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Growth and reproductive effects from dietary exposure to Aroclor 1268 in mink (Neovison vison), a surrogate model for marine mammals

Folland, William R; Newsted, John L; Fitzgerald, Scott D; Fuchsman, Phyllis C; Bradley, Patrick W; Kern, John; Kannan, Kurunthachalam; Remington, Richard E; Zwiernik, Matthew J
Polychlorinated biphenyls (PCBs) from the commercial mixture Aroclor 1268 were historically released into the Turtle-Brunswick River estuary (southeastern Georgia, USA) from industrial operations. Sum PCBs (ΣPCBs) in blubber samples from Turtle-Brunswick River estuary bottlenose dolphins (Tursiops truncatus) have been reported at concentrations more than 10-fold higher than those observed in dolphins from adjacent regional estuaries. Given that toxicity data specific to Aroclor 1268 and applicable to marine mammals are limited, predicting the toxic effects of Aroclor 1268 in dolphins is uncertain, particularly because of its unique congener profile and associated physiochemical characteristics compared with other PCB mixtures. American mink (Neovison vison) were chosen as a surrogate model for cetaceans to develop marine mammalian PCB toxicity benchmarks. Mink are a suitable surrogate species for cetaceans in toxicity studies because of similarities in diet and taxonomic class, and a characteristic sensitivity to PCBs provides a potential safety factor when using mink toxicology data for cross-species extrapolations. Effects of dietary exposure to Aroclor 1268 on reproduction, growth, and mortality in mink were compared with both a negative control and a positive control (3,3',4,4',5-pentachlorobiphenyl, PCB 126). Aroclor 1268 dietary ΣPCB concentrations ranged from 1.8 µg/g feed wet weight to 29 µg/g feed wet weight. Whelp success was unaffected by Aroclor 1268 exposure at any level. Treatment mean litter size, kit growth, and kit survival were adversely affected relative to the negative control at dietary ΣPCB concentrations of 10.6 µg/g feed wet weight and greater.
PMID: 26313468
ISSN: 1552-8618
CID: 4286282

Enzyme induction and histopathology elucidate aryl hydrocarbon receptor-mediated versus non-aryl hydrocarbon receptor-mediated effects of Aroclor 1268 in American mink (Neovison vison)

Folland, William R; Newsted, John L; Fitzgerald, Scott D; Fuchsman, Phyllis C; Bradley, Patrick W; Kern, John; Kannan, Kurunthachalam; Zwiernik, Matthew J
Polychlorinated biphenyl (PCB) concentrations reported in preferred prey and blubber of bottlenose dolphins from the Turtle-Brunswick River estuary (Georgia, USA) suggest the potential for adverse effects. However, PCBs in Turtle-Brunswick River estuary dolphins are primarily derived from Aroclor 1268, and predicting toxic effects of Aroclor 1268 is uncertain because of the mixture's unique composition and associated physiochemical characteristics. These differences suggest that toxicity benchmarks for other PCB mixtures may not be relevant to dolphins exposed to Aroclor 1268. American mink (Neovison vison) were used as a surrogate model for cetaceans to characterize mechanisms of action associated with Aroclor 1268 exposure. Mink share similarities in phylogeny and life history with cetaceans and are characteristically sensitive to PCBs, making them an attractive surrogate species for marine mammals in ecotoxicity studies. Adult female mink and a subsequent F1 generation were exposed to Aroclor 1268 through diet, and effects on enzyme induction, histopathology, thyroid hormone regulation, hematology, organ weights, and body condition index were compared to a negative control and a 3,3',4,4',5-pentachlorobiphenyl (PCB 126)-positive control. Aroclor 1268 dietary exposure concentrations ranged from 1.8 µg/g wet weight to 29 µg/g wet weight. Anemia, hypothyroidism, and hepatomegaly were observed in mink exposed to Aroclor 1268 beyond various dietary thresholds. Cytochrome P450 induction and squamous epithelial proliferation jaw lesions were low in Aroclor 1268 treatments relative to the positive control. Differences in enzyme induction and the development of squamous epithelial proliferation jaw lesions between Aroclor 1268 treatments and the positive control, coupled with effects observed in Aroclor 1268 treatments not observed in the positive control, indicate that mechanisms additional to the aryl hydrocarbon receptor-mediated pathway are associated with Aroclor 1268 exposure.
PMID: 26267837
ISSN: 1552-8618
CID: 4286252

Novel Finding of Widespread Occurrence and Accumulation of Bisphenol A Diglycidyl Ethers (BADGEs) and Novolac Glycidyl Ethers (NOGEs) in Marine Mammals from the United States Coastal Waters

