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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:
October 1-4, 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (GLP)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Clear pale yellow liquid
- Lot No.: RP-690-11890-1603
- Expiration date of the lot: October 27, 1991
- Analytical purity: 90 - 99%
- Impurities (identity and concentrations): Formamide 1 - 9%
- Storage condition of test material: At -20°C in the dark (stable for 30 days)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: Approx . 17 weeks
- Weight at study initiation: 2677 - 3077 g
- Housing: single housing in cages with perforated floors and equipped with an automatic drinking system (ITL, Bergen, The Netherlands)
- Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 g/day.
- Water: Tap-water diluted with decalcified water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C (fluctuations were noted, but were considered not to have affected study integrity)
- Humidity (%): 55% (fluctuations were noted, but were considered not to have affected study integrity)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied (volume or weight with unit): 0.5 ml
- Concentration: undiluted
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: intact and ahved skin of the dorsal flank
- Type of wrap if used: Surgical gauze patch 2x3 cm mounted on Micropore tape (3M, St. Paul, USA); the dressing was wrapped around the abdomen and secured with an elastic bandage (Coban, 3M, St. Paul, USA)

REMOVAL OF TEST SUBSTANCE
- Washing: Remaining test substance was removed using a tissue moistened with tap-water and subsequently a dry tissue
- Time after start of exposure: 4 hours

SCORING SYSTEM:

ERYTHEMA AND ESCHAR FORMATION
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)

OEDEMA FORMATION
0: No oedema
1: Very slight oedema ( barely perceptible)
2: Slight oedema (edges of area well defined by definite raising)
3: Moderate oedema (raised approximately 1 mm)
4: Severe oedema (raised more than 1 mm and extending beyond area of exposure)

The test results were evaluated according to the EEC criteria for general classification and labelling requirements for dangerous substances and preparations (EEC Directive 91/325/EEC, Amendment to Annex VI of the Directive 67/548/EEC).
A primary irritation index (PII) was calculated by combining the average skin irritation scores for erythema and oedema after 24 and 72 hours. Using the following primary irritation index scheme, the degree of irritation can be obtained (Draize, JH, Woodard, G and Calvery, HO (1944)):

PII 0: non-irritating
PII 0.1 - 2.0: mildly irritating
PII 2.1 - 5.0: moderately irritating
PII 5.1 - 8.0: severely irritating

Note: Where the scoring procedure and the clinical judgement were not in agreement, the assessment of irritancy was based on the latter.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
The observed skin irritation consisted of very slight erythema and very slight oedema in all three animals. The skin irritation had resolved within 48 hours after exposure in two animals and within 72 hours in the third animal. There was no evidence of a corrosive effect on the skin.
Other effects:
No staining of the treated skin by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test
period and no mortality occurred.

Any other information on results incl. tables

 Calculatiuons for EEC classification:

Reading Erythema/Edema in animal No.

1

2

3

24 h

1/1

1/0

1/1

48 h

0/0

0/0

1/0

72 h

0/0

0/0

0/0

mean

0.3/0.3

0.3/0

0.7/0.3

 

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information EEC and GHS criteria
Conclusions:
The test substance is not irritating.
Executive summary:

The study was carried out in accordance with OECD Guideline 404 under GLP conditions.

The test substance was applied onto shaved skin of three female New Zealand White rabbits using semi-occlusive dressings for 4 hours, followed by four observations at approximately 1, 24, 48 and 72 hours after removal of the dressings and remaining test substance. Under the conditions of this study, the test substance resulted in slight erythema and slight oedema. The skin irritation had resolved within 48 to 72 hours after exposure in the three animals. No corrosive effect occurred on the skin in all three rabbits. In the area of application, no staining of the treated skin by the test substance was observed. No signs of systemic intoxication were observed during the study period.

Conclusions: The test substance is not irritating.