Quantitative description of mixture toxicity: Effect of level of response on interactions

Haas, Charles N.; Cidambi, Kaushik; Kersten, Sean; Wright, Kenneth E.

doi:10.1002/etc.5620150824

Cited by 29 publications

(22 citation statements)

References 16 publications

(17 reference statements)

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“…The deviations of ␤ 2 and ␤ 3 from zero were evaluated using a t test [15]. Mixture effects were analyzed by applying the computational framework proposed by Jonker [16] and Haas et al [17]. Following their derivations, the binary TU mixture model can be generalized to…”

Section: Discussionmentioning

confidence: 99%

“…The reference models are defined by G ϭ 0 in Equations 2 and 3. Details of the model applications have been outlined by Jonker [16] and Haas et al [17]. In short, G enables the quantification of four distinct deviations from the reference model: No deviation; synergism/antagonism in all mixture combinations (S/A); toxicant ratio-dependent deviation (TR), where the deviation pattern (S/A) depends on the mutual proportion of the toxicants in the mixture; and effect level-dependent deviation (EL), where the deviation (S/A) depends on the dose level tested.…”

Section: Predominantly Synergismmentioning

confidence: 99%

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Toxicity of simple mixtures to the nematode Caenorhabditis elegans in relation to soil sorption

Jonker

Sweijen

Kammenga

2004

Enviro Toxic and Chemistry

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Single and combined toxicity of copper-zinc, copper-cadmium, cadmium-lead, copper-carbendazim, and copper-carbendazimiprodione to the nematode Caenorhabditis elegans in soil was studied. The one-week population increase was estimated as the toxicity endpoint. The aim was to study the relationship between mixture interactions in the soil and the combined toxic effect. Soil sorption was quantified using the Freundlich adsorption constant. Joint toxicity patterns were quantified by comparing mixture effects to the effect of individual constituents and were related to total metal concentrations in the soil, water-soluble concentrations, and 0.01 M CaCl2-extractable concentrations. The metal with the highest adsorption constant influenced the sorption of metal with the lowest adsorption constant when both were combined, indicating interaction. Consequently, both the composition of the mixture as well as the relative toxicity of individual mixture constituents differed between total, water-soluble, and CaCl2-extractable concentrations, which was taken into account in the data quantification procedure that was applied. Both the additive and the independent model were generally inadequate to describe the effects of metal mixtures. Compared to the additive model, synergism was observed at dose levels higher than the median effect isobole. A general relationship between mixture interactions in the soil and the combined toxicity was not found.

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Section: Discussionmentioning

confidence: 99%

Section: Predominantly Synergismmentioning

confidence: 99%

Toxicity of simple mixtures to the nematode Caenorhabditis elegans in relation to soil sorption

Jonker

Sweijen

Kammenga

2004

Enviro Toxic and Chemistry

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“…Haas et al (1996) evaluated published results on the interactions between endrin and malathion in flagfish using a single component Weibull dose-response relationship. They showed an interaction which Hermanutz et al (1985) had reported.…”

Section: Supporting Publications 2012:en-347 92mentioning

confidence: 99%

Repeated and multiple stress (exposure to pesticides) on aquatic organisms

Dennis

Tiede

Thompson

2012

EFSA Supporting Publications

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A systematic literature search identified publications relevant to repeated (94 papers) and mixture exposure (152 papers) of aquatic organisms. Limited data are available on pulsed exposure of pesticides and reports on repeated pulse or fluctuating exposures are even rarer. Although there has been recognition of the need for more realistic testing scenarios these lack a systematic approach. Among the reports on pesticide mixtures most of the plant studies evaluated interactions between mixtures of herbicides or fungicides / algicides. A small number of reports evaluated the effects on invertebrates of mixtures of pesticides with the same mode of action and these showed additive toxicity. More studies in invertebrates assessed interactions between pesticides with different modes of action including herbicide/ insecticide combinations some of which showed toxicity greater than additive. The majority of studies in fish have investigated the toxicity of insecticide mixtures. The toxicity of most combinations was at most additive, with a small number antagonistic. A small number of papers reported mixture effects of pesticides in amphibians; more than additive effects were observed with atrazine combinations. Simple models can be used to determine the additive toxicity of pesticide mixtures based on concentration addition or independent action. More complex models to determine the scale of synergy are species-and dose-dependent and rely on an understanding of the interactions involved. Further work is required to develop a greater understanding of the species, dose and time dependence of exposure to pesticide mixtures in which more complex interactions occur. In the interim, in the majority of cases the increase in toxicity is no greater than 3 fold when compared to additive, the deviation from additivity decreases with the increasing number of components in the mixture, and where no known interactions have been reported this may be an appropriate factor to include in risk assessments. KEY WORDSPulsed, mixtures, pesticides, aquatic organisms, synergism, additive effects DISCLAIMERThe present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors 1 Question No EFSA-Q-2011-00786. Repeated and Multiple Stress in Aquatic OrganismsSupporting publications 2012:EN-347 2The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the...

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“…However, there are few examples in the literature of effects greater than three times the effects expected from additivity (ECETOC, 2001). Non-additive interactions increase as dose of the mixture increases but may be significant at low, environmentally relevant doses (Haas et aL, 1996). For regulatory purposes, dose addition is considered to provide the reasonable worst case estimate of toxicity for similar and dissimilar mixtures (Faust et aL, 2000;Grimme et aL, 1996).…”

Section: Risk Calculation Procedures For Component Dose Addition Apprmentioning

confidence: 99%

The Toxicology of Chemical Mixtures Risk Assessment for Human and Ecological Receptors

Sterner¹,

Robinson²,

Mattie³

et al. 2005

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REPORT DOCUMENTATION PAGE ublic reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the lata needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing ,is burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently alid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2 I. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)kir Force Materiel Command*** HEPB SUPPLEMENTARY NOTES ABSTRACT4ixtures of chemicals represent a concern in all areas of toxicology and a challenge to risk Issessors as most sites with environmental contamination, including Department of Defense sites, involve simultaneous or sequential exposures of multiple chemicals to human or ýcological receptors.A major concern with mixtures is that they may lead to outcomes (health effects) or increased toxicity (synergism) not expected from the risk 'haracterization of individual chemicals at the site.The focus of this literature review is :o examine the principles used to determine toxicity in chemical mixtures risk assessment for luman and ecological receptors at hazardous waste sites.This review provides an overview of 'urrent practices useful to a remedial project manager or risk assessor prior to their first ",hemical mixtures risk assessment. 5.SUBJECTTERMS

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Quantitative description of mixture toxicity: Effect of level of response on interactions

Cited by 29 publications

References 16 publications

Toxicity of simple mixtures to the nematode Caenorhabditis elegans in relation to soil sorption

Toxicity of simple mixtures to the nematode Caenorhabditis elegans in relation to soil sorption

Repeated and multiple stress (exposure to pesticides) on aquatic organisms

The Toxicology of Chemical Mixtures Risk Assessment for Human and Ecological Receptors

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