Xue, Jingchuan; Kannan, Kurunthachalam
Bisphenol A diglycidyl ether (BADGE)- and bisphenol F diglycidyl ether (BFDGE)-based epoxy resins have a broad range of applications, including serving as inner coatings of food and beverage cans and as protective coatings in marine construction. Prior to this study, no studies had examined the occurrence and bioaccumulation of BADGEs or BFDGEs in aquatic organisms. In this study, BADGE, BFDGE, and nine of their derivatives were determined in 121 tissue (liver, kidney, blubber, and brain) samples from eight species of marine mammals collected from the U.S. coastal waters of Florida, California, Washington, and Alaska. BADGE·2HCl was the predominant compound found in the majority (78.5%) of the marine mammal tissues analyzed, at concentrations of up to 2950 ng/g (wet weight (wt)) found in the liver of a sea otter from Kachemak Bay, Alaska. The measured concentrations of BADGE·2HCl in marine mammals were on the order of hundreds of nanograms per gram tissue, which are some of the highest concentrations ever reported for this compound in biota. Males contained greater concentrations of BADGE·2HCl than did females. BADGE·2HCl also was found in the brain tissues of sea otters. Trace levels of BADGE·2HCl were found in the livers of polar bears from Alaska, which suggested that BADGEs are widely distributed in the oceanic environment.
PMID: 26800265
ISSN: 1520-5851
CID: 4286432

Eliciting parental support for the use of newborn blood spots for pediatric research

Yeung, Edwina H; Louis, Germaine Buck; Lawrence, David; Kannan, Kurunthachalam; McLain, Alexander C; Caggana, Michele; Druschel, Charlotte; Bell, Erin
BACKGROUND:Biomarkers of exposures such as infection or environmental chemicals can be measured in small volumes of blood extracted from newborn dried blood spots (DBS) underscoring their potential utility for population-based research. However, few studies have evaluated the feasibility and utility of this resource; particularly the factors associated with parental consent, and the ability to retrieve banked samples with sufficient remaining volume for epidemiologic research. METHODS:At 8 months postpartum, 5,034 mothers of infants born (2008-2010) in New York (57 counties excluding New York City) were asked to consent for the use of residual DBS for the quantification of cytokines and environmental chemicals. Mothers were part of the Upstate KIDS study, a longitudinal birth cohort designed to evaluate child development through 3 years of age. Information on parental and infant characteristics was obtained from birth certificates and maternal report at 4 months postpartum. Multivariate logistic regression was used to identify factors associated with parental consent and with successful retrieval of DBS. RESULTS:Sixty-two percent (n = 3125) of parents consented. Factors significantly associated with consent included non-Hispanic ethnicity (odds ratio 2.04; 95% CI: 1.43-2.94), parity (1.29; 1.05-1.57), maternal obesity (1.42; 1.11-1.80) and reported alcohol use during pregnancy (1.51; 1.12-2.06). However, these associations corresponded to small absolute differences in proportions (4 to 8%), suggesting that the two groups remained comparable. Infant characteristics such as preterm delivery did not significantly differ by consent status among singletons and only ventilator use (OR 2.39; 95% CI: 1.06-5.41) remained borderline significant among twins in adjusted analyses. Among consented infants, 99% had at least one 3.2 mm punch successfully retrieved for biomarker analyses and 84% had a full DBS circle available. CONCLUSION/CONCLUSIONS:Parental characteristics varied slightly by consent, and the availability of samples for research purposes was high, demonstrating the feasibility of this resource for population based research.
PMCID:4741027
PMID: 26846420
ISSN: 1471-2288
CID: 4286442

Fate of Parabens and Their Metabolites in Two Wastewater Treatment Plants in New York State, United States

Wang, Wei; Kannan, Kurunthachalam
Little is known about the occurrence and fate of parabens and their metabolites in wastewater treatment plants (WWTPs). In this study, mass loadings, removal efficiencies, and environmental emission of six parabens, four of their metabolites (4-hydroxy benzoate, 3,4-dihydroxy benzoate, methyl-protocatechuate, and ethyl-protocatechuate) and benzoic acid were studied based on the concentrations determined in wastewater influent, primary effluent, final effluent, suspended particulate matter (SPM), and sludge collected from two WWTPs (denoted as WWTP(A) and WWTP(B)) in the Albany area of New York State. The median respective concentrations of sum of parabens (Σparabens = 6 parent compounds) and paraben-metabolites (Σmetabolites = 4 metabolites) were 73.1-158 and 5460-10,000 ng/L in influents, and 1.96-5.57 and 2060-2550 ng/L in final effluents. The concentrations of Σmetabolites were significantly higher than those of Σparabens in sludge and SPM. The removal efficiencies for parabens (89.6-99.9%) were higher than those for their metabolites (25.9-90.6%). The respective mass loadings of parabens and their metabolites were 46.3 and 6210 mg/d/1000 people for WWTP(A) and 176 and 63,100 mg/d/1000 people for WWTP(B). The environmental emission of parabens and their metabolites through WWTP discharges was 4.85-6.16 and 1270-2050 mg/d/1000 people, respectively.
PMID: 26727649
ISSN: 1520-5851
CID: 4286412

