Asymmetric phthalates—A special case for risk assessment

Phthalic acid diesters are ubiquitously present in the environment due to their intensive use as plasticizers. Human exposure to these contaminants has been proved by determining phthalates and their metabolites in human urine and blood. Particular phthalates with ester chain lengths of C4-C6 possess reprotoxic properties [T. Lovekamp-Swan & B. J. Davis, Environmental Health Perspectives 111 (2003) 139–145]. Asymmetric phthalic acid diesters with “critical” C4–C6 chain lengths have been pre-registered in REACH but information on their human metabolism is scarce. Theoretically, two different monoesters with either “critical” or “uncritical” ester moieties may be formed. Thus, for an adequate assessment of possible health risks of asymmetric phthalic acid esters it is essential to know, which of the monoesters are preferably formed by human metabolism. In order to gain insight into the metabolism of asymmetric phthalates, conversion of 11 asymmetric phthalic acid diesters was investigated by in vitro hydrolysis experiments using rat and human liver S9 homogenates. All asymmetric phthalates were fast hydrolysed into mixtures of both possible monoesters and as consequence; organisms are exposed to mixtures of phthalic acid monoesters. Based on these results, the risk assessment of asymmetric phthalic acid diesters seems to be more complex than that of symmetric phthalates because two different monoesters can be formed. This has implications for the risk assessment and the exposure assessment, as in case of asymmetric phthalic acid diesters with a critical chain length, the same metabolites can be formed which are responsible for the reprotoxic effects of already classified reprotoxic phthalates