Faculty Bibliography

Human exposure to poly- and perfluoroalkyl substances (PFASs) is widespread and has received considerable attention in recent years due to their link with adverse health outcomes, including bone health. Nevertheless, no earlier studies have reported serum PFAS concentrations, and their association with incident osteoporosis in populations in Saudi Arabia. In this clinical case-control study, serum samples collected from 208 individuals (n = 100 cases and n = 108 controls) aged 40-89 years from Jeddah, Saudi Arabia, were analyzed for 17 PFASs. Unconditional logistic regression was used to calculate odds ratios (ORs) for association between serum PFAS concentrations and osteoporosis, stratified by gender, age, serum calcium and vitamin D, previous history of fractures and thyroid disorders. Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorobutanoic acid (PFBA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), perfluoro-n-pentanoic acid (PFPeA) and perfluoroundecanoic acid (PFUnDA) were detected in >80% of serum samples analyzed. PFOS (overall median concentration: 5.08 ng/mL), PFHxS (1.49 ng/mL), PFOA (1.33 ng/mL) and PFNA (0.55 ng/mL) accounted for 94% and 80% of the total serum PFASs concentrations in cases and controls, respectively. Serum PFOA, PFNA and PFUnDA concentrations increased with age in Saudi women. Results from the crude models showed that individuals in the 2nd, 3rd and 4th quartiles of serum PFAS concentrations had 2.3-96-fold increase in odds of diagnosis for osteoporosis compared with those in the 1st quartile (rank order: PFUnDA > PFOA > PFNA > PFOS > PFHxS). Our results suggest that exposure to PFOA, PFOS, PFNA, PFHxS and PFUnDA was associated with osteoporosis in this sample of adult Saudi population.

BACKGROUND:Experimental evidence suggests that exposures to phthalates and bisphenols may interfere with processes related to glucose and lipid metabolism, insulin sensitivity, and body weight. Few studies have considered the possible influence of chemical exposures during pregnancy on maternal weight gain or metabolic health outcomes postpartum. OBJECTIVE:To examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with maternal weight gain 6 years postpartum. METHODS:We analyzed urine samples for bisphenol, phthalate and creatinine concentrations from early and mid-pregnancy in 1192 women in a large, population-based birth cohort in Rotterdam, the Netherlands, and examined postpartum weight gain using maternal anthropometrics before pregnancy and 6 years postpartum. We have used covariate-adjusted linear regressions to evaluate associations of early and mid-pregnancy bisphenols and phthalate metabolites with weight change. Mediator and interaction models have been used to assess the role of gestational weight gain and breastfeeding, respectively. Sensitivity analysis is performed among women without subsequent pregnancies. RESULTS:Among all 1192 mothers included in the analysis, each log unit increase in the average bisphenol A and all assessed phthalate groupings were associated with increased maternal weight gain. As a proxy for phthalate exposure, each log unit increase in averaged phthalic acid was associated with 734 g weight gain (95% CI 273-1196 g) between pre-pregnancy and 6 years postpartum. Mediation by gestational weight gain was not present. Breastfeeding and ethnicity did not modify the effects. Stratification revealed these associations to be strongest among overweight and obese women. Among women without subsequent pregnancies (n = 373) associations of bisphenols, HMW phthalate metabolites and di-2-ethylhexylphthalate metabolites attenuated. For phthalic acid, LMW phthalate metabolites and di-n-octylphthalate metabolites associations increased. Similarly to the whole group, stratification yielded significant results among overweight and obese women. DISCUSSION/CONCLUSIONS:In a large population-based birth cohort, early and mid-pregnancy phthalate exposures are associated with weight gain 6 years postpartum, particularly among overweight and obese women. These data support ongoing action to replace phthalates with safer alternatives.

