Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Buehler test

The dermal sensitization potential of "reaction products of alcohols, C14 - 18, C18 unsat., esterified with phosphorus pentoxide and salted with amines, C12 -14,-tert-alkyl" was evaluated in Hartley-derived albino guinea pigs (Smedley, 2012).

Ten male and ten female guinea pigs were topically treated with 100% (as received) of the test item once per week, for 3 consecutive weeks. Following a 2-week rest period, a challenge was performed whereby the 20 test and 10 previously untreated (naïve) challenge control guinea pigs were topically treated with 50% w/w of the test item in mineral oil. Challenge responses in the test animals were slightly higher than those of the challenge control animals. Following a 1-week rest period, a rechallenge was performed in which the 20 test and 10 previously untreated (naïve) rechallenge control guinea pigs were topically treated with 50% w/w of the test material in mineral oil. Rechallenge responses in the test animals were slightly higher than those of the control animals. Following a 2-week rest period, a second rechallenge was performed in which the 20 test and 10 previously untreated (naïve) second rechallenge control guinea pigs were topically treated with 50% w/w test item in mineral oil. Second rechallenge responses in the test animals were slightly higher than those of the control animals. An α-Hexylcinnamaldehyde (HCA) positive control group consisting of 10 HCA test and 10 HCA control guinea pigs was included in this study. The animals were treated as above with the HCA test animals receiving 5% w/v HCA in ethanol for induction and 2.5% and 1.0% w/v HCA in acetone for challenge.

Following challenge with 50% w/w test item in mineral oil, dermal scores of ± were noted in 6/20 test animals at the 24 -hour scoring interval. At the 48 -hour scoring interval, dermal scores of ± were noted in 5/20 test animals. Dermal reactions in the remaining test and challenge control animals were limited to scores of 0. Group mean dermal scores were noted to be slightly higher in the test animals as compared with the challenge control animals. Based on the response noted in the challenge control animals, a rechallenge was conducted to attempt to elicit additional responses.

Following rechallenge with 50% w/w test material in mineral oil, dermal scores of ± were noted in 9/20 test animals at the 24- and 48-hour scoring intervals. Dermal reactions in the remaining test and rechallenge control animals were limited to scores of 0. Group mean dermal scores were slightly higher in the test animals as compared to the rechallenge control animals. Therefore, a second rechallenge was conducted in an attempt to elicit an additional response in the test animals.

Following second rechallenge with 50% w/w of the test substance in mineral oil, dermal scores of ± were noted in 9/20 test animals at the 24- and 48-hour scoring intervals. Dermal reactions in the emaining test and rechallenge control animals were limited to scores of 0. Group mean dermal scores were noted to be slightly higher in the test animals as compared with the second rechallenge control animals.

Following challenge with 2.5% w/v alpha-hexylcinnamaldehyde (HCA) in acetone, dermal scores of 1 or 2 were noted in all HCA test animals at the 24-hour and 48-hour scoring intervals. Dermal reactions in the HCA control animals were limited to scores of 0 or ±. Group mean dermal scores were higher in the HCA test animals compared to the HCA control animals. Following challenge with 1.0% w/v HCA in acetone, dermal scores of 1 were noted in 8/10 HCA test animals at the 24-hour scoring interval, and in 4/10 test animals at the 48-hour scoring interval. Dermal reactions in the HCA control animals were limited to scores of 0 or ±. Group mean dermal scores were higher in the HCA test animals compared to the HCA control animals.

Based on the results of this study, the "reaction product of alcohols, C14 - 18, C18 unsat., esterified with phosphorus pentoxide and salted with amines, C12 -14,-tert-alkyl" is not considered to be a contact sensitiser in guinea pigs, as the criterion for sensitisation (dermal scores ≥ 1 in at least 15% of the test animals) was not met. The results of the HCA positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitisers.

EpiDerm

In an in vitro supporting study, the MatTek EpiDerm 3D skin model was used in combination with a direct reactivity test to predict the sensitisation potential of the test article (reaction products of alcohols, C14 - 18, C18 unsat., esterified with phosphorus pentoxide and salted with amines, C12 -14,-tert-alkyl) (Wilga, 2012).

