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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:
From October 06, 1999 to December 08, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonium 2-mercaptopropionate
EC Number:
236-526-4
EC Name:
Ammonium 2-mercaptopropionate
Cas Number:
13419-67-5
Molecular formula:
C3H9NO2S
IUPAC Name:
ammonium 2-sulfanylpropanoate
Test material form:
liquid
Details on test material:
colourless

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Three New Zealand White rabbits supplied by David Percival Ltd, Maston, Sandbach, Cheshire, UK were used. At the start of the study the animals weighed 2.58 to 2.87 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, UK) was allowed throughout the study.

The temperature and relative humidity were controlled to remain within target ranges of 17 to 23 °C and 30 to 70 % respectively. Occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. 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)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
Test performance:
On the day before the test each rabbit was dipped 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 0.5 mL of the test substance was introduced under a 2.5 cm x 2.5 cm 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 2.5 cm x 4.0 cm). To prevent the animals 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.

Observations:
Four hours after application the corset and patches were removed from each animal and any residual test substance removed by gentle swabbing with cotton wool soaked in 74 % Industrial Methylated Spirits.
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 following 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.
Any other skin reactions, if present, were also recorded. Additional observations were made on days 7 and 14 to assess the reversibility of skin reactions.

Interpretation of results:
Calculation of primary irritation index and grading of the irritancy potential using the Draize scheme:
The scores for erythema and oedema at the 24 and 72-hour readings 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 substance. The test substance was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity":
Primary irritation index:
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:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
of three
Time point:
14 d
Score:
4.2
Reversibility:
not fully reversible within: 14 d
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
- Well-defined erythema was noted at all treated skin sites 1-hour after patch removal and at the 24, 48 and 72-hour observations. Very slight erythema was noted at two treated skin sites at the 7-day observation.
- Moderate oedema was noted at one treated skin site with slight oedema at two treated skin sites 1-hour after patch removal and at the 24-hour observation. Slight oedema was noted at all treated skin sites at the 48 and 72-hour observations. Very slight oedema was noted at two treated skin sites at the 7-day observation.
- Scattered areas of blanching of the skin were noted at all treated skin sites with scattered haemorrhage of the dermal capillaries also noted at two treated skin sites 1-hour after patch removal.
- Light brown discolouration of the epidermis was noted at all treated skin sites at the 24-hour observation. Light brown discolouration of the epidermis, loss of skin flexibility and/or loss of skin elasticity were noted at all treated skin sites at 48 and 72-hour observations. Crust formation was noted at all treated skin sites at the 7-day observation. Reduced regrowth of fur was noted at all treated skin sites with glossy skin also noted at one treated skin site at the 14-day observation.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the study conditions, the test substance produced a primary irritation index of 4.2.
Executive summary:

A study was conducted to determine the irritancy potential of the test substance to the skin of the New Zealand White rabbit according to OECD Guideline 404 and EU Method B.4, in compliance with GLP. A single 4 h, semi-occluded application of the test substance to the intact skin of three rabbits produced well-defined erythema and slight to moderate oedema. Blanching of the skin, haemorrhage of the dermal capillaries, light brown discolouration of the epidermis, loss of skin elasticity, loss of skin flexibility, crust formation, reduced regrowth of fur and glossy skin were also noted. Under the study conditions, the test substance produced a primary irritation index of 4.2 (Sanders, 2000).

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