Environmental exposure assessment of co-formulants in plant protection products under REACH.

It is a regulatory requirement to assess co-formulants in plant protection products (PPP) under the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation. The standard environmental exposure assessment framework for chemicals under REACH is a multicompartmental mass-balanced model and, at the local scale, is designed for use with urban (wide dispersive) or industrial (point source) emissions. However, the environmental release of co-formulants used in PPP is to agricultural soil and indirectly to waterbodies adjacent to a field and, for sprayed products, to the air. The Local Environment Tool (LET) has been developed to assess these specific emission pathways for co-formulants in a local-scale REACH exposure assessment, based on standard approaches and models used for PPP. As such, it closes a gap between the standard REACH exposure model's scope and REACH requirements to assess co-formulants in PPP. When combined with the output of the standard REACH exposure model, the LET includes an estimate of the contribution from other nonagricultural background sources of the same substance. The LET is an improvement over the use of higher tier PPP models for screening purposes because it provides a simple standardized exposure scenario. A set of predefined and conservatively selected inputs allows a REACH registrant to conduct an assessment without requiring detailed knowledge of PPP risk assessment methods or typical conditions of use. The benefit to the co-formulant downstream user (formulators) is a standardized and consistent approach to co-formulant assessment, with meaningful and readily interpretable conditions of use. The LET can serve as an example to other sectors of how to address possible gaps in the environmental exposure assessment by combining a customized local-scale exposure model with the standard REACH models. A detailed conceptual explanation of the LET model is provided here together with a discussion on its use in a regulatory context. Integr Environ Assess Manag 2023;19:1544-1554. © 2023 BASF SE, Bayer AG et al. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

ECETOC TRAv3: An In-depth Comparison of Publicly Available Measurement Data Sets With Modelled Estimates of Occupational Inhalation Exposure to Chemicals.

In this study, 129 exposure situations (ESs) with six or more measured inhalation exposures to dust from solids or vapour from liquids in occupational settings were compared with modelled European Centre of Ecotoxicology and Toxicology of Chemicals (ECETOC) targeted risk assessment tool, version 3 (TRAv3) estimates. The measurement data were extracted from previously published studies examining TRAv3 performance and pooled into a curated database. The comparison exercise focussed on the vapour exposure scenarios, as there were too few dust scenarios for a meaningful analysis of any required model corrections. A group of experts in the exposure modelling field retrieved and reviewed the input parameters used in these ESs. Where considered appropriate, modifications were applied to better match the input parameter definitions and the scope of applicability of the TRAv3. Differences and mean absolute error (MAE) were calculated between the log-transformed modelled exposure value and the 75th percentile of each measured data set and regression analysis was performed. The results indicated that the TRAv3 overestimated 80% of the measured data sets. Both over- and underestimations were mostly by factors 1-5. The calculated MAE for liquids was 0.7, indicating that on average the difference between the 75th percentile and the TRAv3 estimate was less than one order of magnitude. A multiple linear regression showed that some input parameters such as medium volatility, certain process categories (PROC), industrial setting, and the presence of local exhaust ventilation are associated with underestimations. The results of the regression analysis can be used by TRAv3 users to review the degree of over- or underestimation in their current exposure assessments, compared to the curated database. Although multiple linear regression is an appropriate methodology to characterize the TRAv3's performance, more data sets are still needed in view of some remaining data gaps. Nevertheless, the results of the current analysis are being used by ECETOC to further develop the tool as a suitably conservative screening tool for use in REACH chemical safety assessment of occupational exposure to chemicals.

The ECETOC-Targeted Risk Assessment Tool for Worker Exposure Estimation in REACH Registration Dossiers of Chemical Substances-Current Developments.

(1) Background: The ECETOC Targeted Risk Assessment (TRA) tool is widely used for estimation of worker exposure levels in the development of dossiers for REACH registration of manufactured or imported chemical substances in Europe. A number of studies have been published since 2010 in which the exposure estimates of the tool are compared with workplace exposure measurement results and in some instances an underestimation of exposure was reported. The quality and results of these studies are being reviewed by ECETOC. (2) Methods: Original exposure measurement data from published comparison studies for which six or more data points were available for each workplace scenario and a TRA estimate had been developed to create a curated database to examine under what conditions and for which applications the tool is valid or may need adaptation. (3) Results: The published studies have been reviewed for completeness and clarity and TRA estimates have been constructed based on the available information, following a set of rules. The full review findings are expected to be available in the course of 2021. (4) Conclusions: The ECETOC TRA tool developers periodically review the validity and limitations of their tool, in line with international recommendations.

REACH Specific Environmental Release Categories for Plant Protection Product Applications.

