The physical toxicity of chemicals. II. Factors affecting physical toxicity in aqueous solutions

McGowan, J. C.

doi:10.1002/jctb.5010020607

Cited by 43 publications

(3 citation statements)

References 19 publications

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“…McGowan (1952) extended Ferguson's arguments with additional data and analyses, addressing some of the earlier points. Mullins (1954) provided an extensive and detailed review of the theory and current understanding of phase partitioning, molar volume fractions, chemical activity, membrane characteristics, and narcotic and nonnarcotic toxicity.…”

Section: Review Of Issuesmentioning

confidence: 99%

Evaluation of the Inherent Toxicity Concept in Environmental Toxicology and Risk Assessment

McCarty

Borgert²,

Burgoon³

2020

Enviro Toxic and Chemistry

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Intrinsic/inherent chemical properties are characteristic, irrespective of the number of molecules present. However, toxicity is an extensive/extrinsic biochemical property that depends on the number of molecules. Paracelsus, often considered the father of toxicology, noted that all things are poisonous. Because dose magnitude (i.e., number of molecules) determines the occurrence of poisonous effects, toxicity cannot be an intrinsic/inherent biochemical property. Thus, toxicology's task is to determine case-specific risks resulting in adverse effects produced by the interaction of toxic doses/exposures, toxic mechanisms, and case-specific influencing factors. Experimental testing results are known to vary within and between chemicals, test organisms, and experimental conditions and repetitions; however, hazard-based approaches treat toxicity as a fixed and constant property. A logical alternative is the standard-risk, case-specific risk model. In this approach, testing data are defined as standard risks where the nature, magnitude, and toxicity effect is standardized to the organism, chemical, and test conditions. Interpolation/extrapolation of standard risks to site-specific conditions (i.e., case-specific risks) is challenging, requiring understanding of the influences of the complex interactions within and between differing species, conditions, and toxicitymodifying factors. Therefore, Paracelsus's paradigm is perhaps better abbreviated as "dose-causality-response", because a key interpretive requirement is establishing toxicity causality by separating mode/mechanism of toxic action from modifying factor influences in overall toxicity responses. Unfortunately, the current knowledge base is inadequate. Moving to a standardrisk-specific-risk paradigm would highlight the importance of improving the toxicity causality knowledge base. Thereby, a rationale would be provided for enhancing the design and interpretation of toxicity testing that is necessary for achieving advances in routine translation of standard-risk to specific-risk estimates-the raison d'être of regulatory risk decision making.

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Section: Review Of Issuesmentioning

confidence: 99%

Evaluation of the Inherent Toxicity Concept in Environmental Toxicology and Risk Assessment

McCarty

Borgert²,

Burgoon³

2020

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

show abstract

“…This approach was restricted to substances with limited chemical reactivity, substances with a so-called “physical action”. Soon after, McGowan recognized the importance of the molecular volume and hydrogen bonding to biological activity, and Mullins expanded the thermodynamic treatment . Hansch and co-workers introduced the partition coefficient between octanol and water ( K ow or P ow ) as an additive parameter describing hydrophobicity and extended the QSAR equations into linear free energy relationships. , The P ow has since then remained the most frequently used parameter in QSAR studies …”

Section: Quantitative Structure−activity (And Toxicity) Relationshipsmentioning

confidence: 99%

Toward a Comprehensive Molecular Design Framework for Reduced Hazard

2010

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“…In a series of 3 papers, McGowan (1951, 1952a, 1952b) continued the theoretical development started by Ferguson. McGowan used molar concentrations, rather than using Ferguson's chemical activity directly, and further promoted the quantitative structure–activity relationship (QSAR) approach to interpret toxicity test results, employing molar volume/parachor and hydrogen bonding as the molecular descriptors.…”

Section: Brief Historical Perspective On Body And/or Tissue Residues mentioning

confidence: 99%

Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues

McCarty

Landrum

Luoma

et al. 2010

Integr Envir Assess & Manag

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The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residue-effect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions.

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The physical toxicity of chemicals. II. Factors affecting physical toxicity in aqueous solutions

Cited by 43 publications

References 19 publications

Evaluation of the Inherent Toxicity Concept in Environmental Toxicology and Risk Assessment

Evaluation of the Inherent Toxicity Concept in Environmental Toxicology and Risk Assessment

Toward a Comprehensive Molecular Design Framework for Reduced Hazard

Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues

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