A Unified Theory for Quantal Responses to Mixtures of Drugs: Non-Interactive Action

Hewlett, P. S.; Plackett, R. L.

doi:10.2307/2527657

Cited by 162 publications

(72 citation statements)

References 14 publications

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“…To date, two basic concepts have been developed to quantify the combined effects of toxicants on organisms, dose addition (DA) and response addition (RA) [1]. Dose addition is applied for mixtures in which substances exert effects through the same primary site or sites of action.…”

Section: Introductionmentioning

confidence: 99%

Response predictions for organisms water‐exposed to metal mixtures: A meta‐analysis

Vijver

Elliott

Peijnenburg

et al. 2011

Enviro Toxic and Chemistry

113

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To develop a multimetal toxicity model requires insight into the relationships between the composition of metal mixtures and their toxicological effects on organisms. As a first step in developing such a model, quantitative data from binary and higher mixture studies of Cu, Cd, and Zn were compiled and used to assess trends in toxicological effects on various organisms. The findings of this meta-analysis show relatively little occurrence of additive effects compared with antagonistic and synergistic effects. This observation held true irrespective of test species, environmental compartment, or metal concentrations in the mixture. However, the type of effect was significantly correlated with the metal combination tested and the selected toxicological endpoint. It was also found that different methods were used for assessing deviation from additivity in the various individual studies. For robust comparison, standardization on this point is required. Toxicological responses of organisms to metal mixtures were shown to be hard to predict and were often slightly less than or slightly more than additive. The interactions observed could not be explained by metal-metal interactions alone. We therefore conclude that with current scientific knowledge it is not yet possible to predict responses to metal mixtures in individual cases; at best this is possible only in terms of general patterns. Nevertheless, in the context of environmental risk policy, the assumption of additivity produces a conservative prediction of toxicity, because toxicity of a metal mixture will be either predicted correctly or overpredicted by default in approximately 75% of all cases. The use of models based on noninteraction is satisfactory from this regulatory perspective.

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Section: Introductionmentioning

confidence: 99%

Response predictions for organisms water‐exposed to metal mixtures: A meta‐analysis

Vijver

Elliott

Peijnenburg

et al. 2011

Enviro Toxic and Chemistry

113

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show abstract

“…Thus, synergism is thought to exist when the mixture effect exceeds those of the most effective single component (22,23). For our analysis we have used both approaches to evaluating combination effects.…”

mentioning

confidence: 99%

Mixtures of Four Organochlorines Enhance Human Breast Cancer Cell Proliferation

Payne¹,

Scholze²,

Kortenkamp³

2001

Environmental Health Perspectives

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“…The joint action toxicity of the botanical mixtures was determined by two models: (1) the concentration-addition model by Anderson and Weber (1975), modified by Otitoloju (2003) with Relative Toxic Units (RTU) estimations; (2) synergistic ratios (SR) model (Hewlett and Plackett, 1969;Chukwu et al, 2009). …”

Section: Joint Action Toxicity Of Botanical Mixturesmentioning

confidence: 99%

The joint action effects of the binary mixtures of some botanical piscicides on post juvenile Clarias gariepinus

A¹,

K²,

A³

2016

Int. J. Fish. Aquac.

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A Unified Theory for Quantal Responses to Mixtures of Drugs: Non-Interactive Action

Cited by 162 publications

References 14 publications

Response predictions for organisms water‐exposed to metal mixtures: A meta‐analysis

Response predictions for organisms water‐exposed to metal mixtures: A meta‐analysis

Mixtures of Four Organochlorines Enhance Human Breast Cancer Cell Proliferation

The joint action effects of the binary mixtures of some botanical piscicides on post juvenile Clarias gariepinus

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