The European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation requires that quantitative environmental risk assessment is carried out for hazardous substances used as coformulants in plant protection products (PPPs), if registered above 10 t/y. The European Crop Protection Association (ECPA) has developed generic exposure scenarios and specific environmental release categories (SpERCs) to support these risk assessments. The SpERCs offer refinements to the default release factors defined in environmental release categories (ERCs) and are intended to be used with nested multimedia mass balance models as part of the assessment of regional predicted environmental concentrations. Based on the application method of PPPs, 2 scenarios were defined for which SpERCs were developed: 1) spraying of PPPs and 2) direct application of granular products or treated seeds to soil. The SpERC for spray applications includes release factors to air and soil that depend on the vapor pressure of the coformulant. Calculations are presented to support the subSpERCs describing the transition from nonvolatile to volatile behavior. The most recent version of the spray application SpERC defines a release factor for surface water and more conservative release factors to soil compared with previous versions. Use of the ECPA SpERCs allows the coformulant emissions from PPPs to be fully accounted for in the regional-scale environmental risk assessment for a given substance, along with all other sources of emissions. Qualitative and quantitative justification for the ECPA-derived SpERCs is presented and serves as the background documentation to the online European Chemicals Agency (ECHA) SpERC factsheets. The approach developed here whereby regional-scale SpERCs are used in combination with a customized local-scale exposure model is potentially applicable for other sectors that are required to conduct exposure assessments outside the scope of the standard environmental REACH models. Integr Environ Assess Manag 2020;16:472-480. © 2020 Syngenta Crop Protection AG. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

REACH Worker Exposure Model for Co-formulants Used in Plant Protection Products.

Background: Substances used as co-formulants in plant protection products (PPP) may require registration under Regulation (EC) No. 1907/2006 (REACH), and additionally where an exposure assessment is required, this must take into consideration the specifics of the PPP use. Objectives: This work reports a customized screening level model developed to support human health risk assessment of operators, workers, and bystanders (OWB) for co-formulants used in PPP. The OWB model was designed to closely integrate with REACH generic exposure scenarios (GES) for PPP developed by the European Crop Protection Association (ECPA). The use of these tools in combination is expected to lead to a more standardized and hence efficient risk assessment of co-formulants. This study describes the basis for OWB exposure predictions as well as benchmarking against relevant REACH exposure models for equivalent tasks. The benchmarking was carried out to gain some insight into the initial assumption that the most commonly used tier 1 REACH model would be more conservative than the specific PPP models used for regulatory risk assessments under PPP legislation. Method: Existing exposure models with regulatory acceptance for the most common types of PPP and their professional and consumer uses were selected. The German BBA model was used to assess spray applications. Granule and seed dispersal was assessed using the US Environmental Protection Agency (EPA) Pesticide Handlers Exposure Database (PHED). ECETOC TRA was employed to assess exposure during certain tasks performed in seed treatment, not covered by these PPP models. Where the underlying models featured multiple exposure determinants, the exposure was calculated for all permutations, and the worst-case exposure selected and reported for use in risk assessment. The PPP models are based on measured data collected during actual application of PPP; hence, the worst-case exposure predicted was expected to reflect a realistic worst case for these tasks. Results: OWB was implemented as an Excel spreadsheet. Exposure models, parameters, and exposure and risk estimates are reported in a REACH-compliant output format to facilitate the registration of co-formulant uses. As would be expected, benchmarking OWB against the PPP-specific exposure models demonstrated equivalence with the worst-case prediction from these underlying PPP models. For the scenarios modelled, the tier 1 ECETOC TRA gave more conservative predictions than OWB. The reduction in conservatism is attributed to the underlying PPP models being based on measured data collected specifically during the use of PPP, compared to the data underlying ECETOC TRA, based mainly on industrial workplace uses. Conclusions: OWB provides inhalation and dermal exposure estimates for co-formulants used in PPP which are equivalent to the worst-case estimates from existing specialized PPP exposure models based on measured data. OWB has simplified information requirements in comparison to higher-tier REACH or PPP models. Use of OWB in combination with the defined ECPA GES facilitates an efficient and standardized REACH risk assessment and registration of co-formulant uses in PPP. A defined assessment framework and default inputs potentially decreases the anticipated inter-user variability compared with the use of higher-tier PPP or REACH models in this screening level context.

Development of REACH Generic Exposure Scenarios for Substances Used as Coformulants in Plant Protection Products.

