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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:
From 30th of July 2014 to 8th of September 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP study performed according to OECD Guideline 406 and EPA OPPTS 870.2600.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test

Test material

Constituent 1
Chemical structure
Reference substance name:
4-hydroxymethyl-1,3-dioxolan-2-one
EC Number:
213-235-0
EC Name:
4-hydroxymethyl-1,3-dioxolan-2-one
Cas Number:
931-40-8
Molecular formula:
C4H6O4
IUPAC Name:
4-(hydroxymethyl)-1,3-dioxolan-2-one
Details on test material:
- Name of test material (as cited in study report): JEFFSOL GC (glycerin carbonate)
- Substance type: Clear light yellow to clear yellow liquid
- Physical state: liquid
- Analytical purity: no data
- Lot/batch No.: BLW0008870
- Expiration date of the lot/batch: 20 June 2015
- Stability under test conditions: no data
- Storage condition of test material: Room temperature, 21 to 26°C

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elm Hill Breeding Laboratories
- Age at study initiation: dose range: ~ 5 weeks; main study: ~ 6 weeks at start of dosing (day 1)
- Weight at study initiation: dose range: 300-332 grams; main study: 339-463 grams at the outset (day 1) of the main study
- Housing: Animals were individually housed by sex upon receipt through the 4th day they were in-house. Animals were group housed by sex on the 4th day they were in house (dividers on the cages were removed) and individually housed upon assignment to study.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Study animals were acclimated to their housing for a minimum of 5 and 7 days respectively for the Dose Range and Main Assay prior to their irst day of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 24 °C
- Humidity (%): 31 to 89%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
vehicle control group, test groups received glycerine carbonate as received
Concentration / amount:
Dose range: 10%, 25%, 50% and 100% as received
Based on the results of the dose range test, an induction dose and challenge dose of 100% (as received) was chosen for this study.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
vehicle control group, test groups received glycerine carbonate as received
Concentration / amount:
Dose range: 10%, 25%, 50% and 100% as received
Based on the results of the dose range test, an induction dose and challenge dose of 100% (as received) was chosen for this study.
No. of animals per dose:
Dose range: 4 naïve animals
Induction and challenge phase: 20 animals (10/sex) for the treatment group and 10 animals/sex for the vehicle control group; 6 animals per group for the positive control group

Details on study design:
RANGE FINDING TESTS: Primary irritation screen: Prior to initiation of the main study, the irritation potential was determined. The entire dorsal area of four naive animals were clipped free of hair the day prior to dose. Four concentrations of the test article (10%, 25%, 50% or 100%) were dosed on four separate site). The location of each of the four applications of test article differed in each of the four animals to compensate for any site-to-site variations. For grading of the response, the procedure for primary challenge was used, except that only 24-hour grades were obtained. The concentration chosen for induction was generally one that produced mild irritation. The highest non-irritating concentration was used for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
The test sites of application on each animal were clipped free of hair with a small animal clipper the day prior to each induction and challenge application. The test area (~ 4-6 cm²) was divided into application sites. The test article or vehicle or positive control was applied to a 25 mm Hill Top Chamber patch. The animal was placed in a restrainer and the patch applied to the clipped surface as quickly as possible after the test article preparation has been applied to the patch. The patch was occluded with a rubber dental dam by pulling it tightly over the animal and fastening it to the bottom of the restrainer with binder clips. The restrainer was adjusted to minimize movement of the animal during the exposure period. Both edges of the dental dam were under the front and back adjustable braces of the restrainer.
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: glycerine carbonate unchanged
- Control group: vehicle control group: vehicle water; positive control group: 1-chloro-2,4-dinitrobenzene (DNCB) @ 0.3% in 80% EtOH
- Site: 1 site near the head
- Frequency of applications: 3 times
- Duration: 6 hours
- Concentrations: 100%

B. CHALLENGE EXPOSURE
Fifteen days after the last induction exposure, the animals were challenged in the same manner but the patches were applied to freshly clipped skin sites that have not been exposed previously. The vehicle control group was challenged with the test article and the vehicle. Approximately twenty hours and forty-nine minutes after removal of the challenge patch, all animals were depilated with Nair Lotion Hair Remover. The depilatory was placed on the test sites and surrounding areas and left on for 11-13 minutes. The depilatory was then thoroughly washed off with water and animals patted dry and returned to their cages. The inside of each cage was wiped to remove any depilatory that might have contaminated the cage. Approximately three hours and twenty minutes after depilation, test site skin reactions were observed and the 24 hour score recorded. The grading was repeated twenty-three hours and three minutes later (48-hour grade).

Challenge controls:
Test article group: vehicle challenge
Vehicle control group
Positive control group: DNCB @ 0.2% in Acetone
Positive control substance(s):
yes
Remarks:
DNCB

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of toxicity
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Distilled water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no signs of toxicity.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of toxicity
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Distilled water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no signs of toxicity.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Glycerine carbonate at 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no signs of toxicity
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Glycerine carbonate at 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no signs of toxicity.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Glycerine carbonate at 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no signs of toxicity
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Glycerine carbonate at 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no signs of toxicity.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.2% DNCB
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
anticipated positive response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.2% DNCB. No with. + reactions: 6.0. Total no. in groups: 6.0. Clinical observations: anticipated positive response.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.2% DNCB
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
anticipated positive responses
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.2% DNCB. No with. + reactions: 6.0. Total no. in groups: 6.0. Clinical observations: anticipated positive responses.

Any other information on results incl. tables

Clinical observations:

There were no signs of systemic toxicity and all animals gained weight during the main study.

Challenge phase:

The positive control group, induced and challenged with DNCB, exhibited the anticipated positive response at challenge, indicating that the methods employed in this study were valid.

All dermal irritation scores at the 24- and 48 -hour observations were zero for the test article group animals challenged with the test article.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, induction with glycerine carbonate as received did not elicit a delayed contact hypersensitivity response in guinea pigs when challenged as received.

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