Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals (2017) / Chapter Skim
Currently Skimming:
5 Lessons Learned and Reflections on the Statement of Task
5 Lessons Learned and Reflections on the Statement of Task
Pages 153-162
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 153... ...
This decision was driven partly by the statement of task, which specified that the committee should complete systematic reviews of human and animal toxicology data for two or more chemicals that affect an endocrine hormone system. The committee's reliance on systematic-review methods is also consistent with recommendations made by previous National Academies committees (NRC 2014a,b)
|
From page 154... ...
As discussed in Chapter 3, it is dif ficult to compare the effects of different levels of phthalate exposure in animals and humans directly because animal studies typically report administered doses whereas studies in humans rely on the measurement of phthalate metabolites in urine or other body fluids. The committee considered human exposure and pharmacokinetic data that were found through literature reviews to address this ques tion qualitatively.
|
From page 155... ...
It is therefore unclear that changes in testosterone or AGD in the absence of other apical reproductive end points would meet the first part of the committee's definition of an adverse effect -- "a biological change in an organism that results in an impairment of functional capacity." The committee also considered whether phthalate-induced changes in fetal testosterone or AGD might increase the susceptibility of an organism to other influences. Sufficient androgen activity is required for proper male reproductive-tract development, and this activity is a consequence of multiple inputs at the molecular level.
|
From page 156... ...
REFLECTIONS AND LESSONS LEARNED FROM THE SYSTEMATIC REVIEWS Selection of Example Chemicals The specification that the systematic reviews be performed on chemicals that "act through an endocrine-mediated pathway" and "that affect the estrogen, androgen, or perhaps other endocrine systems" led to extensive discussions about how stringent the committee should be about using mechanistic data to guide chemical selection. The committee's goal was to identify candidate chemicals that were presumed to be associated with endocrine effects.
|
From page 157... ...
They include the need for improved reporting of study design, conduct, and results on the part of scientists to facilitate risk of bias evaluations; approaches for displaying behavioral and categorical data within a systematic review; and inclusion of subject-matter expertise on the review team, including expertise in meta-analysis and other statistical approaches. It is often not clear if a study used best practices in the study design and conduct but failed to report those good practices, or if there were issues in study conduct that would result in potential bias.
|
From page 158... ...
For example, the committee used mechanistic evidence to support the finding that DEHP effects on AGD in humans were biologically plausible. The OHAT hazard identification scheme also allows consideration of mechanistic data to upgrade or downgrade the initial hazard determination.
|
From page 159... ...
End-Point Concordance The methods used to assess fetal testosterone, AGD, and hypospadias were qualitatively similar between animal and human studies, and this simplified the analysis of whether the responses seen were concordant or discordant. In addition, end-point consistency between human and animal studies provided additional confidence in biological plausibility for hazard identification.
|
From page 160... ...
Indeed, differences in exposure between animal studies and those observed in the general human population spanned several orders of magnitude. Strategies to help resolve apparent discrepancies often rest on an improved understanding of health effects seen in people, revisions to animal-testing guidelines that help improve their predictive value, consideration of animal studies that include additional end points, and efforts to use mechanistic and pharmacokinetic data to bridge these seemingly disparate data streams (NRC 2007, 2009)
|
From page 161... ...
2011. Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York.
|
From page 162... ...
2015. Handbook for Conducting a Literature-based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.