5-bromo-5-nitro-1,3-dioxane

Endpoint summary

Description of key information

The test item is not skin sensitising and demonstrated no photo skin sensitising potential.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Weight of Evidence Approach

A weight of evidence approach was conducted as no significant reliable study is available for a final conclusion.

 

Report of the sensitisation property of the test substance, R9700872, 1975 

In a non GLP but guideline similar guinea pig maximization (GPM) test, the test substance was tested for skin sensitization.

Based on a range finding study the concentrations for intradermal application of 0.1% and for epicutaneous application of 2.5% were determined. For the main test 25 guinea pigs of the strain Pirbright white were used.

Induction: For the intradermal application 6 injections (2x test substance, 2x test substance with Freund´s adjuvant, 2x with Freund´s adjuvant) of the 0.1% test substance were administrated.

After 8 days the test substance (2.5%) was applied epicutaneously for 24 hours.

Challenge was conducted epicutaneously after 14 days on the shaved flank with 2.5% test substance in a mixture of methylcellulose 45%, ethanol 45% and 10% Tween 80. For control the vehicle was applied at another area.

Evaluation of scores was conducted after 24, 48 and 72 hours. No reactions were observed on the 25 test animals. Based on the result the test substance is not skin sensitising under the conducted test conditions.

 

Examination of allergenic causing properties on guinea pig, R9700871, 1972

In a non GLP and non-guideline compliant study the skin sensitisation property of the test substance was tested in a study comparable to guinea pig maximization test. In the induction phase the test substance was injected 10 times in 2 -3 days intervals on the left flank of 10 guinea pigs. The substance was diluted at a concentration of 1% with olive oil.

After the intradermal injection an epicutaneous application was conducted with the 1% test substance for 48 hours.

After a period of 14 days the challenge was conducted epicutaneously with a concentration of 2.5%.

Reading was conducted after 24, 48 and 72 hours. 5 control animals were also used, treated only with the vehicle.

In the test group skin reactions after 24 hours were observed at 8 of 10 treated animals, after 48 hours 2/10 and after 72 hours 0/10. In the control groups only after 24 hours reactions were observed at 3 of 5 animals, after 48 hours and 72 hours no reactions were observed.

As the skin reactions were completely reversible, the findings were considered as signs of primary irritation and not as an indication for sensitisation.

Based on this result the test substance is determined to be not sensitising.

 

Gruvberger B. and Bruze M., 1997

Guinea pig maximisation test

In the publication of Gruvberger B. and Bruze M., 1997 with limited evidence the sensitisation of the test substance formulation was investigated in a guinea pig maximization test and in humans.

The test substance was commercially available as 10 % w/v solution in propylene glycol, is a formaldehyde-releasing preservative recommended for rinse-off products.

In the guinea pig maximization test the test substance was administrated intradermal 0.25% and topically 0.5% for the induction in 24 animals. For the challenge the test substance in ethanol 99.5 % at 0.25 % was applied topically. Rechallenge was performed one week after the challenge.

Vehicle and positive control (2-methylol phenol) groups were also tested.

Based on the results of a 24-h reading after patch removal the authors concluded that the test substance was demonstrated to be a strong sensitizer in the guinea pig.

 

Guinea Pig Photosensitivity, R9700884, 1978

In a non GLP and non-guideline compliant study the test substance was tested for photosensitivity with guinea pigs.

The test substance (10% in propylene glycol) was diluted to a concentration of 50%. The test substance was applied 10 times topically to the dorsal and ventral site of 10 guinea pigs (6 hours per day) over a 14 day period; it was accompanied by UV exposure (300-400 nm) for 10 minutes /day. 5 days after the induction two challenge applications (24 hours apart) were conducted in the same areas.

Challenge sites were graded on a scale of one to four, with four representing a severe erythematous response over a period of 15 minutes, 24- and 72 hours. The presence of edema was noted at the irradiated and non-irradiated sites at induction and challenge. The challenge irradiation does not indicate any evidence of increased irritation due to photosensitivity.

Based on this result the test substance was determined to be not photosensitizing.

 

Conclusion

The test substance as such is not skin sensitising and revealed no photo skin sensitising potential. When tested as commercial product in a published study, the authors concluded a strong sensitisation potential (Gruvberger and Bruze, 1977). However, the study was not conducted in accordance with the Guinea Pig Maximisation Guideline 406 and with limited information and deficiencies in evaluation and is therefore considered as not reliable.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

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

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for skin sensitisation, under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.