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Description of key information

Key value for chemical safety assessment

Skin sensitisation

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Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From May 5 to June 4, 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted according to internationally accepted testing guidelines and performed according to GLP. Justification for Read Across is reported in the endpoint summary and in the Category Justification Report attached to the Section 13 of this dossier.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted May 12, 1981
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Ltd. Tierfarm, 4334 Sisseln, Switzerland.
- Age at study initiation: approximately 10 weeks old.
- Weight at study initiation: between 313 to 422 g.
- Housing: individually housed in Macrolon cages (Type 3).
- Diet: standard guinea pig pellets NAFAG No. 846, Gossau SG, ad libitum.
- Water: fresh water, ad libitum.
- Acclimation period: guinea pigs were reportd to be acclimatized, but number of days was not reported.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Photoperiod: 12 hours light cycle day.
Route:
intradermal and epicutaneous
Vehicle:
other: see concentration
Concentration / amount:
Concentration of the test substance in physiological saline and adjuvant mixture: 1 % (intradermal induction)
Approximately 0.4 g paste of 30 % test substance in vaseline (epidermal induction)
Approximately 0.2 g paste of 10 % test substance in vaseline (epidermal challenge)
Route:
epicutaneous, occlusive
Vehicle:
other: see concentration
Concentration / amount:
Concentration of the test substance in physiological saline and adjuvant mixture: 1 % (intradermal induction)
Approximately 0.4 g paste of 30 % test substance in vaseline (epidermal induction)
Approximately 0.2 g paste of 10 % test substance in vaseline (epidermal challenge)
No. of animals per dose:
10 male and 10 female per group.
Details on study design:
INDUCTION PROCEDURES
The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.

First Induction, intradermal application:
Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
- adjuvant and saline (1:1)
- test compound in physiological saline
- test compound in the adjuvant saline mixture
Concentration of in physiological saline and adjuvant mixture: 1 %

Second Induction, epidermal application:
One week later the test substance was incorporated in vaseline and applied on a filter paper patch to the neck of the animals (patch 2 x 4 cm; occluded administration for 48 hours). The application sites were pretreated the day before with 10 % sodium lauryl sulfate (open application). Dose of application: approx. 0.4 g paste of 30 % test substance in vaseline.

CHALLENGE
Two weeks after the epidermal induction application the animals were tested on the flank with test substance in vaseline and the vehicle alone (patch 2 x 2 cm; occluded administration for 24 hours). Dose of application: approx. 0.2 g paste of 10 % test substance in vaseline. The concentrations of the test compound for the induction and challenge periods were determined on separate animals.

CONTROL GROUP
A control group was treated with adjuvant and the vehicle during the induction period.

IRRITATION POTENTIAL
Separate animals were treated with test item for the evaluation of the primary irritation threshold concentration. The tested concentrations of 10 and 30% of test item in vaseline did not induce erythema reactions. 10 % was used as a sub-irritant concentration for the challenge application, to exclude nonspecific reactions in the adjuvant treated animals (s. Magnussen, 1980).

OBSERVATIONS and RECORDS
Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale.
A second evaluation was made 48 hours after removing the dressings. The sensitizing potential of the test compound was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.
Challenge controls:
A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test compound (at least 10 animals) to control the maximal sub-irritant concentration of the test compound in adjuvant treatedanimals.
Positive control substance(s):
yes
Remarks:
Paraphenylene-diamine or Potassium-dichromate.
Positive control results:
The sensitivity of the strain is checked every six months with Paraphenylene-diamine or Potassium-dichromate. The results of the latest reliability check was not provided in the report.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
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: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
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: 0.0. Total no. in groups: 20.0. Clinical observations: none.

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

Number of positive animals per group after occlusive epicutaneous application:

after 24 hours after 48 hours
Control group
vehicle control 0/20 0/20
test compound 0/20 0/20
Test group
vehicle control 0/20 0/20
test compound 0/20 0/20
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 albino guinea pigs was performed to determine the contact allergenic potency of the test compound in albino guinea pigs. This test was based on the OECD Guideline No. 406, adopted May 12, 1981, by the OECD council.

Results

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

Conclusion

According to the CLP Regulation, a substance is classified as skin sensitiser when in the Guinea pig maximisation test the response of at least 30 % of the animals is considered as positive.

In the current experiment none of the animals tested showed any skin reaction.

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

An intracutaneous test performed in 14 guinea pigs and a patch test conducted in 10 humans indicate that CAS No. 67786-25-8 is not a sensitizer (Kimmerle and Solmecke, 1972). Test method is scientifically acceptable, nevertheless many details are missing.

Thus, the result on the most similar substance within the category of Stilbene Fluorescent Whitening Agents (CAS 16470-24-9) was here reported as key study (Ciba-Geigy Ltd., 1987).

This substance can be considered the best representative within the category, since it has the same sulphonation degree, a very high structural similarity (Tanimoto distance > 0.9), very similar molecular weight (1165 Vs 1121 of CAS 67786-25-8) and a very high water solubility (650 g/l Vs 1000 g/l of CAS 67786-25-8).

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

Furthermore, 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. The same was performed for CAS 67786-25-8, and a common behaviour regarding this end point within the category was observed.

Skin absorption was also evaluated and calculated for all members of the category (see Category Justification Report, attached to Section 13 of the dossier). 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 performed in order to verify if breakdown products could be formed. Skin absorption is considered the condition for sensitisation to express, therefore no concern for sensitisation properties is arisen for all members of the category.


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 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.

In the Guinea Pig Maximization Test, 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. Based on the category approach, the substance does not meet the criteria for classification as skin sensitizer, according to Regulation (EC) 1272/2008.

*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.