Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: In accordance with REACH Annex VIII (8.8.1) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Relevant studies were reviewed by a qualified toxicologist with a view to fulfilling the requ irements of Annex VIII (8.8.1).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
In accordance with REACH Annex VIII (8.8.1) an assessment of toxicokinetic behaviour has been
conducted to the extent that can be derived from the relevant available information. The assessment
is based on the Guidance on information requirements and chemical safety assessment R.7c: Endpo
int specific guidance (ECHA, May 2008)
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Phosphoric acid, 2-ethylhexyl ester
EC Number:
235-741-0
EC Name:
Phosphoric acid, 2-ethylhexyl ester
Cas Number:
12645-31-7
Molecular formula:
Mono-Ester: C8H19O4P Di-Ester: C16H35O4P Esters of 2-ethylhexan-1-ol with diphosphoric acid: P2O7(H)4-n(C8H17)n where n = 1-4
IUPAC Name:
Reaction mass of bis(2-ethylhexyl) hydrogen phosphate and 2-ethylhexyl dihydrogen phosphate and esters of 2-ethylhexan-1-ol with diphosphoric acid
Details on test material:
Sponsor's identification: Reaction mass of bis(2-ethylhexyl) hydrogen phosphate and 2-ethylhexyl dihydrogen phosphate; Identifier:TIS O2930, Nalco TIS O0543, Nalco TIS O2384, MIN PR-1137; Description: Amber coloured liquid; CAS Number:12645-31-7; Batch number:CI1C0223; Label:PR-1137 CI1C0223; Date received:04 April 2011; Expiry Date:16 March 2013; Storage conditions:Room temperature, in the dark
Specific details on test material used for the study:

REACTION MASS OF BIS(2-ETHYLHEXYL) HYDROGEN PHOSPHATE AND 2-ETHYLHEXYL DIHYDROGEN PHOSPHATE

Results and discussion

Any other information on results incl. tables

TOXICOKINETIC BEHAVIOUR

The substance is composed, as listed in the Section 1.2 of IUCLID. It is an amber coloured liquid and the molecular weight is 210.21 – 322.42 g/mol. The low vapour pressure value (8.5 x 10-2Pa at 25°C) and predicted negative explosive and oxidising properties shows that the substance is non volatile therefore inhalation is not a significant route of exposure. The substance is considered as flammable.

The substance has a low log octanol/water partition coefficient value (Log10 Pow <0.3- 2.18) and low water solubility (5.95 x 10-3– 13.2 g/l at 20°C).

The available acute dermal irritation/corrosion (OECD 404) and repeated dose reproductive screening studies showed evidence of absorption however the repeated dose reproductive screening study did not show evidence of metabolism or excretion.

The test item was non-mutagenic in bacteria , non-clastogenic in mammalian cells in vitro and non-mutagenic in mammalian (CHO) cells in vitro in either the absence or presence of an auxiliary metabolising system.

Absorption

Although the test item is lipophobic in nature the small molecular size of the substance should allow absorption through passive diffusion. This would suggest that the gastrointestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood.

Limited absorption may also take place via the skin due to small molecular size. The substance is corrosive therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

The low vapour pressure value (8.5 x 10-2Pa at 25°C) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.

Distribution

Once absorbed, the substance may be distributed in plasma due to the water solubility and may therefore be distributed systemically. The lipophobic nature of the test item suggests that bioaccumulation in body fat is unlikely.

Metabolism

The results of the repeated dose/reproductive screening study did not show evidence to indicate any test item influenced hepatic metabolism. The results of the genotoxicity assays have shown that genotoxicity is neither enhanced or diminished in the presence

of the S9 metabolising system.

Excretion

There is no evidence to indicate the route of excretion but water-soluble products are not favourable for biliary excretion and therefore urinary excretion may well be a significant route for this material. Any test item that is not absorbed will be excreted in the faeces.

Applicant's summary and conclusion

Conclusions:
The available information suggests that absorption of the test substance from the gastrointestinal tract can take place. Some absorption may also take place via the skin. Once absorbed, the substance would be distributed in the serum and urine is the significant route of excretion. There is no evidence to suggest that the test substance may be metabolised, however no studies have been conducted to identify metabolites.
Executive summary:

The available information suggests that the substance is readily available via the oral route; however, absorption via the skin is also possible. This is supported by the physicochemical properties of the substance. Once absorbed, the substance would result in distribution in the serum. There is no evidence to indicate the route of excretion..