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Description of key information

Skin sensitisation, guinea pig maximisation: not sensitising (Huels, Muermann 1992)
Skin sensitisation, guinea pig: not sensitising (DuPont Haskell, Hood 1966)

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:
1992-04-08 to 1992-05-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted before REACH came into force.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Pirbright White HSD/Win:DH (SPF)
- Age at study initiation: young adult
- Weight at study initiation: 310 - 381 g
- Housing: conventional, up to 5 animals/Macrolon cage type IV
- Diet: ad libitum, Ssniff G 4 Alleindiaet fuer Meerschweinchen
- Water: communal drinking water ad libitum
- Acclimation period: > 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: 1992-04-08 To: 1992-05-08
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Remarks:
Maiskeimoel MEH 56
Concentration / amount:
Intradermal pretest: 0.25, 0.5, 1.0, 2.5, 5, 10 % w/w in corn oil
Epicutaneous pretest: 2.5, 25, 50 % w/w in corn oil, 100% undiluted liquid test article
Epicutaneous induction: 100% undiluted liquid
Intradermal induction: 10% w/w in corn oil
Epicutaneous induction: 100% undiluted liquid
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Remarks:
Maiskeimoel MEH 56
Concentration / amount:
100% undiluted liquid
No. of animals per dose:
Intradermal pretest: 2 animals
Epicutaneous pretest: 4 animals
Main test: 20 animals
Controls to main test: 10 animals
Details on study design:
RANGE FINDING TESTS:
Formulation: Corn oil was found to be an appropriate vehicle, which formed homogeneous mixtures with the liquid test article
Tolerability intradermal: Injection of the test substance in corn oil (0.15 cm3 of the mixtures, 6 concentrations from 0.25 to 10 % w/w) to the shaved flanks of 2 animals. Recording of skin reactions at 24 hours after injection.
Tolerability epicutaneous: Application of the test substance in corn oil (0.1 cm3 each, 3 concentrations: 2.5, 25, and 50 % w/w, and 100% liquid test material without vehicle) to the shaved flanks of 4 animals (4 gauze patches per animal, area 2x2cm each), with occlusive dressing, for 24 hours. Recording of skin reactions after removal of the patch, and at 48 and 72 hours after the start of the application.

MAIN STUDY
A. INTRADERMAL INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period:
- Test groups: 1 group of 20 animals
- Control group:
- Site:
- Frequency of applications:
- Duration:
- Concentrations:

B. EPICUTANEOUS INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period:
- Test groups:
- Control group:
- Site:
- Frequency of applications:
- Duration:
- Concentrations:

B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge:
- Exposure period:
- Test groups:
- Control group:
- Site:
- Concentrations:
- Evaluation (hr after challenge):
Challenge controls:
No naive control group. An FCA-treated control group (as described above) was challenged in the same was as the test group.
Positive control substance(s):
yes
Remarks:
Strain sensitivity to 1-chloro-2,4-dinitrobenzene tested in regular intervals
Positive control results:
Strain sensitivity to 1-chloro-2,4-dinitrobenzene tested in regular intervals, no results given in present report
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.15 cm3 of undiluted liquid test substance (100 %)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No erythema, no edema observable
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
0.15 cm3 of undiluted liquid test substance (100 %)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No erythema, no edema observable
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.15 cm3 of undiluted liquid test substance (100 %)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No erythema, no edema observable
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.15 cm3 of undiluted liquid test substance (100 %). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No erythema, no edema observable.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0.15 cm3 of undiluted liquid test substance (100 %)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No erythema, no edema observable
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0.15 cm3 of undiluted liquid test substance (100 %). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No erythema, no edema observable.
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No erythema, edema observable.
Remarks on result:
no indication of skin sensitisation

Pretest intradermal: All concentrations of the test substance, as well as the vehicle, caused well-defined erythema and edema 24 hours after injection. Therefore the highest concentration, 10 % w/w, was chosen for the intradermal induction in the main study. Pretest epicutaneous: None of the concentrations of the test substance, including the undiluted substance itself, caused any skin irritation upon application in an occlusive patch (24 hours).

Main study, intradermal induction: The injection of Freund¿s Complete Adjuvans (FCA, diluted 1:1 with saline) caused well-defined to severe erythema and edema. 10 animals of the test group and 12 of the control groups developed necrosis. The injection of the test substance (10 % in corn oil) caused very slight erythema and edema, which developed into well-defined erythema and edema in half of the animals 24 hours after the injection. Reactions of the same grade were observed in the control animals after the injection of the vehicle corn oil. Injection of the test substance in FCA (diluted 1:1 with corn oil) caused very slight to well-defined erythema and edema, which developed into moderate edema and erythema after 24 hours; one animal developed necrosis.

Main study, epicutaneous induction: All injection sites of FCA (50% in saline, mixed with corn oil, or mixed with 10% of the test substance and corn oil) were affected by severe erythema, eschar formation, bleeding, and strong edema. Injection sites of the test substance in corn oil, or the pure vehickle in the controls, showed only scale formation.

Main study, challenge: No signs of irritation in the test and control group.

Interpretation of results:
GHS criteria not met
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1966
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Study performed in 1966, probably no GLP, reasonably documented (2-page summary report), but important details missing: Type of coverage (epicutaneous), volume of injection (intradermal), type and duration of challenge. Only five animals per dose. Submitted to US Office of Toxic Substances under TSCA, 1982.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Five guinea pigs each were induced by epicutaneous (9 exposures in 3 weeks) and intradermal application (4 exposures in 4 weeks). Challenge applications followed a 2-week rest period.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted before REACH came into force.
Species:
guinea pig
Strain:
other: Albino, not otherwise specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: 5 guinea pigs
- Strain: Albino
Route:
epicutaneous, open
Vehicle:
not specified
Concentration / amount:
Not specified
Day(s)/duration:
21
Adequacy of induction:
not specified
No.:
#1
Route:
intradermal
Vehicle:
not specified
Concentration / amount:
Not specified
Day(s)/duration:
14
Positive control results:
Not enough info
Reading:
rechallenge
Group:
test group
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation

No signs of irritation observed (in pretest)

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A key skin sensitisation study (guinea pig maximisation) conducted 1992 according to guideline OECD 406 and under GLP is available. The study is considered to be relevant, reliable (Klimisch 1) and adequate for the purposes of risk assessment, classification and labelling.The maximisation study elicited no positive responses in any animal. The test substance is graded as a non-sensitiser.

A supporting study (non-GLP, 1962) with epicutaneous and intradermal induction (5 animals each) confirms these findings; trimethyl orthoformate is not sensitising.


Justification for classification or non-classification

The substance is not sensitising.