Personal environmental exposure to plasticizers and organophosphate flame retardants using silicone wristbands and urine: Patterns, comparisons, and correlations.

Plasticizers (PLs) and organophosphate flame retardants (OPFRs) are ubiquitous in the environment due to their widespread use and potential for leaching from consumer products. Environmental exposure is a critical aspect of the human exposome, revealing complex interactions between environmental contaminants and potential health effects. Silicone wristbands (SWBs) have emerged as a novel and non-invasive sampling device for assessing personal external exposure. In this study, SWBs were used as a proxy to estimate personal dermal adsorption (EDdermal) to PLs and OPFRs in Belgian participants for one week; four morning urine samples were also collected and analyzed for estimated daily intake (EDI). The results of the SWBs samples showed that all the participants were exposed to these chemicals, and the exposure was found to be highest for the legacy and alternative plasticizers (LP and AP), followed by the legacy and emerging OPFRs (LOPFR and EOPFR). In urine samples, the highest levels were observed for metabolites of diethyl phthalate (DEP), di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DnBP) among LPs and di(2-ethylhexyl) terephthalate (DEHT) for APs. Outliers among the participants indicated that there were other sources of exposure that were not identified. Results showed a significant correlation between EDdermal and EDI for DiBP, tris (2-butoxyethyl) phosphate (TBOEP) and triphenyl phosphate (TPhP). These correlations indicated their suitability for predicting exposure via SWB monitoring for total chemical exposure. The results of this pilot study advance our understanding of SWB sampling and its relevance for predicting aggregate environmental chemical exposures, while highlighting the potential of SWBs as low-cost, non-invasive personal samplers for future research. This innovative approach has the potential to advance the assessment of environmental exposures and their impact on public health.

Investigation of in vitro biotransformation of tris (1-chloro-2-propyl) phosphate and confirmation in human urine.

Tris (1-chloro-2-propyl) phosphate (TCIPP) is one of the major organophosphate flame retardants present in the indoor and outdoor environment. Knowledge of biotransformation pathways is important to elucidate potential bioavailability and toxicity of TCIPP and to identify relevant biomarkers. This study aimed to identify TCIPP metabolites through in vitro human metabolism assays and finally to confirm these findings in urine samples from an occupationally exposed population to propose new biomarkers to accurately monitor exposure to TCIPP. TCIPP was incubated with human liver microsomes and human liver cytosol to identify Phase I and Phase II metabolites, by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Using a suspect-screening approach, the established biomarkers bis (1-chloro-2-propyl) hydrogen phosphate (BCIPP) and 1-hydroxy-2-propyl bis (1-chloro-2-propyl) phosphate (BCIPHIPP) were identified. In addition, carboxyethyl bis (1-chloro-2-propyl) phosphate (TCIPP-M1), bis (1-chloropropan-2-yl) (-oxopropan-2-yl) phosphate (TCIPP-M2) and 1-chloro-3-hydroxypropan-2-yl bis (1-chloropropan-2-yl) phosphate (TCIPP-M3) were identified. TCIPP-M2, an intermediate product, was not reported before in literature. In urine samples, apart from BCIPP and BCIPHIPP, TCIPP-M1 and TCIPP-M3 were identified for the first time. Interestingly, BCIPP showed the lowest detection frequency, likely due to the poor sensitivity for this compound. Therefore, TCIPP-M1 and TCIPP-M3 could serve as potential additional biomarkers to more efficiently monitor TCIPP exposure in humans.

Exposure to organophosphate flame retardants and plasticizers is positively associated with wheeze and FeNO and eosinophil levels among school-aged children: The Hokkaido study.

Exposure to organophosphate flame retardants and plasticizers (PFRs) increases the risk of asthma and allergies. However, little is known about its association with type 2 inflammation (T2) biomarkers used in the management of allergies. The study investigated associations among urinary PFR metabolite concentrations, allergic symptoms, and T2 biomarkers. The data and samples were collected between 2017 and 2020, including school children (n = 427) aged 9-12 years living in Sapporo City, Japan, among the participants of "The Hokkaido Study on Environment and Children's Health." Thirteen urinary PFR metabolites were measured by LC-MS/MS. Allergic symptoms were assessed using the International Study of Asthma and Allergies in Childhood questionnaire. For T2 biomarkers, the peripheral blood eosinophil counts, fraction of exhaled nitric oxide level (FeNO), and serum total immunoglobulin E level were measured. Multiple logistic regression analysis, quantile-based g-computation (qg-computation), and Bayesian kernel machine regression (BKMR) were used to examine the associations between the health outcomes of the individual PFRs and the PFR mixtures. The highest concentration of PFR was Σtris(1-chloro-isopropyl) phosphates (ΣTCIPP) (Median:1.20 nmol/L). Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) was significantly associated with a high odds ratio (OR, 95%CI:1.36, 1.07-1.72) for wheeze. TDCIPP (OR, 95%CI:1.19, 1.02-1.38), Σtriphenyl phosphate (ΣTPHP) (OR, 95%CI:1.81, 1.40-2.37), and Σtris(2-butoxyethyl) phosphate (ΣTBOEP) (OR, 95%:1.40, 1.13-1.74) were significantly associated with increased odds of FeNO (≥35 ppb). ΣTPHP (OR, 95%CI:1.44, 1.15-1.83) was significantly associated with high eosinophil counts (≥300/µL). For the PFR mixtures, a one-quartile increase in all PFRs (OR, 95%CI:1.48, 1.18-1.86) was significantly associated with high FeNO (≥35 ppb) in the qg-computation model. The PFR mixture was positively associated with high FeNO (≥35 ppb) and eosinophil counts (≥300/µL) in the BKMR models. These results may suggest that exposure to PFRs increases the probability of asthma, allergies, and T2 inflammation.

The effects of aliphatic alcohols and related acid metabolites in zebrafish embryos - correlations with rat developmental toxicity and with effects in advanced life stages in fish.

The zebrafish embryo toxicity test (ZFET) is a simple medium-throughput test to inform about (sub)acute lethal effects in embryos. Enhanced analysis through morphological and teratological scoring, and through gene expression analysis, detects developmental effects and the underlying toxicological pathways. Altogether, the ZFET may inform about hazard of chemical exposure for embryonal development in humans, as well as for lethal effects in juvenile and adult fish. In this study, we compared the effects within a series of 12 aliphatic alcohols and related carboxylic acid derivatives (ethanol, acetic acid, 2-methoxyethanol, 2-methoxyacetic acid, 2-butoxyethanol, 2-butoxyacetic acid, 2-hydroxyacetic acid, 2-ethylhexan-1-ol, 2-ethylhexanoic acid, valproic acid, 2-aminoethanol, 2-(2-hydroxyethylamino)ethanol) in ZFET and early life stage (ELS, 28d) exposures, and compared ZFET results with existing results of rat developmental studies and LC50s in adult fish. High correlation scores were observed between compound potencies in ZFET with either ELS, LC50 in fish and developmental toxicity in rats, indicating similar potency ranking among the models. Compounds could be mapped to specific pathways in an adverse outcome pathway (AOP) network through morphological scoring and gene expression analysis in ZFET. Similarity of morphological effects and gene expression profiles in pairs of alcohols with their acid metabolites suggested metabolic activation of the parent alcohols, although with additional, metabolite-independent activity independent for ethanol and 2-ethylhexanol. Overall, phenotypical and gene expression analysis with these compounds indicates that the ZFET can potentially contribute to the AOP for developmental effects in rodents, and to predict toxicity of acute and chronic exposure in advanced life stages in fish.