Parabens are widely used as antimicrobial preservatives in personal care products (PCPs). Stretch mark cream is widely used by pregnant and lactating women for the treatment of striae gravidarum. This can be a potential source of paraben exposure, not only to pregnant/lactating women but also to fetuses/newborns. Little is known, however, with regard to the occurrence of parabens in stretch mark creams. In this study, we analyzed eight parabens and their metabolites in 31 popular stretch mark creams originated from various countries including China. The concentrations of Σparaben (sum of eight parabens/metabolites) ranged from 0.007 to 1630 μg/g, with mean and median values of 453 and 273 μg/g, respectively. Methyl- and propyl-parabens accounted for >95% of Σparaben concentrations. We examined the measured paraben concentrations against ingredients listed on the product labels. Parabens were listed as ingredients in those creams that contained concentrations >100 μg/g except for four samples with such high concentrations. Six cream samples that were labeled 'paraben-free' contained trace levels (0.007-9.92 μg/g) of these preservatives. Mean dermal ∑paraben exposure dose from the use of stretch mark creams (30.6 μg/kg bw/day) was well below the current acceptable daily intake value (5 mg/kg bw/day). In comparison to diet and indoor dust ingestion pathways, paraben-laden stretch mark cream may be a major source of paraben exposure in pregnant and lactating women. This study provides information on parabens and other preservatives in stretch mark creams and measures to reduce exposures during pregnancy and lactation.

BACKGROUND:Prenatal maternal plasma persistent organic pollutant (POP) concentrations have been associated with neonatal outcomes. However, the underlying mechanisms remain unknown. Placental epigenetic mechanisms may be involved, but no prior epigenome-wide studies have investigated the impact of maternal POPs on placental DNA methylation. We studied the association between maternal plasma POP concentration in early pregnancy and epigenome-wide placental DNA methylation among 260 pregnant women from the NICHD Fetal Growth Studies. RESULTS:). Out of the 214 CpG sites, 24 (11%) were significantly correlated with placental expression of 21 genes. Notably, higher PFUnDA was associated with increased methylation at 3 CpG sites (cg13996963, cg12089439, cg18145877) annotated to TUSC3, and increased methylation at those 3 CpG sites was correlated with decreased expression of TUSC3 in the placenta. Increased methylation at cg18145877 (TUSC3) and decreased expression of TUSC3 were correlated with shorter birth length. Out of the 214 CpG sites, methylation at 44 CpG sites was correlated (p value < 0.10) with at least one neonatal anthropometry measure (i.e., birth weight, birth length, and head circumference). Seven CpG sites mediated (p value < 0.05) the association between PBDE 47 and neonatal anthropometry measures. Genes annotating the top differentially methylated CpG sites were enriched in pathways related to differentiation of embryonic cells (PBDE 47) and in pathways related to brain size and brain morphology (PFASs). CONCLUSIONS:DNA methylation changes in the placenta were significantly associated with maternal plasma POPs concentration. The findings suggest that placental DNA methylation and gene expression mechanism may be involved in the prenatal toxicity of POPs and their association with neonatal anthropometry measures.

Neonicotinoids (NEOs) are insecticides that are widely used around the world. Following exposure, NEOs get metabolized in human bodies. The biomarkers to assess human NEO exposure are not well described because of the lack of information on the metabolites of NEOs (m-NEOs). In this study, five m-NEOs including N-desmethyl-acetamiprid (N-dm-ACE), 5-hydroxy-imidacloprid (5-OH-IMI), olefin-imidacloprid (Of-IMI), 1-methyl-3-(tetrahydro-3-furylmethyl) guanidine (DIN-G), and 1-methyl-3-(tetrahydro-3-furylmethyl) (DIN-U) were measured in 275 urine samples collected from 10 cities in China. All of the m-NEOs were frequently detected in urine samples with the median concentrations ranging from 0.42 (DIN-G) to 1.02 (5-OH-IMI) ng/mL. The urinary concentrations of N-dm-ACE and 5-OH-IMI measured in China were higher than those reported from Japan and the USA. In comparison to the parent NEO (i.e., acetamiprid, ACE; imidacloprid, IMI; and dinotefuran, DIN) concentrations reported in the same set of samples by our research group, the median ratios of m-NEO to the corresponding parent NEO (m-NEO/NEO) ranged from 4.95 (DIN-G/DIN) to 37.7 (N-dm-ACE/ACE), indicating that NEOs are mainly present as metabolites rather than the parent forms. Furthermore, the ratio of Σm-NEOs/ΣNEOs was significantly (p < 0.01) higher in females than in males, suggesting that NEOs are more readily metabolized in females or females are more highly exposed to m-NEOs. To our knowledge, this is the first study to measure Of-IMI, DIN-G, and DIN-U levels in urine samples from China. We recommend biomonitoring studies to include N-dm-ACE, 5-OH-IMI, and DIN-U (and DIN-G) for clear understanding of human exposure to ACE, IMI, and DIN, respectively.

