Testing Additivity of Lead and Benzo[a]pyrene-induced Neurotoxicity in Caenorhabditis elegans Assays
Abstract
Exposure to environmental contaminants is a recognized cause of neurotoxicity, contributing to the onset of a broad range of neurological conditions. In realistic settings, such exposure involves com- plex mixtures, and the combined effect of their components may differ from what their individual effects would predict. Characterizing such interactions and testing them against a principled notion of additivity is central to assessing the neurotoxicological risk. We take up these questions for two widespread and independently neurotoxic pollutants, lead (Pb) and benzo[a]pyrene (BaP), through a novel C. elegans assay in which nematodes were subjected to single and joint exposures across a range of doses. Morphological damage is quantified on an ordinal scale at the level of individual dopaminergic neurons. To analyze these data, we model the full distribution of the ordinal response as a convex mixture between an unexposed and a maximally affected profile. The weight of this mixture varies with chemical doses, modeled flexibly via monotone splines and, for the joint effect, in a radial coordinate system. Additivity is assessed via a likelihood ratio test against established null models, and is calibrated via parametric bootstrap. Applied to the C. elegans assay, our analysis reveals a localized, asymmetric synergy between Pb and BaP, concentrated where moderate BaP meets high Pb exposure.
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BibTeX
@misc{anceschi2026testing,
title = {{Testing Additivity of Lead and Benzo[a]pyrene-induced Neurotoxicity in Caenorhabditis elegans Assays}},
author = {Niccolo Anceschi and Javier Huayta and Joel N. Meyer and David B. Dunson and Amy H. Herring},
howpublished = {arXiv},
year = {2026},
month = oct,
doi = {10.48550/arxiv.2608.20496},
eprint = {2608.20496},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2608.20496},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - Testing Additivity of Lead and Benzo[a]pyrene-induced Neurotoxicity in Caenorhabditis elegans Assays
AU - Niccolo Anceschi
AU - Javier Huayta
AU - Joel N. Meyer
AU - David B. Dunson
AU - Amy H. Herring
PY - 2026
DA - 2026/10/08
PB - arXiv
DO - 10.48550/arxiv.2608.20496
UR - https://arxiv.org/abs/2608.20496
AB - Exposure to environmental contaminants is a recognized cause of neurotoxicity, contributing to the onset of a broad range of neurological conditions. In realistic settings, such exposure involves com- plex mixtures, and the combined effect of their components may differ from what their individual effects would predict. Characterizing such interactions and testing them against a principled notion of additivity is central to assessing the neurotoxicological risk. We take up these questions for two widespread and independently neurotoxic pollutants, lead (Pb) and benzo[a]pyrene (BaP), through a novel C. elegans assay in which nematodes were subjected to single and joint exposures across a range of doses. Morphological damage is quantified on an ordinal scale at the level of individual dopaminergic neurons. To analyze these data, we model the full distribution of the ordinal response as a convex mixture between an unexposed and a maximally affected profile. The weight of this mixture varies with chemical doses, modeled flexibly via monotone splines and, for the joint effect, in a radial coordinate system. Additivity is assessed via a likelihood ratio test against established null models, and is calibrated via parametric bootstrap. Applied to the C. elegans assay, our analysis reveals a localized, asymmetric synergy between Pb and BaP, concentrated where moderate BaP meets high Pb exposure.
ER -