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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From 23 February, 1988 to 8 March, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mohican Valley Rabbitry; Loudonville, Ohio
- Age at study initiation: Young adult
- Weight at study initiation: 2,736 to 3,450 g at study initiation
- Housing: Individual suspended wire-mesh cages. The animals were maintained in accordance with the recommendations contained in the "guide for care and use of laboratory animals" NIH publication, No. 85023.
- Diet: Purina Certified Rabbit Chow #5322
- Water: Tap water
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature : 71-74 °F
- Humidity (%): 50-74%
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark

IN-LIFE DATES: From: 23 February, 1988 to 8 March, 1988

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL/site
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
0.5 mL dose was applied under secured 1 x 1 inch2 guaze patches that were overwrapped with a gauze binder secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: At the end of 4 h, the collars and bandages were removed and the sites wiped with wet disposable paper towels.

SCORING SYSTEM: Draize

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
5.6
Max. score:
8
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: severely irritating (due to not completely reversible reactions (moderate irritation was still present in one rabbit); in addition desquamation was noted on all sites late in the study period and fissuring was present on two sites
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
2.8
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
2.2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 2.6
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 3.6
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1.6
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 3.6
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 2.3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Average erythema score for all animals at 24h: 3; 48h: 3; 72h: 2.8
Average edema score for all animals at 24h: 3.2; 48h: 2.8; 72h: 2.2
Reversibility: Yes, the highest levels of irritation occurred two to three days after dosing and irritation subsequently decreased although moderate reactions still persisted in one animal after study Day 12.
The test substance induced moderate erythema and moderate to severe oedema on all sites. Irritation decreased as the study progressed, however, moderate irritation was present in one rabbit (score: erythema:2; edema:1) through study Day 11.
Other effects:
Desquamation was noted on all sites late in the study period and fissuring was present on two sites.

Any other information on results incl. tables

Mortality: One rabbit was sacrificed in extremis on Day 3 due to broken back.

Body weight: No remarkable changes occurred.

Result details

Table 1:                           Table for skin irritation study

score (average animals investigated)

time

Erythema

Edema

average score
Draize scores
(0 to maximum 4)

< 1 hr After exposure

2.6

1.5

24 h

3

3.2

48 h

3

2.8

72 h

2.8

2.2

other times

State time

 

 

average score

24h, 48h, 72h

3.0

2.7

reversibility: *

n.c

n.c

Average time for reversibility

 

 

*    c :    completely reversible
  n c :    not completely reversible
     n :    not reversible

Applicant's summary and conclusion

Interpretation of results:
other: Category 1C (corrosive) based on CLP criteria
Conclusions:
Based on the results of the read across study, the test substance is considered to be corrosive.
Executive summary:

A study was conducted to determine the skin irritation potential of the read across substance, Coco TMAC (33% active in water), in New Zealand White rabbits according to OECD 404 Guideline, in compliance with GLP. Six animals were treated with 0.5 mL undiluted read across substance (33%) in a semi-occlusive patch (1” X 1” gauze) that was overwrapped with a gauze binder and secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the 4 h exposure period, after which the tape and read across substance were removed. The Draize classification scoring criteria was used to evaluate the irritation potential. Application sites were observed for erythema and oedema at 4, 24, 48 and 72 h after exposure and then daily up to 14 d. The read across substance induced moderate erythema and moderate to severe edema on all sites. Remission of irritation signs occurred as the study progressed, however, moderate irritation was still present in one rabbit after study Day 12 (erythema: 2 ‘slight’; edema:1 ‘barely perceptible’). In addition, desquamation was noted on all sites late in the study period and fissuring was present on two sites. The Primary Irritation Index was calculated to be 5.6 (indicative of moderate irritation). Under the study conditions, due to persistence of irritation reactions in one animal as well as desquamation on all sites and fissuring on 2 sites, the read across substance is considered to be severely irritating. Under the study conditions, the read across substance (containing 33% a.i.) was found to be severely irritating to rabbit skin; therefore, 100% Coco TMAC can be considered to be corrosive (Naas, 1988). Based on the results of the read across, a similar corrosive potential is expected for the test substance.