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Description of key information

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Skin sensitisation

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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:
other: Study conducted according to internationally accepted testing guidelines and according to the GLP procedures.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland.
- Age at study initiation: males: 7 weeks, females: 8 weeks.
- Weight at study initiation: males: 336 - 461 g, females: 332 - 428 g.
- Housing: single.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: one week.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 40-70 %
- Air changes: 10-15 changes per hour.
- Photoperiod: 12/12 hrs dark / hrs light
Route:
intradermal and epicutaneous
Vehicle:
other: distilled water and petrolatum oil
Concentration / amount:
Intradermal induction: 5 %
Cutaneaous induction: 25 %
Challenge: 10 %
Route:
epicutaneous, occlusive
Vehicle:
other: distilled water and petrolatum oil
Concentration / amount:
Intradermal induction: 5 %
Cutaneaous induction: 25 %
Challenge: 10 %
No. of animals per dose:
Control group: 5 male and 5 female
Test group: 10 male and 10 female
Details on study design:
RANGE FINDING TESTS
The objective of this investigation was to identify irritant test article concentrations suitable for the induction phase of the main study. In addition, a suitable non-irritant concentration of the test article, by the topical route of administration, was identified for the challenge application.
The procedure applied for these investigations was as follows:
_Intradermal injections: intradermal injections (0.1 ml/site) were made into the clipped flank of two guinea-pigs at concentrations of 1, 3 and 5 % of the test article in distilled water. The resulting dermal reactions were assessed 24 hours later.
_Epidermal applications: patches of filter paper ( 2 x 2 cm) were saturated with concentrations of 3, 5, 10 and 25 % of the test article in petrolatum oil and applied to the clipped and shaved flanks of each of four guinea-pigs. The patches were covered by a strip of aluminum foil and firmly secured by elastic plaster wound round the trunk and covered with impervious adhesive tape. This procedure ensured the intensive contact of the test article. The dressings were removed after an exposure period of 24 hours and the reaction sites were assessed for erythema and edema on a numerical basis according to the scale described above. Further examination of the sites were performed 24 and 48 hours after removal of the dressings.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (one intradermal, one epidermal).
- Exposure period: 1 week after intradermal, 48 hours epidermal application.
- Test groups: 5% intradermal application, 25% epidermal application.
- Control group: intradermal with distilled water, epdermal with petrolatum oil.
- Site: scapular region.

B. CHALLENGE EXPOSURE
- No. of exposures: 1 epidermal application.
- Day(s) of challenge: two weeks after epidermal induction.
- Exposure period: 24 hours.
- Test groups: 10 % test article in petrolatum oil, and vehicle alone.
- Control group: 10 % test article in petrolatum oil, and vehicle alone.
- Site: right and left flank.
- Concentrations: 10 %
- Evaluation (hr after challenge): 24 and 48 hours after challenge.
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitro-benzol (DNCB)
Positive control results:
For the induction period a 0.5 % dilution of DNCB in ethanol, and for the challenge procedure a 0.3 % dilution of DNCB was used.
Positive erythema reaction after first challenge procedure after 24 hours:
postive: 6 animals; negative: 3 animals
67 % with positive reaction
According to the results observed it is considered that DNCB possess a strong skin sensitizing (contact allergenic) potential in the guinea pig strain used (Dunkin-Hartley albino guinea pigs; DUHA KFM. Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland).
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10 %. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10 %. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: none.
Interpretation of results:
not sensitising
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
Not sensitising.
Executive summary:

Method

A sensitization test in guinea pigs was performed to determine the contact allergenic potency of the test compound. The test was performed according to the OECD Guideline No. 406.

Results

According to the results a weak allergenic potency of the test article was observed in this test when followed the rating of allergenicity described by Magnusson B. and Kligman A.M. (1969).

Conclusion

According to the CLP Regulation, the results showed that test articol is not a skin sensitizer.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A sensitization test in guinea pigs was performed to determine the contact allergenic potency of the test compound. The test was performed according to the OECD Guideline No. 406. According to the results a weak allergenic potency of the test article was observed in this test when followed the rating of allergenicity described by Magnusson B. and Kligman A.M. (1969). But according to the CLP Regulation, the results showed that test article is not a skin sensitizer.

Within the whole category, nine over fourteen registered substances covering at least one member per group (see data matrix in the Category Justification Report attached to the section 13) was tested and none of the existing tests arisen any concern for skin sensitisation.

All substances of the category were modelled with OECD Toolbox and the provisional results about sensitisation and protein binding were calculated for all members: no alerts were reported for any substance. As it can be noted, the influence of the variability in functional group is very low, more related to the variability in the polarity of the substance than on potential reactivity that can arise a concern. From a metabolic point of view, an estimation with OECD Toolbox of the dermal metabolism was also performed, in order to verify if breakdown products may be formed. Skin adsorption is considered the condition for sensitisation to express, therefore no concern for sensitisation properties can be expected for all members of the category.

 

The same was performed for CAS 41098-56-0 and a common behaviour regarding this end point within the category was observed. Based on all those considerations, the available studies on the analogous substances are representative for the substance under registration that can be considered not skin sensitizer, too. As representative supporting data, the results for CAS 16470-24-9 were considered.


Migrated from Short description of key information:
Non sensitizing

Justification for selection of skin sensitisation endpoint:
Study conducted according to internationally accepted testing guidelines and performed according to GLP.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.4 Respiratory or skin sensitisation section, skin sensitizer means a substance that will lead to an allergic response following skin contact.

The criteria to classify a substance as skin sensitizer, on the basis of results from test animals, are reported into the second adaptation to technical progress*: a substance in considered a skin sensitizer when:

- an adjuvant type test method for skin sensitisation is used and a response of at least 30 % of the animals is considered as positive;

- for a non-adjuvant Guinea pig test method a response of at least 15 % of the animals is considered positive;

- a stimulation index of three or more is considered a positive response in the local lymph node assay.

Under the experimental conditions employed, 0 % of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings.

In conclusion, the available experimental data are adequate for classification and labelling according to the CLP Regulation (EC 1272/2008), and the results show that the substance is not classified as skin sensitizer.

*Commission Regulation (EU) No 286/2011 of 10 March 2011, amending, for the purposes of its adaptation to technical and scientific progress, Regulation (EC) No 1272/2008 of the European Parliament and of the Council on classification, labelling and packaging of substances and mixtures.