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Description of key information

FAT 11127/C is considered to have not shown skin-sensitizing potential when tested in the Buehler assay.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

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Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
other information
Study period:
From February 11, 1994 to August 4, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study terminated owing to animal welfare reasons
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from a reliable in vivo test conducted before the enforcement of Commission Regulation (EU) 640/2012 of 06 July 2012 amending, for the purpose of its adaptation to technical progress, Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) are available.
Specific details on test material used for the study:
Test item : FAT 11127/C
Appearance : Dark blue powder.
Species:
guinea pig
Strain:
not specified
Sex:
male/female
Route:
intradermal
Vehicle:
other: NaCl (0.9 %)
Concentration / amount:
5 % suspension
Day(s)/duration:
7 Days
No. of animals per dose:
3 animals were used
Details on study design:
INDUCTION EXPOSURE
- No. of exposures: 1
- Test groups: 1
- Site: intradermal
- Frequency of applications: Once
- Concentrations: 5 % suspension of FAT 11127/C in NaCl (0.9%)
Positive control substance(s):
no
Remarks on result:
not measured/tested

FAT 11127/C was to be evaluated for Skin sensitization potential according to Guinea pig Maximization test as described in OECD Guideline 406. For the intradermal induction application at the start of the study, a 5 % suspension of FAT 11127/C in NaCl (0.9 %) was used. After this application, a moderate skin reaction was observed, as had previously been seen in a pretest performed in two animals. However, within one week of the intradermal induction, the skin of the neck region and therefore limbs became bluish and on day 9 severe ulceration was observed in most animals of the test group. One male of the test group died on day 8. On day 9, the Study Director decided to terminate the study for animal welfare reasons. Two animals were sent to histopathology. Hence, it was concluded that intradermal injection of FAT 11127/C resulted in severe ulcerative effects in this test. A pretest with epidermal application of FAT 11127/C showed only mild skin reactions. Therefore, a Buehler test is recommended instead of the Maximisation test.

Pathology

The results of the gross pathological and histopathological examination of the skin and axillary lymph node in the two animals sacrificed in moribund condition on study day 9 are presented below.

 

Macroscopical findings:Ulceration and a scab formation of the skin of animals sacrificed.

Additionally, in the female no. 96, the axillary lymph node was reported as enlarged. The spleen was reported as large in both animals, but, upon request of the sponsor, no histopathological examination was performed.

 

Microscopical findings:

The skin was found to be moderately ulcerated in both animals. Furthermore, the subcutaneous tissue revealed a marked abscess formation, accompanied by a moderate chronic inflammation of the dermis and subcutaneous tissue in both guinea pigs and a dermal necrosis in the male no. 89. The epidermis was moderately acanthotic and showed a minimal to moderate paraketosis in both animals, in the female no. 96 also associated with a moderate epidermal hyperkeratosis.

 

Axillary lymph node:

The axillary lymph nodes were found to be activated and were given the diagnosis of a 'chronic reactive hyperplasia' which was minimal in male no. 89 and moderate in female no. 96.

Interpretation of results:
study cannot be used for classification
Executive summary:

FAT 11127/C was to be evaluated for Skin sensitization potential according to Guinea pig Maximization test as described in OECD Guideline 406.

 

For the intradermal induction application at the start of the study, a 5 % suspension of FAT 11127/C in NaCl (0.9 %) was used. After this application, a moderate skin reaction was observed, as had previously been seen in a pretest performed in two animals. However, within one week of the intradermal induction, the skin of the neck region and therefore limbs became bluish and on day 9 severe ulceration was observed in most animals of the test group. One male of the test group died on day 8.

 

On day 9, the Study Director decided to terminate the study for animal welfare reasons.

Conclusion

Intradermal injection of FAT 11127/C resulted in severe ulcerative effects in this test.

