Prenatal Exposure to Di-Isononyl Phthalate (Dinp) Is Associated with Shorter Anogenital Distance in Swedish Boys

Abstract

Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and found in a large number of commonly used consumer products. Due to reported health risk, di-isononyl phthalate (DiNP) has been introduced as a replacement for diethyl hexyl phthalate (DEHP) as a plasticizer in soft PVC. This raises concerns since animal data suggest that DiNP may have anti-androgenic properties similar to DEHP. In addition, biomonitoring data show that human DiNP metabolite levels are rapidly increasing globally. The anogenital distance (AGD) - the distance from the anus to the genitals - is a marker that has been used in animal studies to assess reproductive toxicity. While several studies have examined phthalates and AGD in humans, none has included DiNP. In the current study we examined the relationship between 1st trimester urinary metabolite concentrations of DEP, DBP, DEHP, BBzP as well as DiNP in relation to anogenital distance in 196 Swedish boys at 20 months of age. Most of the phthalate metabolites were associated with a shorter AGD both before and after adjusting for covariates in multiple linear regression models. The strongest and significant associations were found between the shorter of two AGD measures (anoscrotal distance, AGDas) and DiNP metabolites and most strongly for two DINP metabolites (oh-MMeOP and oxo-MMeOP) and the sum of all DiNP metabolites. These findings call into question the safety of the recent substitution of DINP for DEHP, particularly since a shorter male AGD has been shown to be related to male genital birth defects and impaired reproductive function in adult males.