Table 4.

Evidence profile table for developmental effects of DIBP or MIBP

Developmental effects
Outcome		Available studies	Factors that increase confidence	Factors that decrease confidence	Confidence judgement for outcome	Confidence judgement for overall hazard
Gestational (F1) Exposure	Fetal survival	High confidence: BASF, 2007 Borch et al., 2006 Howdeshell et al., 2008 Saillenfait et al., 2006 Saillenfait et al., 2008 Saillenfait et al., 2017 Wang et al., 2017 Medium confidence: Hannas et al., 2012 Furr et al., 2014 Low confidence: Hannas et al., 2011	Dose-response gradient, effect size, and minimal concern for bias in studies by Saillenfait et al., 2006 and Howdeshell et al., 2008 Biological plausibility (support from mechanistic evidence for DBP)		⊕⊕⊕ ROBUST A dose-related increase in post-implantation loss was observed in two Sprague-Dawley rat studies that exposed animals from GD 6-20 and GD 8-18, respectively (Howdeshell et al., 2008, Saillenfait et al., 2006), but not in Wistar rats or mice exposed for a similar duration. Fetal survival was also not affected in studies that exposed Sprague-Dawley rats for shorter durations in mid- to late gestation.	⊕⊕⊕ ROBUST Based on consistent evidence of reduced fetal and postnatal growth across studies, evidence of reduced fetal survival in Sprague-Dawley rats exposed for longer durations in gestation, and slight evidence of structural alterations following gestational exposure.
	Fetal growth	High confidence: BASF, 2007 Borch et al., 2006 Saillenfait et al., 2006 Saillenfait et al., 2008 Saillenfait et al., 2017 Medium confidence: Wang et al., 2017	Consistency Dose-response gradient Effect size Minimal concern for bias		⊕⊕⊕ ROBUST A dose-related decrease in fetal body weights or body weights at birth were consistently in rats at higher dose levels, but were not observed in lower dose studies.
	Fetal structural alterations	High confidence: BASF, 2007 Saillenfait et al., 2006 Saillenfait et al., 2017	Dose-response gradient and minimal concern for bias and sensitivity in the study by Saillenfait et al., 2006	Few studies	⊕◯◯ SLIGHT A dose-related increase in external, visceral, and skeletal malformations was reported in Sprague-Dawley rats by Saillenfait et al., 2006, but not in a similar study in Wistar rats by BASF, 2007. There were no external malformations in a lower dose study by Saillenfait et al., 2017.
	Postnatal survival	High confidence: Saillenfait et al., 2008	Minimal concern for bias	Single study	◯◯◯ INDETERMINATE Effects on postnatal survival following gestational exposure were not observed in the single study that evaluated this outcome.
	Postnatal growth	High confidence: Saillenfait et al., 2008 Medium confidence: Wang et al., 2017	Dose-response gradient and minimal concern for bias in the study by Saillenfait et al., 2008	Few studies	⊕⊕◯ MODERATE A dose-related decrease in postnatal growth was observed in rats exposed during gestation (Saillenfait et al., 2008), but not in a mouse study that tested a single, lower dose of DIBP (Wang et al., 2017).
Postnatal (Weanling or Peripubertal) Exposure	Postnatal growth	Medium confidence: Sedha et al., 2015 Low confidence: Oishi and Hiraga, 1980a Oishi and Hiraga, 1980b Oishi and Hiraga, 1980c * Oishi and Hiraga, 1980d * U. Rochester, 1953 U. Rochester, 1954	Consistency Dose-response gradient Effect size	Concerns for bias and sensitivity in some studies	⊕⊕◯ MODERATE A dose-related decrease in postnatal and adult growth was observed in all available peripubertal exposure studies in rats and mice. However, in the low confidence studies, the reduced growth may have been a secondary effect related to reduced food consumption.

^*indicates MIBP study