Table 4.

Evidence profile table for developmental effects of DEP.

Developmental effects
Outcome	Available studies	Factors that increase confidence	Factors that decrease confidence	Confidence judgement for outcome	Confidence judgement for overall hazard
Fetal survival	High Confidence: Fujii et al. (2005) Procter and Gamble (1994) Hardin et al. (1987), Howdeshell et al. (2008), RTI International (1984), NTP (1988) Medium confidence: Furr et al. (2014), Gray et al. (2000) Low confidence: Setti Ahmed et al. (2018)	• Minimal concerns for bias and sensitivity in most studies	• Effects observed in only one study	◯◯◯ INDETERMINATE A continuous breeding study reported decreased live F2 pups at birth (RTI International 1984). No other studies reported dose-related effects on fetal survival.	⊕⊕◯ MODERATE Based primarily on the consistent reduction in postnatal growth observed across gestational and early postnatal exposure studies.
Postnatal survival	High Confidence: Fujii, et al. (2005), Hardin et al. (1987) Low Confidence: Manservisi et al. (2015)	• Minimal concerns for bias and sensitivity in most studies	• Few studies • Unexplained inconsistency	◯◯◯ INDETERMINATE Decreased postnatal survival of F2 pups was observed in the low confidence study by Manservisi et al. (2015), and there was a nonsignificant trend towards decreased survival of F1 but not F2 pups in the high confidence study by Fujii et al. (2005). Otherwise, no effects were observed.
Fetal growth	High Confidence Fujii et al. (2005), RTI International (1984), NTP (1988), Hardin et al. (1987), Procter & Gamble (1994), Gray et al. (2000) Low Confidence: Setti Ahmed et al. (2018)	• Consistency Minimal concerns for bias and sensitivity		◯◯◯ INDETERMINATE All studies that assessed prenatal growth observed that DEP had little to no effect on fetal body weight or body weight at birth in rats, mice or rabbits.
Postnatal growth	High Confidence Fujii et al. (2005), RTI International (1984), Hardin et al. (1987), Gray et al. (2000) Low Confidence: Pereira and Rao (2007), Manservisi et al. (2015), Oishi and Hiraga (1980), Hu et al. (2016), Setti Ahmed et al. (2018)	• Consistency across studies with longer exposure durations	• Concerns for risk of bias and sensitivity in some studies	⊕⊕⊕ ROBUST Decreased postnatal body weights were observed in offspring in the high confidence multigenerational exposure studies by Fujii et al. (2005) and RTI International (1984), including effects in both F1 and F2 generations in the study by Fujii et al. (2005), and in F1 animals in the low confidence studies by Pereira and Rao (2007), Manservisi et al. (2015), Hu et al. (2016), and Setti Ahmed et al. (2018). No effects on growth were observed following shorter duration gestational exposures (Hardin et al. 1987, Gray et al. 2000) or peripubertal exposure (Oishi and Hiraga 1980).
Fetal structural alterations	High Confidence: NTP (1988), Procter & Gamble (1994) Low Confidence: Setti Ahmed et al. (2018)	• Exposure-response gradient in the study by NTP 1988 Minimal concern for bias and sensitivity	• Few studies	⊕◯◯ SLIGHT A dose-related increase in the percentage of fetuses with a rudimentary or supernumerary rib (a skeletal variation) was observed in rats exposed during gestation (NTP 1988). Findings in rabbits (Procter & Gamble 1994) including fused ribs, missing lumbar, coccygeal vertebrae, hernia umbilicalis, and incurved ribs were not considered to be related to dose. Effects on intestinal development were observed in rats (Setti Ahmed et al. 2018).