Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

Conclusion on toxicokinetics, metabolism and distribution:

Dibutyl phthalate is rapidly absorbed and excreted after oral administration as was demonstrated in studies in laboratory animals. Up to more than 90% of oral doses given to rats or hamsters was excreted in urine within 24-48h. Fecal excretion is low (1.0-8.2%). Also in human oral absorption of DBP takes place. After dermal exposure of rats absorption occurred; ca. 60% of the dose was excreted in urine within 7 days. In feces ca. 12% of the dose was found. An in vitro study revealed slower absorption of DBP by the human skin (2.40 μg/cm2/hour) than by the rat skin (93.35 μg/cm2/hour). Data on absorption after exposure by inhalation are not available. A substantial fraction of DBP is initially excreted in the bile and subsequently enters the enterohepatic circulation. No significant accumulation in tissues was observed in laboratory animals after oral as well as dermal exposure; limited inhalation data revealed an indication for some accumulation in tissues. The major part of DBP is hydrolysed to MBP and the corresponding alcohol prior to absorption by the small intestines, but hydrolysis can also occur in liver and kidneys. The metabolites that occur in urine are MBP, MBP-glucuronide, various ω- and ω-1-oxidation products of MBP (more polar ketones, carboxylates) and a small amount of free phthalic acid . Species differences in the excretion of MBP and its glucuronide were observed; rats excreted a larger proportion unconjugated MBP in urine than hamsters. There are no data on biotransformation after dermal exposure and exposure by inhalation. Transplacental transfer of DBP and its metabolites was demonstrated in an oral study with 14C-labelled DBP in rats. Levels of radioactivity in placenta and embryo were 1/3 of those in maternal plasma; radioactivity in embryonic tissues accounted for less than 0.12-0.15% of the administered dose. MBP accounted for most of the radioactivity in maternal plasma, placenta and embryo. Unchanged DBP was found only in small amounts. No accumulation of radioactivity was seen in maternal or embryonic tissues.