This article reviews the interactions between the REACH (Registration, Evaluation, Authorization and restriction of Chemicals) regulation and the plant protection product regulation for substances used as coformulants in the European Union, and describes generic exposure scenarios developed for their exposure and risk assessment. The REACH exposure scenarios describe the operational conditions and risk management measures used in the risk assessment of a coformulant, and as such these translate as the boundaries of safe use. The generic exposure scenarios are designed to be simple, and closely integrate with REACH use descriptors and customized exposure models. Clustering of application methods and exposure determinants resulted in four generic exposure scenarios, each covering professional workers or consumers, and application of products in liquid, granular form, or applied on seeds. When used in conjunction with appropriate exposure models, the generic exposure scenarios support efficient first-tier risk assessment of coformulants by utilizing a higher level of abstraction and conservatism than typically used in plant protection product assessments.

Potential exposure of German consumers to engineered nanoparticles in cosmetics and personal care products.

The rapid increase in the number of consumer products containing engineered nanoparticles (ENP) raises concerns about an appropriate risk assessment of these products. Along with toxicological data, exposure estimates are essential for assessing risk. Currently, cosmetics and personal care products (C&PCP) represent the largest ENP-containing consumer product class on the market. We analyzed factors influencing the likelihood that ENP-containing products are available to consumers. We modelled potential external exposure of German consumers, assuming a maximum possible case where only ENP-containing products are used. The distribution of exposure levels within the population due to different behavior patterns was included by using data from an extensive database on consumer behavior. Exposure levels were found to vary significantly between products and between consumers showing different behavior patterns. The assessment scheme developed here represents a basis for refined exposure modelling as soon as more specific information about ENPs in C&PCP becomes available.

Bisphenol a: how the most relevant exposure sources contribute to total consumer exposure.

Bisphenol A (BPA) is an endocrine disrupting chemical that is found in human urine throughout industrial societies around the globe. Consumer exposure pathways to BPA include packaged food, household dust, air, and dental fillings. To date, information on the relative contribution of the different pathways to total consumer exposure is lacking, but is key for managing substance-associated risks. We investigated the relative contributions of the pathways known to be most relevant for nine different consumer groups. Our results suggest that the most important pathways for infants and children are the use of polycarbonate (PC) baby bottles and for adults and teenagers the consumption of canned food. Dental surgery can also considerably contribute over a short time directly after the surgery. For infants fed with PC baby bottles with mean dose rates of 0.8 microg/kg(bw)/d the highest exposure dose rate was calculated. This dose rate is far below the tolerable daily intake of 50 microg/kg(bw)/d. However, it is of the same order of magnitude as recently reported concentrations that caused low-dose health effects in rodents. We find a pattern of falling exposure levels with rising age that is supported by urinary concentrations of BPA available for selected consumer groups. Similarly, the exposure levels we predict are confirmed by the levels reported in these studies.

Phthalate exposure through food and consumers' risk perception of chemicals in food.

Phthalates have been detected in various types of retail foods. Consumers' exposure to phthalates is common. Consumers are concerned about chemicals in food. Our aim was to investigate the relationships between consumers' exposure to phthalates through food, consumers' interest in a natural and healthy diet, risk perception of food chemicals, and consumers' diet patterns. We collected data through a mail survey in the adult Swiss-German population (N = 1,200). We modeled exposure to di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), and diethyl phthalate (DEP) based on a food frequency questionnaire and phthalate concentrations reported from food surveys. Using rating scales, we assessed risk perceptions of chemicals in food and interest in a natural and healthy diet. Higher risk perceptions and higher natural and healthy diet interest were associated with higher daily doses of DEHP, BBP, and DEP. No health risk from phthalates in food was identified for the vast majority of the population. Four consumers' diet clusters were discerned, with differences in phthalate exposure, risk perceptions, and interest in a natural and healthy diet. This study shows that even those consumers who express strong interest in natural food and low acceptance of food chemicals, and who try to make respective food choices, are exposed to contaminants such as phthalates.

Estimating the contribution of precursor compounds in consumer exposure to PFOS and PFOA.

The exposure of humans to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) was quantified with emphasis on assessing the relative importance of metabolic transformation of precursor compounds. A Scenario-Based Risk Assessment (SceBRA) approach was used to model the exposure to these compounds from a variety of different pathways, the uptake into the human body and resulting daily doses. To capture the physiological and behavioral differences of age and gender, the exposure and resulting doses for seven consumer groups were calculated. The estimated chronic doses of a general population of an industrialized country range from 3.9 to 520 ng/(kg day) and 0.3 to 140 ng/(kg day) for PFOS and PFOA, respectively. The relative importance of precursor-based doses of PFOS and PFOA was estimated to be 2-5% and 2-8% in an intermediate scenario and 60-80% and 28-55% in a high-exposure scenario. This indicates that sub groups of the population may receive a substantial part of the PFOS and PFOA doses from precursor compounds, even though they are of low importance for the general population. Similar to a preceding study, uptake of perfluorinated acids from contaminated food and drinking water was identified as the most important pathway of exposure for the general population. The biotransformation yields of telomer-based precursors and to a lesser extent perfluorooctanesulfonylfluoride-based precursors were identified as influential parameters in the uncertainty analysis. Fast food consumption and fraction of food packaging paper treated with PFCs were influential parameters for determining the doses of PFOA.

