Reproductive toxicants have a threshold of adversity

Piersma, Aldert H.; Hernández, Lya G.; Benthem, Jan van; Müller, Julia; Leeuwen, F.X.R. van; Vermeire, Theo; Raaij, M.T.M. van

doi:10.3109/10408444.2011.554794

Cited by 49 publications

(28 citation statements)

References 83 publications

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“…Processes believed to be driven by the interaction of toxicants with non-DNA cellular constituents are often evaluated by assuming a threshold dose below which no effect is expected. Toxicologists generally acknowledge and support the existence of homeostatic mechanisms and employ the supposition that adverse effects occur only when these mechanisms are saturated or overloaded [Piersma et al, 2011]. As a result, a NOEL can be derived from the dose-response information generated for safety assessment studies.…”

Section: Discussionmentioning

confidence: 99%

Quantitative approaches for assessing dose–response relationships in genetic toxicology studies

Gollapudi

Johnson

Hernández

et al. 2012

Environ and Mol Mutagen

131

130

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Genetic toxicology studies are required for the safety assessment of chemicals. Data from these studies have historically been interpreted in a qualitative, dichotomous ''yes'' or ''no'' manner without analysis of doseresponse relationships. This article is based upon the work of an international multi-sector group that examined how quantitative dose-response relationships for in vitro and in vivo genetic toxicology data might be used to improve human risk assessment. The group examined three quantitative approaches for analyzing dose-response curves and deriving point-of-departure (POD) metrics (i.e., the no-observed-genotoxic-effectlevel (NOGEL), the threshold effect level (Td), and the benchmark dose (BMD)), using data for the induction of micronuclei and gene mutations by methyl methanesulfonate or ethyl methanesulfonate in vitro and in vivo. These results suggest that the POD descriptors obtained using the different approaches are within the same order of magnitude, with more variability observed for the in vivo assays. The different approaches were found to be complementary as each has advantages and limitations. The results further indicate that the lower confidence limit of a benchmark response rate of 10% (BMDL 10 ) could be considered a satisfactory POD when analyzing genotoxicity data using the BMD approach. The models described permit the identification of POD values that could be combined with mode of action analysis to determine whether exposure(s) below a particular level constitutes a significant human risk. Subsequent analyses will expand the number of substances and endpoints investigated, and continue to evaluate the utility of quantitative approaches for analysis of genetic toxicity dose-response data. Environ. Mol. Mutagen. 54:8-18, 2013. V V C 2012 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Quantitative approaches for assessing dose–response relationships in genetic toxicology studies

Gollapudi

Johnson

Hernández

et al. 2012

Environ and Mol Mutagen

131

130

View full text Add to dashboard Cite

show abstract

“…In keeping with the basic principles of toxicology, a recent evaluation of data on reproductive toxicants indicated that both the dose and the window of exposure determine the outcome (Piersma et al, 2011). Accordingly, if a substance causes critical adverse effects within a window of susceptibility, this still requires a dose above a certain level (Piersma et al, 2011).…”

Section: Windows Of Susceptibility and Data Requirementsmentioning

confidence: 97%

Assessment of three approaches for regulatory decision making on pesticides with endocrine disrupting properties

Marx‐Stoelting

Niemann

Ritz

et al. 2014

Regulatory Toxicology and Pharmacology

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Recent EU legislation has introduced endocrine disrupting properties as a hazard-based "cut-off" criterion for the approval of active substances as pesticides and biocides. Currently, no specific science-based approach for the assessment of substances with endocrine disrupting properties has been agreed upon, although this new legislation provides interim criteria based on classification and labelling. Different proposals for decision making on potential endocrine disrupting properties in human health risk assessment have been developed by the German Federal Institute for Risk Assessment (BfR) and other regulatory bodies. All these frameworks, although differing with regard to hazard characterisation, include a toxicological assessment of adversity of the effects, the evaluation of underlying modes/mechanisms of action in animals and considerations concerning the relevance of effects to humans. Three options for regulatory decision making were tested upon 39 pesticides for their applicability and to analyze their potential impact on the regulatory status of active substances that are currently approved for use in Europe: Option 1, based purely on hazard identification (adversity, mode of action, and the plausibility that both are related); Option 2, based on hazard identification and additional elements of hazard characterisation (severity and potency); Option 3, based on the interim criteria laid down in the recent EU pesticides legislation. Additionally, the data analysed in this study were used to address the questions, which parts of the endocrine system were affected, which studies were the most sensitive and whether no observed adverse effect levels were observed for substance with ED properties. The results of this exercise represent preliminary categorisations and must not be used as a basis for definitive regulatory decisions. They demonstrate that a combination of criteria for hazard identification with additional criteria of hazard characterisation allows prioritising and differentiating between substances with regard to their regulatory concern. It is proposed to integrate these elements into a decision matrix to be used within a weight of evidence approach for the toxicological categorisation of relevant endocrine disruptors and to consider all parts of the endocrine system for regulatory decision making on endocrine disruption.

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“…It has been reported that the TTC for general toxicity can also be applied to both the developmental and reproductive toxicity endpoints (Laufersweiler et al, 2012). Piersma et al concluded that all endpoints in reproductive toxicology have shown thresholds of adversity, thus there is evidence for the presence of dose levels with no appreciable increase in risk (Piersma et al, 2011). For reproductive toxicity, the same TTC values have been suggested as for general toxicity, given that NOAELs of reproductive toxicity studies tend to be similar or higher than those observed in general toxicity studies (Kroes et al, 2007).…”

Section: Inmentioning

confidence: 98%

Criteria for the Research Institute for Fragrance Materials, Inc. (RIFM) safety evaluation process for fragrance ingredients

Api

Belsito

Bruze

et al. 2015

Food and Chemical Toxicology

1,566

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Reproductive toxicants have a threshold of adversity

Cited by 49 publications

References 83 publications

Quantitative approaches for assessing dose–response relationships in genetic toxicology studies

Quantitative approaches for assessing dose–response relationships in genetic toxicology studies

Assessment of three approaches for regulatory decision making on pesticides with endocrine disrupting properties

Criteria for the Research Institute for Fragrance Materials, Inc. (RIFM) safety evaluation process for fragrance ingredients

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