PUBLICATION
Dose addition in chemical mixtures inducing craniofacial malformations in zebrafish (Danio rerio) embryos
- Authors
- Zoupa, M., Zwart, E.P., Gremmer, E.R., Nugraha, A., Compeer, S., Slob, W., van der Ven, L.T.M.
- ID
- ZDB-PUB-200114-1
- Date
- 2020
- Source
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 137: 111117 (Journal)
- Registered Authors
- van der Ven, Leo
- Keywords
- Craniofacial malformations, Dose addition, Mixture toxicity, Zebrafish model
- MeSH Terms
-
- Animals
- Craniofacial Abnormalities/embryology
- Craniofacial Abnormalities/etiology
- Craniofacial Abnormalities/veterinary*
- Fish Diseases/embryology
- Fish Diseases/etiology*
- Silanes/toxicity*
- Triazoles/toxicity*
- Zebrafish/abnormalities
- Zebrafish/embryology*
- Zebrafish/genetics
- PubMed
- 31927004 Full text @ Food Chem. Toxicol.
Citation
Zoupa, M., Zwart, E.P., Gremmer, E.R., Nugraha, A., Compeer, S., Slob, W., van der Ven, L.T.M. (2020) Dose addition in chemical mixtures inducing craniofacial malformations in zebrafish (Danio rerio) embryos. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 137:111117.
Abstract
A challenge in cumulative risk assessment is to model hazard of mixtures. EFSA proposed to only combine chemicals linked to a defined endpoint, in so-called cumulative assessment groups, and use the dose-addition model as a default to predict combined effects. We investigated the effect of binary mixtures of compounds known to cause craniofacial malformations, by assessing the effect in the head skeleton (M-PQ angle) in 120hpf zebrafish embryos. We combined chemicals with similar mode of action (MOA), i.e. the triazoles cyproconazole, triadimefon and flusilazole; next, reference compounds cyproconazole or triadimefon were combined with dissimilar acting compounds, TCDD, thiram, VPA, prochloraz, fenpropimorph, PFOS, or endosulfan. These mixtures were designed as (near) equipotent combinations of the contributing compounds, in a range of cumulative concentrations. Dose-addition was assessed by evaluation of the overlap of responses of each of the 14 tested binary mixtures with those of the single compounds. All 10 test compounds induced an increase of the M-PQ angle, with varying potency and specificity. Mixture responses as predicted by dose-addition did not deviate from the observed responses, supporting dose-addition as a valid assumption for mixture risk assessment. Importantly, dose-addition was found irrespective of MOA of contributing chemicals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping