Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals (2017) / Chapter Skim
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2 Strategy for Evaluating Low-Dose Effects
2 Strategy for Evaluating Low-Dose Effects
Pages 21-40
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From page 21... ...
BOX 2-1 Potential Limitations of Traditional Toxicity Testing for Evaluating Low-Dose Effects of Endocrine Active Chemicals Protocols might not include relevant windows of exposure or evaluation. Studies might not include relevant outcomes.
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In other cases where key uncertainties exist, further action could entail the generation of new data or models to address the uncertainties. If the results of an investigation suggest that adverse outcomes in humans are expected or might be occurring at low doses, the conclusions of previous toxicity testing or toxicity assessments for the chemicals that are under investigation might need to 22
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SURV VEILLANCE E In th context of this report, surveillance re he efers to the p process for de etecting signa (indication that als ns an adverse outcome in a human po n opulation or animal model might be rel a l lated to expo osure to an EA at AC low doses by searchin retrieving and evaluat s) ng, g, ting existing data.
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The study of endocrine-related human diseases, such as prostate cancer and endometriosis, might also identify adverse effects that are not readily detected in rodent studies. For example, endometriosis is a human disease that is difficult to assess in animal models because most nonprimate mammals do not menstruate and consequently do not develop ectopic lesions, which are the pathological hallmarks of endometriosis (Bellofiore et al.
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. Another means of identifying a potential public-health problem is to consider input from advocacy groups, BOX 2-2 Endometriosis: An Example in Which Traditional Toxicity Testing Might Be Inadequate to Evaluate Endocrine Active Chemicals Human disease Endometriosis is characterized by the presence of an ectopic endometrium.
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A previous NRC committee provided the following recommendations regarding the need to use biomonitoring data in surveillance programs: "Develop biomonitoring-based epidemiologic, toxicologic, and exposure-assessment investigations and public-health surveillance to interpret the risks posed by low-level exposure to environmental chemicals. Where possible, enhance existing exposure assessment, epidemiologic, and toxicologic studies with biomonitoring to improve the interpretation of results of such studies" (NRC 2006a, p.
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Surveillance of Endocrine-Mediated Drug Reactions Using Pharmacovigilance The US Food and Drug Administration (FDA) has developed pharmacovigilance4 programs to monitor for adverse drug reactions (ADRs)
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The committee concludes that methods that have been developed for pharmacovigilance programs might be adapted or help inform an EAC surveillance program. The committee notes, however, that EAC surveillance programs that are based solely on voluntary reporting might be limited because people often cannot self-report environmental exposures.
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Will including the new outcome in regulatory testing improve hazard identification -- that is, improve sensitivity? Box 2-5 provides a retrospective example of how the answers to these questions helped establish the measurement of anogenital distance as an outcome measure in regulatory toxicity tests.
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. Systematic Review Systematic reviews provide a method for evaluating evidence in a transparent and consistent manner that reduces bias.
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One way of improving our understanding of mechanistic data involves the development of conceptual models that facilitate the organization of information about biological interactions and toxicity mechanisms. A conceptual model can reflect the initial interactions of a chemical with the biological system and the resulting events that can lead to a specific adverse outcome (Ankley et al.
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Although not very informative for causal inferences, environmental exposure data, such as biomonitoring data, might nevertheless be useful for defining what subset of the data can be considered as low dose (see discussion earlier in this chapter)
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Integration of evidence for low-dose ad verse human effects of EACs involves consideration of both hazard identification and dose re sponse. Recommendation: Environmental exposure data should be used, if available, to define what sub set of the data should be considered as low dose.
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2016. Integrating publicly available data to generate computationally predicted adverse outcome pathways for fatty liver.
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2012. Literature based drug interaction predic tion with clinical assessment using electronic medical records: Novel myopathy associated drug interactions.
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2014. A method for controlling complex con founding effects in the detection of adverse drug reactions using electronic health records.
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2015. Pharmacovigilance from social media: Mining adverse drug reaction mentions using sequence labeling with word embedding cluster features.
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2007. Chemicals causing mammary gland tumors in ani mals signal new directions for epidemiology, chemicals testing, and risk assessment for breast cancer preven tion.
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2007. Workgroup report: National Toxicology Program Workshop on Hormonally Induced Reproductive Tumors -- Relevance of Rodent Bioassays.
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2014. The Navigation Guide systematic review methodology: A rigorous and trans parent method for translating environmental health science into better health outcomes.
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