Table 18.

Evidence profile table for male reproductive effects of DINP.

Outcome	Studies (design in parentheses)	Factors that increase confidence	Factors that decrease confidence	Summary of findings	Confidence judgement for outcome	Confidence judgement for overall hazard
Testosterone	Medium confidence Axelsson et al., 2015a, 2015b (CS) Jurewicz et al., 2013 (CS) Meeker and Ferguson, 2014 (CS) Pan et al., 2015 (CS) Specht et al., 2014 (CS)	Minimal concerns for bias Large effect size in one study (23% decrease with iqr increase in exposure) Exposure-response gradient within one study	Some unexplained inconsistency	Inverse associations between DINP exposure and testosterone levels in 3/5 studies (Specht et al., 2014, Meeker and Ferguson, 2014, Pan et al., 2015), 2 included statistically significant results (Pan et al., 2015, Specht et al., 2014), with the latter being a trend (other studies did not examine exposure-response gradient) (Table 14).	⨁⨁◯ MODERATE	⨁⨁◯ MODERATE Based on testosterone and semen parameters, supported by coherence of slight findings in other outcomes with few available studies
Semen parameters	Medium confidence Axelsson et al., 2015a, 2015b (CS) Jurewicz et al., 2013 (CS) (Pan et al., 2015) (CS) Specht et al., 2014 (CS)	Minimal concerns for bias Exposure-response gradient within one study Consistency for morphology	Some unexplained inconsistency for concentration	Inverse associations between DINP exposure and sperm morphology in all 4 studies, 1 of which was statistically significant (Jurewicz et al., 2013). 2/3 studies for motility (Pan et al., 2015, Axelsson et al., 2015a) and 2/4 studies for concentration (Specht et al., 2014, Pan et al., 2015) also reported inverse associations (Table 5).	⨁⨁◯ MODERATE
Anogenital distance, Hypospadias/Cryptorchidism					⨁◯◯ SLIGHT
Time to pregnancy, pubertal development					◯◯◯ INDETERMINATE

C: cohort, CC: case-control, CS: cross-sectional.