Bibliographic Details
| Title: |
Cumulative Risk Meets Inter-Individual Variability: Probabilistic Concentration Addition of Complex Mixture Exposures in a Population-Based Human In Vitro Model |
| Authors: |
Suji Jang, Lucie C. Ford, Ivan Rusyn, Weihsueh A. Chiu |
| Source: |
Toxics, Vol 10, Iss 10, p 549 (2022) |
| Publisher Information: |
MDPI AG, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Chemical technology |
| Subject Terms: |
cumulative risk, dose addition, concentration addition, inter-individual variability, toxicodynamics, chemical mixtures, Chemical technology, TP1-1185 |
| More Details: |
Although humans are continuously exposed to complex chemical mixtures in the environment, it has been extremely challenging to investigate the resulting cumulative risks and impacts. Recent studies proposed the use of “new approach methods,” in particular in vitro assays, for hazard and dose–response evaluation of mixtures. We previously found, using five human cell-based assays, that concentration addition (CA), the usual default approach to calculate cumulative risk, is mostly accurate to within an order of magnitude. Here, we extend these findings to further investigate how cell-based data can be used to quantify inter-individual variability in CA. Utilizing data from testing 42 Superfund priority chemicals separately and in 8 defined mixtures in a human cell-based population-wide in vitro model, we applied CA to predict effective concentrations for cytotoxicity for each individual, for “typical” (median) and “sensitive” (first percentile) members of the population, and for the median-to-sensitive individual ratio (defined as the toxicodynamic variability factor, TDVF). We quantified the accuracy of CA with the Loewe Additivity Index (LAI). We found that LAI varies more between different mixtures than between different individuals, and that predictions of the population median are generally more accurate than predictions for the “sensitive” individual or the TDVF. Moreover, LAI values were generally |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2305-6304 |
| Relation: |
https://www.mdpi.com/2305-6304/10/10/549; https://doaj.org/toc/2305-6304 |
| DOI: |
10.3390/toxics10100549 |
| Access URL: |
https://doaj.org/article/562bdd9cbe5141eba9e2172ef4636d99 |
| Accession Number: |
edsdoj.562bdd9cbe5141eba9e2172ef4636d99 |
| Database: |
Directory of Open Access Journals |