Couples' urinary concentrations of benzophenone-type ultraviolet filters and the secondary sex ratio

Bae, Jisuk; Kim, Sungduk; Kannan, Kurunthachalam; Buck Louis, Germaine M
The secondary sex ratio (SSR), defined as the ratio of males to females at birth, has been investigated in relation to endocrine disruptors to search for environmental toxicants perturbing human sex selection. Benzophenone (BP)-type ultraviolet (UV) filters, which are used in sunscreens and personal care products, have been reported to exert estrogenic and anti-androgenic activities. This study aimed to evaluate the association between maternal, paternal, and couple urinary concentrations of BP-type UV filters and the SSR, given the absence of previous investigation. The study cohort comprised 220 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and who had a singleton birth during the follow-up period. Couples' urinary concentrations of five BP-type UV filters (ng/mL) were measured using triple-quadrupole tandem mass spectrometry: 2,4-dihydroxybenzophenone (BP-1), 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), and 4-hydroxybenzophenone (4-OH-BP). Modified Poisson regression models were used to estimate the relative risks (RRs) of a male birth for each BP-type UV filter, after adjusting for potential confounders. When maternal and paternal urinary BP-type UV filter concentrations were modeled jointly, both maternal BP-2 (2nd vs 1st tertile, RR, 0.62, 95% confidence interval [CI], 0.43-0.91) and paternal BP-2 (3rd vs 1st tertile, RR, 0.67, 95% CI, 0.45-0.99; p-trend, 0.04) were significantly associated with an excess of female births. Contrarily, maternal 4-OH-BP was significantly associated with an excess of male births (2nd vs 1st tertile, RR, 1.87, 95% CI, 1.27-2.74; 3rd vs 1st tertile, RR, 1.80, 95% CI, 1.13-2.87; p-trend, 0.02). Our findings provide the first evidence suggesting that BP-type UV filters may affect the SSR. However, future corroboration is needed, given the exploratory design of this study.
PMCID:4688162
PMID: 26575635
ISSN: 1879-1026
CID: 4286372

Phthalate metabolites in urine of Chinese young adults: Concentration, profile, exposure and cumulative risk assessment

Gao, Chong-Jing; Liu, Li-Yan; Ma, Wan-Li; Ren, Nan-Qi; Guo, Ying; Zhu, Ning-Zheng; Jiang, Ling; Li, Yi-Fan; Kannan, Kurunthachalam
Phthalates are widely used in consumer products. People are frequently exposed to phthalates due to their applications in daily life. In this study, 14 phthalate metabolites were analyzed in 108 urine samples collected from Chinese young adults using high-performance liquid chromatography-tandem mass spectrometry. The total concentrations of 14 phthalate metabolites ranged from 71.3 to 2670 ng/mL, with the geometric mean concentration of 306 ng/mL. mBP and miBP were the two most abundant compounds, accounting for 48% of the total concentrations. Principal component analysis suggested two major sources of phthalates: one dominated by the DEHP metabolites and one by the group of mCPP, mBP and miBP metabolites. The estimated daily intakes of DMP, DEP, DBP, DiBP and DEHP were 1.68, 2.14, 4.12, 3.52 and 1.26-2.98 μg/kg-bw/day, respectively. In a sensitivity analysis, urinary concentration and body weight were the most influential variables for human exposure estimation. Furthermore, cumulative risk for hazard quotient (HQ) and hazard index (HI) were evaluated. Nearly half of Chinese young adults had high HI values exceeding the safe threshold. This is the first study on the occurrence and human exposure to urinary phthalate metabolites with Chinese young adults.
PMID: 26575634
ISSN: 1879-1026
CID: 4286362

Bisphenol A in Urine of Chinese Young Adults: Concentrations and Sources of Exposure