A pretest with epidermal application of FAT 11127/C showed only mild skin reactions. Therefore, a Buehler test is recommended instead of the Maximisation test.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 10 August, 1994 to 8 September, 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Data from a reliable in vivo test conducted before the enforcement of Commission Regulation (EU) 640/2012 of 06 July 2012 amending, for the purpose of its adaptation to technical progress, Regulation (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) are available.
Specific details on test material used for the study:
Test article: FAT 11127/C
Batch No.: 9309001
Purity: ca. 80 %
Physical properties: solid
Storage conditions: room temperature
Expiry date: June 1999
Species:
guinea pig
Strain:
Pirbright-Hartley
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: 291 to 369 g
- Housing: The animals were housed individually in Macrolon cages (Type 3),
- Diet: The animals received ad libitum standard guinea pig pellets - NAFAG No. 845, Gossau SG.
- Water: ad libitum
- Acclimation period: 7 days.
- Indication of any skin lesions: No

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 to 70 %
- Photoperiod: 12 hours light cycle day.
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
distilled water
Concentration / amount:
50 %
Day(s)/duration:
Weeks 1 to 3
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
distilled water
Concentration / amount:
30 %
Day(s)/duration:
Week 5
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
- 10 male and 10 female guinea pigs in test group.
- 5 males and 5 females in the control group.
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three epidermal occlusive test application during weeks 1 to 3
- Exposure period: 3 weeks
- Test groups: Epidermal induction (weeks 1 to 3)
- Concentration of test article: 50 % in distilled water
- Control group: Distilled water
- Site: Epidermal
- Frequency of applications: once a week
- Duration: 6 hours

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Exposure period: 6 Hours
- Concentration of test article: 30 % in distilled water
- Control group: Distilled water
- Site: Epidermal
- Evaluation: Twenty four and forty eight hours after removing the dressings, the challenge reactions were graded according to a modified Draize scoring scale.
Challenge controls:
Distilled water
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole puriss (Test No. 930025)
Positive control results:
After 24 hrs : 4/20 animals showed a positive result.
After 48 hrs : 6/20 animals showed a positive result.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50 % for induction and 30 % for challenge
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50 % for induction and 30 % for challenge
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
2-Mercaptobenzothiazole puriss. induction 75 % , challenge 20 %
No. with + reactions:
4
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
2-Mercaptobenzothiazole puriss. induction 75 % , challenge 20 %
No. with + reactions:
6
Total no. in group:
20
Interpretation of results:
GHS criteria not met
Conclusions:
FAT 11127/C did not show skin-sensitizing potential in albino guinea pigs.
Executive summary:

The test substance FAT 11127/C was tested for skin sensitization potential according to Buehler test as described in OECD Guideline 406. 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.

 

Epidermal induction consisted of three epidermal occlusive substance applications on the same skin site for 6 hours each (weeks 1 to 3) at concentration of 50 % test substance in distilled water, a rest period of 13 to 15 days, followed by a challenge period (at test substance concentration of 30 % in distilled water) with epidermal occlusive application of the test article for 6 hours (week 5).

 

No animal of the test group was sensitized by FAT 11127/C under the experimental conditions employed. Hence, FAT 11127/C is considered to have not shown skin-sensitizing potential in albino guinea pigs.

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

FAT 11127/C was to be evaluated for skin sensitization potential according to Guinea pig Maximization test (OECD Guideline 406). However, intradermal injections of FAT 11127/C resulted in severe ulcerative effects in this test. Hence, the study was terminated. A pretest with epidermal application of FAT 11127/C showed only mild skin reactions. Therefore, a Buehler test was carried out. In this Buehler test, epidermal induction consisted of three epidermal occlusive applications on the same skin site for 6 hours each (weeks 1 to 3) at concentration of 50 % test substance in distilled water, a rest period of 13 to 15 days, followed by a challenge period (at test substance concentration of 30 % in distilled water) with epidermal occlusive application of the test article for 6 hours (week 5). No animal of the test group was sensitized by FAT 11127/C under the experimental conditions employed. Hence, FAT 11127/C is considered to have not shown skin-sensitizing potential in albino guinea pigs.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

FAT 11127/C is considered to have not shown skin-sensitizing potential when tested in the Buehler assay, hence it does not need to be classified for sensitisation as per the criteria of Regulation (EC) No. 1272/2008.