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Description of key information

The available experimental data in animals support absorption and systemic distribution of the test substance and/or its metabolites or degradation products through the oral and dermal routes. This was evidenced by microscopic and organ weight changes in the liver and the thyroid gland in the OECD 422 study by the oral route and the skin sensitizing properties demonstrated in the LLNA. The registered substance seems to be metabolized in rat as demonstrated by the above-mentioned changes in the liver and thyroid which are considered adaptive non-adverse reactions likely the consequence of hepatic enzyme induction.However, in the absence of specific metabolism studies, no conclusion on the relevance of this variation to human can be drawn. No specific indication on the test substance excretion was obtained from the toxicity studies.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

No specific toxicokinetic studies are available on 1-Phenyldecane-1,3-dione. A toxicokinetic assessment was made, based on the physico-chemical properties of the test substance and the results of toxicity studies (acute oral and dermal toxicity, skin sensitisation, in vitro genotoxicity studies and repeated dose toxicity study).

 

Physico-chemical properties :

Molecular weight: 246.35 g/mol

Water solubility: 387 μg/L (at 20°C)

Partition coefficient in octanol/water: between 4.2 and 6.5 (at 20°C)

Vapour pressure: 9.5 x 10-3Pa (at 25°C)

 

Absorption and distribution :

Oral:

In the acute oral toxicity studies, no mortality nor significant clinical signs indicative of systemic toxicity were reported in rats exposed to one single oral (gavage) administration of 1-Phenyldecane-1,3-dione up to the limit dose of 5000 mg/kg bw.

In the OECD 422 rat study, there was no test item related mortality and the only clinical signs reported consisted in decreased activity and/or piloerection noted after the first administration only in two females given 1000 mg/kg/day. Body weight gains and food consumption were reduced in some animals given 300 and 1000 mg/kg/day. Adaptative non-adverse test item-related changes were observed in the liver (i.e. increased weight and centrilobular hepatocellular hypertrophy) for both sexes at 1000 mg/kg/day and for males given 300 mg/kg/day and in the thyroid glands (i.e. increased weight and diffuse follicular cell hypertrophy) at all dose levels for both sexes. These observations support the absorption and systemic distribution of the registered substance and/or its metabolites or degradation products by the oral route.

Dermal route:

In the acute dermal toxicity study performed in rats, a single dermal application of 1- phenyldecane-1,3-dione at 2000 mg/kg body weight for 24 hours induced no mortality nor effect on body weight but some clinical signs consisting in lethargy, hunched posture, shallow respiration, piloerection, ptosis, and/or chromodacryorrhoea between Days 1 and 4. General erythema, erythema maculate, scales, scabs and/or fissures were seen in the treated skin area and/or left flank of the animals during the 14 -day observation period.

In the in vivo skin sensitization test (LLNA) performed in mouse, no mortality occurred and piloerection was noted for the animals treated at 25% and 50% on Day 3 only. The auricular lymph nodes of the animals treated at 50% were considered enlarged. Mean DPM/animal values for the experimental groups treated with test substance concentrations 10 25 and 50% were 1832, 3293 and 7402 DPM, respectively. The SI values calculated for the substance concentrations 10, 25 and 50% were 2.3, 4.1 and 9.2, respectively. Therefore, since the test item elicits a SI ≥ 3 and the data showed a clear dose-response, it was concluded that based on these results the test item should be considered as a skin sensitizer. These results showed that the registered substance is able to pass the dermal barrier to encounter the systemic circulation and induce the proliferation of lymphocytes in the lymph node draining the site of application.

Whereas the low water solubility and high log PoW of 1- phenyldecane-1,3-dione suggest alow potential of dermal / percutaneous absorption, the clinical signs reported in the acute dermal toxicity srudy and the induction of lymphocytes proliferation in the LLNA supports its capacity to penetrate the skin.  

Metabolism:

No specific toxicological effects indicative of metabolic alteration were observed in the acute toxicity studies in rodents.

The changes in the liver and thyroid noted in the OECD 422 rat study are considered adaptive non-adverse reactions likely the consequence of hepatic enzyme induction and thus indication of increased metabolic activity.

The outcome of the in vitro genotoxicity tests (Ames test, Mouse Lymphoma Assay and micronucleus test in human lymphocytes) was not affected by the presence of metabolic activation. The tests showed no mutagenic or clastogenic effects in the presence or in the absence of exogenous liver S9 metabolization system.

Elimination

There is no indication of a preferred route of excretion for 1- phenyldecane-1,3-dione.