Table 5.

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

Factor	Rating	Basis
Risk of bias across studies	–1	“Allocation concealment” and “blinding” risks of bias were a) truly present, and b) these risks of bias are shown empirically to influence study outcome in preclinical experimental animal studies.
Indirectness	0	Mammalian data are empirically recognized as direct evidence of human health (Kimmel et al. 1984; U.S. EPA 1996) and there are no data to counteract this assumption.
Inconsistency	0	Point estimates across similar studies (e.g., mouse gavage) are consistent with overlapping confidence bounds. Estimates of change in birth weight from studies in the meta-analysis are consistently in the same direction and have low heterogeneity. Results are also consistent in magnitude and direction of effect estimates. Results of the meta-analysis do not appear to be strongly influenced by an individual study.
Imprecision	0	Mammalian data included in the meta-analysis showed relatively small CIs in final estimates. 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 studies were consistent among their findings regardless of size and funding source; the search was comprehensive, and no unpublished studies were found that presented results out of the range of estimates reported by published studies.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”)	Moderate	“High” + (–1) = “moderate”
Summary of findings from meta-analysis	NA	Average change in birth weight = –0.023 g [–0.029, –0.016] per 1-unit increase in dose (mg/kg BW/day)
Summary of findings from qualitative analysis	NA	The dose–response data showed mixed results, generally with lower doses showing increased weight compared with the control group (mostly nonsignificant) and higher doses showing decreased weight (some statistically significant and other not significant).
Overall strength of evidence	Sufficient
NA, not applicable. Ratings: –1, 1 level downgrade in quality. 0, no change in quality. Studies included in meta-analysis [source ID]: Abbott et al. 2007 [528], Hines et al. 2009 [260], Lau et al. 2006 [635] (birth weight data), White et al. 2007 [566], White et al. 2009 [312], White et al. 2011 [3862], and Wolf et al. 2007 [571] (cross-foster and windows of sensitivity data). Other studies [source ID]: Boberg 2008 et al. [3061], Fenton et al. 2009 [264], Hinderliter et al. 2005 [711], Hu et al. 2010 [68], Lau et al. 2006 [635] (fetal weight data), Onishchenko et al. 2011 [3610], Staples 1984 et al. [1871], Yahia et al. 2010 [103], and York 2002 [5122].