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Administrative data

Link to relevant study record(s)

Description of key information

No data of the target substance are available, however, it is likely that the data of the read-across substance Di-n-octylphthalate, DnOP (1,2-Benzenedicarboxylic acid, di-C8-alkylesters) are also valid for the test substance:
rapidly absorbed via the oral route, the bioavailability of DnOP from oral exposure is assessed as 100% for both adults and children, studies indicated a decrease in dermal absorption with increasing side chain, means not 100 %, however, because no exact absorption factors are available, 100 % is used for the CSA, default inhalative absorption rate of 100 % expected
distribution is assumed to be widespread in the body after exposure, with no evidence of accumulation.
rapidly metabolised (hydrolysis to the monoesters)
elimination the substance and their respective metabolites is expected rapid, as for other assessed phthalates
excreted in the urine and faeces

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

The target substance is a phthalate ester with linear C8 and C10 alkyl chains and the source substance 1 a phthalate ester with linear C6, C8 and C10 alkyl chains. While experimental data are not available for the assessment of the toxicokinetic properties of the C8-C10 or the C6-C10-phthalate and read-across for toxicokinetic property assessment, it is possible to characterise the toxicokinetic endpoints for the substances. Based on structurally similarity to other phthalate esters, e.g to the similar substance 1,2-Benzenedicarboxylic acid, di-C8-alkyl esters with two linear C8-alkyl chains (difference is only one C8 vs. C10), similar toxicokinetic behaviour can be expected. They are regarded as a High Molecular Weight Phthalate Ester (HMWPE) according to the definitions of the American Chemistry Council Phthalate Esters Panel HPV Testing Group (2001) and of the OECD (2004). This group includes chemically similar substances produced from alcohols having backbone carbon lengths of C6 or greater. Due to their similar chemical structure, class members generally have similar physicochemical, biological toxicokinetic and toxicological properties or display an expected trend. Various reviews of different phthalate esters by the Australian National Industrial Chemicals Notification and Assessment Scheme (NICNAS, 2008b) are available. The data on the toxicokinetics indicate that phthalates in general are likely to be rapidly absorbed via the oral route. Studies indicated a decrease in dermal absorption with increasing side chain. There is minimal or no evidence of accumulation in rodent tissues. The read-across substance 4, 1,2-Benzenedicarboxylic acid, di-C8-alkyl esters (Di-n-octyl phthalate = DnOP), which is a phthalate ester with two linear alkyl chains and is a major component both in the target substance and read-across substance 1, is rapidly absorbed from the gastrointestinal tract following oral administration. It is metabolised predominantly to mono-n-octylphthalate (MnOP) and eliminated in urine. The bioavailability of DnOP from oral exposure is assessed as 100% for both adults and children. Information on dermal absorption of DnOP is not available. Similarly to other high molecular weight phthalates, the bioavailability of DnOP from dermal absorption is expected to be low (2–4%). Data on absorption of inhaled DnOP are not available; therefore, a default bioavailability of 100% is considered (NICNAS, 2015). Phthalate distribution is generally, or for DnOP in particular, assumed to be widespread in the body after exposure, with no evidence of accumulation (NICNAS, 2015). As with other phthalates, DnOP undergoes hydrolysis to form the primary metabolite, mono-n-octyl phthalate MnOP, which subsequently metabolises further into oxidative metabolites and phthalic acid (PA). The secondary metabolites may undergo Phase II detoxification to produce glucuronide conjugates with increased water solubility, before being excreted in the urine and/or faeces. MnOP in blood was measured in rats dosed with 2000 mg/kg of DnOP by gavage. The biological half-life in the blood was 3.3 hours, with peak blood levels observed three hours after administration. MnOP was also detected in the testes within 1–2 hours of administration, with peak levels observed six hours after administration. In male rats treated for two days with 559 mg/kg/day of DnOP, 31% of the administered dose recovered in the urine was as straight chain monoesters with varying alkyl side chain lengths. The remaining amount in the urine was represented by PA and MnOP. The parent compound was not found in the urine (NICNAS, 2015). Similar results were obtained from oral studies where PA, MnOP and monocarboxy propyl phthalate (MCPP) were detected in the urine of adult female rats after a single oral dose of 300 mg/kg. There were also five other oxidative metabolites identified in the urine: mono-carboxymethyl phthalate (MCMP), mono-(5-carboxy-n-pentyl) phthalate (MCPeP), mono-(7-carboxy-n-heptyl) phthalate (MCHpP), one isomer of mono-hydroxy-n-octyl phthalate (MHOP) i.e. mono-(7-hydroxy-n-octyl) phthalate), and one isomer of mono-oxo-n-octyl phthalate ((MOOP) mono-(7-oxo-n-octyl) phthalate). The metabolite levels decreased significantly 24 hours after administration. Overall, elimination of DnOP and their respective metabolites is rapid, as for other assessed phthalates (NICNAS, 2015). There is minimal or no evidence of accumulation in rodent tissues (NICNAS, Phthalates Hazard Compendium, 2008 b). Comparison of the toxicokinetics of the target substance and the RA substance 1: Based on the fact that all isomers of the target substance are also contained in the RA substance, it is reasonable to assume that any metabolite created during the metabolism of the target substance will also be created during the metabolism of the RA substance 1. The predicted metabolites would be mono octyl ester, mono decyl ester, metabolites of octanol and decanol and Phthalic acid for both substances. In addition, metabolism of the RA substance would produce mono hexyl ester and metabolites of hexanol. Hence it is likely that the target substance and the source substance 1 are very well absorbed orally and via inhalation, poorly absorbed dermally (2-4 %), and rapidly metabolized. The distribution is similar based on similar metabolites and both substances are well and nearly fully eliminated. The metabolites are excreted mainly via the urine. There is minimal or no evidence of accumulation in rodent tissues.

Literature:

NICNAS, 2008 a; Existing Chemical Hazard Assessment Report, di-n-octyl phthalate, Australian Government of Health and Ageing NICNAS

NICNAS, 2008 b; Phthalate Hazard Compendium, A summary of physicochemical and human health hazard data for 24 ortho-phthalate chemicals, Australian Government of Health and Ageing NICNAS, June 2008

NICNAS, 2008 c; Existing Chemical Hazard Assessment Report, diundecyl phthalate, Australian Government of Health and Ageing NICNAS

NICNAS, 2015; Existing Chemical Hazard Assessment Report, di-n-octyl phthalate, Australian Government of Health and Ageing NICNAS