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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:
09 May 1984 - 29 May 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study report did not cite any specific test guideline, and the claim of GLP compliance does not refer to a particular GLP standard (such as the OECD guidelines for GLP, etc.), however the methodology used is consistent with one of the methods noted in OECD test guideline 406, and the study report is well detailed. The study was concluded to be essentially reliable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
The modified Magnusson-Kligman method used in the study is described in the test guideline.
Deviations:
not applicable
GLP compliance:
yes
Remarks:
Note that the GLP compliance page of the report does not cite any specific GLP regulations.
Type of study:
Freund's complete adjuvant test
Justification for non-LLNA method:
The modified Magnusson-Kligman method used in the study is also described in the test guideline OECD 406.

Test material

Constituent 1
Chemical structure
Reference substance name:
Dimethyl carbonate
EC Number:
210-478-4
EC Name:
Dimethyl carbonate
Cas Number:
616-38-6
Molecular formula:
C3H6O3
IUPAC Name:
dimethyl carbonate
Details on test material:
- Name of test material (as cited in study report): Dimethyl Carbonate
- Physical state: Not specified.
- Analytical purity: Not reported
- Purity test date: Not reported
- Lot/batch No.: Batch 93519
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Satisfactory (identity and purity confirmed statisfactory by in-house Infra-red analysis).
- Storage condition of test material: Room temperature.
- Other:

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Porcellus Animal Breeding Station, Healthfield, Sussex.
- Age at study initiation: Not reported.
- Weight at study initiation: 320 to 410 g.
- Housing: No more than four to a cage, polypropylene cages with stainless steel tops
- Diet (e.g. ad libitum): Ad libitum access to Guinea Pigs maintenance diet (Special Diet Services Limited, Witham, Essex).
- Water (e.g. ad libitum): Ad libitum access to drinking water.
- Acclimation period: 8 Days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 25°C.
- Humidity (%): 36 - 89% Relative Humidity.
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark.


IN-LIFE DATES: From: 09 May 1984 To: 29 May 1984

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: No vehicle or 50:50 FCA and water for the Intradermal induction; no vehicle for the topical (epicutaneous) induction, and ethanol for the challenge.
Concentration / amount:
100% or 25% for the intradermal induction; 25% or 50% in ethanol and 100% (neat) for the challenge.
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
other: No vehicle or 50:50 FCA and water for the Intradermal induction; no vehicle for the topical (epicutaneous) induction, and ethanol for the challenge.
Concentration / amount:
100% or 25% for the intradermal induction; 25% or 50% in ethanol and 100% (neat) for the challenge.
No. of animals per dose:
15
Details on study design:
RANGE FINDING TESTS:
Various concentrations of test material in ethanol were applied topically or injected into groups of female guinea pigs which had been pre-treated with Freund's Complete Adjuvant (FCA). SKin reactions to the topical and intradermal applications were assessed.
Concentrations for the main test were determined as follows;
Intradermal injection - the maximum concentration resulting in reaction at or below the severity defined as acceptable.
Topical induction - the maximum concentration giving a slight irritant response (pre-treatment with sodium lauryl sulphate s required when no irritancy is produced by the neat material)
First challenge - the highest level corresponding to the maximum concentration giving no irritant response on topical application and mid and low level doses of test material at lower concentrations.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (Intradermal then topical)
- Exposure period: Intradermal injection, then 48-hour topical exposure, 7 days after the intradermal induction.
- Test groups: Single 0.1 mL intradermal injections of the following: 50:50 FCA in water; 100% test substance; 25% test substance in 50:50 FCA in water. 0.25 mL test substance used in topical induction.
- Control group: Single 0.1 mL injection of 50:50 FCA in water. An untreated patch was held in place over the injection sites during the topical induction phase of the test.
- Site: Scapula.


B. CHALLENGE EXPOSURE
- No. of exposures: Single
- Day(s) of challenge: One challenge, 14 days after the appliaction of the topical induction patches.
- Exposure period: Patches were applied for 24 hours, followed by observations at 24 and 48 hours after removal of the patches.
- Test groups: 3 patches applied to the backs of each animals. Patches were saturated wth 0.03 mL of test material solution - 100%, 50%, and 25% in ethanol.
- Control group: Challenge procedure was the same for the control group as for the test group.
- Site: Back.
- Concentrations: As described in "Test groups"
- Evaluation (hr after challenge): 24 and 48 hours after removal of the patches.


OTHER:
Positive control substance(s):
no

Results and discussion

Positive control results:
No positive control group was applied in the study.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
up to 100%
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: up to 100%. No with. + reactions: 0.0. Total no. in groups: 15.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
up to 100%
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
All animals completed the study in apparent good health
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: up to 100%. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: All animals completed the study in apparent good health.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
up to 100%
No. with + reactions:
0
Total no. in group:
15
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
up to 100%
No. with + reactions:
0
Total no. in group:
15

Any other information on results incl. tables

Fluctuations in the temperature of the animal room were recorded during the study (18°C - 25°C); these were not considered to have influenced the outcome.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
No reactions were recorded following challenge at concentrations up to 100%. Since the result was so unequivocal, no further challenge was deemed neccesary. The material is concluded to have no allergenic potential in the guinea pig.
Executive summary:

.