Registration Dossier

Administrative data

Description of key information

Based on the delayed contact hypersensitivity study in guinea pigs according to OECD guideline 406, performed by Pharmakon Research International, Inc. in 1987, it is concluded that the substance is not sensitising to the skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-05 to 1987-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
Experiment performed according to the OECD 406 guideline adopted in 1981, which is intended primarily for use with guinea pig.
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: no apparent change in the physical appearance of the test article during administration

OTHER SPECIFICS:
- Name of test material (as cited in study report): 5601-88-1
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Inc., Denver, Pennsylvania
- Weight at study initiation: 300-600g
- Housing: two per cage, wire mesh cages.
- Diet (e.g. ad libitum): Wayne Guinea Pig Diet, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: minimum 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: May 28, 1987 To: June 27, 1987
Route:
epicutaneous, occlusive
Vehicle:
other: 80% ethanol
Concentration / amount:
0.4ml per site
first induction: 70%
second and third induction: 40%
challenge 40%
Route:
epicutaneous, occlusive
Vehicle:
other: 80% ethanol
Concentration / amount:
0.4ml per site
first induction: 70%
second and third induction: 40%
challenge 40%
No. of animals per dose:
dose range: 6
test article: 20 (10 male, 10 female)
positive control: 6 (3 male, 3 female)
negative control: 10 (5 male, 5 female)
naive: 4 (2 male, 2 female)
Details on study design:
2 RANGE FINDING TESTS:
3 males, 3 females: each animal is exposed to 4 different concentrations of the test material (1%, 10%, 25%, 100%): 80% ethanol as the vehicle.
1 male, 1 female: each animal is exposed to 4 different concentrations of the test material (50%, 60%, 70%, 80%): 80% ethanol as the vehicle
primary challenge responses were graded
Highest non-irritatting concentration = concentration in vehicle that induced responses not exceeding 2 "+" and 2 "0" grades in the group of 4 animals.
the dose chosen for induction: 70%,
the dose chosen for challenge: 40%


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 4 (3 inductions, 1challenge)
- Exposure period: -
- Test groups: test substance in vehicle (80% ethanol)
- Control group: vehicle only
- Site: L shoulder (first induction); R shoulder (second and third induction)
- Frequency of applications: once a week
- Duration: 6 h
- Concentrations: 70% (first induction); 40% (second and third induction)


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 29
- Exposure period: -
- Test groups: test substance in vehicle
- Control group: vehicle only
- Site: naive site on left flank
- Concentrations: 40%
- Evaluation (hr after challenge): 24 and 48h


OTHER:
24h after challenge, all animals were depilated with Neet Cream Hair Remover (Whitehall Laboratories, Inc., New York). A minimum of 2h after depilation test sites were graded. The grading was repeated 24h later (48h grade).
Challenge controls:
Four naive animals (2 males, 2 females) were induced with the test material (40% concentration) on challenge day in the same manner as the test group and control groups.
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene
Positive control results:
Sensitising effects were observed in all six animals of the positive control group.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
severity= 0.1
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
severity= 0.1
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
No. with + reactions:
3
Total no. in group:
9
Clinical observations:
severity= 0.4
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
1
Total no. in group:
9
Clinical observations:
severity= 0.2
Key result
Reading:
other: naive control
Hours after challenge:
24
Group:
negative control
Dose level:
40%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
severity= 0.0
Key result
Reading:
other: naive control
Hours after challenge:
48
Group:
negative control
Dose level:
40%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
severity= 0.1
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.3%
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
severity= 3.0
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.3%
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
severity= 3.0
Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the observations made in the assay, the test article induced at 70% (1st) and 40% (2nd and 3rd) and challenged at a 40% concentration, did not cause delayed contact hypersensitivity in guinea pigs.
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Only one GLP study conducted in accordance with OECD guideline 406 is available. The study examined the skin sensitising effect on guinea pigs, using 20 animals in total. Positive, solvent and negative controls were included in the study. Animals were induced 3 times with either 70% (1st induction), or 40% (2nd and 3rd induction) the test substance. A challenge was performed using a 40% solution. At both 24 and 48 hours after the challenge none of the animals expressed positive reactions. Furthermore all controls showed expected results, resulting in a valid assay. Based on this study it was concluded that the substance did not cause delayed contact hypersensitivity in guinea pigs and is therefore considered not sensitizing.

An in vitro or in chemico skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study (initiated before October 11th 2016) is available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

- Based on the available information and the criteria of the CLP Regulation, the substance does not need to be classified as a skin sensitizing substance.

- No data are reliable available on respiratory sensitization. Therefore, no conclusion can be made on the classification for this endpoint.