Biological assessment of occupational exposure to di(isononyl) phthalate (DiNP)

Outline of reasons and objectives
Di(isononyl) phthalate (DINP) is mainly used as a plasticizer in the flexible PVC industry, as a substitute for di(2-ethylhexyl) phthalate (DEHP). The industrial process is based on extrusion, and then gelling, in order to obtain a solid compound (compounding). It is also possible to obtain solutions referred to as “plastisols”. Unlike DEHP, DINP is not classified as reprotoxic (toxic for reproduction) by the European Union, but new information has been provided by recent publications that highlight the endocrine-disrupting activity of DINP. Three main objectives were set for this study: to assess occupational exposure to DINP in the flexible PVC industry, to estimate the daily internal dose for employees exposed to DINP, and to assess any co-exposure both to DINP and to DEHP.

Approach
With the help of the CARSATs (the French Regional Occupational Health and Pension Insurance Funds) and of the Services de Sante au Travail (company or inter-company occupational health services), we approached several companies from the industrial sectors of flexible PVC who manufactured and/or used solid granulated compounds obtained by mixing PVC, DINP and various additives. Three companies from the compounding sector took part in the study. Urine samples were taken daily, at the beginnings and ends of the shifts, for 5 consecutive days, from 47 volunteers who were employees potentially exposed to DINP. Other samples were taken from 27 employees considered as controls not occupationally exposed and mainly working in administrative departments. The methodology used was based on urine assays for three metabolites of DINP, namely mono-(4-methyl-7-hydroxyoctyl) phthalate (7-OH-MINP), mono-(4-methyl-7-oxoxyoctyl) phthalate (7-oxo-MINP), and mono-(4-methyl-7-carboxyheptyl) phthalate (7-cx-MINP), using a high-performance liquid chromatography technique coupled with tandem mass spectrometry (HPLC-MS/MS). To determine whether there was co-exposure to DEHP, the urinary metabolites of that phthalate were also assayed.

Main results
Analysis of the 358 urine samples from the 47 employees using DINP and of the 216 samples collected from the 27 controls did not show occupational exposure to DINP that was higher in the exposed employees than in the controls, with daily internal doses (median at 3.3 g/kg of bodyweight per day) very much lower than the acceptable daily doses (European and US ADDs). Only one internal dose measured at 137.3 g/kg/day exceeded the ADD advocated by the United States. Conversely, the concentrations of metabolites of DEHP that were measured in the collected urine samples bear witness to occupational exposure to that phthalate and confirm that it is still used.