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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:
3-14 April 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
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Minors deviations were observed but not considered to have compromised the validity or integrity of the study.
Principles of method if other than guideline:
Minor deviations observed: relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the protocol, the animal's breeder was CEGAV, the animals were given 110 pelleted diet (instead of 112).
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
-sex: male
- Source: CEGAV, 61350 Saint Mars d'Egrenne, France
- Age at study initiation: no data
- Weight at study initiation: 3.2 ± 0.1 kg
- Housing: individually in polystyrene cages
- Diet (e.g. ad libitum): free access to 110 pelleted diet (UAR, Villemoisson, Epinay sur orge, France)
- Water (e.g. ad libitum): water filtered, ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+/-3°C
- Humidity (%): 30-70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
undiluted
Duration of treatment / exposure:
3 minutes and 4 hour(s)
Observation period:
14 days
Number of animals:
3
Details on study design:
ADMINISTRATION:
- Area of exposure: application for 4 hours on the right flank and for 3 minutes on the left flank
- Total quantity applied: 500 mg
- Administration frequency: once
- Removal of test substance: residual was wiped off by means of moistened cotton pad.

EXAMINATIONS:
- Scoring system: Draize's score
- Examination time points: 1h, 24 h, 48 h and 72 hours after the patch removal. When persistent irritation reactions were noted at 72 hours, the observation period was extended up daily to their complete reversibility (day 10).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: not evaluated in the two other animals
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
AFTER 3-MINUTE EXPOSURE: No cutaneous reaction was observed but a brown coloration of the skin which could have masked a possible very slight erythema between days 1 and 3.
AFTER 4-HOUR EXPOSURE:
- A brown coloration of the skin was noted in all animals. It could have masked a possible very slight or a well-defined erythema in 2 animals, up to day 3 (72h) or 5 but no cutaneous reaction was noted afterwards. In these two animals, no oedema was observed. However, it should be noted that in worst case, the mean irritation scores would have remained lower than 2, for these 2 animals.
- In the third rabbit, the brown coloration was resolved by the 24-hour scoring interval and a well-defined erythema was recorded: grade 2-erythema from day 2 up to day 5 and a grade 1 up to day 9. Moreover, a slight oedema (grade 2) was noted on day 3.
MEAN SCORES OVER 24, 48 AND 72h:
- For erythema: not calculable for 2 animals because of the skin coloration and 2.0 in the third animal.
- For oedema: 0.0, 0.0 and 0.7.

Any other information on results incl. tables

Table 1: individual cutaneous examinations and mean values of the scores recorded at each reading (24, 48 and 72 hours) for the first animal (application for 3 minutes)

 

Rabbit number

Dermal irritation

scores

Mean irritation score (1)

1h (D1)

24h (D2)

48h (D3)

72h (D4)

994

Erythema

C1

C1

C1

0

(2)

Oedema

0

0

0

0

0.0

Other

*

*

*

C

 

(1)  mean of scores on days 2, 3 and 4, (2): not calculated

* : none, D = day, h = hour

C = Brown coloration of the skin

C1 = brown coloration of the skin which could have masked a possible very slight erythema

 

 

Table 2: individual cutaneous examinations and mean values of the scores recorded at each reading (24, 48 and 72 hours) for each animal (application for 4 hours)

 

Rabbit number

Dermal irritation

scores

Mean irritation score (1)

1h (D1)

24h (D2)

48h (D3)

72h (D4)

994

Erythema

C2

C2

C1

C1

(2)

Oedema

0

0

0

0

0.0

Other

*

*

*

*

 

576

Erythema

C2

C2

C1

0

(2)

Oedema

0

0

0

0

0.0

Other

*

*

*

C

 

577

Erythema

C2

2

2

2

2.0

Oedema

0

0

2

0

0.7

Other

*

C

C

C

 

 

Rabbit number

Dermal irritation

Scores

D5

D6

D7

D8

D9

D10

994

Erythema

C1

0

-

-

-

-

Oedema

0

0

-

-

-

-

Other

*

C

-

-

-

-

576

Erythema

-

-

-

-

-

-

Oedema

-

-

-

-

-

-

Other

-

-

-

-

-

-

577

Erythema

2

1

1

1

1

0

Oedema

0

0

0

0

0

0

Other

C

C

C

C

C

C

(1)  mean of scores on days 2, 3 and 4, (2): not calculated

* : none, D = day, h = hour

C = Brown coloration of the skin

C1 = brown coloration of the skin which could have masked a possible very slight erythema

C2= brown coloration of the skin which could have masked a possible well-defined erythema

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
not skin irritating
Conclusions:
Under these experimental conditions, the test substance CDBC is slightly irritant when applied topically to rabbits.
Executive summary:

The potential of the test substance CDBC to induce skin irritation was evaluated in rabbits according to OECD (404) and EC guidelines, and in compliance with the principles of GLP.

In the first instance, the test substance was applied for periods of 3 minutes and 4 hours to a single male rabbit. Since the test substance was not severely irritant on the first animal, it was than applied for 4 hours to two other animals. A single dose of 500 mg of CDBC in its original form was applied to the closely-clipped skin of one flank. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until reversibility of cutaneous reactions. The mean values of the scores for erythema and oedema were calculated for each animals.

After a 3-minute exposure (one animal): no cutaneous reactions were observed. A brown coloration of the skin was noted; it could have masked a possible very slight erythema between days 1 to 3.

After a 4 -hour exposure (three animals): A brown coloration of the skin was noted in all animals; it could have masked a possible very slight or well-defined erythema up to day 3 (one animal) or 5 (one animal). No cutaneous reactions were observed afterwards in these two animals. In the third animal, a well-defined erythema was noted from day 2 to day 5, then a very slight erythema was recorded up to day 9. A slight oedema was noted on day 3.

Mean scores over 24, 48 and 72 hours were not calculable for eryhtema because of the skin coloration for two animals. In the third animal, mean scores were 2.0 for erythema and 0.7 for oedema.

Under these experimental conditions, the test substance CDBC is slightly irritant when applied topically to rabbits.