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Description of key information

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
Study period:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler 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 Limited Animal Production 4332 Stein / Switzerland
- Weight at study initiation: 283 to 359 g.
- Housing: The animals were housed individually in Macrolon cages (Type 3), assigned to the different groups by means of random numbers generated by the random number generator, identified by individual ear tags
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: September 22, 1993

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day
Route:
intradermal and epicutaneous
Vehicle:
other: distilled water
Concentration / amount:
Epidermal applications (induction and challenge)
The concentrations for the epidermal applications were selected on account of the primary irritation potential of the test article. Prior to the study the following concentrations of FAT 46014/G have been examined on separate animals (% w/v):
1, 5, 10, 20, 30, and 50 % FAT 46014/G in distilled water. 50 % in distilled water was the highest possible concentration of the test article.
Erythema reactions were observed with 10, 20, 30, and 50 % FAT 46014/G in distilled water.
Therefore the following concentrations were used:
Epidermal induction (weeks 1 to 3)
Concentration of test article: 30 %
Vehicle: distilled water
Epidermal challenge (week 5)
Concentration of test article: 5 %
Vehicle: distilled water
Route:
epicutaneous, occlusive
Vehicle:
other: distilled water
Concentration / amount:
Epidermal applications (induction and challenge)
The concentrations for the epidermal applications were selected on account of the primary irritation potential of the test article. Prior to the study the following concentrations of FAT 46014/G have been examined on separate animals (% w/v):
1, 5, 10, 20, 30, and 50 % FAT 46014/G in distilled water. 50 % in distilled water was the highest possible concentration of the test article.
Erythema reactions were observed with 10, 20, 30, and 50 % FAT 46014/G in distilled water.
Therefore the following concentrations were used:
Epidermal induction (weeks 1 to 3)
Concentration of test article: 30 %
Vehicle: distilled water
Epidermal challenge (week 5)
Concentration of test article: 5 %
Vehicle: distilled water
No. of animals per dose:
The test was performed on 10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control group, respectively
Details on study design:
This test consists of an induction period with three epidermal occlusive test article applications on the same skin site for 6 hours each (weeks 1 t o 3), a rest period of 13 to 15 days, followed by a challenge period with epidermal occlusive application of the test article for 6 hours (week 5 ).
For all epidermal applications in the test and control group the following self-adhesive and occlusive chamber was used:
Hill Top Chamber"11 full system: 25 mm (Hill Top Research, Inc., Cincinnati , USA)
Approximate volume applied: 0.35 ml/chamber ( fully loaded)

Control group
The control group was treated with the vehicle during the induction period . Like in the test group the maximum sub - irritant concentration of FAT 46014/G was tested during challenge in these animals.
Challenge controls:
No data
Positive control substance(s):
yes
Remarks:
potassium-dichromate
Positive control results:
None
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
No. with + reactions:
11
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 11.0. Total no. in groups: 19.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
No. with + reactions:
9
Total no. in group:
19
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 9.0. Total no. in groups: 19.0.

None

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Remarks:
Migrated information
Conclusions:
FAT 46014/G is, therefore, classified as a sensitiser in albino guinea pigs according to the EEC Classification criteria (Commission Directive 93/21/EEC, April 27, 1993).
Executive summary:

A key study was conducted to determine the skin sensitisation potential of FAT 46014/G (purity: 99.8 %) in guinea pigs. Test was carried out in GLP compliance and followed the OECD guideline 406.Under the experimental conditions employed, 58 and 47 % of the 19 animals of the test group showed skin reactions 24 and 48 hours after removing the dressings, respectively.

FAT 46014/G is therefore, classified as a sensitiser in albino guinea pigs according to the EEC Classification criteria (Commission Directive 93/21/EEC, April 27, 1993).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A key study was performed to determine the sensitising potential of test item FAT 46014/G (with 99.8 % purity) by Buehler test. The substance was tested at 30 % and 5 % concentration in distilled water in induction as well as challenge application. The study was performed as per OECD test guideline and in accordance to GLP.

Under the experimental conditions employed, 58 % and 47 % of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings, respectively.According to the maximisation grading, FAT 46014/G showed a severe grade of skin-sensitising (contact

allergenic) potential in albino guinea pigs. FAT 46014/G is , therefore, classified as a sensitiser in albino guinea pigs according to the EEC Classification criteria (Commission Directive 93/21/EEC, April 27, 1993).

In a supporting study, 50 % and 45 % of the animals of the test groups showed skin reactions at 24 and 48 hours.Hence, FAT 46014/G is classified as a moderate sensitiser (at 5 % concentration) in albino guinea pigs according to the grading of Magnusson and Kligman.

According to the EEC classification criteria (Commission Directive 83/467/EEC, July 29, 1983) FAT 46014/G (purity: 99.8 %) did show a skin-sensitising (contact allergenic) potential in albino guinea pigs.

In another supporting study,skin sensitizing study was carried out to assess the possible allergenic potential of FAT 46'014/H (purity: approx. 32 % (a.i.) when administered to the skin of albino guinea pigs.

For this purpose the " modified Buehler-Test" was used. Twenty test females were induced three times during induction and challenged with the test substance.

Grade of 0 and + were considered to be representative of insignificant responses, whereas those of 1 or greater are considered to be significant. In this study, the test animals treated with the test article at 15% were observed with significant response at 24-or 48-hour challenge reading.

The response of at least 15% positive animals is considered positive "R43" following the commission 93/21/EEC, Commission Directive of April 27, 1993 adapting to technical progress for the 18th time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances.

The results from the first challenge will be not taken into account since the control group I was observed with significant responses

The results for the test substance FAT 46'014/H at the concentration of 15 % is considered to be a non-sensitizer.


Migrated from Short description of key information:
FAT 46014/G is found to be a skin sensitiser.

Justification for selection of skin sensitisation endpoint:
GLP guideline study

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

FAT 46014/G is found to be skin sensitiser.