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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:
3 May 1984 - 5 Jun 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1984

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: EPA TS-792 Dermal irritation. Health effects test guidelines, EPA, August 1982; EPA 560/6-82-001
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elkhorn Rabbitry, 5265 Starr Way, Watsonville, CA 95076
- Age at study initiation: young adults
- Weight at study initiation: 3.1 to 3.6 kg
- Housing: individually
- Diet (e.g. ad libitum): 150 g of Certified Purina Chow Diet 5322
- Water (e.g. ad libitum): d libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16.7 to 18.9°C
- Humidity (%): 40 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: one test site shaved, one test site shaved+abraded
Vehicle:
physiological saline
Controls:
other: vehicle-treated sites on the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
The test compound was moistened with a few drops physiological saline (0.9%) to make a thick paste.
Duration of treatment / exposure:
24 h
Observation period:
14 d
Number of animals:
6 (3 males, 3 females)
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm
- Type of wrap if used: Blenderm (semi-impervious hypoallergenic surgical tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done):skin was wiped, if the material adhered
- Time after start of exposure: 24 h

SCORING SYSTEM: according to Draize scale

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other:
Remarks:
this animal has severe razor burns, thus should be regarded as abraded
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 2 d
Remarks on result:
other: this animal has severe razor burns, thus should be regarded as abraded
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 3 d
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: intact skin
Irritant / corrosive response data:
One rabbit was severely razor-burned during preclipping and still exhibited very slight erythema (score 1) at dosing. Consequently, the "non-abraded" sites were actually abraded and these sites exhibited necrosis and sloughling earlier than the non-abraded sites of the other animals. However, four of the remaining five rabbits possessed sites which exhibited necrosis and sloughing; therefore, the razor burns on this rabbit did not affect the overall final irritation rating of the compound.

Intact skin:
- erythema scores:
Erythema scores for the intact sites were first obtained after wrap removal (after 24 h of exposure). The erythema scores for this period ranged from slight (score 1) in one animal, to welldefined (score 2) in three animals, and to moderate-to-severe (score 3) in two animals. The scores remained the same or improved slightly through Day 7 for all except two animals, of which animal number 2 had severe razor burns. In this animal the application site had progressed
to necrosis by the second day, followed by eschar formation and sloughing within the first week.
During the second week, the test compound application site for three of the remaining four animals had also progressed to necrosis with eschar formation and sloughing.
- edema scores:
Edema at the intact sites was negligible. Three animals exhibited very slight edema formation (score 1). This had cleared by the third day after application in two animals and by Day 7 in the third rabbit.

Abraded skin:
The erythema at the abraded sites of all six animals were evaluated as moderate tn severe (score 3) when wraps were removed 24 h after application of the test compound. In four of the animals this had progressed to necrosis by the third day with eschar formation and sloughing developing within the first week. The application site on a fifth animal progressed to eschar formation during the second week.
Edema at the abraded sites was more prevalent and slightly more severe, but still reversible within 3 days.
Other effects:
none reported

Any other information on results incl. tables

Animal

Intact skin

Abraded skin

 

Erythema scores

Day 1/2/3/7/14

Edema scores

Day 1/2/3/7/14

Erythema scores

Day 1/2/3/7/14

Edema scores

Day 1/2/3/7/14

1

2/2/1/1/4

0/0/0/0/0

3/3/4/4/4

0/0/0/0/0

2*

3/4/4/4/4

1/0/0/0/0

3/4/4/4/4

2/0/0/0/0

3

2/1/1/2/4

0/0/0/0/0

3/4/4/4/4

1/0/0/2/0

4

3/3/3/3/4

0/1/0/0/0

3/3/3/3/4

1/1/0/0/0

5

1/1/1/1/1

0/0/0/0/0

3/4/4/4/4

2/1/0/0/0

6

2/3/3/3/3

1/1/0/1/0

3/3/3/3/3

2/0/0/0/0

* this animal has severe razor burns, thus should be regarded as abraded

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Guanidine hydrochloride is legally classified as irritating to the skin (CLP, EU GHS (Regulation (EC) No 1272/2008)).
Executive summary:

In a primary dermal irritation study according to EPA guideline 560/6-82-001 (Primary Dermal Irritation), August 1982, 6 young adult New Zealand White rabbits were dermally exposed to 0.5 mg of Guanidine hydrochloride (>98%) for 24 hours to 2.5 cm x 2.5 cm body surface area to intact and abraded skin using semi-occlusive dressing. Animals then were observed for 14 days. The scoring system was according to Draize.

On intact skin, erythema scores after 24 h ranged from slight (score 1) in one animal, to well-defined (score 2) in three animals, and to moderate-to-severe (score 3) in two animals. The scores remained the same or improved slightly through day 7 for all except two animals, of which one animal had severe razor burns. In this animal the application site had progressed to necrosis by the second day, followed by eschar formation and sloughing within the first week.

During the second week, the test compound application site for three of the remaining four animals had also progressed to necrosis with eschar formation and sloughing.

Edema at the intact sites was negligible. Three animals exhibited very slight edema formation (score 1). This had cleared by the third day after application in two animals and by Day 7 in the third rabbit.

The erythema at the abraded sites of all six animals were moderate to severe (grade 3) after 24 h. In four of the animals this had progressed to necrosis by the third day with eschar formation and sloughing developing within the first week. The application site on a fifth animal progressed to eschar formation during the second week. Edema at the abraded sites was more prevalent and slightly more severe, but still reversible within 3 days.

The irritation response on intact skin sites was not reversible within 14 days.