Phosphoric acid, mono- and di-C6-10-alkyl esters

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

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 requirements of Annex VIII (8.8.1).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

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: Endpoint specific guidance (ECHA, May 2008)

GLP compliance:

no

Remarks:

Not relevant for assessment

Test material

Test material information

Constituent 1

Reference substance name:

Phosphoric acid, mono- and di-C6-10-alkyl esters

EC Number:

269-616-7

EC Name:

Phosphoric acid, mono- and di-C6-10-alkyl esters

Cas Number:

68307-94-8

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)

IUPAC Name:

Esterification Products of Phosphorus Pentoxide and Alcohols C6-C10 (even numbered)

Details on test material:

Details on the test material used in the studies assessed are presented in the respective endpoint study records.

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 slightly viscous liquid and the molecular weight ranges from 98.0 - 518 g/mol. The low vapour pressure value (3.1 x 10^-1 Pa 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 has a high log octanol/water partition coefficient value (Log₁₀ Pow 3.15 - >6.5) and low water solubility (0.183 – 8.77 x 10^-11 g/l; Butler, 2012). The available acute oral/dermal studies and the repeated dose/reproductive screening studies showed evidence of absorption and metabolism but did not show any evidence of excretion.

The test item is 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. The test item is not a skin sensitizer, however it is considered an irritant.

Absorption

Results of the repeated dose/reproductive screening study in rats showed evidence to support the gastric absorption of the test item . This is supported by the lipophilic nature of the substance (log₁₀ Pow 3.15 - >6.5). This would suggest that the gastro-intestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood.

Absorption may also take place via the skin. Although the substance is not a skin sensitizer there is evidence of dermal irritation.

Therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

The low vapour pressure value (3.1 x 10^-1 Pa at 25°C) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.

Distribution

Systemic distribution is evident from the repeated dose/reproductive screening study as a result of the organ changes observed. The lack of evidence to suggest the test item is a skin sensitizer suggests that it does not bind to carrier proteins in the circulatory system.

Once absorbed, the substance may potentially accumulate in the adipose tissue due to the high log octanol/water partition coefficient value (Log₁₀ Pow 3.15 - >6.5).

Metabolism

The results of the repeated dose/reproductive screening study showed the evidence of an adaptive response in the liver and thyroids in rats ; which is normally associated with enhanced metabolism. The results of the genotoxicity assays have shown that genotoxicity is neither enhanced or diminished in the presence of the S9 metabolising systems

Excretion

There is no evidence to indicate the route of excretion but poor water-soluble products are not favourable for urinary excretion and therefore biliary excretion may well be a significant route for this material. As there is evidence of hepatic metabolism this does

not, however, rule out urinary excretion. The main reason for xenobiotic metabolism is to render the product more water soluble thereby facilitating urinary excretion. Any test item that is not absorbed will be excreted in the faeces.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: See summary in conclusions section
The available information suggests that absorption of the test substance from the gastrointestinal tract can take place, primarily as a consequence of the high log octanol/ water coefficient of the test item. Some absorption may also take place via the skin. Once absorbed, enhanced metabolism may occur and the substance would result in accumulation in the adipose tissues. Biliary excretion may well be significant route for the substance.

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

accumulation in the adipose tissues. Biliary excretion is considered to be the significant route for the substance.