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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Reproductive toxicants have a threshold of adversity
Aldert H Piersma1, Lya G Hernandez, Jan van Benthem
1Laboratory for Health Protection Research, Center for Substances and Integrated Risk Assessment, National Institute for Public Health and the Environment, RIVM, Bilthoven, The Netherlands. aldert.piersma@rivm.nl
Critical Reviews in Toxicology
|May 26, 2011
Summary
The threshold dose approach remains valid for assessing reproductive toxicants, unlike the linear extrapolation paradigm used for genotoxic carcinogens, which is a debatable worst-case scenario.
Area of Science:
- Reproductive toxicology
- Chemical risk assessment
- Regulatory science
Background:
- Current regulatory discussions suggest applying the linear extrapolation risk assessment paradigm to reproductive toxicants.
- This paradigm was originally developed for genotoxic carcinogens.
- This approach contrasts with the established threshold dose approach for reproductive hazard assessment.
Purpose of the Study:
- To survey the scientific basis of the current threshold approach for reproductive hazard and risk assessment.
- To evaluate the suitability of the linear extrapolation paradigm for reproductive toxicants.
- To provide clarity on risk assessment and Classification, Labelling and Packaging (CLP) for reproductive toxicants.
Main Methods:
- Review of the scientific literature on reproductive toxicology and risk assessment paradigms.
- Analysis of testing procedures for reproductive toxicity, including exposure windows and determined parameters.
- Examination of dose-response relationships in reproductive toxicology.
- Comparison of the threshold approach with the linear extrapolation model for genotoxic carcinogens.
Main Results:
- The linear extrapolation risk assessment paradigm for genotoxic carcinogens is presented as a debatable worst-case scenario.
- The scientific basis for the threshold dose approach in reproductive toxicology is surveyed.
- Testing methodologies, including exposure details and dose-response relationships, are discussed.
Conclusions:
- The threshold dose approach is scientifically valid and remains appropriate for the risk assessment of reproductive toxicants.
- The linear extrapolation paradigm is not suitable for reproductive toxicants.
- Current risk assessment and CLP conclusions for reproductive toxicants are supported by the threshold approach.
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