2,3-Epoxypropyl neodecanoate, oligomeric reaction products with phosphorous acid

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Assessment, based on physico-chemical properties of the test item and on toxicological data. Experimental toxicokinetic studies were not performed.

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see Remarks

Remarks:

The assessment of the toxicokinetik of the test item is based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

Description of key information

There were no studies available in which the toxicokinetic properties (absorption, distribution, metabolism, elimination) of

2,3-Epoxypropyl neodecanoate, oligomeric reaction products with phosphorous acid were investigated. A data waiver is claimed.

Based on the molecular structure, molecular weight, water solubility, vapour pressure and octanol-water partition coefficient it can be expected that only oral absorption rates is significantly existent.The results from the acute and repeated oral toxicity dose studies confirm that the substance has moderate oral absorption rates. Based on a low log Kow which indicates only moderate lipophilicity of the test item, significant dermal absorption is not expected. Additionally, due to the low vapour pressure of the test item significant respiratory absorption via vapour is also not expected.

The test item could be distributed in the body in a moderate amount.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There were no studies available in which the toxicokinetic properties (distribution, metabolism, elimination) of the test item were investigated. Therefore the following remarks on the toxicokinetics of 2,3-Epoxypropyl neodecanoate, oligomeric reaction products with phosphorous acid are based on physicochemical properties of the test item and on toxicological data.

The test item is a colourless viscous liquid with a molecular weight of Mw = 530 g/mol. It is moderately soluble in water (2.7 mg/L; Infracor GmbH, 2002) and has a low vapour pressure (1 Pa; Infracor GmbH, 2002) under normal ambient conditions. The partition coefficient octanol/water was determined as log Kow = 3.58 at 24.5 °C (Lange, 2017), indicating that a significant bioaccumulation is not to be expected.

With regard to hydrolysis, the test item was tested for hydrolysis according to OECD Guideline No. 111 (2004) and was found to be slightly hydrolytically unstable at pH 7.0. Therefore, slightly dissociation is expected at physiological pH values.

Oral and GI absorption:

Due to the fact, that the test item is only slightly hydrolytically unstable, it is not expected that it is significantly hydrolysed in the gastro-intestinal tract. In fact, the acute oral toxicity is low (LD50 (rat ) > 2000 mg/kg bw) and only slight signs of toxicity were observed (BSL Bioservice, 2004). No mortality occured. However, oral absorption could not be excluded based on the results of the repeated dose toxicity study (LPT, 2018). In this study according to OECD 422 with Wistar rats exposed to 75, 225, and 750/600/450 mg/kg bw/day, the test item caused some mortality in the adults at 750 mg/kg/day. Therefore, the high dose level was stepwise reduced due to mortality. In the Mid dose group of the parental generation also minor clinical effects were observed. Thus, an indication of oral uptake of the substance is given.

Dermal absorption:

Based on the log Kow which indicates only a moderate lipophilicity of the test item, significant dermal absorption is not expected. In fact, the test item shows neither skin irritating nor skin sensitizing properties (both LPT, 2016).Acute or long-term dermal toxicity studies are not available for the test substance.

Respiratory absorption:

Due to the low vapour pressure of the test item significant respiratory absorption via vapour is not expected.

Distribution:

The physico-chemical information (high molecular weight, moderate lipophilicity and water solubility) indicates that the test item could be distributed only in a moderate amount.

Accumulative potential:

The partition coefficient octanol/water was determined as log Kow = 3.58 at 24.5 °C (Lange, 2017), indicating that a significant bioaccumulation is not to be expected.

Excretion:

No data are available regarding the excretion of absorbed 2,3-Epoxypropyl neodecanoate, oligomeric reaction products with phosphorous acid.

Based on the results of two mammalian in vitro genotoxicity tests (both LPT, 2016; all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of the test item will not be generated in mammals in the course of hepatic biotransformation.