Table 3.

Evidence profile table for female reproductive effects of DIBP

Female Reproductive Effects
Outcome		Available studies	Factors that increase confidence	Factors that decrease confidence	Confidence judgement for outcome	Confidence judgement for overall hazard
Gestational (F1) or Postnatal (Weanling) Exposure	Female morphological development	High confidence: Saillenfait et al., 2006 Saillenfait et al., 2008 Borch et al., 2006 Medium confidence: Sedha et al., 2015	Biological plausibility (coherence with effects observed in males)	Concerns for study sensitivity	⊕◯◯ SLIGHT Increased female AGD was observed, but was not always statistically significant (Borch et al., 2006, Saillenfait et al., 2008). A non-significant increase in displaced ovaries was observed by Saillenfait et al., 2006. DIBP did not accelerate female puberty in a 20-day pubertal assay (Sedha et al., 2015).	⊕◯◯ SLIGHT Based on limited evidence for effects on female AGD and ovary displacement in F1 females following gestational exposure, and for effects on maternal weight gain in F0 females following maternal exposure. There were concerns for study sensitivity because most gestational exposure studies were designed to evaluate male reproductive effects, and the exposure windows may not have been the most sensitive for detecting F1 female or maternal toxicity.
	Reproductive organ weight	Medium confidence: Sedha et al., 2015		Single study	◯◯◯ INDETERMINATE No effects on were observed on uterus, ovary, or vagina weight in 3- or 20-day assays in prepubescent females.
Maternal (F0) Exposure	Maternal body weight	High confidence: Borch et al., 2006 BASF, 2007 Saillenfait et al., 2006 Saillenfait et al., 2017 Medium confidence: Saillenfait et al., 2008 Howdeshell et al., 2008 Low confidence: Furr et al., 2014 Hannas et al., 2011 Hannas et al., 2012 Wang et al., 2017	Dose-response gradient and minimal concern for bias in the study by BASF, 2007	Concerns for study sensitivity	⊕◯◯ SLIGHT Corrected maternal body weight was significantly decreased in one study (BASF, 2007). Otherwise, any effects on maternal weight gain were concurrent with decreased gravid uterine weight or decreased offspring body weight, and therefore appeared to be secondary effects related to fetal toxicity.
	Reproductive organ weight	High confidence: BASF, 2007 Saillenfait et al., 2006 Saillenfait et al., 2006	Minimal concerns for bias	Concerns for study sensitivity	◯◯◯ INDETERMINATE Saillenfait et al., 2006 reported decreased gravid uterine weight, which appeared to be a secondary effect related to fetal toxicity. Otherwise, no effects on female reproductive organ weight were observed.
	Gestation length	High confidence: Saillenfait et al., 2008	Minimal concern for bias	Single study Concerns for study sensitivity	◯◯◯ INDETERMINATE Effects on gestation length were not observed in one study that began exposing dams at mid-gestation, which may not be the most sensitive window of exposure for this endpoint