Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 4-19,1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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)
Deviations:
yes
Remarks:
stability/purity not reported
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Amount received: 662.77 g (gross weight)
- pH: 8 (litmus paper)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Denver, PA
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 2.325-2.607 kg
- Housing: Rabbits were housed individually in cages sized in accordance with the ''Guide for the Care and Use of Labolatory Animals'' of the Institute of National Research Council.
- Diet: Purina Lab Rabbit Chow (H.F.) ad libitum
- Water:fresh tap water, ad libitum
- Acclimation period: minimum 5d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3 (63°-73°F)
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light):12h light, 12h dark


Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL/site (6 cm²)

Duration of treatment / exposure:
The test article was administrated once per site:
3 min, 60 min, 4h, 24 h
Observation period:
14d
Number of animals:
Six (6) :3♂ and 3♀
Details on study design:
TEST SITE
- Area of exposure: 5 sites on the dorsal trunk
- Type of wrap if used: impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): by using water and a gauze
- Time after start of exposure: 3 min, 60 min, 4h, 24h

SCORING SYSTEM:
Draize Evaluation of Dermal Irritation, Primary Irritation Index

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
6 animals
Time point:
other: 4h exposure
Score:
8
Max. score:
8
Reversibility:
not reversible
Remarks on result:
other: necrosis at 24 hour reading time point in 5/6 animals
Irritation parameter:
erythema score
Remarks:
3-minute exposure
Basis:
mean
Remarks:
6 animals
Time point:
24/48/72 h
Score:
3.7
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: necrosis in all animals
Irritation parameter:
edema score
Remarks:
3-minute exposure
Basis:
mean
Remarks:
6 animals
Time point:
24/48/72 h
Score:
3.5
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: necrosis in all animals
Irritant / corrosive response data:
animals have been exposed for 60min, 4h, and 24h. All animals scored 4 (necrosis) for erythema and edema immediately after unwrapping.
Severe erythema and severe edema remained present in all animals at all observation periods during the study (up to 14 days).


Any other information on results incl. tables

 

 Animal No.  Sex  Body Weight Initial (kg)  Body weight Final (kg)
 1  M 2.405   2.752
 2  M  2.514  2.707
 3  M  2.387  2.673
 4  F  2.591  2.847
 5  F  2.607  2.903
 6  F  2.325  2.495

Table 1: 3-minute exposure

 

 

Rabbit/sex

sex

0 hours*

24 hours

48 hours

72 hours

Day 4 - 14

 

erythema

edema

erythema

edema

erythema

edema

erythema

edema

erythema

edema

1M

2

0

4N

4

4N

4

4N

4

4N

4

2M

1

0

4N

4

4N

4

4N

4

4N

4

3M

2

0

4N

4

4N

4

4N

4

4N

4

4F

1

0

4N

4

4N

4

4N

4

4N

4

5F

0

0

1

0

2

0

4N

4

4N

4

6F

2

0

4N

4

4N

4

4N

4

4N

4

mean

1.3

0

3.5

3.3

3.7

3.3

4

4

4

4

Mean erythema 24/48/72h

3.7

Mean edema 24/48/72h

3.5

*: immediately after unwrap

N = Necrosis

 

 

 

Table 2: 60-minute, 4-hour and 24-hour exposure

 

 

Rabbit/sex

sex

0 hours*

24 hours

48 hours

72 hours

Day 4 - 14

 

erythema

edema

erythema

edema

erythema

edema

erythema

edema

erythema

edema

1M

4N

4

4N

4

4N

4

4N

4

4N

4

2M

4N

4

4N

4

4N

4

4N

4

4N

4

3M

4N

4

4N

4

4N

4

4N

4

4N

4

4F

4N

4

4N

4

4N

4

4N

4

4N

4

5F

4N

4

4N

4

4N

4

4N

4

4N

4

6F

4N

4

4N

4

4N

4

4N

4

4N

4

mean

4

4

4

4

4

4

4

4

4

4

Mean erythema 24/48/72h

4.0

Mean edema 24/48/72h

4.0

*: immediately after unwrap

N = Necrosis

 

 

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS Category 1B (H314) according to Regulation (EC) No 1272/2008
Conclusions:
The test article was considered to be severe dermal irritant at both 4 and 24 hour exposures.
The Dermal Irritation Toxicity Category is Class I (corrosive).
The DOT Packing Group Classification is Class I (corrosive at less than 3 min).
Primary Dermal Irritation Index at 4h and 24h exposure=8.00 (according to Draize scoring system).
No reading time point at 1 hour after 3-minute exposure was available in order to definetly find a conclusion on subcategory 1A or 1B. Since after immediate observation after 3-minute exposure well-defined erythema (score 2) was found in 3 out of 6 animals it is not assumed that after on hour necrosis would have been formed. Therefore, a classification category 1B is considered.
Executive summary:

The test substance was examined undiluted for skin irritation in groups of 3 rabbits per sex. The test material was applied (semi-occlusive) directly on the intact and abraded skin sites. The skin was abraded using a burred needle, the abrasion penetrated the stratum corneum, but not the derma. The test article was administrated once per site for 3 min, 60 min, 4h, or 24 h. Necrosis was observed after 3 min exposure. The animals that had been exposed for 60 min, 4 h, or 24h scored 4 (necrosis) for erythema and edema immediately after unwrapping. Severe erythema and severe edema remained present in all animals at all observation periods during the study (up to 14 days).