Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review.

Abstract

At the request of the U.S. Environmental Protection Agency (U.S. EPA), the National Toxicology Program organized an independent and open peer review to evaluate the scientific evidence on low-dose effects and nonmonotonic dose-response relationships for endocrine-disrupting chemicals in mammalian species. For this peer review, "low-dose effects" referred to biologic changes that occur in the range of human exposures or at doses lower than those typically used in the standard testing paradigm of the U.S. EPA for evaluating reproductive and developmental toxicity. The demonstration that an effect is adverse was not required because in many cases the long-term health consequences of altered endocrine function during development have not been fully characterized. A unique aspect of this peer review was the willing submission of individual animal data by principal investigators of primary research groups active in this field and the independent statistical reanalyses of selected parameters prior to the peer review meeting by a subpanel of statisticians. The expert peer-review panel (the panel) also considered mechanistic data that might influence the plausibility of low-dose effects and identified study design issues or other biologic factors that might account for differences in reported outcomes among studies. The panel found that low-dose effects, as defined for this review, have been demonstrated in laboratory animals exposed to certain endocrine-active agents. In some cases where low-dose effects have been reported, the findings have not been replicated. The shape of the dose-response curves for reported effects varied with the end point and dosing regimen and were low-dose linear, threshold-appearing, or nonmonotonic. The findings of the panel indicate that the current testing paradigm used for assessments of reproductive and developmental toxicity should be revisited to see whether changes are needed regarding dose selection, animal-model selection, age when animals are evaluated, and the end points being measured following exposure to endocrine-active agents.

Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

“…In fetuses and neonates, Taylor et al (2008) observed low levels of the enzyme that conjugate BPA (uridine diphosphate-glucuronosyl-transferase), implying that both oral and non-oral administration of BPA during neonatal life provide the same internal active dose. The EPA-National Toxicology Program's Report of the Endocrine Disruptors-USA (U.S.EPA 1993) has defined the LOAEL dose for BPA as 50 mg/kg per day and the 'safe dose' as 1000 times lower (50 mg/kg per day) (Melnick et al 2002, Shelby 2008. In this work, we used the safe dose of BPA and a dose 100 times lower.…”

Developmental estrogen exposures predispose to prostate carcinogenesis with aging☆

“…However, no histopathologic abnormalities were observed in young adulthood. Furthermore, the low-dose estrogenic response in the prostate gland has not been consistently reported (71), due in part to species/strain differences, background estrogen levels and other experimental variables, and is a matter of considerable debate (72,73). To examine this issue in the neonatal rat model, we administered estradiol over a 7-log range of doses on neonatal days 1, 3 and 5 in both Sprague-Dawley rats and the more estrogen-sensitive Fischer 344 rats (74).…”

Emission patterns and risk assessment of polybrominated diphenyl ethers and bromophenols in water and sediments from the Beijiang River, South China

“…Bisphenol A (BPA), another environmental estrogen and an endocrine disruptor, is a synthetic chemical primarily used to produce polycarbonate plastics and epoxy resins (Cooper et al, 2008;EC, 2003;Melnick et al, 2002). Due to the diverse uses of BPA in consumer products, it has been regularly detected in a wide range of environmental matrices, including air, water, sewage sludge and sediments (Huang et al, 2012;Lee et al, 2013;Xiong et al, 2015), even human blood and tissues (Vandenberg et al, 2010;Zhang et al, 2013).…”