BACKGROUND:Exposure to bisphenols and phthalates might influence bone health. We hypothesized that exposure to bisphenols and phthalates during fetal life has persistent effects on bone development. OBJECTIVES/OBJECTIVE:To analyze the associations of fetal exposure to bisphenols and phthalates with bone health in school-aged children. METHODS:Among 1,362 mother-child pairs participating in a population-based cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at first, second and third trimester with high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Total body bone mineral density (BMD) and bone area (BA) were measured using dual-energy X-ray absorptiometry (DXA) at 6 and 10 years, and were both used to calculate bone mineral content (BMC) and area-adjusted BMC (aBMC, a measure of volumetric BMD). RESULTS:and -0.12 (95% CI, -0.20 to -0.04) g). Maternal third trimester low molecular weight (LMW) phthalate concentrations were associated with higher aBMC at 6 years whereas, maternal third trimester di-n-octylphthalate (DNOP) concentrations were associated with lower aBMC at 10 years. However, these associations did not remain statistically significant after multiple testing correction. DISCUSSION/CONCLUSIONS:Maternal first trimester BPS concentrations are associated with lower BMD and aBMC in school-aged children. These findings should be considered as hypothesis generating and need further replication and exploration of potential underlying mechanisms.

Developmental exposure to bisphenol A (BPA) is associated with liver dysfunction and diseases in adulthood. The aims of this study were to assess the effects of prenatal BPA exposure on the hepatic transcriptome and proteome in female and male offspring and to understand adverse outcome pathways (AOPs) to observed phenotypic effects. Pregnant Wistar rats were exposed to 50 or 5000 μg BPA/kg bw/day, or 17β-estradiol (E2, 50 μg/kg bw/day) from embryonic day 3 to 18. The liver transcriptome and proteome profiles were analyzed in the newborn (postnatal day 1; PND1) and weaning (PND21) rat offspring. Based on the differentially expressed genes/proteins derived from transcriptome and proteome profiles, we performed pathway, transcription factor, and disease enrichment analyses. A principal component analysis of transcriptome data demonstrated that prenatal BPA exposure caused masculinization of the hepatic transcriptome in females. Both of transcriptomic and proteomic data showed that prenatal BPA exposure led to the disruption of cell cycle, lipid homeostasis, and hormone balance in offspring. Most of the effects at the transcript level were extended from newborn to weaning in males, but were moderated until weaning in females. The alterations at the transcript and protein levels were accordant with the observation of increases in body weight and anogenital distance and changes in hepatosomatic index in the offspring. Collectively, we constructed AOPs with evidence of sex- and age-specific actions of prenatal BPA exposure in the offspring.

