4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane

Endpoint summary

Description of key information

Study conducted according to OECD test guideline 406; young adult Pribright guinea pigs were tested using the Maximization test method, Trooxabicyclooctan (a.i. 100 %) in physiological  saline (5%) solution for epicutaneous apllication, result: skin sensitizer

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

17 July 1992

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was conducted prior to implementation of the new requirement to use as in vivo method the LLNA.

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Hagemann
- Females (if applicable) nulliparous and non-pregnant: not specified
- Weight at study initiation: 391-528 g (males); 368-462 g (females)
- Housing: conventional; 1 or 2 animals per cage Makrolon®, type IV with embedding
- Diet (e.g. ad libitum): pell. Altromin® MS, hay and apple ad libitum
- Water (e.g. ad libitum): acidified, demineralized water (pH 2-3) ad libitum
- Acclimation period: 12 days
- Indication of any skin lesions: No

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 52-68
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

48 h

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

a) 0.1 ml FCA + vehicle (1 + 1)
b) 0.1 ml ZK 39294;. 5% (w/v)
c) 0.1 ml ZK 39294; 10% (w/v) + FCA (1 +·1) = 5% (w/v)

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

24 h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS: A local tolerance study (pretest) was performed to ensure an intracutaneously tolerable concentration for the induction procedure which does not lead to necrosis (reddenings and swellings are allowed). The high concentration of 5% used in the present test for intracutaneous application is a recommended concentration for induction procedure, provided that the treatment does not produce excessive irritation. The reactions were recorded 24 hours after application. Furthermore, an epicutaneously tolerable concentration for the epicutaneous challenge was determined under occlusive conditiqns. Since no irritation after single epidermal application of the test item was observed in the local tolerance study on the skin of rabbits, the original substance was also tested epidermally for its local tolerance. Two concentrations, namely ca. 25%, and pure substance, were applied to the lateral backs.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 8 days and 48 h for intradermal and epicutaneous exposure, respectively.
- Test groups:
Intradermal:
A. Test group
a) 0.1 mL FCA + vehicle (1 + 1)
b) 0.1 mL ZK 39294;. 5% (w/v)
c) 0.1 mL ZK 39294; 10% (w/v) + FCA (1 +·1) = 5% (w/v)


epicutaneous:
The same area of skin (4 x 6 cm) in which intradermal injections were performed was reshaved on day 8 of the test and epidermally treated with approximately 1 mL sodium lauryl sulphate (10% (w/v)] in liquid paraffin. 24 hours later, on day 9, 0.2 mL of the original liquid compound was spread over a 2 x 4 cm filter paper {Whatmann, no. 3M) for use in the test group, whereas for the control group only 0.9% (w/v) NaCl-solution was used.
This filter paper was subsequently applied to the above-mentioned area pretreated with sodium lauryl sulphate. The patch was bandaged occlusively for 48 hours. The test item (pure) had previously been proved not to provoke any irritation on the skin atter epidermal administration under occlusion.
- Control group:
Intradermal:
B. Control group
a) 0.1 mL FCA + vehicle (1, + 1)
b) 0.1 mL vehicle
c) 0.1 mL FCA + vehicle (1 + 1)
Epicutaneous:
0.9% NaCl
- Site: In the neck region (right to left side of the spine) of each animal an overall area of 4 x 6 cm
- Frequency of applications: each once
- Duration: 8 days and 48h
- Concentrations: Intradermal 5%, Epicutaneously: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: once
- Day(s) of challenge: on day 23
- Exposure period: 24 h
- Test groups: Approximately 0.1 mL ZK 39294 (original substance)., which previously proved to be well tolerated locally,. was spread over a 2 x 2 cm piece of filter paper. This patch was placed in the middle of the shorn area of skin and bandaged occlusively for 24 hours.
- Control group: 0.9% NaCl
- Site: a skin area of 5 x 5 cm on the right flank

Positive control substance(s):

not required

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

mercaptobenzothiazol

No. with + reactions:

3

Total no. in group:

10

Remarks on result:

other: In the test more than 30% of the animals reacted positively to the challenge with mercaptobenzothiazoL

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.9% NaCl

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.9% NaCl

No. with + reactions:

2

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

7

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

9

Total no. in group:

10

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

The results of this study indicate that Trioxabicyclooctan has contact-sentitizing potential in the guinea-pig in the maximization test.

Executive summary:

In a dermal sensitisation study according to OECD TG 406, (1992) with Trioxabicyclooctan (a.i. 100 %) in physiological  saline (5%) solution for epicutaneous apllication, young adult Pribright guinea pigs were tested using the Maximization test method. Positive control substance was 2-mercaptobenzothiazole with a sensitisation rate of over 30 %.

Since the test substance was found not to cause a primary skin irritation in the dose range - finding study, the treated areas of the animals were irritated with sodium lauryl sulfate prior to the topical induction. After the challenge, 9 (90%) of the test substance animals responded with redness and swelling to the 100% test substance. There were no skin reactions in the control group. The controls exhibited no dermal reactions following the challenge with 100% test substance formulation. Therefore, the sensitisation rate was 0 %.

For the challenge concentration, which is the highest non-irritant dose, 100 % of the test item was used. In this study, Trioxabicyclooctan (a.i. 100 %), is a dermal sensitiser.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In a dermal sensitisation study according to OECD TG 406, (1992) with Trioxabicyclooctan (a.i. 100 %) in physiological  saline (5%) solution for epicutaneous apllication, young adult Pribright guinea pigs were tested using the Maximization test method. Positive control substance was 2-mercaptobenzothiazole with a sensitisation rate of over 30 %.

Since the test substance was found not to cause a primary skin irritation in the dose range - finding study, the treated areas of the animals were irritated with sodium lauryl sulfate prior to the topical induction. After the challenge, 9 (90%) of the test substance animals responded with redness and swelling to the 100% test substance. There were no skin reactions in the control group. The controls exhibited no dermal reactions following the challenge with 100% test substance formulation. Therefore, the sensitisation rate was 0 %.

For the challenge concentration, which is the highest non-irritant dose, 100 % of the test item was used. In this study, Trioxabicyclooctan (a.i. 100 %), is a dermal sensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available information Trioxabicyclooctan needs to be classified according to Regulation (EC) No. 1272/2008 (CLP) as skin sensitizer Category 1.