Faculty Bibliography

The occurrence of 14 phthalate metabolites was found in human urine samples collected from seven Asian countries: China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam. Phthalate metabolites were found in all samples, indicating widespread exposure of humans to phthalates in these Asian countries. The highest total (the sum of 14 phthalates) phthalate metabolite concentrations were found in samples collected from Kuwait (median: 1050 ng/mL), followed in decreasing order by samples from India (389 ng/mL), China (234 ng/mL), Vietnam (133 ng/mL), Japan (120 ng/mL), Korea (117 ng/mL), and Malaysia (94.9 ng/mL). The creatinine-adjusted median concentrations of total phthalates for urine samples from Kuwait, India, China, Vietnam, Japan, Korea, and Malaysia were 692, 506, 289, 119, 103, 104, and 169 μg/g creatinine, respectively. Monomethyl phthalate (mMP), monoethyl phthalate (mEP), mono (2-isobutyl phthalate) (miBP), mono-n-butyl phthalate (mBP), and metabolites of di-(2-ethylhexyl) phthalate (DEHP) were the dominant compounds, collectively accounting for >95% of the total concentrations in the samples from the seven countries. The profiles of urinary phthalate metabolite concentrations varied among the samples collected from the seven countries. Urine samples from Kuwait contained the highest concentrations of mEP (median: 391 ng/mL), mBP (94.1 ng/mL), and the metabolites of DEHP (202 ng/mL), whereas samples from China and Japan contained the highest concentrations of miBP (50.8 ng/mL) and mMP (17.5 ng/mL), respectively. mEP was the predominant metabolite in urine samples from India and Kuwait (accounting for 49% of the total), mBP and miBP were the predominant compounds in samples from China (52%), and DEHP metabolites were the predominant compounds in samples from Korea (46%) and Vietnam (52%). Based on the urinary concentrations of mEP, mBP, miBP, and DEHP metabolites of the samples from the seven Asian countries, we estimated daily intake rates of diethyl phthalate (DEP), dibutyl phthalate (DBP), and DEHP. The results indicated that people in the seven Asian countries are exposed to DEP, DBP, and DEHP at levels well below the reference doses (RfD) suggested as unsafe by the U.S. Environmental Protection Agency (EPA). The estimated exposure doses to DEHP in Kuwait, however, were above the RfD recommended by the EPA.

Reports on residue levels and accumulation profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in human adipose tissue are scarce in Korea. In this study, concentrations and accumulation features of PCDD/Fs and DL-PCBs were determined in the samples of adipose tissue collected from Korean women in 2007-2008. The total dioxin-like toxic equivalent (TEQ) concentrations (3.4-42 pg g(-1) lipid wt) in Korean adipose tissues were similar to those reported in European and other Asian countries. The relative contributions of individual compounds to total TEQs were as follows: non-ortho PCBs (mean: 45%) > PCDFs (28%) > PCDDs (24%) > mono-ortho PCBs (3%), a pattern similar to those reported for seafoods in Korea. The dominant PCDD/F congeners found in adipose tissues were OCDD and 2,3,4,7,8-PeCDF and dominant PCBs were 118, 156 and 105. No correlation was found between subject's age and concentrations of dioxin-like contaminants. Body mass index was not correlated with concentrations of PCDD/Fs and was negatively (p < 0.001) correlated with concentrations of DL-PCBs. The results of this study provide baseline information on PCDD/Fs and DL-PCBs in adipose tissues of the general population in Korea.

Hair samples collected from e-waste recycling workers (n=23 males, n=4 females) were analyzed to assess occupational exposures to polybrominated diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) at a large e-waste recycling facility in Taizhou, eastern China. Hair samples from a reference population composed of residents of Shanghai (n=11) were analyzed for comparison. The mean concentration of ∑PBDEs (range, 22.8-1020 ng/g dw; mean, 157 ng/g dw) found in hair samples from e-waste recycling workers was approximately 3 times higher than the mean determined for the reference samples. The congener profiles of PBDEs in hair from e-waste recycling workers were dominated by BDE 209, whereas the profiles in the reference-population samples showed comparable levels of BDE 47 and BDE 209. Total PCDD/F concentrations in hair from e-waste workers (range, 126-5820 pg/g dw; mean, 1670 pg/g dw) were approximately 18-fold greater than the concentrations measured in hair from the reference population. Concentrations of PCDFs were greater than concentrations of PCDDs, in all of the hair samples analyzed (samples from e-waste and non-e-waste sites). Tetrachlorodibenzofurans (TCDFs) were the major homologues in hair samples. Overall, e-waste recycling workers had elevated concentrations of both PBDEs and PCDD/Fs, indicating that they are exposed to high levels of multiple persistent organic pollutants.

