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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 2 December 1998 and 5 December 1998
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
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 17 July 1992
Deviations:
yes
Remarks:
On one occasion the temperature was below the limit specified in the protocol (17 C). This deviation was considered not to affect the purpose or integrity of the study
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Commission Directive 92/69/EEC
Deviations:
yes
Remarks:
On one occasion the temperature was below the limit specified in the protocol (17 C). This deviation was considered not to affect the purpose or integrity of the study
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
431-620-3
EC Name:
-
Cas Number:
162537-11-3
Molecular formula:
C8 H15 N O4
IUPAC Name:
2-[(methoxycarbonyl)amino]-3,3-dimethylbutanoic acid
Details on test material:
004 (Vendor Lot# 4-9126-7-01-01)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Animals were supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK. At the start of the study the animals weighed 2.74 to 3.24 kg and were 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 with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.

The animal room was maintained at a temperature of 16 to 20 C and relative humidity of 43 to 54%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
Material was used as supplied
Controls:
no
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
72 hours
Number of animals:
3
Details on study design:
On the day before the test each rabbit was clipped free of fur from the dorsal flank area 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 0.5g of test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5cm x 2.5cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5cm x 4.0cm). To prevent the animals from interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were 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 was removed by gentle swabbing with cotton wool soaked in distilled water.

Approximately one hour following the 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 scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No dermal reactions were noted during the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material, BMS 214702-01, produced a primary irritation index of 0.0 to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.
Executive summary:

Methods

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 93/21/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

Results

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced no dermal reactions

Conclusions

The test material, BMS 214702-01, produced a primary irritation index of 0.0 to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.