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Statistically significant deviations from additivity: What do they mean in assessing toxicity of mixtures?
Ecotoxicol Environ Saf. 2015 Dec; 122:37-44.EE

Abstract

There is increasing attention from scientists and policy makers to the joint effects of multiple metals on organisms when present in a mixture. Using root elongation of lettuce (Lactuca sativa L.) as a toxicity endpoint, the combined effects of binary mixtures of Cu, Cd, and Ni were studied. The statistical MixTox model was used to search deviations from the reference models i.e. concentration addition (CA) and independent action (IA). The deviations were subsequently interpreted as 'interactions'. A comprehensive experiment was designed to test the reproducibility of the 'interactions'. The results showed that the toxicity of binary metal mixtures was equally well predicted by both reference models. We found statistically significant 'interactions' in four of the five total datasets. However, the patterns of 'interactions' were found to be inconsistent or even contradictory across the different independent experiments. It is recommended that a statistically significant 'interaction', must be treated with care and is not necessarily biologically relevant. Searching a statistically significant interaction can be the starting point for further measurements and modeling to advance the understanding of underlying mechanisms and non-additive interactions occurring inside the organisms.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Liu Y
Institute of Environmental Sciences (CML), Leiden University, 2300 RA Leiden, The Netherlands. Electronic address: liu@cml.leidenuniv.nl.
Vijver MG
Institute of Environmental Sciences (CML), Leiden University, 2300 RA Leiden, The Netherlands.
Qiu H
Institute of Environmental Sciences (CML), Leiden University, 2300 RA Leiden, The Netherlands.
Baas J
Centre for Ecology & Hydrology (CEH), MacLean Building, Benson Lane, OX10 8BB Wallingford, Oxfordshire, United Kingdom.
Peijnenburg WJ
Institute of Environmental Sciences (CML), Leiden University, 2300 RA Leiden, The Netherlands; National Institute of Public Health and the Environment (RIVM), Center for Safety of Substances and Products, 3720 BA Bilthoven, The Netherlands.

MeSH

CadmiumCopperDrug SynergismLettuceModels, TheoreticalNickelPlant RootsReproducibility of Results

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26188643

Citation

Liu, Yang, et al. "Statistically Significant Deviations From Additivity: what Do They Mean in Assessing Toxicity of Mixtures?" Ecotoxicology and Environmental Safety, vol. 122, 2015, pp. 37-44.
Liu Y, Vijver MG, Qiu H, et al. Statistically significant deviations from additivity: What do they mean in assessing toxicity of mixtures? Ecotoxicol Environ Saf. 2015;122:37-44.
Liu, Y., Vijver, M. G., Qiu, H., Baas, J., & Peijnenburg, W. J. (2015). Statistically significant deviations from additivity: What do they mean in assessing toxicity of mixtures? Ecotoxicology and Environmental Safety, 122, 37-44. https://doi.org/10.1016/j.ecoenv.2015.07.012
Liu Y, et al. Statistically Significant Deviations From Additivity: what Do They Mean in Assessing Toxicity of Mixtures. Ecotoxicol Environ Saf. 2015;122:37-44. PubMed PMID: 26188643.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Statistically significant deviations from additivity: What do they mean in assessing toxicity of mixtures? AU - Liu,Yang, AU - Vijver,Martina G, AU - Qiu,Hao, AU - Baas,Jan, AU - Peijnenburg,Willie J G M, Y1 - 2015/07/17/ PY - 2015/05/05/received PY - 2015/07/07/revised PY - 2015/07/08/accepted PY - 2015/7/20/entrez PY - 2015/7/21/pubmed PY - 2016/6/10/medline KW - Biologically relevant KW - Lettuce KW - Metal mixtures KW - Reproducibility KW - Statistically significant SP - 37 EP - 44 JF - Ecotoxicology and environmental safety JO - Ecotoxicol Environ Saf VL - 122 N2 - There is increasing attention from scientists and policy makers to the joint effects of multiple metals on organisms when present in a mixture. Using root elongation of lettuce (Lactuca sativa L.) as a toxicity endpoint, the combined effects of binary mixtures of Cu, Cd, and Ni were studied. The statistical MixTox model was used to search deviations from the reference models i.e. concentration addition (CA) and independent action (IA). The deviations were subsequently interpreted as 'interactions'. A comprehensive experiment was designed to test the reproducibility of the 'interactions'. The results showed that the toxicity of binary metal mixtures was equally well predicted by both reference models. We found statistically significant 'interactions' in four of the five total datasets. However, the patterns of 'interactions' were found to be inconsistent or even contradictory across the different independent experiments. It is recommended that a statistically significant 'interaction', must be treated with care and is not necessarily biologically relevant. Searching a statistically significant interaction can be the starting point for further measurements and modeling to advance the understanding of underlying mechanisms and non-additive interactions occurring inside the organisms. SN - 1090-2414 UR - https://www.unboundmedicine.com/medline/citation/26188643/Statistically_significant_deviations_from_additivity:_What_do_they_mean_in_assessing_toxicity_of_mixtures DB - PRIME DP - Unbound Medicine ER -