ObjectivesOur objectives in this study were to expand a previously reported U.S. market basket survey using a larger sample size and to estimate levels of PBDE intake from food for the U.S. general population by sex and age.MethodsWe measured concentrations of 13 polybrominated diphenyl ether (PBDE) congeners in food in 62 food samples. In addition, we estimated levels of PBDE intake from food for the U.S. general population by age (birth through ≥60 years of age) and sex.ResultsIn food samples, concentrations of total PBDEs varied from 7.9 pg/g (parts per trillion) in milk to 3,726 pg/g in canned sardines. Fish were highest in PBDEs (mean, 1,120 pg/g; median, 616 pg/g; range, 11.14–3,726 pg/g). This was followed by meat (mean, 383 pg/g; median, 190 pg/g; range, 39–1,426 pg/g) and dairy products (mean, 116 pg/g; median, 32.2 pg/g; range, 7.9–683 pg/g). However, using estimates for food consumption (excluding nursing infants), meat accounted for the highest U.S. dietary PBDE intake, followed by dairy and fish, with almost equal contributions. Adult females had lower dietary intake of PBDEs than did adult males, based on body weight. We estimated PBDE intake from food to be 307 ng/kg/day for nursing infants and from 2 ng/kg/day at 2–5 years of age for both males and females to 0.9 ng/kg/day in adult females.ConclusionDietary exposure alone does not appear to account for the very high body burdens measured. The indoor environment (dust, air) may play an important role in PBDE body burdens in addition to food.

Elevated levels of polybrominated diphenyl ethers (PBDEs), a type of brominated flame retardant, were recently detected in U.S. nursing mothers' milk. These halogenated compounds chemically and toxicologically resemble others such as polychlorinated biphenyls (PCBs), whose route of intake is almost exclusively through food of animal origin. This study is the first to report the levels of PBDEs in U.S. foods in a market basket survey of 30 food types (total of 32 food samples) from three major supermarket chains in Dallas, TX. Food samples were almost exclusively foods of animal origin: meat, fish, and dairy products. Thirteen PBDE congeners were measured for each sample. Levels were then compared to existing PBDE food studies from other countries where available. In this study, levels of PBDEs are highest in fish, then meat, and lowest in dairy products; median levels were 1725 (range 8.5-3078), 283 (range 0.9-679), and 31.5 (0.2-1373), parts per trillion (ppt), or pg/g, wet weight, respectively. Nonfat milk did not have any detectable PBDE levels. In fish, PBDE congener 47 (2,2',4,4'-tetraBDE) contributes up to 70% of the total PBDEs, followed by congeners 100 (2,2',4,4',6) and 99 (2,2',4,4',5). In meat congener 99 predominates, followed by 47. In dairy, BDE 47 predominates followed by 99. U.S. food PBDE levels measured in this study are higher than reported in two other published market based studies from Spain and Japan. Although these findings are preliminary and will be updated with analyses of new samples, they suggest that food is a major route of intake for PBDEs.

Polybrominated diphenyl ethers (PBDEs), a type of brominated flame retardant chemically and toxicologically similar to polychlorinated biphenyls (PCBs), are a class of emerging environmental and human contaminants. They have recently been detected in U.S. milk, blood, and food at the highest levels in the world. This pilot study was undertaken with the aim of determining levels of PBDE in the U.S. indoor environment, to assess the potential exposure to PBDEs from computer surfaces and carpets. Food of animal origin is the usual source of polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofurans (PCDF), and PCBs in humans, but there may also be environmental sources for intake of PBDEs. It was also our aim to characterize the PBDE congener profile in these indoor environmental samples. Four computer wipe samples and 9 domestic vacuum-sweeping samples were analyzed for 13 PBDE congeners, PBDEs 17 (2,2',4), 28 (2,4,4'?), 47 (2,2',4,4'?), 66 (2,3',4,4'?), 77 (3,3',4,4'?), 85 (2,2',3,4,4'?), 99 (2,2'4,4',5), 100 (2,2',4,4',6), 138 (2,2',3,4,4',5'?), 153 (2,2',4,4',5,5'?), 154 (2,2',4,4',5,6'?), 183 (2,2',3,4,4',5',6), and 209 (2,2',3,3',4,4',5,5',6,6'?). All samples tested positive for PBDEs. PBDE 209 was the dominant congener in all 4 computer wipe samples and in 7 out of the 9 vacuum dust samples. The congener profiles observed in this study varied considerably, a finding that has been observed previously. However these congener profiles differ from the pattern seen in U.S. human milk, human blood and in food, where PBDEs 47 and 99 predominate.

The proper balance of excitatory and inhibitory neurons is crucial for normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors (TFs), Ascl1 and Ptf1a, have contrasting functions in specifying these neurons. To understand how Ascl1 and Ptf1a function in this process, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a directly regulate distinct homeodomain TFs that specify excitatory or inhibitory neuronal fates. In addition, Ascl1 directly regulates genes with roles in several steps of the neurogenic program, including Notch signaling, neuronal differentiation, axon guidance and synapse formation. By contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Ascl1 and Ptf1a bind sequences primarily enriched for a specific E-Box motif (CAGCTG) and for secondary motifs used by Sox, Rfx, Pou and homeodomain factors. Ptf1a also binds sequences uniquely enriched in the CAGATG E-box and in the binding motif for its co-factor Rbpj, providing two factors that influence the specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding of how these DNAbinding proteins function in neuronal development, particularly as key regulators of homeodomain TFs required for neuronal subtype specification.

Under a mandate from the U.S. Congress, the National Toxicology Program (NTP) of the U.S. Department of Health and Human Services conducts animal bioassays for carcinogenicity of potentially toxic chemicals to which the U.S. population might be exposed. Methyleugenol, a natural as well as synthesized substance, was nominated for study because it is structurally similar to safrole, a known animal carcinogen. Methyleugenol was found to be a very potent multisite carcinogen in male and female F344/N rats and B6C3F1 mice at all doses tested in 2-year NTP bioassays using gavage dosing. For this reason, human toxicokinetic studies were added to the traditional NTP protocol. A commercial brand of gingersnaps was found by chemists at the Centers for Disease Control and Prevention to contain a relatively high concentration of methyleugenol. After thorough scientific and clinical review, and approval by a National Institutes of Health institutional review board for the protection of human subjects, a study was conducted with nine healthy adult male and female human volunteers. The volunteers were given 12 gingersnaps for breakfast. Blood was drawn immediately before the meal and at 15, 30, 60, and 120 min afterward. The mean +/- SD fasting level of methyleugenol in serum was 16.2 +/- 4.0 pg/g wet weight. Peak blood levels were found at 15 min (mean +/- SD, 53.9 +/- 7.3 pg/g wet weight), followed by a rapid decline; the half-life of elimination was about 90 min. The peak levels were within the range of methyleugenol blood levels in the U.S. population, as measured concurrently in a subset of nonfasting participants in the Third National Health and Nutrition Examination Survey (NHANES III).