citation: Harley KG, Marks AR, Chevrier J, Bradman A, Sjödin A, Eskenazi B.( Exit NIEHS 2010. PBDE Concentrations in Women's Serum and Fecundability. Environ Health Perspect. Jan 26. [Epub ahead of print]

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Beauty Chemicals Tied to Early Puberty in Girls

Exposure to three common classes of chemicals in young girls may disrupt the timing of pubertal development, according to a multi-city epidemiologic study of young girls. The authors conclude that these exposures may put these girls at risk for health complications later in life.

Girls 6-8 years old were enrolled in the study beginning in 2004 from New York City, Cincinnati, and northern California. Urine samples were analyzed for phenols, phthalates, and phytoestrogens and compared to breast and pubic hair development assessed as the girls got older. The data show that the three different classes of chemicals were widely detectable in the study population and that exposure to certain chemicals was associated with early breast development. Use of personal care products such as lotions and shampoo that contain phthalates, especially formulations with fragrance, was associated with early breast and pubic hair development.

Previous research has shown that early pubertal development in girls can have adverse social and medical effects including cancer and diabetes later in life. The current research demonstrates an association between chemicals that girls are exposed to on a frequent basis and early puberty. While the researchers conclude that more research is needed, these data are an important first step in evaluating the effects of these common agents and future health risks.

Citation: Wolff MS, Teitelbaum SL, Pinney SM, Windham G, Liao L, Biro F, Kushi LH,Erdmann C, Hiatt RA, Rybak ME, Calafat AM; Breast Cancer and Environment Research Centers.( Exit NIEHS 2010. Investigation of Relationships between Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols and Pubertal Stages in Girls. Environ Health Perspect. Mar 22. [Epub ahead of print]

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Mother's Exposure to Urban Air Pollutants Affects Children's Cognitive Abilities

An NIEHS-supported study carried out in Krakow, Poland reports prenatal exposure to air pollutants adversely affected the cognitive development of children at age five. These findings confirm a similar study conducted earlier in New York City.

The study was conducted in a cohort of 214 children born to healthy non-smoking women in Krakow, Poland between 2001 and 2006. During pregnancy, the mothers wore small backpack mounted personal air monitors to estimate their babies' exposures to polycyclic aromatic hydrocarbons (PAHs). PAHs are released into the air as fossil fuels are burned for purposes such as transportation, heating, and energy production. Exposure to these compounds is widespread in urban environments throughout the world.

At age five, the children took a standard intelligence examination. They were divided into two groups: children with exposures higher and lower than the median prenatal exposure to PAHs (17.96 nanograms/cubic meter of air). Children in the high exposure group scored worse on the intelligence exam by about 4 IQ points. This effect was comparable to the study conducted with the New York City children and is similar to studies on lead poisoning. The finding is of concern because IQ is an important predictor of future academic and economic performance.

Citation: Edwards SC, Jedrychowski W, Butscher M, Camann D, Kieltyka A, Mroz E, et al.( Exit NIEHS 2010. Prenatal Exposure to Airborne Polycyclic Aromatic Hydrocarbons and Children's Intelligence at Age 5 in a Prospective Cohort Study in Poland. Environ Health Perspect. Apr 14. [Epub ahead of print]

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Key to Hormone-Resistant Prostate Tumors Discovered

NIEHS-supported researchers at the University of California San Diego have found that prostate cancer treatments designed to suppress or block the production of male hormones trigger an inflammatory response that could be partly responsible for the development of resistance to these therapies within 12-18 months. These findings make a strong case for combining androgen ablation therapy with drugs already commercially available that block lymphotoxin signaling in B cells.

Androgen suppression can be achieved by surgical removal of the testicles, by taking female sex hormones, or by taking other androgen suppressors. Using a mouse model of prostate cancer, the researchers demonstrated that androgen deprivation killed tumor cells but caused them to release proinflammatory factors. This release led to the infiltration of the tumor by leukocytes. Further studies implicated B cells and the lymphotoxin they produced as promoters of castration-resistance prostate cancer.

Several strategies to deplete B cells in mice all delayed the growth of castration-resistant prostate cancer, which is the most malignant and aggressive form of the disease. The current study used two mouse models, but the investigators have already confirmed their finding with human prostate cancer tissues. The researchers note that extrapolation of their findings to humans suggests that castration-resistant prostate cancer could be delayed by about three years when the B cell depletion therapy is incorporated into standard treatments.

Citation: Ammirante M, Luo JL, Grivennikov S, Nedospasov S, Karin M.( Exit NIEHS 2010. B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature 11:464(7286):302-305.

(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training.)

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