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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-05-31 to 1990-08-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992-07-17
Principles of method if other than guideline:
According to Buehler et al., 1980
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The test was conducted before the implementation of OECD 429 in 2002.

Test material

Constituent 1
Chemical structure
Reference substance name:
α,α,α-trifluoro-4-nitro-m-cresol
EC Number:
201-818-2
EC Name:
α,α,α-trifluoro-4-nitro-m-cresol
Cas Number:
88-30-2
Molecular formula:
C7H4F3NO3
IUPAC Name:
4-nitro-3-(trifluoromethyl)phenol
impurity 1
Chemical structure
Reference substance name:
5-chloro-α,α,α-trifluoro-2-nitrotoluene
EC Number:
204-280-7
EC Name:
5-chloro-α,α,α-trifluoro-2-nitrotoluene
Cas Number:
118-83-2
Molecular formula:
C7H3ClF3NO2
IUPAC Name:
4-Chloro-1-nitro-2-(trifluoromethyl)benzene
impurity 2
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
Dihydrogen oxide
impurity 3
Chemical structure
Reference substance name:
3-Carboxy-4-nitrophenol
Cas Number:
610-37-7
Molecular formula:
C7H5NO5
IUPAC Name:
3-Carboxy-4-nitrophenol
Test material form:
liquid
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

OTHER SPECIFICS: dark brown liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc.
- Microbiological status of animals, when known: SPF
- Age at study initiation: young adult
- Weight at study initiation: 446 - 550 g
- Housing: individually, in screen-bottom stainless steel cages
- Diet: ad libitum, certified guinea pig chow #5026 (Purina Mills, Inc.)
- Water: ad libitum
- Acclimation period: at least 7 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: 1990-06-06 To: 1990-07-16

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
deionized
Concentration / amount:
0.4 mL, 1.0 % w/v
Day(s)/duration:
day 0, day 7, and day 14; 6 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, open
Vehicle:
water
Remarks:
deionized
Concentration / amount:
0.4 mL, 0.1 % w/v
Day(s)/duration:
2 weeks after last induction; 6 h
No. of animals per dose:
Test group: 10
Naive control group: 10
positive control group: 4
Details on study design:
RANGE FINDING TESTS:
yes, two range finding groups, 4 animals each.
1st group: undiluted, 75 % w/v, 50 % w/v, 25 % w/v
Due to the level of irritation, a second range finding study ws conducted
2nd group: 10 % w/v, 5 % w/v, 1 % w/v, 0.1 % w/v

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 1
- Control group: 2, naive and positive control
- Site: back of the animals
- Frequency of applications: once a week
- Duration: 3 week
- Concentrations: 1.0 % w/v

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: two weeks after the last inducton exposure
- Exposure period: 6 h
- Test groups: 1
- Control group: 2, naive and positive control
- Site: back of the animals
- Concentrations: 0.1 % w/v
- Evaluation (hr after challenge): 24, 48
Positive control substance(s):
yes
Remarks:
0.3 % w/v 2,4-dinitrochlorobenzene (DNCB) in 80 % ethanol/deionized water

Results and discussion

Positive control results:
The mean score of DNCB (all animals) 24 h after challenge was 2.0 (max. score 3.0).

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 % w/v
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 % w/v
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 % w/v
No. with + reactions:
4
Total no. in group:
4
Clinical observations:
subcutanous hemorrhaging, possible necrotic areas
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1 % w/v
No. with + reactions:
4
Total no. in group:
4
Clinical observations:
subcutanous hemorrhaging, possible necrotic areas
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1 w/v
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1 % w/v
No. with + reactions:
0
Total no. in group:
10

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance showed no skin sensitizing potential.
Executive summary:

In a primary sensitisation study similar to OECD guideline 406, a group of young adult Dunkin-Hartley guinea pigs (10♂, 446 - 550 g) were epicoutanously treated with the test substance (3x 0.4 mL, 1.0 % w/v in deionized water, once a week for 6 h) at the back (Hazleton Laboratories, 1990). After an incubation period of 2 weeks, the animals were challenged with 0.4 mL of a 0.1 % w/v water solution for 6 h at the back. Readings were done 24 and 48 h after the challenge injection. The sensitizing score was determined according to Buehler et al. (1980). The test substance caused no sensitisation response. A positive control group of 4 animals was treated with 2,4-dinitrochlorobenzene (0.3 % w/v in 80 % ethanol/dionized water). All animals of the positive control group showed signs of sensitisation.