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Description of key information

Based on a guinea pig maximization study, performed according to the OECD guideline 406 (Allen, 1996; Klimisch 1) , the test substance is considered not sensitising to the skin.

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:
1994-10-24 - 1994-11-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Murine Local Lymph Node Assay (LLNA) is the first-choice method for in vivo testing according to the REACH Regulation. However, this reliable GPMT test was performed before entry into force of the REACH Regulation.
Specific details on test material used for the study:
- Name of test material (as cited in study report): AMINE C-8
- Substance type: dark brown slightly viscous liquid with crystalline sediment
- Physical state: liquid
- Analytical purity: no data
- Composition of test material, percentage of components: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: at room temperature
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd., Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 307-399 g
- Housing: singly or in pairs in solid floor polypropylene cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22 °C
- Humidity (%): 50-63%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction: 0.5% (w/v) in distilled water
Topical induction: undiluted
Topical challenge: 50% and 75% (v/v) in distilled water
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction: 0.5% (w/v) in distilled water
Topical induction: undiluted
Topical challenge: 50% and 75% (v/v) in distilled water
No. of animals per dose:
10 test animals and 5 control animals
Details on study design:
RANGE FINDING TESTS:
For the intradermal injections, 4 animals were injected with 0.1%, 0.5%, 1% or 5% test material and erythema was assessed 24, 48 and 72 hours and 7 days after injection. For the topical induction and challenge, 2 animals were treated with 25%, 50%, 75% and 100% test material under occlusion. The highest concentration without severe irritation after intradermal injection was used in the main test. The highest concentration producing mild-moderate irritation after topical induction was used in the main study. The highest non-irritating dose and one lower dose after topical challenge were used in the main test.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 injections and one occlusive topical application
- Exposure period: one week between injection and topical application; 48 hours topical application
- Test groups: 0.1 ml injection of 1) FCA + water (1:1); 2) 0.5% test material; 3) 0.5% test material + FCA (1:1)
- Control group: 0.1 ml injection of 1) FCA + water (1:1); 2) water; 3) 50% formulation of FCA + water (1:1)
- Site: 40 mm x 60 mm on shoulder region
- Frequency of applications: one series of 3 injections followed by one topical induction 1 week later
- Duration: 7 days between intradermal and topical induction, 48 hours topical exposure, 24 hours observation after topical exposure
- Concentrations: undiluted test material for topical induction

B. CHALLENGE EXPOSURE
- No. of exposures: 3 per animal
- Day(s) of challenge: 1 day
- Exposure period: 1 day
- Test groups: 50% and 75% of test material (right flank)
- Control group: vehicle (left flank)
- Site: flanks
- Concentrations: 0, 50% and 75%
- Evaluation (hr after challenge): 24 and 48 h
Challenge controls:
Distilled water (vehicle) was used as the negative control.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow-coloured staining
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow-coloured staining
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow-coloured staining
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow-coloured staining
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow-coloured staining
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow-coloured staining
Key result
Reading:
1st reading
Group:
positive control
Dose level:
2-mercaptobenzothiazole at 5% in arachis oil B.P.
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Group:
positive control
Dose level:
2-mercaptobenzothiazole at 5% in arachis oil B.P.
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

After intradermal injection, erythema was noted at the exposure sites, mainly in the test group animals (well-defined after 24h and very slight to well-defined after 48h). After topical induction, all test group animals showed yellow-coloured staining and very slight to well-defined erythema. The control group animals did not show skin reactions. After topical challenge, all animals, including control group animals showed yellow-coloured staining. No other skin reactions were observed.

No adverse effects in body weight (gain) was observed when comparing test group animals and control group animals.

Interpretation of results:
GHS criteria not met
Conclusions:
In the guinea pig maximisation test, the test material was negative for skin sensitisation.
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 (Allen, 1996). The study examined the skin sensitising effect on guinea pigs, using 15 animals in total. Positive, solvent and negative controls were included in the study. Animals were induced 3 times with 0.5% the test substance. A challenge was performed using a 50% or 75% solution in vehicle (water). At both 24 and 48 hours after the challenge at 50% or 75%, 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.

No in vitro skin sensitisation studies were performed.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data and the criteria laid down in the CLP regulation, the test substance does not need to be classified as a skin sensitising substance.

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