Abstract
Organophosphate esters (OPEs) are widely used and harmful to organisms and human health. Dust ingestion is an important exposure route for OPEs to humans. In this study, by integrating ToxCast high-throughput in vitro assays with in vitro to in vivo extrapolation (IVIVE) via physiologically based Toxicokinetic (PBTK) modeling, we assessed the hepatocyte-based health risk for humans around the world due to exposure to two typical OPEs (TPHP and TDCPP) through the dust ingestion exposure route. Results showed that the health guidance value of TPHP and TCDPP obtained in this study was lower than the value obtained through animal experiments. In addition, probabilistic risk assessment results indicate that populations worldwide are at low risk of exposure to TPHP and TDCPP through dust ingestion due to low estimated daily intakes (EDIs) which are much lower than the reference dose (RfDs) published by the US EPA, except in some regional cases. Most margin of exposure (MOE) ranges of TDCPP for children are less than 100, which indicates a moderately high risk. Researchers should be concerned about exposure to TDCPP in this area. The method proposed in this study is expected to be applied to the health risk assessment of other chemicals.
Highlights
For the two studied organophosphate esters (OPEs), AC50 values for the 4 ToxCast HTS assays related to the liver and calculated human equivalent doses (HEDs) are presented in Table 1 after cytotoxicity filtering
The study in Australia analyzed the relationship between concentrations of OPEs and indoor products, and the results showed that significantly higher concentrations of tris (1-dichloro-2-propyl) phosphate (TDCPP) (p < 0.001, medians of 0.93 and 0.26 mg/g in carpeted and uncarpeted houses, respectively) were found in dust collected from carpeted houses
The health risk assessment of OPEs is challenging due to the uncertainties of traditional risk assessment and the lack of global surveys. We addressed this challenge by converting in vitro ToxCast hepatocyte assays data from Environmental Protection Agency (EPA) into HEDs that could be applied in an margin of exposure (MOE) risk assessment approach using population based in vivo extrapolation (IVIVE) via physiologically based Toxicokinetic (PBTK) model, and by integrating estimated daily intakes (EDIs) of OPEs in different populations worldwide
Summary
Due to the acceleration of industrialization and the widespread use of polymer materials, fires occur frequently all over the world, seriously endangering the safety of people’s lives and property. People’s awareness of fire safety is increasing, and all kinds of flame retardants (FRs) are produced and applied [1,2]. Organophosphate flame retardants (OPFRs) have been widely used all over the world because of their low price, low toxicity and low smoke [3,4]. In the process of production and use, OPFRs are mainly added into the material by doping and mixing rather than chemical bonding, which makes it easier to enter the environment [6]. The molecular structure of organophosphate esters (OPEs) consists of a phosphate skeleton and three substituent groups. With the increase of molecular weight, lgKow of OPEs tends to increase, but water solubility and vapor pressure decrease
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