Siloxanes are used in a wide range of industrial applications, such as fuel additives, automotive polishes and waxes, and antifoaming agents, as well as in personal care products and biomedical devices. Despite the potential for environmental occurrence, few studies have reported sources and pathways of siloxanes in the environment. In this study, we determined concentrations of four cyclic siloxanes, namely, octamethylcyclotetrasiloxane (D₄), decamethylcyclopentasiloxane (D₅), dodecamethylcyclohexasiloxane (D₆), and tetradecamethylcycloheptasiloxane (D₇) as well as 13 linear siloxanes (L₄ to L₁₆), in sediments sampled from the Songhua River and in sewage sludge sampled from treatment plants that discharge wastewater into the Songhua River in northeastern China. Siloxanes were found in all of the sediment samples at total concentrations (sum of all cyclic and linear siloxanes) as high as 2050 ng/g dry weight (dw). The respective total concentration ranges for cyclic (D₄, D₅, D₆, and D₇) and linear (L₄ to L₁₆) siloxanes in sewage sludge were 602 to 2360 and 98 to 3310 ng/g dw. Cyclic siloxanes were found at greater concentrations than linear siloxanes in sediment samples. However, the summed concentrations of linear siloxanes were higher than the summed concentrations of cyclic siloxanes in sludge samples. Among cyclic siloxanes, D₇ and D₅ were the dominant compounds in both sediment and sludge. Among linear siloxanes, L₁₀ and L₁₁ together accounted for 55% of the total concentrations in sludge samples, and L₆ accounted for 30% of the total concentration in sediment samples. To our knowledge, this is the first report to document concentrations and compositions of organosiloxanes in sediments and sewage sludge from China.

The first survey of persistent organic pollutant (POP) concentrations in air across several Indian agricultural regions was conducted in 2006-2007. Passive samplers comprising polyurethane foam (PUF) disks were deployed on a quarterly basis at seven stations in agricultural regions, one urban site and one background site. The project was conducted as a sub-project of the Global Atmospheric Passive Sampling (GAPS) Network. In addition to revealing new information on air concentrations of several organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), the study has demonstrated the feasibility of conducting regional-scale monitoring for POPs in India using PUF disk samplers. The following analytes were detected with relatively high concentrations in air (mean for 2006 and 2007, pg/m(3)): α- and γ-hexachlorocyclohexane (HCH) (292 and 812, respectively); endosulfan I and II (2770 and 902, respectively); p,p'-DDE and p,p'-DDT (247 and 931, respectively); and for the sum of 48 PCBs, 12,100 (including a site with extremely high air concentrations in 2007) and 972 (when excluding data for this site).

Thyroid hormones (THs) play critical roles in the regulation of growth and development, including brain development, in both humans and animals. Until recently, TH levels were assayed with measurements in serum, using immunoassay (IA)-based methods. IA methods are sensitive but are compromised by the lack of adequate specificity. Furthermore, measurements of TH levels in blood do not necessarily reflect the levels and profiles found in critical organs such as the brain. Measurement of TH levels in the brain is critical for studies that assess the effects of environmental contaminants on TH homeostasis. In this study, we developed a selective and sensitive method for the analysis of six THs, l-thyroxine (T(4)), 3,3',5-triiodo-l-thyronine (T(3)), 3,3',5'-triiodo-l-thyronine (rT(3)), 3,5-diiodo-l-thyronine (3,5-T(2)), 3,3'-diiodo-l-thyronine (3,3'-T(2)), and 3-iodo-l-thyronine (3-T(1)), in the brain and thyroid gland (TG) using isotope ([(13)C]T(4))-dilution liquid chromatography (LC)/tandem mass spectrometry (MS/MS). Proteins in the (rat) brain and TG were digested by pronase, and THs were extracted with a solid-phase extraction method and analyzed by LC/MS/MS. The instrumental calibration range for each TH ranged from 0.5 to 200 ng/mL and showed excellent linearity (r > 0.9995). The instrumental detection limits for THs were in the range of 7.5-13.5 pg, in positive ion mode, and 13.5-16.5 pg, in negative ion mode. The optimized procedural recoveries for THs (except for 3-T(1)), spiked into a pig-brain matrix, were between 97.6% and 109%, with a coefficient of variation (CV) of 1.2-8.2%, for the brain, and between 96.4% and 101%, with a CV of 1.8-8.6%, for the TG. Concentrations of THs in the brain and TG of the five rats were 2.20-3.65 ng/g T(4), 1.56-2.20 ng/g T(3), and below the limit of detection (<LOD) for the other THs, in the brain, and 88.9-274 ng/mg T(4), 14.1-49.1 ng/mg T(3), 2.79-12.0 ng/mg rT(3), 0.176-0.535 ng/mg 3,5-T(2), 0.340-0.880 ng/mg 3,3'-T(2), and <LOD for 3-T(1), in the TG. This method can permit more comprehensive evaluation of TH homeostasis in the brain and other critical organs following exposure to environmental contaminants.

