Human biomonitoring of phthalate exposure in Austrian children and adults and cumulative risk assessment.

Phthalates are a class of chemicals widely used as plasticisers in a multitude of common consumer products. Through contact with such products, people are regularly exposed to phthalates, which are suspected to contribute to adverse health effects, particularly in the reproductive system. In the present study, 14 urinary phthalate metabolites of 10 parent phthalates were analysed by HPLC-MS/MS among the Austrian population aged 6-15 and 18-81 years in order to assess phthalate exposure. In the total study population, ranges of urinary phthalate metabolite concentrations were n.d.-2,105 μg/l (median 25 μg/l) for monoethyl phthalate (MEP), n.d.-88 μg/l (10 μg/l) for mono-n-butyl phthalate (MnBP), n.d.-248 μg/l (28 μg/l) for mono-isobutyl phthalate (MiBP), n.d.-57 μg/l (1.8 μg/l) for mono-benzyl phthalate (MBzP), n.d.-20 μg/l (n.d.) for mono-(2-ethylhexyl) phthalate (MEHP), n.d.-80 μg/l (2.6 μg/l) for mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), n.d.-57 μg/l (1.9 μg/l) for mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), n.d.-219 μg/l (11 μg/l) for mono-(5-carboxy-2-ethylpentyl) phthalate (5cx-MEPP), n.d.-188 μg/l (1.6 μg/l) for 3-carboxy-mono-proply phthalate (3 cx-MPP), n.d.-5.5 μg/l (n.d.) for mono-cyclohexyl phthalate (MCHP), n.d.-4.5 μg/l (n.d.) for mono-n-pentyl phthalate (MnPeP), n.d.-3.4 μg/l (n.d.) for mono-n-octyl phthalate (MnOP), n.d.-13 μg/l (n.d.) for mono-isononyl phthalate (MiNP), and n.d.-1.1 μg/l (n.d.) for mono-isodecyl phthalate (MiDP). Generally, children exhibited higher levels of exposure to the majority of investigated phthalates, except to MEP, which was found in higher concentrations in adults and senior citizens at a maximum concentration of 2,105 μg/l. Individual daily intakes were estimated based on urinary creatinine and urinary volume excretion and were then compared to acceptable exposure levels, leading to the identification of exceedances of mainly the Tolerable Daily Intakes (TDI), especially among children. The execution of a cumulative risk assessment based on Hazard Indices showed cause for concern mainly for children, as well as in rare cases for adults. Although phthalate exposure seems to have decreased in previous years, the wide distribution and existing exceedances of acceptable levels indicate that phthalate exposure should be further monitored in order to identify exposure sources and enable appropriate minimisation measures.

Hartmann C ，Uhl M ，Weiss S ，Koch HM ，Scharf S ，König J ... -  《-》

Biomonitoring of phthalate metabolites in the Canadian population through the Canadian Health Measures Survey (2007-2009).

Human exposure to phthalates occurs through multiple sources and pathways. In the Canadian Health Measures Survey 2007-2009, 11 phthalate metabolites, namely, MMP, MEP, MnBP, MBzP, MCHP, MCPP, MEHP, MEOHP, MEHHP, MnOP, and MiNP were measured in urine samples of 6-49 year old survey respondents (n=3236). The phthalate metabolites biomonitoring data from this nationally-representative Canadian survey are presented here. The metabolites MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP were detected in >90% of Canadians while MMP, MCHP, MnOP and MiNP were detected in <20% of the Canadian population. Step-wise regression analyses were carried out to identify important predictors of volumetric concentrations (μg/L) of the metabolites in the general population. Individual multiple regression models with covariates age, sex, creatinine, fasting status, and the interaction terms age×creatinine, age×sex and fasting status×creatinine were constructed for MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP. The least square geometric mean (LSGM) estimates for volumetric concentration (μg/L) of the metabolites derived from respective regression models were used to assess the patterns in the metabolite concentrations among population sub-groups. The results indicate that children had significantly higher urinary concentrations of MnBP, MBzP, MEHP, MEHHP, MEOHP and MCPP than adolescents and adults. Moreover, MEP, MBzP, MnBP and MEOHP concentrations in females were significantly higher than in males. We observed that fasting status significantly affects the concentrations of MEHP, MEHHP, MEOHP, and MCPP metabolites analyzed in this study. Moreover, our results indicate that the sampling time could affect the DEHP metabolite concentrations in the general Canadian population.

Saravanabhavan G ，Guay M ，Langlois É ，Giroux S ，Murray J ，Haines D ... -  《-》

Trends of the internal phthalate exposure of young adults in Germany--follow-up of a retrospective human biomonitoring study.

