Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

Little information is available on the substance itself. However, the phthalate esters are thought to exhibit similar behaviour and studies on other high molecular weight phthalate esters indicate that they are rapidly absorbed and metabolised to the corresponding monoester in the gastrointestinal tract. Excreted occurs primarily via the urine.For example, a phthalate ester of similar chain length -

diisodecylphthalate (DIDP) which is an C-10 alcohol ester rather than a mixed C-9 -11 ester - has been extensively examined and the data reviewed by ECHA (Evaluation of new scientific evidence concerning DINP and DIDP in relation to Entry 52 of Annex XVII to Regulation (EC) No. 1907/2006 (REACH)).

 

Absorption

Absorption of DIDP from the gastro-intestinal tract has been observed to decrease with increasing dose (56% at a low dose of 0.1 mg/kg, 46% at a dose of 11.2 mg/kg and 17% at a dose of 1,000 mg/kg suggesting that absorption may be via a saturable mechanism.

 

Absorption via the dermal route is regarded as low. Elsisi et al describe the dermal absorption of a number of phthalate diesters in rats (Fund. Appl. Toxicol., 12(1): 70-77, 1989). Dimethyl, diethyl, dibutyl, diisobutyl, dihexyl, di(2-ethylhexyl), diisodecyl, and benzyl butyl phthalate were examined, being applied to an area of skin area on the back of male F344 rats. Animals were housed for 7 days in a metabolic cage that allowed separate collection of urine and faeces which were collected every 24 hours. The amount of 14C excreted was taken as an index of the percutaneous absorption. As the length of the alkyl side chain increased, the amount of 14C excreted in the first 24 hours decreased significantly. The cumulative percentage dose excreted in 7 days was greatest for diethyl, dibutyl, and diisobutyl phthalate (approximately 50–60% of the applied 14C; and intermediate (20–40%) for benzyl butyl, and dihexyl phthalate. Urine was the major route of excretion of all phthalate diesters except for diisodecyl phthalate which was poorly absorbed and showed almost no urinary excretion. After 7 days, the percentage dose for each phthalate remaining in the body was minimal and showed no specific tissue distribution with most of the unexcreted dose remaining in the area of application. These findings support the (Q)SAR calculations for the substance itself using the SkinPerm model which indicates a maximum dermal absorption of 6.00E-7 mg/cm2/hour.

 

When inhaled as an aerosol DIDP appears readily absorbed although it can be assumed that some particles are cleared from the nasopharyngeal region and swallowed and that the mucociliary transport system in the tracheobronchial tree transfers deposited particles upward to the oropharynx where they are swallowed and pass through the gastro-intestinal tract.

 

Distribution

In tissues, DIDP or its metabolites are mainly recovered in the gastro-intestinal tract, liver and kidneys, following absorption by the oral or inhalation routs. In contrast, muscle and adipose tissue contain most of the dose remaining in the body following dermal exposure.

 

Metabolism

Those phthalate esters that have been examined indicate that, for all the investigated substances, the first step in systemic metabolism of any absorbed di-ester is rapid hydrolysis to the mono-ester, which can be then followed by further hydrolysis and/or oxidation and glucuronidation (Arch. Toxicol. (2003), 77: 561-567, 2003).

 

Excretion

The phthalate esters are considered to be eliminated from the organism in a few days, and none of them is considered to accumulate in the organism (Critical Reviews in Toxicology, 36: 695-726, 2006).

 

The ECHA evaluation report on DIDP indicates no parent DIDP or its mono-ester but only metabolites of the mono-ester and phthalic acid to have been found in urine. DIDP was not detected in bile extracts 24 and 72 hours following dosing. In faeces the oxidative derivative of the mono-ester and unchanged DIDP were detected. Metabolic pathway(s) resulting in complete hydrolysis leading to phthalic acid is saturable, and that consequently monoester elimination is increased with increasing exposure. DIDP is rapidly eliminated and not accumulated in tissues with less than 1% of administered radioactivity being recovered in tissues after 72 hours. By both oral and inhalation routes, excretion is shared between urine and faeces. By dermal exposure, only faecal elimination appears to occur but this may be a reflection of the low rate of absorption resulting in low recovery of the administered dose.

 

Kato et al. (Toxicology 236: 114-122, 2007) have observed rapid clearance of DIDP metabolites in a study with rats administered a single oral dose of 300 mg/kg DIDP. The half-life of all metabolites was estimated to be around 14 hours.