(1R)-1-[(4R,4aR,8aS)-2,6-bis(3,4-dimethylphenyl)tetrahydro[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5th March 1993 to 16th June 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline studies with restrictions. Information relating to the test animals, exposure and test system were not described in the main body of the report but were given in the protocol only.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Details on test material:

Purity 97.3%
Batch No.: 9236-23

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS (information provided in study protocol)
- Source: E.S.D, Romans, 01400, Chatillon-sur-Chalaronne, FRANCE
- Age at study initiation: adult (about 3 months old)
- Weight at study initiation: 2.00 to 3.00 kg
- Housing: Animals individually housed in stainless steel cages (internal dimensions 500 x 600 x 400 mm).
- Diet (e.g. ad libitum): About 150 g/animal/day of pelleted complete rabbit diet (Diet reference 112 C - Usine d'Alimentation Rationnelle, Villemaisson, 91360 Epinay-sur-Orge, FRANCE).
- Water (e.g. ad libitum): Softened and filtered mains drinking water available ad libitum (via automatic system).
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS (information provided in study protocol)
- Temperature (°C): 19 ± 3 °C
- Humidity (%): minimum35%
- Air changes (per hr): minimum 12 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial)I12 hours dark

IN-LIFE DATES: Not specified

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Sterile Codex liquid paraffin

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.46 g
- Batch no. (if required): T 8810 B
- Purity: Not specified

Duration of treatment / exposure:

4 h

Observation period:

72 hours

Number of animals:

6 animals

Details on study design:

TEST SITE (information provided in study protocol)
- Area of exposure: The test material is applied to the animal's skin, to an area about 6 cm2 and then covered with a Codex hydrophilic eight layer gauze pad, of the same surface.
- % coverage: Not specified
- Type of wrap if used: The test article will be applied under a semi-occlusive dressing composed of a gauze pad approximately 2.5 cm x 2.5 cm, maintained in contact with the skin with a perforated tape. This tape will be applied on a crimped gauze bandage which will fully cover the clipped area to avoid possible imitation reactions and be wrapped around the animal without blocking the respiratory and abdominal movements.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The bandages were removed and, if necessary, excess test article which had not penetrated was wiped away with a gauze pad moistened with pure plive oil. Readings were then carried out 1 hour later.
- Time after start of exposure: 4 h

SCORING SYSTEM: As specified in OECD Guideline 404 (1981)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 h

Score:

1.17

Max. score:

2

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h

Score:

0.67

Max. score:

1

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 h

Score:

0.33

Max. score:

1

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

0

Results 5

Irritation parameter:

erythema score

Basis:

other: Mean overall score for 24, 48 and 72 h.

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Max. duration: 48 h; Max. value at end of observation period: 0

Remarks:

Mean overall score for 24, 48 and 72 h

Results 6

Irritation parameter:

edema score

Basis:

animal: All

Time point:

other: 1, 24, 48 and 72 h

Score:

0

Results 7

Irritation parameter:

edema score

Basis:

other: Mean overall score for 24, 48 and 72 h.

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: Max. duration: 0 h; Max. value at end of observation period: 0

Remarks:

Mean overall score for 24, 48 and 72 h

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 3 days

Other effects:

None reported

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

From the results obtained under the experimental conditions employed, application of the test article to the rabbit skin provoked a weak irritation but the effects were fully reversible by 72 hours after treatment.

Executive summary:

The test material, Millad®3988, was evaluated for its acute primary cutaneous irritation and corrosivity potential in male rabbits. The results obtained under the experimental conditions employed demonstrated that application of this test article to the rabbit skin provoked a weak irritation (erythema) but the effects were fully reversible by 72 hours after treatment. No oedema was observed over the 72 hour post exposure period.