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:

LLNA study:

In a mouse lymphoma assay, performed according to OECD, EC and EPA test guidelines, mouse were treated with 0%, 25%, 50%, or 100% of Radiagreen RA on three consecutive days by open application on the ears. Three days after the last exposure all animals were injected with 3H-methyl thymidine. Radioactivity measurements of the lymph nodes were performed. No skin reactions were observed in any of the animals examined. The majority of nodes were considered normal in size, no macroscopic abnormalities of the surrounding area were noted. One animal treated with 100% showed marked body weight loss, hunched posture, lethargy, hypothermia and ptosis at day 6. This animal was excluded from analysis. All other animals did not show any effect on body weight or systemic toxicity. The SI values for 25, 50 and 100% were 1.6, 4.4 and 6.3, respectively. EC3 value was determined to be 37.5%. Based on these results the substance is a skin sensitiser.

Human patch test:

Thirty five volunteers with healthy skin were tested in order to assess the risk for skin sensitisation of Radiagreen RA. The test item was applied under firm occlusion altoghether 10 times for 48 hours: 9 times to the same spot of the skin of the upper arm or back for induction and once for 48 hours to a naive site of the skin for challenge after a rest period of 14 days. Skin reactions were read prior to each patch application during the induction phase of the trial, and immediately, 24, and 48 hours after patch removal at challenge. No skin reaction was observed in any of the volunteers at any reading. Based on this study it can be concluded that there is no or only a minimal risk of skin sensitisation when Radiagreen RA is coming into contact with human skin.

Company health records:

For Radiagreen RA a medical record on skin sensitisation is provided by the manufacturing company. From this it is clear that operators and lab technicians might be exposed during sampling and analysis of these samples, although operators have RMMs such as gloves and overall in place. Thirty three sampling times over a period of 5 years are recorded, showing that mainly the same operators and technicians have dealt with this work, so if exposure might have taken place, this did not result in skin sensitisation.

Discussion:

Several publications have shown that for some type of substances LLNA studies gave positive results while GPMT studies gave negative results. The publications of e.g. Kreiling et al. (Food Chem Tox, 46, p. 1896 -1904, 2008) and Garcia et al. (Reg Tox Pharm, 58, p. 301 -7, 2010) describe the results of LLNA and GPMT testing for several fatty acids having a chain length from C4 to (>)C18. For most substances the LLNA gave positive results (12 out of 19), while the GPMT did give only one positive result (1 out of 19). As these test substances were either endogenous physiological constituents, common and widely used natural constituents of food and/or cosmetics, or nonionic sugar lipid surfactants, the high number of positives in the LLNA test was unexpected. Radiagreen RA does contain fatty acids C8 -C10 as starting product resulting in different glycerol (e.g. mono-, di-, tri- etc) octanoates and decanoates. In addition, a literature search shows that decanoic acid, octanoic acid and glycerol does not show sensitising properties in human patch tests and in other tests with humans (see Toxnet, mainly HSDB and IUCLID data sheets).

Taking all this information into account, it is concluded that Radiagreen RA is not expected to have sensitising properties and thus does not have to be classified accordingly.


Migrated from Short description of key information:
The mouse lympohoma skin sensitisation study was performed according to OECD Guideline 429 and GLP prinicples. In addition, a human patch test was performed with healthy volunteers according to GCP principles, company data and publicly available data are present. Based on all this information, it is concluded that Radiagreen RA is not sensitising to humans.

Justification for classification or non-classification

Based on all information available, the substance is not classified as skin sensitizer according to CLP Regulation (EC) No. 1272/2008.