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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 April 2013 - 03 May 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Due to the inconclusive results obtained in the in vitro study, an in vivo study is required to conclude of the skin irritation potential of 4,4'-Isopropylidenediphenol, ethoxylated, esters with acrylic acid and isononanoic acid.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: colorless viscous liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder: CEGAV, Argenvilliers, France
- Age at study initiation: 2 to 4 months old on the day of treatment
- Mean body weight at study initiation: 2923 g (range: 2875 g to 3015 g)
- Fasting period before study: no
- Housing: the animals were individually housed in noryl cages
- Diet: 110 pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 23 April 2013 to 03 May 2013.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL/flank.
Duration of treatment / exposure:
3 min, 1 h, 4 h.
Observation period:
1, 24, 48 and 72 h after removal of the dressing; if relevant, daily until reversibility of reactions
Number of animals:
Three males
Details on study design:
TEST SITE
- Area of exposure: The test item was placed on a gauze pad, which was then applied to a skin area of approximately 6 cm2.
A dosage-volume of 0.5 mL/flank was used.
During each exposure time, a dry gauze pad was applied to the opposite flank, in order to check that no alteration of the skin is induced by the semi-occlusive dressing and restraining bandage.
The untreated flank acted as control.
The gauze pad was held in place by a non-irritating semi-occlusive dressing and a restraining bandage. After required period of contact with the skin, the dressing was removed.
After removal of the dressing, any residual test item was wiped off by means of a dry cotton pad.

- Coverage: 6 cm2
- Type of wrap if used: gauze pad held in place by a non-irritation semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: using a dry cotton pad
- Time after start of exposure: at removal of each dressing (see Duration of exposure)

SCORING SYSTEM:

- Erythema and eschar formation:
0 no erythema
1 very slight erythema (barely perceptible)
2 well-defined erythema
3 moderate to severe erythema
4 severe erythema (beet redness) to slight eschar formation (injuries in depth)

- Edema formation:
0 no edema
1 very slight edema (barely perceptible)
2 slight edema (edges of area well-defined by definite raising)
3 moderate edema (raised approximately 1 millimeter)
4 severe edema (raised more than 1 millimeter and extending beyond area of exposure)

- Any other lesions were noted

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: Day 4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: Day 4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
After a 4-hour exposure, a very slight erythema was noted in 2/3 animals from day 1 to day 3.
No edema was observed in any animals.
Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:
.            erythema: 0.0, 0.7, 0.7; showing no significant inflammation,
.            edema: 0.0, 0.0; 0.0; showing no inflammation.
Other effects:
No unscheduled deaths occurred during the study and no clinical signs indicative of systemic toxicity were noted in any animals.
The body weight of the animals was unaffected by the test item treatment.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the test item was slightly irritant when applied topically to rabbits.
However, the test item should not be classified as irritating to skin according to the criteria of CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential corrosive and irritant properties of the test item following dermal application on rabbits.

This study was conducted in compliance with OECD Guideline No. 404 and the principles of Good Laboratory Practices.

Methods

The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit.

After the 4-hour application, since the mean value from grading at 24, 48 and 72 hours after patch removal was < 2.3 for erythema or for edema, the test item was applied on the skin of two otheranimalsfor 4 hours.

A dosage-volume of 0.5 mL/flank was used.

The test item was placed on a gauze pad, which was then applied to a skin area of approximately 6 cm2. The gauze pad was held in place by a non-irritation semi-occlusive dressing and a restraining bandage.After required period of contact with the skin, the dressing was removed.

Each animal was observed at least once a day for mortality and clinical signs. For each exposure period, cutaneous reactions were evaluated approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until the reversibility of cutaneous reactions. The mean values of the scores for erythema and edema were calculated for each animal. Body weight was recorded on the day of treatment and at the end of the evaluation of cutaneous reactions.

On completion of the observation period, the animals were used subsequently for the evaluation of the ocular irritation potential of the same test item.

 

Results

No unscheduled deaths occurred during the study and no clinical signs indicative of systemic toxicity were noted in any animals.

The body weight of the animals was unaffected by the test item treatment.

After a 4-hour exposure, a very slight erythema was noted in 2/3 animals from day 1 to day 3.

No edema was observed in any animals.

Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:

.            erythema: 0.0, 0.7, 0.7; showing no significant inflammation,

.            edema: 0.0, 0.0; 0.0; showing no inflammation.

 

Conclusion

Under the experimental conditions of this study, the test item was slightly irritant when applied topically to rabbits.

However, the test item should not be classified as irritating to skin according to the criteria of CLP Regulation.