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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:
between 21 April 1999 and 11 May 1999.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 17 July 1992
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
Test material form:
liquid
Details on test material:
Sponsor’s identification : BEROL 1872 (C14 Alkyl polyethoxy glycidylether)
Batch number : 996185
Date received : 15 April 1999
Description : pale yellow slightly turbid liquid
Storage conditions : room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks
- Weight at study initiation: 2.57 to 2.74 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: between 21 April 1999 and 11 May 1999.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch
Duration of treatment / exposure:
Initial animal, three suitable test sites were selected on the back of the rabbit: 3 minutes, 1 hour and 4 hours
Two additional animals: 1 site, 4 hours
Observation period:
up to 14 days
Number of animals:
Total 3.
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: Each patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
- Time after start of exposure: Initial animal: One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application.
Two additional animals: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : one hour following the removal of the patches, and 24, 48 and 72 hours later, and on Days 7 and 14

SCORING SYSTEM:
- Method of calculation: scored according to the following scale from Draize J H, (1977) for Erythema and Eschar Formation and Oedema Formation.
Additionally the Primary Irritation Index was calculated and Grading of the Irritancy Potential Using the Draize Scheme:
The scores for erythema and oedema at the 24 and 72-hour readings (4-hour exposure) were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.47:
Primary Irritation Index - Classification of Irritancy
0 - Non-irritant
> 0 to 2 - Mild irritant
> 2 to 5 - Moderate irritant
> 5 to 8 - Severe irritant

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:
2
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible
Remarks:
Moderate desquamation observed after 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible
Remarks:
Moderate desquamation observed after 14 days.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible
Irritant / corrosive response data:
After 3 min. exposure: Only Grade 1 (Very slight erythema (barely perceptible) ) erythema observed 1 hour and 24 hour after exposure.

After 1 hr. exposure: Grade 2 (Well-defined erythema) erythema observed at 1 hour and 24 hours after exposure, Grade 1 (Very slight erythema (barely perceptible) ) erythema at 48 and 72 hours, accompanied by oedema grade 1 (Very slight oedema (barely perceptible) ) at these time points. Erythema and oedema was cleared at day 7 (with moderate desquamation) and 14

After 4 hrs: See table.
PII score: (Sum all scores at 24 & 72 hrs / no. of animals) = 23/6 = 3.8
This classifies as 'Moderate irritant'
Other effects:
- Other adverse local effects: See table
Loss of skin flexibility and/or elasticity was noted at two treated skin sites at the 72-hour observation. Crust formation was noted at two treated skin sites with moderate desquamation at the remaining treated skin site at the 7-day observation.
Moderate desquamation was noted at two treated skin sites at the 14-day observation.
- Other adverse systemic effects: No systemic effects observed

Any other information on results incl. tables

Table: Individual Scores - Rabbit Number and Sex

Skin Reaction

Observation time

male 1

male 2

male 3

Total

Erythema/Eschar Formation

1 hour

2

2

2

(6)

24 hour

2

2

2

6

48 hour

2

2

2

(6)

72 hour

2

2 Le

2 LeLf

6

7 days

0 D

0 Cf

0 CfLf

(0)

14 days

0

0 D

0 D

(0)

Oedema Formation

1 hour

2

1

1

(4)

24 hour

2

2

2

6

48 hour

1

2

2

(5)

72 hour

1

2

2

5

7 days

0

0

0

(0)

14 days

0

0

0

(0)

 ( ) = Total values not used for calculation of primary irritation index

Cf = crust formation

D = moderate desquamation

Le = loss of skin elasticity

Lf - loss of skin flexibility

Sum of 24 and 72-hour Readings (S): 23

Primary Irritation Index (S/6): 23/6 = 3.8

Classification: Moderate irritant

Applicant's summary and conclusion

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
The test material produced a primary irritation index of 3.8 and was classified as a MODERATE lRRlTANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

 

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema (grade 2) and slight oedema (grade 2). Loss of skin elasticity and flexibility, crust formation and moderate desquamation were also noted.

Erythema and oedema were resolved by observation after 7 days. Two animals still showed moderate desquamation at the end of the observation period of 14 days, but in view of the continuous diminishing effects, full recovery is expected.

 

In conclusion:

The test material produced a primary irritation index of 3.8 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.

 

For GHS: Mean value of ≥ l.5 - ≤ 2.3 for erythema/eschar or for oedema in at least 2 of 3 tested animals from grades at 24,48 and 72 hours or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions when not included in the irritant category above.

As all animals have a 2 for erythema, this results to GHS Cat.3 "Mild irritant"

 

For CLP: Mean value of ≥ 2.3 - ≤ 4.0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from grades at 24,48 and 72 hours or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions when not included in the irritant category above.

There are no mean scores above ≥ 2.3. This result to "No classification".