Considerations for Assessing the Risks of Combined Exposure to Multiple Chemicals

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doi:10.1787/ceca15a9-en

Cited by 34 publications

(6 citation statements)

References 80 publications

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“…Ideally, a comprehensive QSAR prediction should consider all sources of the substance X (to facilitate aggregate exposure estimation using co-use scenarios), taking into account all exposure routes and potential effects on the exposed individuals. In practice, however, it is not uncommon for modelers to establish a boundary to limit the scope of the prediction to reduce the level of complexity of the model and its prediction, make simpler the interpretation of the model output, or take into account specific regulatory considerations (OECD 2018 ). The conceptual model is then expanded by adding all possible exposure pathway scenarios to simulate the exposure magnitude, which includes dermal, inhalation, and/or ingestion exposures.…”

Section: Resultsmentioning

confidence: 99%

A problem formulation framework for the application of in silico toxicology methods in chemical risk assessment

Achar,

Cronin,

Firman

et al. 2024

Arch Toxicol

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The first step in the hazard or risk assessment of chemicals should be to formulate the problem through a systematic and iterative process aimed at identifying and defining factors critical to the assessment. However, no general agreement exists on what components an in silico toxicology problem formulation (PF) should include. The present work aims to develop a PF framework relevant to the application of in silico models for chemical toxicity prediction. We modified and applied a PF framework from the general risk assessment literature to peer reviewed papers describing PFs associated with in silico toxicology models. Important gaps between the general risk assessment literature and the analyzed PF literature associated with in silico toxicology methods were identified. While the former emphasizes the need for PFs to address higher-level conceptual questions, the latter does not. There is also little consistency in the latter regarding the PF components addressed, reinforcing the need for a PF framework that enable users of in silico toxicology models to answer the central conceptual questions aimed at defining components critical to the model application. Using the developed framework, we highlight potential areas of uncertainty manifestation in in silico toxicology PF in instances where particular components are missing or implicitly described. The framework represents the next step in standardizing in silico toxicology PF component. The framework can also be used to improve the understanding of how uncertainty is apparent in an in silico toxicology PF, thus facilitating ways to address uncertainty.

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Section: Resultsmentioning

confidence: 99%

A problem formulation framework for the application of in silico toxicology methods in chemical risk assessment

Achar,

Cronin,

Firman

et al. 2024

Arch Toxicol

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“…Predicted "provisional PNECs" from the NORMAN ecotoxicology database (Aalizadeh et al, 2017;NORMAN, 2022;von der Ohe et al, 2011) were also used to characterize the biotic and abiotic properties of APIs where experimental data were not available.…”

Section: Software and Datamentioning

confidence: 99%

“…As an alternative to limited available PNECs, QSAR lowest PNECs (provisional PNECs) generated by Aalizadeh et al (2017) from the NORMAN ecotoxicological database were also used to screen and rank APIs (Figure 4A; NORMAN, , 2022. We were able to match 428 APIs to provisional PNECs (~50%), 78 of which also had experimental PNECs, permitting comparisons between results (Figure 4B and C).…”

Section: Qsar-predicted Toxicity As a Supplement To Test Datamentioning

confidence: 99%

Predicting Environmental Risks of Pharmaceuticals from Wholesale Data: An Example from Norway

Welch

Moe

Sharikabad

et al. 2023

Enviro Toxic and Chemistry

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Environmental risk assessment (ERA) of pharmaceuticals relies on available measured environmental concentrations, but often such data are sparse. Predicted environmental concentrations (PECs), calculated from sales weights, are an attractive alternative but often cover only prescription sales. We aimed to rank, by environmental risk in Norway, approximately 200 active pharmaceutical ingredients (APIs) over 2016–2019, based on sales PECs. To assess the added value of wholesale and veterinary data, we compared exposure and risk predictions with and without these additional sources. Finally, we aimed to characterize the persistence, mobility, and bioaccumulation of these APIs. We compared our PECs to available Norwegian measurements, then, using public predicted‐no‐effect concentrations, we calculated risk quotients (RQs) and appended experimental and predicted persistence and bioaccumulation. Our approach overestimated environmental concentrations compared with measurements for 18 of 20 APIs with comparable predictions and measurements. Seventeen APIs had mean RQs >1, indicating potential risk, while the mean RQ was 2.05 and the median 0.001, driven by sex hormones, antibiotics, the antineoplastic abiraterone, and common painkillers. Some high‐risk APIs were also potentially persistent or bioaccumulative (e.g., levonorgestrel [RQ = 220] and ciprofloxacin [RQ = 56]), raising the possibility of impacts beyond their RQs. Exposure and risk were also calculated with and without over‐the‐counter sales, showing that prescriptions explained 70% of PEC magnitude. Likewise, human sales, compared with veterinary, explained 85%. Sales PECs provide an efficient option for ERA, designed to overestimate compared with analytical techniques and potentially held back by limited data availability and an inability to quantify uncertainty but, nevertheless, an ideal initial approach for identification and ranking of risks. Environ Toxicol Chem 2023;00:1–18. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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“…Pests that harm crops are produced more frequently due to widespread pesticide usage in agriculture, but pests that are resistant to pesticides have also arisen. Increasing agricultural productivity necessitates using more insecticides (Mostafalou and Abdollahi, 2013). Numerous potentially hazardous compounds have been discharged into the environment in large quantities due to the increasing use of agricultural pesticides in the fields…”

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confidence: 99%

Genotoxicity and genomic instability in oral epithelial cells of agricultural workers exposed to pesticides using micronucleus and comet assay in Nineveh, Iraq

Al-Hamadany

Khalaf

Alkateb

2023

JANS

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In agriculture, pesticides are used to preserve plants, but they might be dangerous for farmers and the environment. The present study aimed to use the comet assay and the micronucleus (MN) test to assess the genotoxic effects on lymphocytes and buccal exfoliation in pesticide-exposed male agricultural workers. The samples were collected from 102 workers having exposure to pesticides (Roundup SL, Weed waster, and paraquat 20% SL) and 100 control individuals (without pesticide exposure) from different Mosul, Iraq, neighbourhoods. With the help of the comet assay and the MN test, exfoliated buccal cells from the individuals were analyzed for DNA damage. Each individual's lymphocytes and epithelial baseline cells had their comet tail length assessed, along with any other nuclear abnormalities such as nuclear buds, karyolysis, karyorrhexis, and binucleate cells. The results showed that the frequency of MN considerably rose in the exposed group, and that group also revealed nuclear anomalies linked to cytotoxic or genotoxic effects. There were significant disparities in the amount of DNA damage between recently exposed employees and controls and recently exposed and followed-up cases. In comparison to controls, there was a considerable increase in the and frequency of cells that migrated in exposed workers. However, it was shown that confounding factors, such as age and the varying length of pesticide exposure, substantially impacted DNA damage. Educational programs for agricultural workers are critical to limit the use of chemicals in agriculture, given the evidence of a genetic risk associated with exposure brought on by the extensive use of pesticides.

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Considerations for Assessing the Risks of Combined Exposure to Multiple Chemicals

Cited by 34 publications

References 80 publications

A problem formulation framework for the application of in silico toxicology methods in chemical risk assessment

A problem formulation framework for the application of in silico toxicology methods in chemical risk assessment

Predicting Environmental Risks of Pharmaceuticals from Wholesale Data: An Example from Norway

Genotoxicity and genomic instability in oral epithelial cells of agricultural workers exposed to pesticides using micronucleus and comet assay in Nineveh, Iraq

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