Predictability of the Toxicity of Multiple Chemical Mixtures to Vibrio Fischeri: Mixtures Composed of Similarly Acting Chemicals

Altenburger, Rolf; Backhaus, Thomas; Boedeker, Wolfgang; Faust, Martin L.; Scholze, Martin; Grimme, L. Horst

doi:10.1897/1551-5028(2000)019<2341:pottom>2.3.co;2

Cited by 258 publications

(237 citation statements)

References 22 publications

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“…Conversely, when both cypermethrin and Pb 2þ were causing toxicity, both concentration addition (CA) and independent action (IA) modeling techniques were used. For a binary mixture, the CA and IA models can be expressed using Equations 1 and 2, respectively [27,28].…”

Section: Discussionmentioning

confidence: 99%

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Joint toxicity of a pyrethroid insecticide, cypermethrin, and a heavy metal, lead, to the benthic invertebrate Chironomus dilutus

Mehler

Lydy

et al. 2011

Enviro Toxic and Chemistry

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Abstract-Insecticides and heavy metals are frequently detected in the environment, but few studies have assessed the joint toxicity of organic and inorganic contaminants. Joint toxicity of a pyrethroid insecticide, cypermethrin, and a heavy metal, Pb 2þ , was evaluated in the present study. An antagonistic toxic response was observed when the benthic invertebrate Chironomus dilutus was simultaneously exposed to the two contaminants in both water and sediment exposures. Pre-exposure bioassays with midges were also conducted, and toxicity of cypermethrin was significantly reduced for midges that were pre-exposed to Pb 2þ . In addition, the impact of Pb 2þ on the bioavailability of cypermethrin to midges was measured using Tenax extraction. No significant difference was noted in the amount of Tenax-extractable cypermethrin when different amounts of Pb 2þ were added to sediment. Results suggested that altered organism sensitivity may contribute to the observed antagonistic interaction between cypermethrin and Pb 2þ

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Section: Discussionmentioning

confidence: 99%

“…Previous studies [17,27,28] have shown that chemicals with differing MOAs tend to be best modeled by IA, and those with similar MOA tend to best be modeled by CA. The IA model better predicted joint toxicity of cypermethrin and Pb 2þ , indicating that MOA for the contaminants may differ.…”

Section: Antagonistic Joint Toxicity Of Cypermethrin and Leadmentioning

confidence: 96%

Joint toxicity of a pyrethroid insecticide, cypermethrin, and a heavy metal, lead, to the benthic invertebrate Chironomus dilutus

Mehler

Lydy

et al. 2011

Enviro Toxic and Chemistry

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“…Other authors require that a similar effect is localized at least in the "same site of primary action", while a dissimilar effect is distinguished from this by the criterion of differences in a substances" fundamental structure (different "parent compounds") [37]. However, recent research has shown that mixtures which were designed of components known to act either by identical or by completely different molecular mechanisms of action were in fact better predicted by concentration addition or independent action respectively [7,9,38,39].…”

Section: The Quest For the Right Conceptmentioning

confidence: 99%

The scientific assessment of combined effects of risk factors: different approaches in experimental biosciences and epidemiology

Boedeker¹,

Backhaus

2010

Eur J Epidemiol

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To cite this version:Wolfgang Boedeker, Thomas Backhaus. The scientific assessment of combined effects of risk factors: different approaches in experimental biosciences and epidemiology. European Journal of Epidemiology, Springer Verlag, 2010, 25 (8) Abstract (233 words)The analysis of combined effects of substances or risk factors has been a subject to science for more than a century. With different goals, combined effect analysis was addressed in almost all experimental biosciences. The major theoretical foundation can be traced back to two distinct origins. First, to the work by the pharmacologist Loewe on the concept of concentration additivity and second to the biometrician Bliss and the concept of independent action. In the search for a general solution and a unified terminology the interrelations of the concepts have extensively been studied and experimental findings reviewed. Meanwhile there seems to be consensus in experimental sciences that each concept has its role in predicting combined effect of agents and both are used for hazard und risk management.In contrast, epidemiologists describe combined effects mainly in terms of interactions in regression models. Although this approach started from a probabilistic model equivalent to the concept of independent action this origin is rarely acknowledged and effect summation is usually the preferred concept nowadays. Obscure biological meaning, the scale dependency of interaction terms as well as unavoidable residual confounding are taken as reasons why no new insights in combined effect analysis are likely to occur from epidemiology.In this paper we sketch the history of ideas and the state of the arts in combined effect analysis. We point to differences and common grounds in experimental biosciences and epidemiology.

