Reaction products of neodecanoic acid and titanium (IV) isopropoxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Assessment of Toxicokinetic Behaviour

Adequacy of study:

key study

Study period:

2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets scientific standards

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Objective of study:

toxicokinetics

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

tetratitanium(4+) 2,2,3,5-tetramethylhexanoic acid 2,2-diethylhexanoic acid 2,2-dimethyloctanoic acid 2,4-dimethyl-2-(propan-2-yl)pentanoic acid tris(2-ethyl-2,5-dimethylhexanoic acid) propan-2-yl 2,2,3,5-tetramethylhexanoate propan-2-yl 2,2-diethylhexanoate propan-2-yl 2,2-dimethyloctanoate propan-2-yl 2,4-dimethyl-2-(propan-2-yl)pentanoate tris(propan-2-yl 2-ethyl-2,5-dimethylhexanoate) bis(2,2,3,5-tetramethylhexanoate) 2,2-diethylhexanoate 2,2-dimethyloctanoate 2,4-dimethyl-2-(propan-2-yl)pentanoate pentakis(2-ethyl-2,5-dimethylhexanoate) hexakis(propan-2-olate)

EC Number:

700-347-4

Molecular formula:

Since this is a complex mixture of substances, no single formula can be assigned

IUPAC Name:

tetratitanium(4+) 2,2,3,5-tetramethylhexanoic acid 2,2-diethylhexanoic acid 2,2-dimethyloctanoic acid 2,4-dimethyl-2-(propan-2-yl)pentanoic acid tris(2-ethyl-2,5-dimethylhexanoic acid) propan-2-yl 2,2,3,5-tetramethylhexanoate propan-2-yl 2,2-diethylhexanoate propan-2-yl 2,2-dimethyloctanoate propan-2-yl 2,4-dimethyl-2-(propan-2-yl)pentanoate tris(propan-2-yl 2-ethyl-2,5-dimethylhexanoate) bis(2,2,3,5-tetramethylhexanoate) 2,2-diethylhexanoate 2,2-dimethyloctanoate 2,4-dimethyl-2-(propan-2-yl)pentanoate pentakis(2-ethyl-2,5-dimethylhexanoate) hexakis(propan-2-olate)

Test material form:

solid: flakes

Applicant's summary and conclusion

Executive summary:

In accordance with Annex VIII (point 8.8) of Regulation (EC) No 1907/2006 (REACH), a paper-based toxicokinetics assessment has been conducted for the test item. Summaries of studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII, point 8.8 of REACH. The assessment of the likely toxicokinetic behaviour of the substance was provided to the extent that can be derived from the relevant available information at the time of the assessment. The assessment is based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, May 2008). The assessment was conducted in July 2011.

TOXICOKINETIC BEHAVIOUR

The test item is composed of titanium salt and alkyl acids. It is a dark yellow liquid and the molecular weight is estimated to be more than 500g/mol. The test item is non-volatile (vapour pressure of 1.4 x 10-1 Pa at 25 degrees centigrade and predicted negative explosive and oxidising properties therefore inhalation is not a significant route of exposure.

The test item has a high log octanol/water partition coefficient (Log10 Pow > 6.70) and very low water solubility (<1.69 x 10-4 g/l at 20.0 +/- 0.5 degrees centigrade. The available acute oral and dermal studies, as well as the oral sub-acute and reproductive screening studies in rats showed evidence of absorption, metabolism and excretion. The test item is non-mutagenic and non-clastogenic. The substance is however an irritant and a skin sensitizer.

Absorption

Results of the acute oral study, 28-day repeated dose study and the reproduction / developmental toxicity screening study in rats show evidence to support the gastric absorption of the test item. This is supported by the lipophilic nature of the substance. 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 corrosive there is evidence of dermal and ocular irritation. Therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

The low vapour pressure value (1.4 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 oral acute, sub-acute and reproductive screening tests as a result of the organ changes observed. The positive response in a skin sensitisation study (LLNA) in mouse suggests that the test item may bind to carrier proteins in the circulatory system thereby facilitating systemic distribution. Once absorbed, the substance may potentially accumulate in the adipose tissue due to the high log octanol / water partition coefficient value (Log10 Pow > 6.70).

Metabolism

The results of the 28-day oral repeated-dose and the reproductive screening study showed the evidence of an adaptive response in the livers in rats, which is normally associated with enhanced metabolism. The metabolism is likely to facilitate the renal excretion of the test substance by rending the material more polar. The results of the in vitro genotoxicity assays do not show any evidence that the addition of the S9 metabolising system either enhances or diminishes the genotoxic potential of the substance.

Excretion

The results of the 28-Day and reproductive toxicity screening test would suggest that the most likely route of excretion is the kidney however biliary or faecal secretion may also apply.

CONCLUSIONS

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, the substance would result in accumulation in the adipose tissues and urine is the significant route of excretion