Didodecyl 3,3'-thiodipropionate

Endpoint summary

Description of key information

LLNA (OECD 429): not sensitizing

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

LLNA:

The test substance was assessed for its skin sensitizing properties in a Local Lymph Node Assay (LLNA) according to OECD Guideline 429 and under GLP. 

In the pre-screen test, very slight irritation was observed in both animals at 50% and in one animal at 25%. No mortality occurred, and no clinical signs of systemic toxicity were observed in the animals. Furthermore, no effect on body weight was observed in both animals treated at 50%. At 25%, slight to moderate body weight loss was observed in both animals; however, as there were no corroborative findings, it was considered that the results for these animals were not affected. At 25 and 50%, ear thickness did not exceed +25% on Days 3 or 6. Mean ear punch weight at 25 and 50% was 33.12 and 28.57 mg, respectively. All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted for any of the animals. Mean lymph node weight at 25 and 50% was 3.78 and 4.87 mg, respectively. Ear punch weight and lymph node weight showed no dose-related response. As no control group was included in the pre-screen test, no further assessments could be made. Based on these results, concentrations for the LLNA Main study were set at 50, 25 and 10%.

In the Main study, three experimental groups of five female CBA/J mice were treated with test material concentrations of 10, 25 or 50% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone (Acetone/Olive oil (4:1 v/v)). 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 and pooled for each animal. 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 subsequently calculated for each group.

Ear thickness did not exceed +25% on Day 3 or 6 in the test item-treated animals. Mean ear punch weight at 10, 25 and 50% were 30.19, 30.28, 31.04 mg, respectively. The mean ear punch weight for the vehicle control group was 29.54 mg. No test item-related effect on ear thickness or ear weight was observed. All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. Mean lymph node weights at 10, 25 and 50% were 4.59, 4.57 and 3.89 mg, respectively. The mean lymph node weight for the vehicle control group was 4.42 mg. No test item-related effects were observed on lymph node weight. No macroscopic abnormalities of the surrounding area were noted for any of the animals. 

Mean DPM/animal values for the experimental groups treated with test material concentrations at 10, 25 and 50% were 675, 454 and 376 DPM, respectively. The mean DPM/animal value for the vehicle control group was 475 DPM. The SI values calculated for the test material concentrations of 10, 25 and 50% were 1.4, 1.0 and 0.8, respectively.

Since there was no indication that the test material elicits a SI ≥ 3 when tested up to 50%, the test substance was considered not to be a skin sensitizer under the conditions of the assay.

 

Optimization test:

The test substance was investigated for its sensitizing potential in a Maurer Opimisation test which was performed by CIBA-Geigy (Siss4733, 1976). Pirbright White guinea pigs (10 male and 10 female animals) were treated at induction as follows: 0.1 ml of a 0.1% solution of the test substance, diluted in polyethylene glycol and saline (70:30), was intradermally injected at the flank, back and neck of the animals on 3 consecutive days over 3 consecutive weeks. In the first week, the test substance was mixed only with the vehicle, in the second and third week with the vehicle and an adjuvant. Flank and back were treated at first injection, back at 2nd and 3rd injection, neck at 4th-9th injection. Dinitrochlorobenzene (DNCB, 0.1% solution) served as positive control. On day 33, the compound, dissolved in vehicle, was again injected intradermally at the previously untreated flank. Challenge reactions were recorded after 24 hours.

Twenty-one hours after administration of the test substance in week one, the animals were chemically depilated with Butoquick® and three hours later the skin reaction was assessed under artificial lighting (Luxram E 27, "Daylight"). The two largest diameters of the erythematous reaction in vertical alignment were measured (mm) and the skin-fold thickness was determined with a skin-fold gauge (mm). The individual "reaction volume" (μL) was calculated from these values for each reaction from each animal. 24 hours after challenge, the reaction site was evaluated in the same manner as during the first testing week. For each animal the mean value + one standard deviation was calculated for the reaction volumes of the intracutaneous injections from the first testing week. Skin sensitization was defined to occur of the challenge reaction whenever the reaction volume exceeded the mean value + one SD of the pre-sensitization responses.

In the positive control group, 20/20 animals showed a positive reaction, one animal was affected in the negative control group and two animals in the group of animals that were treated with the test substance. Under the conditions of the study, it was concluded, that the test substance has not a skin sensitizating potential.

Respiratory sensitisation

Endpoint conclusion

Additional information:

No data available.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for sensitisation is not warranted under Regulation (EC) No.1272/2008.