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Only limited information is available on uptake and fate of diisobutyl phthalate (DIBP) in vivo, however supporting information is available for the homologues dibutyl phthalate (DBP) and diethylhexyl phthalate (DEHP).

DIBP is absorbed by rat skin (Elsisi et al., 1989) with around 50-60% of the applied dose excreted over 7 days, primarily in urine. No information is available on uptake following oral or inhalation exposure.

Information summarized in the EU risk assessment report for DPB (EU, 2003) indicates rapid uptake and excretion after oral administration, with greater than 90% excreted in urine within 24-48 hr by rats and hamsters; faecal excretion is low. After dermal exposure, rats excreted around 60% of an applied dose of DBP within 7 days with around 12% of the dose found in faeces.

DEHP is similarly well absorbed from the gut (EU, 2008) with recovery of around 50% of the dose from rats, non-human primates and humans given up to about 200 mg/kg bw; at higher doses, absorption in non-human primates is dose-limited in contrast to rodents. Limited data on toxicokinetics following inhalation or dermal exposure indicate that DEHP can be absorbed through the lungs whereas absorption through the skin appears to be limited, with route-dependent uptake of 75% and 50%, respectively (EU, 2008). In vitro data (Scott et al., 1989) indicate that rat skin is approx. 2-fold more permeable than is human skin to topically applied DEHP.

The metabolism of phthalate esters is typified by rapid hydrolysis to the mono ester and the corresponding alcohol within the gut (EU 2003; 2008), although further hydrolysis is reported in the liver and kidneys for DBP. In vitro studies with DIBP demonstrate hydrolysis to monoisobutyl phthalates by carboxyesterases (Mentelin and Butte, 1989).

Information on DBP shows that it is initially excreted in the bile and subsequently enters the enterohepatic with subsequent metabolism. Monobutyl phthalate forms MBP-glucuronide, and undergoes subsequent omega- and omega-1 oxidation.

Phthalate esters are not associated with accumulation in body tissues.

 

For the purposes of risk characterisation of DIBP, it is proposed to assume 100% absorption for human oral and inhalation exposures. For dermal absorption, information indicating excretion of approximately 60% of an applied dose by rats together with other findings suggesting that human skin is less permeable to phthalate diesters than is rat skin leads to a conservative estimate of 50% uptake by human skin. 

EU (2003) European Union Risk Assessment Report: dibutyl phthalate, volume 29. Office for Official Publications of the European Communities, Luxembourg.

EU (2008) European Union Risk Assessment Report: bis(2-ethylhexyl) phthalate, volume 80. Office for Official Publications of the European Communities, Luxembourg.