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DIOXIN 2003 BOSTON
Citation:
Birnbaum, L S. DIOXIN 2003 BOSTON. Presented at Dioxin 2003, Boston, MA, August 24-29, 2003.
Description:
DIOXON 2003 BOSTON
SESSION SUMMARY REPORT
Toxicology of BFRs
This oral session is comprised of seven presentations dealing with the potential health effects of BFRs. Talks involve both in vivo and in vitro studies in mice, rats, and cultured cells, and are from eight different countries. The studies largely involve individual PBDE congeners, but some also include PCBs, TBBPA, and HBCD.
The first four papers focus on developmental effects of early life stage exposure. Per Eriksson and co-workers demonstrate that exposure of infantile mice during the period of rapid brain growth to BDE-99 and/or PCB-52 is associated with developmental neurotoxicity, and that these compounds can interact and enhance these effects at low doses. They suggest that there may be multiple mechanisms involved in the effects observed. The other three in vivo studies expose pregnant rats to BDE-99 and examine effects on the reproductive system of the offspring. Liechtensteiger et al. compared the effects of BDE-99 with those of Aroclor 1254 on sexual development, with a dual focus on regions of the brain involved in control of reproduction and the reproductive organs themselves. They observed alterations in puberty and effects on sex organ weights in the offspring when they reached adulthood. They also noted changes in the expression of certain estrogen-related genes. Interestingly, the effects of the commercial PCB mixture and the specific PBDE congener were not identical. They concluded that BDE-99 is an endocrine disruptor. Two papers from the laboratory of Chahoud also looked at effects on the reproductive system of rats whose mothers were treated with low doses (as low as a single dose of 60 ?g/kg) of BDE-99 during gestation. Talsness and co-workers observed effects on the ultrastructure of the ovary of the female offspring at adulthood, which resembled those seen following exposure to PTU, the classic anti-thyroid agent. Kuriyama and Chahoud examined the male offspring from the same study and observed changes in male sex organ weights indicative of an impairment of male fertility. They also noted a decrease in sperm number and decrease in T4 levels.
The remaining three papers involve in vitro studies of individual chemicals in various cell lines. They also examine the issue of whether these chemicals are dioxin-like in their effects. Jacobs et al. used data sets with 12 PBDE congeners relative to TCDD in six cell lines, involving induction of EROD and were analyzed using principle component analysis and partial least squares regression techniques. The PBDEs did not behave as TCDD, suggesting that any binding of PBDEs to the Ah receptor is via a different mechanism than TCDD. Peters and co-workers also looked at the dioxin-like effects of eight environmentally relevant PBDE congeners in human breast cancer cells. These common congeners were not Ah receptor agonists, supporting their lack of inclusion in the dioxin-TEF scheme. However, they could directly inhibit EROD activity, which is often used as a biomarker for Ah receptor activation. Canton et al. focused on the possible effects of environmentally relevant BFRs on sex hormone synthesis and metabolism. They observed that 6-OH-BDE-47, which has been found in human blood, can inhibit the activity of aromatase, an enzyme that catalyzes the conversion of androgens to estrogens, in human cells. However, neither TBBPA nor HBCD were active in this assay.
Thus, these papers support the hypothesis that certain BFRs have biological activity in multiple systems at low doses.
This abstract has been reviewed by the National Health and Environmental Research
Laboratory and cleared for presentation. It does not necessarily represent EPA policy.
PREPARED BY
LINDA S. BIRNBAUM
SESSION CHAIR
NHEERL/US EPA
RESEARCH TRIANGLE PARK, NC 27709
919-541-2655 PHONE
919-541-4284 FAX
BIRNBAU