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“…This strategy also allowed tackling the question of whether effect thresholds of individual mixture components were protective against combination effects. A series of studies was designed to test multi-component mixtures with wellknown mechanisms and modes of action for their components to investigate the following: 1) reference mixtures composed of compounds with entirely similar and dissimilar action [7,8]; 2) mixtures with components in concentrations at and below statistically significant effects [9]; and 3) 2 different biological systems (bacteria and algae) to provide a proof of principle [7,9]. As a prerequisite to meet the goal of analyzing low effect concentrations in the mixture experiments rigorous concentrationresponse estimations were performed employing a so-called "best fit modeling," based on the simultaneous application of different nonlinear concentration-effect regression models [10].…”

mentioning

confidence: 99%

“…See Table S1 for the number of citations and rank of all the "Top 100" papers, which in this essay are references [7,8].…”

mentioning

confidence: 99%

Simplifying complexity: Mixture toxicity assessment in the last 20 years

Altenburger

Backhaus

Boedeker³

et al. 2013

Enviro Toxic and Chemistry

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127

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Chemical monitoring provides ample evidence that organisms in their environment are exposed to complex cocktails of contaminants rather than individual chemicals. Thus, the challenge emerges on how to assess potential combined effects of such mixture exposures. The body of toxicological and ecotoxicologcial literature in the 90s suggested that combined effects of toxicological significance may indeed be caused in humans and the environment by an exposure to chemical mixtures. Furthermore, abundant statements seemed to agree that synergy was a major problem for environmental risk assessment. At the same time it was clear that an assessment of synergies based on the experimental testing of all possible mixtures occurring or anticipated in the environment was not a viable option for risk assessment. Moreover, existing uncertainty factors in chemical risk assessment are not intended to account for mixture effects, and formulating additional factors that would ensure the desired level of protection could not be based on any evidence. Therefore, it seemed as if chemical risk assessment was stuck in a deadlock without any management option, and revisiting component-based methodologies for assessing combined effects appeared as the most promising approach.The empirical evidence of the time was derived mainly from studies of binary pesticide mixtures in short-term aquatic toxicity assays, which were analyzed by a plethora of different and often conflicting approaches. The confusion in terminology, methods, and conceptual premises reached almost Babylonian proportions, which lead to the widespread perception of unpredictability as the dominating feature of mixture (eco) toxicology. The various mathematical models and tools available fostered the assessment of combined effects without explicitly formulating the underlying, often fundamentally different assumptions of the different approaches. Furthermore, these assumptions were all too often not translated into consistent guidelines for the experimentalist, and descriptive tools seemed all too simplistic for a sound mixture toxicity assessment.

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Predictability of the Toxicity of Multiple Chemical Mixtures to Vibrio Fischeri: Mixtures Composed of Similarly Acting Chemicals

Cited by 258 publications

References 22 publications

Joint toxicity of a pyrethroid insecticide, cypermethrin, and a heavy metal, lead, to the benthic invertebrate Chironomus dilutus

Joint toxicity of a pyrethroid insecticide, cypermethrin, and a heavy metal, lead, to the benthic invertebrate Chironomus dilutus

The scientific assessment of combined effects of risk factors: different approaches in experimental biosciences and epidemiology

Simplifying complexity: Mixture toxicity assessment in the last 20 years

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