Gao, Chongjing; Liu, Liyan; Ma, Wanli; Zhu, Ningzheng; Jiang, Ling; Ren, Nanqi; Li, Yi-Fan; Kannan, Kurunthachalam
Bisphenol A (BPA) is an endocrine disrupting environmental chemical. Urinary concentrations of BPA were measured in samples collected nationwide from Chinese young adults. The geometric mean urinary concentration of BPA in Chinese young adults was 2.23 ng/mL. The estimated daily exposure dose for BPA was 64.8 ng/kg bw/day. Contributions of various BPA sources to exposure in Chinese young adults were estimated. Dietary intake was the primary exposure pathway. The contribution of dietary intake, indoor dust, paper products and personal care products to BPA intake was 72.5 %, 0.74 %, 0.98 %, 0.22 % of the total exposure dose, respectively. This is the first study on the occurrence of BPA in young adults from most provinces and autonomous regions of China. The results can be used to establish a database for BPA exposure assessment for Chinese general population.
PMID: 26679324
ISSN: 1432-0800
CID: 4286402

Occurrence of phthalate diesters (phthalates), p-hydroxybenzoic acid esters (parabens), bisphenol A diglycidyl ether (BADGE) and their derivatives in indoor dust from Vietnam: Implications for exposure

Tran, Tri Manh; Minh, Tu Binh; Kumosani, Taha A; Kannan, Kurunthachalam
Phthalate diesters (phthalates), esters of p-hydroxybenzoic acid (parabens), and bisphenol A diglycidyl ether (BADGE) are used in personal care products, food packages, household products, or pharmaceuticals. These compounds possess endocrine-disrupting potentials and have been reported to occur in the environment. Nevertheless, no previous studies have reported the occurrence of these compounds in indoor dust from Vietnam. In this study, nine phthalates, six parabens, and four BADGEs were determined in indoor dust samples collected from Hanoi, Hatinh, Hungyen, and Thaibinh, in Vietnam. Total concentrations of phthalates, parabens, and BADGEs in indoor dust ranged from 3440 to 106,000 ng/g (median: 22,600 ng/g), 40-840 ng/g (median: 123 ng/g), and 23 to 1750 ng/g (median: 184 ng/g), respectively. Based on the measured median concentration of phthalates, parabens, and BADGEs in indoor dust, we estimated human exposure doses to these compounds through indoor dust ingestion for various age groups. The exposure doses to phthalates, parabens, and BADGEs decreased with age and ranged from 19.4 to 90.4 ng/kg-bw/d, 0.113-0.528 ng/kg-bw/d, and 0.158-0.736 ng/kg-bw/d, respectively. This is the first study on the occurrence and human exposure of phthalates, parabens, and BADGEs in indoor dust from Vietnam.
PMID: 26498104
ISSN: 1879-1298
CID: 4286342

Placental transfer of and infantile exposure to perchlorate

Zhang, Tao; Ma, Yufang; Wang, Dou; Li, Rudan; Chen, Xiaojia; Mo, Weiwen; Qin, Xiaolei; Sun, Hongwen; Kannan, Kurunthachalam
Fetuses and infants are vulnerable to perchlorate toxicity. We assessed fetal and infantile exposure to perchlorate in two Chinese cities (Nanchang and Tianjin). Perchlorate was widely found (82%-100%) in breast milk, dissolved infant formula, infants' urine, maternal and cord blood samples. Perchlorate levels in infants' urine (mean ± standard deviation: 22.4 ± 35.6 ng mL(-1)), breast milk (36.6 ± 48.1 ng mL(-1)), and cord blood (3.18 ± 3.83 ng mL(-1)) samples collected from Nanchang and Tianjin were approximately an order of magnitude higher than those reported for the U.S. Perchlorate concentrations in cord blood were comparable to that in maternal blood, indicating that perchlorate is transferred from mother to fetus through placenta. Among all infants providing urine samples, the average daily intake of perchlorate (DOSEU) was estimated to be 1.17 ± 1.57 μg kg(-1) bw d(-1), and 40% of these infants had DOSEU exceeding the RfD (0.7 μg kg(-1) bw d(-1)) recommended by U.S. EPA. However, approximately 70% of exclusively breast-fed infants had perchlorate exposure dose via breast milk exceeding the RfD. For breast-fed infants, breast milk was the overwhelmingly predominant exposure pathway; while infant formula and indoor dust ingestion were major perchlorate exposure sources for formula-fed infants. To our knowledge, this is the first report to assess the fetal and infantile exposure to perchlorate in China.
PMID: 26432537
ISSN: 1879-1298
CID: 4286322