Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Additional information:

Two Murine Local Lymph Node Assays have been conducted on ADONA. Both studies indicate that ADONA is a skin sensitizer.

 

In the first study, 3M 06-403, conducted according to OECD Test Guideline 429,concentrations selected for the main study were based on the results of a preliminary study. In the main study, groups of five mice were treated with ADONA concentrations of 0, 25, 50 or 100% (corresponding to 0, 7.5, 15 and 29.9% of the main active component) in dimethylformamide on three consecutive days, by open application on the ears. Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of disintegrations per minute (dpm) and a stimulation index (SI) was calculated for each test article group. No skin reactions were observed in any of the animals examined. The majority of nodes were considered normal in size, except for the enlarged nodes of four animals treated at 100%. No macroscopic abnormalities of the surrounding area were noted. The SI values calculated for the 25, 50 and 100% concentrations were 1.8, 2.7 and 4.9 respectively. The data showed a dose response and an EC3 value of 56.8% (17% as the active ingredient) was calculated. Based on these results and according to the recommendations made in the test guidelines, ADONA is regarded as skin sensitizer (GHS Category 1, EC labeling phrase R 43).

 

In the second study, 3M 07-106, ADONA was tested according to OECD Test Guideline 429. ADONA was tested as supplied (100%) and diluted in DMSO (25 and 50%). None of these concentrations (corresponding to approximately 7.5, 15 and 29.9% of the active ingredient) caused significant irritation in a preliminary irritation screen. In the definitive study, animals (5/group) were administered 25 µL of vehicle (DMSO), positive control (25% alpha-hexylcinnamaldehyde in DMSO), or 25, 50, or 100% ADONA by topical application to the dorsum of each ear once daily for three consecutive days. A naïve control group (5 animals) was left untreated. Clinical observations were recorded daily. Body weights were recorded on days 1 and 6. Ear swelling measurements were recorded on days 1, 3 and 6. Following euthanasia on day 6, the number of proliferating lymph node cells in the auricular lymph nodes were determined using a 5-bromo-2’-deoxyuridine (BrdU) flow cytometry method. The Stimulation Index (SI) was calculated and substances with a SI > or = 3 are considered to be potential sensitizers. The lymph node cell suspensions were also stained with antibodies and analyzed by flow cytometry to determine %B cells, %T cells and B:T cell ratios. Materials that induce a =25% (1.25-fold) increase over the vehicle (or naïve) controls in %B cells or B:T cell ratio are considered sensitizers. All animals survived the in-life phase of the study and appeared normal with the exception of one animal in the 100% test article group which appeared emaciated, exhibited a wet anogenital area and showed a small (1.4 g) decrease in body weight. These findings were not believed to be test article-related since all other animals in this group appeared normal. This animal was not be injected with BrdU and no lymph nodes were harvested from this animal. Ear swelling measurements and individual animal observations indicated that none of the test article concentrations were irritating. The SI for the positive control group was 15.3, indicating that the test was valid. SI values for the 25, 50 and 100% test article groups were 0.8, 2.4 and 3.8, respectively, relative to the DMSO control group. The SI for the 100% dose group was 8.9 relative to the naïve control group. ADONA elicited 1.05, 1.22 and 1.91-fold increases in %B cells at 25, 50 and 100%, respectively, relative to the DMSO control group and a 1.62-fold increase at 100% relative to the naïve control group. The test article elicited 1.04, 1.20 and 2.21-fold increases in B:T cell ratios at 25, 50 and 100%, respectively, relative to the DMSO control group and a 1.79-fold increase at 100% relative to the naïve control group. Topical application of ADONA at 100% (29.9% active ingredient) resulted in a SI greater than 3 and greater than 25% increases in %B cells and the B:T cell ratios. The calculated EC3 value (the estimated concentration which would induce a SI of 3) for the test article was 54.8% (16.4% as the active ingredient). Under the conditions of the test and according to established criteria for interpretation of LLNA test results, it is concluded that ADONA is a weak dermal sensitizer.


Migrated from Short description of key information:
Two Murine Local Lymph Node Assays have been conducted on ADONA. Both studies indicate that ADONA is a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion
Additional information:

ADONA meets the DSD criteria for classification as a skin sensitizer (Xi; R43), and it meets the CLP criteria for classification as Skin Sens. 1B.

Justification for classification or non-classification