Human reconstructed epidermis (RHE) tissues were treated with six concentrations of the test articles, and the induction of genes associated with stress (and controlled by the Nrf2/Keap1/ARE signaling pathway) was monitored. The test articles were also assayed for their ability to react with glutathione in the absence of cells. The gene induction and glutathione reactivity data were used in combination to allow a proprietary algorithm to predict a toxicity index for each compound. The analysis of the test article (reaction products of alcohols, C14 - 18, C18 unsat., esterified with phosphorus pentoxide and salted with amines, C12 -14,-tert-alkyl) was exposed at 0.1-25% in the test system and indicated a sensitisation potency of non-weak.

Positive and negative controls were run with each analysis in each respective vehicle. Reference controls performed as expected and met acceptance criteria. Benzoic acid was found to be a non-sensitiser and p-benzoquinone was found to be an extreme sensitiser. The test article was found to have an Tox Index of 1.5, which corresponds to a predicted potency category: Non-Weak (exposure regimen 0.1 - 25 %).

LLNA

The disregarded study (Sanders, 2012c) to evaluate the skin sensitisation potential of the "reaction products of alcohols, C14 - 18, C18 unsat., esterified with phosphorus pentoxide and salted with amines, C12 -14,-tert-alkyl" was conducted according to OECD 429 and EU Method B.42 Following a preliminary screening test in which no clinical signs of toxicity were noted at a concentration of 75% v/v, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each of five animals, were treated with 50 µL (25 µL per ear) of the test item as a solution in acetone/olive oil 4:1 at concentrations of 75%, 50% or 25% v/v. A further group of five animals was treated with acetone/olive oil 4:1 alone. A concurrent positive control test, using a group of five animals, was also performed with the known sensitiser,α-Hexylcinnamaldehyde tech., 85%, at a concentration of 25% v/v in acetone/olive oil 4:1. The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group was 2.06 (25% v/v), 3.35 (50% v/v), 4.74 (75% v/v) and 7.8 (25% v/v, positive control). The concentration of test item expected to cause a 3 fold increase in 3HTdR incorporation (EC3 value) was calculated to be 43%. In conclusion, the test item is considered to be a sensitiser under the conditions of the test.Nevertheless, this study is disregarded due to following scientifical findings. Ball et al. (2011) outlined that the observations made for the LLNA often overestimate the sensitisation potential for some substances such as surfactants, fatty acids, fatty alcohols and siloxanes. Since the registered substance is an UVCB with an amino / phosphorus pentoxide group bounded to a long carbon chain, surfactant properties of the test substance can be foreseen. Thus, the substance might lead to false positive results within the LLNA. This conclusion is confirmed by the findings of Smedley (2012) and Wilga (2012), who reported no sensitisation potential for the test substance performing the Buehler test and an EpiDerm skin model.

Literature

Ball et al. (2011) Evaluating the sensitization potential of surfactants: Integrating data from the local lymph node assay, guinea pig maximization test, and in vitro methods in a weight-of-evidence approach. Regulatory Toxicology and Pharmacology 60: 389 -400.


Migrated from Short description of key information:
No positive reactions were observed in the Buehler test for the test substance.

Justification for selection of skin sensitisation endpoint:
The key study performing the Buehler test is regarded as the most reliable study. The LLNA often overestimates the sensitisation potential for some chemicals.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Justification for selection of respiratory sensitisation endpoint:
No relevant route of exposure.

Justification for classification or non-classification

Skin Sensitisation

According to the classification criteria outlined in section 3.4.2.2 (Guidance on the Application of CLP criteria, 2012), if there is evidence in humans that the substance can lead to sensitisation by skin contact in a substantial number of persons, or if there are positive results from an appropriate animal test, the classification as Skin Sensitiser is assigned. Based in the available key information, this substance does not meet the requirement under EU CLP (Regulation (EC) No. 1272/2008) for classification as a skin sensitiser. The substance is not sensitizing.