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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:
1 December 1987 to 15 December 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion''.
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
No further details specified in the study report.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three New Zealand White rabbits were supplied by Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, U.K. At the start of the study the animals weighed 2.05 - 2.27 kg and were approximately twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written on the inner surface of the ear and on a cage label using a black indelible marker-pen.
The animals were individually housed in suspended metal cages. Free access to mains drinking water and food {Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K.} was allowed throughout the study.
The animal room was maintained at a temperature of 16 – 20 °C and relative humidity of 45 - 48%. On one occasion the temperature fell outside the lower limit specified in the protocol {17 °C}, this is considered not to affect the purpose or integrity of the study. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
A quantity of 0.5g of the test material, moistened with 0.5 ml of distilled water, was introduced.
Duration of treatment / exposure:
4 hour exposure
Observation period:
14 days
Number of animals:
Three animals
Details on study design:
Approximately twenty-four hours prior to the commencement of the test, each of a group of three rabbits was prepared by closely clipping the fur from the dorsal/flank areas using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position over the test material with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals from interfering with the patches the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP). The animals were then returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether.
Approximately one hour following removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale i.e. Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, “The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics”.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.89
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.78
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
Very slight or well-defined erythema was noted at all treatment sites one hour after removal of the wrappings. Very slight erythema persisted at one treatment site at subsequent 24, 48 and 72-hour observations. Another treatment site appeared normal during this period. Well-defined erythema, extending 3 - 4 cm beyond the treatment site, persisted in the remaining treatment site at the 24 and 48-hour observations, with very slight erythema at the 72-hour observation.
Very slight erythema was confined to one treatment site on day seven. Desquamation was also noted at two treatment sites at this time.
Slight to severe oedema was noted at all treatment sites one hour after treatment. The oedema at one treatment site extended ventrally below the treatment site. The oedema regressed and no oedema was noted on days seven and fourteen.
Other effects:
No other effects referenced in the study report.

Any other information on results incl. tables

INDIVIDUAL DAILY AND INDIVIDUAL MEAN SCORES FOR DERMAL IRRITATION/CORROSION

TEST MATERIAL: DISPERSIONSBLAU F-60 768

SKIN REACTION

READING (HOURS)

INDIVIDUAL SCORES – RABBIT NUMBER:

54

59

135

ERYTHEMA/ESCHAR FORMATION

1

24

48

72

7 days

14 days

1

1

1

1

1 D

0

2

2 R

2 R

1

0 D

0

1

0

0

0

0

0

TOTAL

24, 48 & 72 HOURS

3

5

0

MEAN VALUES*

1.0

1.7

0.0

OEDEMA FORMATION

1

24

48

72

7 days

14 days

4 Oe

2 Oe

1

1

0

0

3

2

1

0

0

0

2

0

0

0

0

0

TOTAL

24, 48 & 72 HOURS

4

3

0

MEAN VALUES*

1.3

1.0

0.0

*MEAN VALUES = means of the 24, 48 and 72-hour readings.

R = reaction extending 3 – 4 cm beyond treatment site

Oe = oedema extending ventrally below treatment site

D = desquamation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
A single, 4-hour, semi-occluded dermal application of the test material to the intact skin of three rabbits produced very slight or well-defined erythema and slight to severe oedema. Very slight erythema was confined to one treatment site on day seven. Other adverse dermal reactions were confined to desquamation at two treatment sites at this time. All treatment sites appeared normal on day fourteen. Based on the results of this study, the substance is not classified as a skin irritant according to CLP criteria.
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 that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion''. The results of the study will be used to classify the test material according to the E.E.C. Directive of 29 July 1983 83/467/EEC adapting Council Directive 67/548/EEC on the regulations relating to classification, packaging and labelling of dangerous substances.

 

A single, 4-hour, semi-occluded dermal application of the test material to the intact skin of three rabbits produced very slight or well-defined erythema and slight to severe oedema. Very slight erythema was confined to one treatment site on day seven. Other adverse dermal reactions were confined to desquamation at two treatment sites at this time. All treatment sites appeared normal on day fourteen.

Conclusion

Based on the results of this study, the substance is not classified as skin irritant according to CLP criteria.