Exposure And Metabolic Characteristics Of Phthalates In Infants At Different Developmental Stages

Phthalate acid esters(PAEs)are important endocrine disruptors,and they have been widely used as an additive in a variety of plastic products and personal skin care products.As sensitive population,infants are more likely to be exposed to PAEs due to their special physiological conditions and behavior patterns after losing the protection of uterine environment.The toxicity of phthalate esters mainly depends on the dose and form of exposure in in human body.Therefore,evaluating the exposure burden and metabolic characteristics of phthalate esters is of scientific significance for the health risk assessment of such pollutants in early life stage.In this study,infants aged 0-6 months were selected as the research objects,and ten metabolites of six PAEs commonly exposed in the population were selected as the target compounds.Urine samples were serially collected at six time points(at birth,14 days,28 days,42 days,3 months,and 6 months).Phthalate metabolites were measured by HPLC-MS/MS combined with stable isotope dilution assay.From the exposure burden of PAEs,except that the detection rates of Monobenzyl phthalate(MBz P)and Mono-cyclo-hexyl phthalate(MCHP)are 58.80% and 4.99% respectively,the detection rates of Monomethyl phthalate(MMP),Monoethyl phthalate(MEP),Mono-n-butyl phthalate(MBP),Mono-iso-butyl phthalate(Mi BP),Mono(2-ethyl-5-oxohexyl)phthalate(MEOHP),Mono(2-ethyl-5-hydroxyhexyl)phthalate(MEHHP),Mono(2-ethylhexyl)phthalate(MEHP)and Mono-(2-ethyl-5-carboxypentyl)phthalate(MECPP)are all over 97%.Data showed that infants were generally exposed to the investigated phthalate esters,especially for Di(2-ethylhexyl)phthalate(DEHP),Di-n-butyl phthalate(DBP),Diisobutyl phthalate(DIBP),Diethyl phthalate(DEP)and Dimethyl phthalate(DMP).Further study found that the exposure burden of phthalates increased with the infant growth,and the exposure burden of DEHP was higher for female infants than for male infants.The types,concentration and ratio of free/conjugated forms of PAEs metabolites have significant differences in the profile of PAEs metabolites at infant different developmental stages.DMP and DEP exist in free form.DBP and DIBP exist in glucuronide-conjugated form.As for the metabolites of DEHP,MECPP and MEHP exist in free form,while MEOHP and MEHHP exist in glucuronide-conjugated form.With the increase of infant age,the ability of long chain PAEs metabolites in urine to transfer to hydrophilic glucuronic conjugation was gradually enhanced,and male infants were higher than female infants.By comparing the hydroxylation and oxidation capacity of DEHP metabolites,it was found that the metabolic capacity of ? oxidation was stronger than that of ? oxidation.In the present study,multiple samples of infants were collected from 0 to 6 months after birth,and the exposure profiles and dynamic changes of 10 PAEs metabolites were explored at different development stages,which has enriched the previous single-sampling exposure study and provided basic data for the reasonable risk assessment of the infantile PAEs exposure and growth and development in early life.