Table 6.

Non­mammalian summary of findings, quality of evidence, and strength of evidence.

Factor	Rating	Basis
Risk of bias across studies	–1	“Sequence generation,” “allocation concealment,” and “blinding” risks of bias were: a) truly present; and b) these risks of bias are shown to empirically influence study outcome in preclinical experimental animal studies.
Indirectness	–1	We lacked an empirical basis supporting that these non­mammalian data were directly relevant to the human health outcome of interest, and the routes of exposure varied from how humans would be exposed to PFOA. Some evidence supports indirectness, in particular: Embryonic development in mammalian organisms (i.e., in utero development and live birth) is fundamentally different from development in non­mammalian organisms (i.e., development in egg and hatching), and the route of exposures for the non­mammalian organisms (i.e., eggs injected with or immersed in PFOA-containing solution) are not applicable to humans or other mammalian organisms.
Inconsistency	0	Results appear to divide based on measurement of outcome (weight vs. length); however, results are consistent between comparable studies (comparable for outcome, species, and exposure route).
Imprecision	0	The zebrafish and fruit fly data have a relatively large sample size, and while no confidence bounds are given, the effect estimates are reasonably close to each other (–5% to –20% change). Although some studies did not report CIs, data show statistically significant responses at high doses—indicating small CIs.
Publication bias	0	We found no reason to suspect publication bias. The search was comprehensive, the studies were of various sizes and had various funding sources, and no unpublished studies were found that presented results out of the range of estimates reported by published studies.
Overall quality of evidence (initial rating is “high”)	Low	“High” + (–2) = “Low”
Summary of findings from qualitative analysis	NA	Dose–response data show mostly nonstatistically significant increases in body weight, even at the highest tested doses. The length data show mixed results, with two studies demonstrating statistically significant decreases in length and the other two studies showing statistically nonsignificant increases in length.
NA, not applicable. Ratings: –1, 1 level downgrade in quality. 0, no change in quality. Studies [source ID]: Hagenaars et al. 2011 [59], Jiang et al. 2012 [3926], O’Brien et al. 2009 [236], Pinkas et al. 2010 [187], Spachmo and Arukwe 2012 [3932], and Wang et al. 2010 [86].