Interactions and their impact on the applicability of Concentration Addition for environmentally realistic mixtures

• Regulatory guidelines make heavy use of Concentration Addition (CA) as a tool for predicting and assessing the toxicity of chemical mixtures. CA assumes that the compounds in a mixture do not interact with each other, neither in their toxicokinetic nor in their toxicodynamic phase. However, several of those interactions are described in the scientific literature for almost all major groups of environmental chemicals. These result in essentially synergistic or antagonistic mixture toxicities, i.e. higher, respectively lower mixture toxicities than expected by CA. With a view on the regulatory risk assessment of chemical mixtures, it is hence important to quantify the range of expectable synergisms, respectively antagonisms. I discuss the quantitative consequences of interactions for the predictive power of CA using two published studies on the hazards and risks of environmentally realistic mixtures. One case study concerns the human health effects of a mixture of anti-androgens, the other the ecotoxicity of a pesticide mixture. Based on a series of simulation studies in which interactions were gradually assumed to occur in the mixtures, I outline the limiting cases (worst case situations) as well as the fundamental relationship between expectable deviations from CA and number of mixture components, mixture ratio and number of interacting substances in the mixture.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Ekologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Ecology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Mikrobiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Microbiology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Geovetenskap och miljövetenskap -- Miljövetenskap (hsv//swe)

NATURAL SCIENCES  -- Earth and Related Environmental Sciences -- Environmental Sciences (hsv//eng)

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