cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-ylmethyl benzoate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-05-24 to 2006-06-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

Comparable to OECD Guideline 404 and EU Guildine B.4 study with acceptable restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

: 1) the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) to guarantee a good contact and uniform distribution of the test substance on the skin

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

: 1) the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) to guarantee a good contact and uniform distribution of the test substance on the skin

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate from the Swiss GLP Monitoring Authorities

Test material

Test material information

Constituent 1

Reference substance name:

cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-ylmethyl benzoate

EC Number:

262-765-9

EC Name:

cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-ylmethyl benzoate

Cas Number:

61397-56-6

Molecular formula:

C18H15BrCl2O4

IUPAC Name:

[(2R,4R)-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methyl benzoate

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-16479671-AAA (T001095)
- Physical state: solid (powder)
- Appearance: White powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst / The Netherlands
- Age at study initiation: 12-13 weeks (male); 8-9 weeks (female)
- Weight at study initiation: 2463 g (male); 1726 and 2021 g (females)
- Housing: Housed in a wire cage in compliance with AALAC regulations. Animals were housed ndividually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd., Fullinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 8/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd.
- Water: Community tap water from Fullinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: From 2006-05-24 to 2006-05-28 under laboratory conditions after health examination.


ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 17-23 deg C, monitored continuously and values outside of the range may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study.
- Humidity (%): air conditioned with relative humidity between 30-70% monitored continuously and values outside of the range may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study.
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hrs light and 12 hrs dark


IN-LIFE DATES: From: 2006-05-24 To: 2006-06-01

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with 0.5 mL purified water
- Concentration (if solution): no data


VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after exposure

Number of animals:

3 (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: The left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The test substance was applied with a 4 cm x 4 cm surgical gauze patch
- % coverage: no data
- Type of wrap if used: The test substance was applied with a 4 cm x 4 cm surgical gauze patch. The gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 hours


SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.
If evident, corrosive or staining properties of the test substance were described and recorded.

Commission Directive 2004/73/EC, April 29, 2004, Grading of Skin Reactions
Erythema and Eschar Formation:
No erythema =0
Very slight erythema = 1
Well-defined erythema = 2
Moderate to severe erythema = 3
Severe erythema (beef redness) or eschar formation (injuries in depth preventing erythema) reading = 4

Oedema Formation:
No oedema = 0
Very slight oedema (barely perceptible) = 1
Slight oedema (edges of area well-defined by definite raising) = 2
Moderate oedema (edges raised approximately 1 mm) = 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) = 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 16

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal: 16

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal: 17

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicaable

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal: 17

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal: 18

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal: 18

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test substance did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.
Neither alterations of the treated skin were observed, nor were corrosive effects evident on the skin.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining produced by the test substance of the treated skin was observed.
The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), the test substance is considered to be "not irritating" to rabbit skin, and therefore should not be classified.