The exposure of the general population to phthalates is of increasing public health concern. Variations in the internal exposure of the population are likely, because the amounts, distribution and application characters of the phthalate use change over time. Estimating the chronological sequences of the phthalate exposure, we performed a retrospective human biomonitoring study by investigating the metabolites of the five most prominent phthalates in urine. Therefore, 24h-urine samples from the German Environmental Specimen Bank (ESB) collected from 240 subjects (predominantly students, age range 19-29 years, 120 females, 120 males) in the years 2002, 2004, 2006 and 2008 (60 individuals each), were analysed for the concentrations of mono-n-butyl phthalate (MnBP) as metabolite of di-n-butyl phthalate (DnBP), mono-iso-butyl phthalate (MiBP) as metabolite of di-iso-butyl phthalate (DiBP), mono-benzyl phthalate (MBzP) as metabolite of butylbenzyl phthalate (BBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) and mono-(2-carboxymethyl hexyl) phthalate (2cx-MMHxP) as metabolites of di(2-ethylhexyl) phthalate (DEHP), monohydroxylated (OH-MiNP), monooxidated (oxo-MiNP) and monocarboxylated (cx-MiNP) mono-iso-nonylphthalates as metabolites of di-iso-nonyl phthalates (DiNP). Based on the urinary metabolite excretion, together with results of a previous study, which covered the years 1988-2003, we investigated the chronological sequences of the phthalate exposure over two decades. In more than 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of people living in Germany to all five phthalates throughout the period investigated. The medians in samples from the different years investigated are 65.4 (2002), 38.5 (2004), 29.3 (2006) and 19.6 μg/l (2008) for MnBP, 31.4 (2002), 25.4 (2004), 31.8 (2006) and 25.5 μg/l (2008) for MiBP, 7.8 (2002), 6.3 (2004), 3.6 (2006) and 3.8 μg/l (2008) for MBzP, 7.0 (2002), 5.6 (2004), 4.1 (2006) and 3.3 μg/l (2008) for MEHP, 19.6 (2002), 16.2 (2004), 13.2 (2006) and 9.6 μg/l (2008) for 5OH-MEHP, 13.9 (2002), 11.8 (2004), 8.3 (2006) and 6.4 μg/l (2008) for 5oxo-MEHP, 18.7 (2002), 16.5 (2004), 13.8 (2006) and 10.2 μg/l (2008) for 5cx-MEPP, 7.2 (2002), 6.5 (2004), 5.1 (2006) and 4.6 μg/l (2008) for 2cx-MMHxP, 3.3 (2002), 2.8 (2004), 3.5 (2006) and 3.6 μg/l (2008) for OH-MiNP, 2.1 (2002), 2.1 (2004), 2.2 (2006) and 2.3 μg/l (2008) for oxo-MiNP and 4.1 (2002), 3.2 (2004), 4.1 (2006) and 3.6 μg/l (2008) for cx-MiNP. The investigation of the time series 1988-2008 indicates a decrease of the internal exposure to DnBP by the factor of 7-8 and to DEHP and BzBP by the factor of 2-3. In contrast, an increase of the internal exposure by the factor of 4 was observed for DiNP over the study period. The exposure to DiBP was found to be stable. In summary, we found decreases of the internal human exposure for legally restricted phthalates whereas the exposure to their substitutes increased. Future investigations should verify these trends. This is of increasing importance since the European Commission decided to require ban or authorization from 1.1.2015 for DEHP, DnBP, DiBP and BzBP according to REACh Annex XIV.

Göen T ，Dobler L ，Koschorreck J ，Müller J ，Wiesmüller GA ，Drexler H ，Kolossa-Gehring M ... -  《-》

Austrian reference values for phthalate metabolite exposure in children/adolescents and adults.

Reference values (RV95) are statistically derived values comprising the rounded 95th percentiles within the 95% confidence interval and indicate the upper margin of background exposure to chemical substances in a population at a given time period. Based on representative national human biomonitoring data on several urinary phthalate metabolites in children, adolescents and adults from 2010 to 2011, RV95 were derived for the Austrian population based on a IUPAC guideline and the recommendation of the German Human Biomonitoring Commission. The RV95 (rounded values) for phthalate metabolites in children and adolescents aged 6-15 years are 110 μg/l (confidence interval of 95th population percentile: 83.7-163) for mono-ethyl phthalate (MEP), 45 μg/l (40.9-60.6) for mono-n-butyl phthalate (MnBP), 130 μg/l (126-161) for mono-isobutyl phthalate (MiBP), 25 μg/l (17.8-33.6) for mono-benzyl phthalate (MBzP), 100 μg/l (94.0-126) for the sum of the di(2-ethylhexyl) phthalate (DEHP) metabolites including mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP), and 1.5 μg/l (0.64-1.6) for mono-cyclohexyl phthalate (MCHP). In adults aged 18-81 years, RV95 are 440 μg/l (353-636) for MEP, 40 μg/l (33.1-52.1) for MnBP, 110 μg/l (87.3-118) for MiBP, 10 μg/l (7.2-11.8) for MBzP, 50 μg/l (44.6-68.3) for the sum of MEHP, 5OH-MEHP, 5oxo-MEHP and 5cx-MEPP, and 1.5 μg/l (0.95-1.8) for MCHP. For almost all investigated metabolites, children and adolescents exhibit higher RV95 than adults, with the exceptions being MEP and MCHP. Compared to available RV95 for Germany and Canada, Austrian values are lower for all investigated population groups.

Hartmann C ，Uhl M ，Weiss S ，Scharf S ，König J ... -  《-》

Phthalate Metabolites, Consumer Habits and Health Effects.

Wallner P ，Kundi M ，Hohenblum P ，Scharf S ，Hutter HP ... -  《-》