Acid Catalysed Reaction Products of 3,7-dimethyl-2,6-octadienal in the presence of ethanol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 7, 2001 - May 29, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Acid Catalysed Reaction Products of 3,7-dimethyl-2,6-octadienal in the presence of ethanol

IUPAC Name:

Acid Catalysed Reaction Products of 3,7-dimethyl-2,6-octadienal in the presence of ethanol

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): CITRATHAL R
- Description: Colourless to pale yellow liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): CITRATHAL R
- Description: Colourless to pale yellow liquid
- Analytical purity: not applicable (as it is an UVCB substance)
- Composition of test material, percentage of components: as defined in section 1.2
- Lot/batch No.: 9000416199
- Expiration date of the lot/batch: August 27, 2001
- Storage condition of test material: In the original container, at room temperature (range of 17-23 'C), away from direct sunlight

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Centre Lago, F-01540 Vonnas, France
- Age at study initiation: 33-34 weeks (male) and 30-31 weeks (females)
- Weight at study initiation: 3.7-4.2 kg
- Housing: Animals were housed individually in stainless steel cages
- Diet: Free access to pelleted diet for rabbits (Provimi Kliba 3418). Haysticks were abailable during the study period.
- Water: Free access to tap water
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 23
- Humidity (%): 30 - 70
- Air changes (per hr): approx 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: May 14, 2001 to May 29, 2001

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

15 days

Number of animals:

1 male and 2 females

Details on study design:

TEST SUBSTANCE PREPARATION
The substance was applied as such.

TEST SITE
Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 square centimeters (10x10 cm). The skin of the animals was examined one day before treatment and regrown fur of all animals was again clipped.

APPLICATION
The test substance was placed on a surgical gauze patch (ca. 2.5 x 2.5 cm). This gauze patch was applied to approx. 6 square centimeters of 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
Yes, at the end of the exposure period, using lukewarm tap water.

OBSERVATIONS
- Mortality/Viability: Daily
- Toxicity: Daily
- Body Weight: At start of acclimatization, on the day of application and at termination
- Necropsy: Not applicable
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7, 10, 14 and 15 days after the removal of the dressings and test substance.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 15 days

Remarks on result:

no indication of irritation

Remarks:

Mean value of score at 24, 48 and 72h after patch removal

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Remarks:

Mean value of score at 24, 48 and 72h after patch removal.

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Remarks:

Mean value of score at 24, 48 and 72h after patch removal.

Results 4

Irritation parameter:

edema score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours (in all animals)

Remarks on result:

no indication of irritation

Remarks:

Mean value of score at 24, 48 and 72h after patch removal.

Irritant / corrosive response data:

See section "Any other information on results incl. tables"

Other effects:

- Scaling was present at the test site of the male from 7 to 10 days after treatment and in both females from 72 hours to 7 days after treatment
- No staining by the test material was observed
- No clinical signs of systemic toxicity were observed
- No mortality occurred
- No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin
- Body weights were within the normal range of variability

Any other information on results incl. tables

Animal number	Sex	Evaluation Interval; time after patch removal	Erythema	Oedema	Scaling?
58	M	1 hour	2	1	No
59	F		2	1	No
60	F		2	1	No
58	M	24 hours	2	1	No
59	F		2	1	No
60	F		2	1	No
58	M	48 hours	2	0	No
59	F		1	0	No
60	F		2	0	No
58	M	72 hours	2	0	No
59	F		1	0	Yes
60	F		1	0	Yes
58	M	7 days	1	0	Yes
59	F		0	0	Yes
60	F		0	0	Yes
58	M	10 days	1	0	Yes
59	F		0	0	No
60	F		0	0	No
58	M	14 days	1	0	No
59	F		0	0	No
60	F		0	0	No
58	M	15 days	0	0	No
59	F		0	0	No
60	F		0	0	No

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a skin irritation study with rabbits, performed in accordance with OECD 404 (1992) and according to GLP principles, irritation was observed; not sufficent to classify the substance in accordance with the CLP Regulation.

Executive summary:

In a skin irritation study in rabbits, conducted in accordance with OECD 404 (1992), EU Method B.4 (1992) and according to GLP principles, 1 male and 2 female rabbits were semi-occlusively exposed for 4 hours to 0.5 mL of the substance. Well-defined erythema was observed in all animals 1 hour after treatment and persisted in the male up to the 72-hour reading, in one female up to the 24-hour reading and in the other female up to the 48-hour reading. Very slight erythema was evident in the male up to 14 days after treatment and in both females up to 72 hours after treatment. Very slight swelling was noted in all animals from 1 to 24 hours after treatment. Scaling was present at the test site of the male from 7 to 10 days after treatment and in both females from 72 hours to 7 days after treatment. No significant clinical signs of systemic toxicity nor mortalities were observed. Based on the results of this study, the substance does not need to be classified for skin irritation/corrosion in accordance with the CLP Regulation.