In the first part of a series of studies to account for perfluorooctane sulfonate (PFOS)-induced sheep red blood cell (SRBC)-specific immunoglobulin M (IgM) antibody suppression in mice, a survey of clinical and immunotoxicological endpoints was examined. Adult female B₆C₃F₁ mice were exposed orally for 28 days to a total administered dose (TAD) of 0, 0.1, 0.5, 1, or 5 mg PFOS/kg. Uterus wet weight was significantly decreased compared with control at the 5 mg/kg dose. No indications of wasting syndrome, malnutrition, alteration of thyroid homeostasis, or signs of overt toxicity were observed. Numbers of splenic CD19+/CD21⁻, CD19+/CD21+, B220+/CD40+, CD4+/CD154⁻, CD4+/CD154+, and MHC-II+ cells were not altered. Additionally, ex vivo interleukin-4 (IL-4), IL-5, and IL-6 production by in vitro anti-CD3- or phorbol myristate acetate-stimulated CD4+ T-cells was not affected. Ex vivo IL-6 production by B-cells was significantly increased by in vitro stimulation with either anti-CD40 or lipopolysaccharide. Increased IL-6 production by B-cells was the most sensitive endpoint assessed resulting in alterations at the lowest dose tested (0.1 mg/kg TAD) following anti-CD40 stimulation. Further studies are required to characterize effects on inflammatory markers such as IL-6 at environmentally relevant concentrations of PFOS and to determine the key events associated with PFOS-induced IgM suppression to address potential human health risks.

The levels of six perfluorocarboxylates (PFCAs), four perfloroalkylsulfonates (PFASs), and one sulfonamide were measured in paired samples of maternal serum, umbilical cord serum, and breast milk. The maternal and cord sera were strongly correlated with each other for all measured compounds (r>0.5 and p<0.01). Nevertheless, there was a significant difference in compound composition profile between the two sera matrices, with a more depletion of the longer chain compounds in cord serum. The transfer efficiency values from maternal to cord serum (TFCS/MS) decreased by 70% with each increasing unit of -CF2 chain within a PFCA group, and for perfluorooctanesulfonate (PFOS), by a half compared to perfluorooctanoate (PFOA). In contrast to the strong correlation in concentrations between the two sera matrices, the pattern of compounds in breast milk differed considerably with those in sera. Accordingly, compound- and matrix-specific transfer must be considered when assessing prenatal and postnatal exposure.

The present study examines BPA pharmacokinetics in neonatal rats following s.c. injection or oral delivery of 10 μg BPA/kg BW and compares susceptibility to estrogen-induced prostate intraepithelial neoplasia (PIN) following either exposure route. Serum BPA in PND3 rats was measured using HPLC-MS-MS. Free and total BPA at C(max) were 1.77 and 2.0 ng/ml, respectively following injection and 0.26 and 1.02 ng/ml, respectively following oral exposure. The AUC(0-2) for free and total BPA was 4.1-fold and 1.8-fold greater, respectively, in s.c. vs. oral delivery. While exposure route affected BPA metabolism, internal dosimetry following s.c. injection of 10 μg BPA/kg BW is similar to BPA levels observed in humans. Prostates from aged rats given s.c. or oral BPA neonatally and T+E implants as adults exhibited nearly identical, heightened susceptibility to PIN incidence and score as compared to neonatal oil-controls. These findings on prostate health are directly relevant to humans at current BPA exposure levels.

Synthetic musk compounds are used in a wide range of personal care and other consumer products. Despite this fact, few studies have reported the occurrence of synthetic musks in house dust or exposure of humans through the ingestion of indoor dust. In the present study, we determined the concentrations and profiles of two polycyclic musks (PCMs; Galaxolide(®) [HHCB] and Tonalide(®)), three nitro musks (NMs; musk ketone [MK], musk moskene [MM], and musk xylene [MX]), and one metabolite of HHCB (HHCB-lactone), in 88 indoor-dust samples from homes, dormitories, offices, and laboratories in China. In addition, we analyzed 12 dust samples collected from inside the housings of electrical/electronic devices that were located in 10 of the houses. Synthetic musks were detected in all of the dust samples analyzed, with total concentrations (sum of PCM and NM concentrations) varying from 4.42 to 688 ng g⁻¹ (mean ± SD: 126 ± 16.2 ng g⁻¹; median: 82.7 ng g⁻¹). HHCB was the predominant compound in all of the dust samples analyzed accounting on average for 42.2% of the total musk concentrations. Concentrations of synthetic musks in dust samples from homes and offices were higher than the concentrations found in samples from dormitories and laboratories. Concentrations of synthetic musks in dust samples increased with the increasing number of occupants in homes. Based on the concentrations, levels of exposure to musks by way of dust ingestion were calculated to be up to 25.8 ng d⁻¹ for adults and 138 ng d⁻¹ for toddlers.