Some phthalates are developmental and reproductive toxicants in animals. Exposure to phthalates is considered to be potentially harmful to human health as well. Based on a comprehensive literature research, we present an overview of the sources of human phthalate exposure and results of exposure assessments with special focus on human biomonitoring data. Among the general population, there is widespread exposure to a number of phthalates. Foodstuff is the major source of phthalate exposure, particularly for the long-chain phthalates such as di(2-ethylhexyl) phthalate. For short-chain phthalates such as di-n-butyl-phthalate, additional pathways are of relevance. In general, children are exposed to higher phthalate doses than adults. Especially, high exposures can occur through some medications or medical devices. By comparing exposure data with existing limit values, one can also assess the risks associated with exposure to phthalates. Within the general population, some individuals exceed tolerable daily intake values for one or more phthalates. In high exposure groups, (intensive medical care, medications) tolerable daily intake transgressions can be substantial. Recent findings from animal studies suggest that a cumulative risk assessment for phthalates is warranted, and a cumulative exposure assessment to phthalates via human biomonitoring is a major step into this direction.

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IntroductionPhthalates are mostly used as plasticizers in PVC products. Annually more than 1 000 000 tonnes of phthalates are consumed in Western Europe (AgPU, 2006). Among the most important phthalates are di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP) and di(2-propylheptyl) phthalate (DPHP). As ubiquitous environmental contaminants phthalates are taken up by the general population. This has raised concern because phthalates are considered to be endocrine-disrupting chemicals. It is supposed that phthalates and other endocrine-disrupting chemicals might have contributed to adverse trends in reproductive medicine, which show an increase in testicular cancer and hypospadias as well as a decrease in sperm counts (Sharpe & Irvine, 2004). Human phthalate metabolism: single oral dose experimentsDi(2-ethylhexyl) phthalate For many years DEHP was the most important PVC plasticizer. Therefore, we decided to study intensively human metabolism of DEHP. For this purpose a healthy male volunteer at the age of 61 took three different oral doses of isotopically labelled DEHP -about 5, 29 and 650 lg ⁄ kg body weight (Koch et al., 2004a(Koch et al., , 2005a. By using D4-ring-labelled DEHP interference by the omnipresent background exposure to DEHP was avoided. After 24 h the urinary excretion rate for the sum of five metabolites, namely 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-MMHP), was between 65 and 70% for all three doses. This outcome was in contrast to previous studies, which had hypothesized that a great amount of DEHP is excreted with faeces (Schmid & Schlatter, 1985). After 2 days more than 65% of the highest dose 1 taken up were excreted as the sum of the four oxidative metabolites, whereas only 7.3% was excreted as MEHP (Table 1). We found that urinary DEHP excretion follows a multi-phase elimination model. In the second elimination phase MEHP showed the shortest half-life with 5 h, whereas for 2cx-MMHP a half-life of around 24 h was estimated. Interestingly, there were two maximum concentrations SummaryIn human metabolism studies we found that after oral application of di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP) and di(2-propylheptyl) phthalate (DPHP), at least 74, 44 and 34%, respectively, are excreted via urine. In contrast to the short chain phthalates, their oxidized products, not the simple monoesters, were found to be the main metabolites. Based on urinary phthalate metabolite concentrations we estimated in 102 German subjects between 6 and 80 years of age median daily intakes (lg ⁄ kg ⁄ day) of 2.7 for DEHP, 2.1 for di-nbutyl phthalate, 1.5 for diisobutyl phthalate, 0.6 for DiNP, and 0.3 for butylbenzyl phthalate. In general, children have higher exposures compared...