Environmental Factor – January 2022: Impact of variability in animal test data discussed by Kleinstreuer


The U.S. Environmental Protection Agency (EPA) requested the National Academies of Sciences, Engineering, and Medicine to review the variability of data from animal exams for chemical security and the relevance of such data to human well being. On Dec. 9, the National Academies panel on “Variability and Relevance of Current Laboratory Mammalian Toxicity Tests and Expectations for New Approach Methods (NAMs) for Use in Human Health Risk Assessment” held a public workshop to listen to from stakeholders. Participants shared their wants and expectations for toxicity data used to tell chemical security selections, and so they discussed how data variability impacts analysis strategies.

Kleinstreuer co-moderated a session of the Dec. 9 workshop. (Photo courtesy of Steve McCaw / NIEHS)

Nicole Kleinstreuer, Ph.D.
, performing director of the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods( (NICEATM), is a member of the National Academies panel. Environmental Factor spoke together with her concerning the National Academies examine and the way this mission suits into different ongoing NICEATM actions.

EF: What had been your impressions of the workshop?

Kleinstreuer: The audio system raised provocative questions that may assist direct the panel’s efforts to deal with the cost offered by EPA. Several discussions targeted on what the variability in animal data represents. That is, does it come up from variations in animal biology that will be analogous to heterogeneity in the human inhabitants? Or is it merely a measure of inconsistency in responses resulting from variations in examine protocols and experimental observe?

EF: Your workplace helps to advertise alternate options to animal use for security testing. How does your participation on this panel match into that work?

Kleinstreuer: Variability in animal data has great implications for growth and acceptance of alternate options to animal use, or NAMs, for chemical security testing. For many toxicity endpoints, an animal test is the one obtainable reference in opposition to which to evaluate the efficiency of a nonanimal different. When you repeat an animal test, you typically discover that you just get the identical final result perhaps 60% or 70% of the time. That makes it unreasonable to ask a nonanimal different to agree with the animal test 80% or 90% of the time, which generally appears to be the expectation when the efficiency of the choice is evaluated.

EF: Is there a greater possibility for evaluating NAMs?

Kleinstreuer: I believe so. Rather than evaluating new strategies to animal exams, human well being threat evaluation is perhaps higher served by specializing in whether or not NAMs are protecting and are mechanistically and biologically related to people. NICEATM and collaborators examined how this may work for eye irritation in a paper revealed final yr. We discovered that in vitro fashions derived from human cells and tissues are extra reflective of human biology and fewer variable than the at present used animal test.

EF: But animal strategies have been used for a very long time, and persons are going to proceed to match new strategies to them. Was there info offered on the workshop that might assist researchers appropriately think about animal data variability in this context?

Kleinstreuer: Two wonderful meta-analyses offered by David Allen [from ILS, the contractor supporting NICEATM], and Katie Paul Friedman [from EPA] proposed quantitative confidence intervals that could possibly be thought-about when evaluating NAMs to reference animal requirements. This strategy might present a extra practical customary for analysis of new strategies.

EF: What’s subsequent for the panel?

Kleinstreuer: The panel met once more shortly after the December workshop to evaluation what we heard and plan subsequent steps. We will maintain extra public conferences in 2022, and we anticipate to concern a report with suggestions late in the yr.

Citation: Clippinger AJ, Raabe HA, Allen DG, Choksi NY, van der Zalm AJ, Kleinstreuer NC, Barroso J, Lowit AB. 2021. Human-relevant approaches to evaluate eye corrosion/irritation potential of agrochemical formulations. Cutan Ocul Toxicol 40(2):145–167.

(Catherine Sprankle is a communications specialist for ILS, the contractor supporting NICEATM.)