Identifying sources of phthalate exposure with human biomonitoring: results of a 48h fasting study with urine collection and personal activity patterns.

Human biomonitoring studies measuring phthalate metabolites in urine have shown widespread exposure to phthalates in the general population. Diet is thought to be a principle route of exposure to many phthalates. Therefore, we studied urinary phthalate metabolite patterns over a period of strict fasting and additionally recorded personal activity patterns with a diary to investigate non-dietary routes of exposure. Five individuals (3 female, 2 male, 27-47 years of age) fasted on glass-bottled water only over a 48-h period. All urine void events were captured in full, and measured for metabolites of the high molecular weight (HMW) di-(2-ethylhexyl) phthalate (DEHP), di-isononyl phthalate (DINP) and di-isodecyl phthalate (DiDP), and the low molecular weight (LMW) di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), butylbenzyl phthalate (BBzP), dimethyl phthalate (DMP), and diethyl phthalate (DEP). In all, 21 metabolites were measured in a total of 118 urine events, including events before and after the fasting period. At the onset of the study all phthalate metabolite concentrations were consistent with levels found in previous general population studies. Metabolites of the HMW phthalates (DEHP, DiNP and DiDP) showed a rapid decline to levels 5-10 times lower than initial levels within 24h of the fast and remained low thereafter. After food consumption resumed, levels rose again. By contrast, metabolites of the LMW phthalates including DMP, DEP, BBzP, DnBP and DiBP showed a cyclical pattern of rising and declining concentrations suggestive of ongoing non-food exposures. Furthermore, metabolites of most of the LMW phthalates (BBzP, DnBP and DiBP) tracked each other remarkably well, suggesting concurrent exposures. Diary entries could not help explain exposure sources for these phthalates, with one exception: rises in MEP concentrations around males' showers suggest personal care products as a major source of DEP. Exposure to HMW phthalates in this cohort appears to be driven by dietary intake, while non-dietary routes such as use of personal care products and ubiquitous sources including dust and indoor air appear to explain exposure to LMW phthalates.

Koch HM ，Lorber M ，Christensen KL ，Pälmke C ，Koslitz S ，Brüning T ... -  《-》

Internal phthalate exposure over the last two decades--a retrospective human biomonitoring study.

Wittassek M ，Wiesmüller GA ，Koch HM ，Eckard R ，Dobler L ，Müller J ，Angerer J ，Schlüter C ... -  《INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH》

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 ... -  《-》

Levels of phthalate metabolites in urine among mother-child-pairs - results from the Duisburg birth cohort study, Germany.

Phthalates are used ubiquitously and human exposure is widespread. Some phthalates are anti-androgens and have to be regarded as reproductive and developmental toxicants. In the Duisburg birth cohort study we examine the associations between hormonally active environmental agents and child development. Here we report the concentrations of 21 primary and secondary phthalate metabolites from seven low molecular weight (LMW) phthalates (DMP, DEP, BBzP, DiBP, DnBP, DCHP, DnPeP) and five high-molecular weight (HMW) phthalates (DEHP, DiNP, DiDP, DPHP, DnOP) in 208 urine samples from 104 mothers and their school-aged children. Analysis was performed by multidimensional liquid chromatography coupled to tandem mass spectrometry (LC/LC-MS/MS), using internal isotope-labeled standards. In both children and mothers, 18 out of 21 phthalate metabolites were detected above the limits of quantification (between 0.2 and 1.0 μg/l) in nearly all urine samples. Among the LMW phthalates, the excretion level (geometric mean) of the ΣDiBP metabolites was most prominent in children (103.9 μg/l), followed by ΣDnBP (56.5 μg/l), and MEP (39.1 μg/l). In mothers ΣDiBP (66.6 μg/l) was highest, followed by MEP (50.5 μg/l), and ΣDnBP (36.0 μg/l). Among the HMW phthalates, ΣDEHP was highest in children and mothers (55.7/28.9 μg/l). Compared to reference values derived from the German Human Biomonitoring Commission, children's metabolite concentrations were within background levels, whereas for mothers considerably higher exposure to the LMW phthalates DnBP and DiBP, and the HMW phthalate DEHP was detected (MiBP: 10.7%; MnBP: 11.7%; ΣDEHP: 23.3% of the samples were above the reference values). The LMW metabolites from DMP, DiBP, and DnBP, and the HMW metabolites from DEHP and DiNP were correlated between the mothers and children, probably indicating shared exposure in the immediate surrounding environment. Children showed higher excretion levels for most of the secondary metabolites than mothers, confirming previous findings on higher oxidized metabolite levels in children. The LMW metabolites ΣDiBP, ΣDnBP, and MMP, and the HMW metabolites ΣDEHP were negatively associated with children's age. The LMW metabolites ΣDiBP, ΣDnBP, and MBzP were inversely associated with body mass index of the children. The LMW ΣDiBP metabolites revealed a significant association with nicotine metabolites in urine from both children and mothers. Further analyses are ongoing to study long-term phthalate exposure and the associations with puberty outcome in these children.

Kasper-Sonnenberg M ，Koch HM ，Wittsiepe J ，Wilhelm M ... -  《-》

Phthalate metabolites in obese individuals undergoing weight loss: Urinary levels and estimation of the phthalates daily intake.

Human exposure to chemicals commonly encountered in our environment, like phthalates, is routinely assessed through urinary measurement of their metabolites. A particular attention is given to the specific population groups, such as obese, for which the dietary intake of environmental chemicals is higher. To evaluate the exposure to phthalates, nine phthalate metabolites (PMs) were analyzed in urine collected from obese individuals and a control population. Obese individuals lost weight through either bariatric surgery or a conservative weight loss program with dietary and lifestyle counseling. Urine samples were also collected from the obese individuals after 3, 6 and 12months of weight loss. Individual daily intakes of the corresponding phthalate diesters were estimated based on the urinary PM concentrations. A high variability was recorded for the levels of each PM in both obese and control urine samples showing the exposure to high levels of PMs in specific subgroups. The most important PM metabolite as percentage contribution to the total PM levels was mono-ethyl phthalate followed by the metabolites of di-butyl phthalate and di 2-ethyl-hexyl phthalate (DEHP). No differences in the PM levels and profiles between obese entering the program and controls were observed. Although paralleled by a significant decrease of their weight, an increase in the urinary PM levels after 3 to 6months loss was seen. Constant figures for the estimated phthalates daily intake were observed over the studied period, suggesting that besides food consumption, other human exposure sources to phthalates (e.g. air, dust) might be also important. The weight loss treatment method followed by obese individuals influenced the correlations between PM levels, suggesting a change of the intake sources with time. Except for few gender differences recorded between the urinary DEHP metabolites correlations, no other differences were observed for the urinary PM levels as a function of age, body mass index or waist circumference. Linear regression analysis showed almost no significance of the relationship between measured urinary PMs and serum free thyroxine, thyroid-stimulating hormone (TSH) for all obese individuals participating to the study, while for the control samples, several PMs were significantly associated with the serum TSH levels.

Dirtu AC ，Geens T ，Dirinck E ，Malarvannan G ，Neels H ，Van Gaal L ，Jorens PG ，Covaci A ... -  《-》