Estimating consumer exposure to PFOS and PFOA.

Perfluorinated compounds have been used for more than 50 years as process aids, surfactants, and for surface protection. This study is a comprehensive assessment of consumer exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) from a variety of environmental and product-related sources. To identify relevant pathways leading to consumer exposure to PFOS and PFOA a scenario-based approach has been applied. Scenarios represent realistic situations where age- and gender-specific exposure occurs in the everyday life of consumers. We find that North American and European consumers are likely to experience ubiquitous and long-term uptake doses of PFOS and PFOA in the range of 3 to 220 ng per kg body weight per day (ng/kg(bw)/day) and 1 to 130 ng/kg(bw)/day, respectively. The greatest portion of the chronic exposure to PFOS and PFOA is likely to result from the intake of contaminated foods, including drinking water. Consumer products cause a minor portion of the consumer exposure to PFOS and PFOA. Of these, it is mainly impregnation sprays, treated carpets in homes, and coated food contact materials that may lead to consumer exposure to PFOS and PFOA. Children tend to experience higher total uptake doses (on a body weight basis) than teenagers and adults because of higher relative uptake via food consumption and hand-to-mouth transfer of chemical from treated carpets and ingestion of dust. The uptake estimates based on scenarios are within the range of values derived from blood serum data by applying a one-compartment pharmacokinetic model.

Assessments of direct human exposure: the approach of EU risk assessments compared to scenario-based risk assessment.

The awareness of potential risks emerging from the use of chemicals in all parts of daily life has increased the need for risk assessments that are able to cover a high number of exposure situations and thereby ensure the safety of workers and consumers. In the European Union (EU), the practice of risk assessments for chemicals is laid down in a Technical Guidance Document; it is designed to consider environmental and human occupational and residential exposure. Almost 70 EU risk assessment reports (RARs) have been finalized for high-production-volume chemicals during the last decade. In the present study, we analyze the assessment of occupational and consumer exposure to trichloroethylene and phthalates presented in six EU RARs. Exposure scenarios in these six RARs were compared to scenarios used in applications of the scenario-based risk assessment approach to the same set of chemicals. We find that scenarios used in the selected EU RARs to represent typical exposure situations in occupational or private use of chemicals and products do not necessarily represent worst-case conditions. This can be due to the use of outdated information on technical equipment and conditions in workplaces or omission of pathways that can cause consumer exposure. Considering the need for exposure and risk assessments under the new chemicals legislation of the EU, we suggest that a transparent process of collecting data on exposure situations and of generating representative exposure scenarios is implemented to improve the accuracy of risk assessments. Also, the data sets used to assess human exposure should be harmonized, summarized in a transparent fashion, and made accessible for all risk assessors and the public.

What are the sources of exposure to eight frequently used phthalic acid esters in Europeans?

Phthalic acid esters (phthalates) are used as plasticizers in numerous consumer products, commodities, and building materials. Consequently, phthalates are found in human residential and occupational environments in high concentrations, both in air and in dust. Phthalates are also ubiquitous food and environmental contaminants. An increasing number of studies sampling human urine reveal the ubiquitous phthalate exposure of consumers in industrialized countries. At the same time, recent toxicological studies have demonstrated the potential of the most important phthalates to disturb the human hormonal system and human sexual development and reproduction. Additionally, phthalates are suspected to trigger asthma and dermal diseases in children. To find the important sources of phthalates in Europeans, a scenario-based approach is applied here. Scenarios representing realistic exposure situations are generated to calculate the age-specific range in daily consumer exposure to eight phthalates. The scenarios demonstrate that exposure of infant and adult consumers is caused by different sources in many cases. Infant consumers experience significantly higher daily exposure to phthalates in relation to their body weight than older consumers. The use of consumer products and different indoor sources dominate the exposure to dimethyl, diethyl, benzylbutyl, diisononyl, and diisodecyl phthalates, whereas food has a major influence on the exposure to diisobutyl, dibutyl, and di-2-ethylhexyl phthalates. The scenario-based approach chosen in the present study provides a link between the knowledge on emission sources of phthalates and the concentrations of phthalate metabolites found in human urine.