Per- and polyfluoroalkyl substances (PFASs) are used in specialty/functional textiles to impart oil, water, and stain repellency. Little is known, however, with regard to the occurrence of PFASs in textiles including infant clothing. In this study, 13 perfluoroalkyl acids (PFAAs), comprising four perfluoroalkyl sulfonic acids (PFSAs; C4-C10) and nine perfluoroalkyl carboxylic acids (PFCAs; C4-C12) were determined in 160 textile samples collected from the United States. Two extraction methods, one involving a simple solvent extraction (i.e., before oxidation) and the other with an oxidative treatment (i.e., after oxidation) of textile extracts, were used. The sum concentrations of 13 PFAAs (i.e., ∑PFAA) in textile extracts before oxidation ranged from <LOD to 63.7 μg/m² (<LOD-285 ng/g), with a mean value of 3.18 μg/m² (14.2 ng/g). ∑PFAA concentrations were the highest in flame retarded textiles (n = 23; mean: 13.3 μg/m²; 59.4 ng/g), followed by water repellent textiles (n = 56; 2.88 μg/m²; 12.9 ng/g) and infant clothes (n = 81; 0.521 μg/m²; 2.33 ng/g). C4-C10 PFCAs accounted for at least three-quarters of the ∑PFAA content in our textile samples. Textile extracts analyzed after oxidative treatment exhibited ∑PFAA concentrations 10-fold higher than those in extracts analyzed prior to oxidation, which suggested that PFAA precursors are used in textiles. Precursors that generated C4-C5 PFCAs, upon oxidation, were more prevalent than those that yielded PFOA. The calculated dermal exposure doses in infants of PFAAs present in clothes were at least 1-2 orders of magnitude below the reference doses proposed by the United States Environmental Protection Agency. This is the first time that the oxidative treatment was applied in the analysis of PFASs in textiles, and our results suggest the existence of PFCA precursors in textiles.

Objective/UNASSIGNED:(rs7975232) with osteoporosis risk in the Saudi population. Methods/UNASSIGNED:< 0.05 considered as significant. Results/UNASSIGNED:= 0.01, respectively). Conclusion/UNASSIGNED:were found to be significantly determinant risk factors for osteoporosis progression in the Saudi population.

The need to dispose of dredged sediments and development of appropriate technology for their safe utilization has become a growing problem in recent years. It has been proposed that dredged, fresh sediments can be utilized in agriculture or environment; however there is also growing interest in the use of thermally-treated sediments. Hence, the aim of this study was threefold: 1) to evaluate the effect of two incineration temperatures (300 °C and 600 °C) on the chemical and ecotoxicological properties of sediment; 2) select the appropriate treatment for further phytoremediation experiments with zucchini; and 3) assess the impact of sediment admixture on the physico-chemical parameters of soil, based on the responses of Aliivibrio fischeri and growth of zucchini (Cucurbita pepo L. cv 'Black Beauty'). A range of chemical (inductively-coupled plasma optical emission spectrophotometry for macro- and trace elements; gas chromatography for polychlorinated biphenyls (PCBs)), ecotoxicological (Microtox assay), and plant morphology (biomass measurement) as well as physiological analyses (spectrophotometry for chlorophyll) were applied. River sediments incinerated at 600 °C resulted in better chemical and ecotoxicological properties than incinerated at 300 °C or no incinerated. Incineration at 600 °C removed PCBs from sediment. In culture experiments conducted with zucchini, sediment treated at 300 °C demonstrated a 51-81% reduction in PCB concentrations compared to untreated sediment. After four weeks of growth, the raw sediment showed a significant increase in K, Fe, Cr, Pb, Zn concentrations, whereas the thermally-processed sediment showed a decrease in Ca, Na, P, Cd, Cu, Ni, and Zn concentrations. Both the fresh and thermally-treated sediment types influenced plant growth positively: they demonstrated higher biomass production than plants grown in control soil; however, plants grown on soil with thermally-processed sediment demonstrated lower biomass than those grown in raw sediment. Chlorophyll content was affected negatively by admixtures of soil with treated or untreated sediment, while a lower chlorophyll a/b ratio was observed in plants grown on an admixture of thermally-treated sediment with soil. Our findings suggest that the use of sediments as a growth medium component may be a promising way for their utilization and transformation from waste material to a valuable resource enhancing the benefits to the environment.