Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986

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:
88% aqueous solution of lactic acid

Test animals

Species:
rabbit
Strain:
New Zealand White

Test system

Type of coverage:
semiocclusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Concentration: 88 %
Duration of treatment / exposure:
4 hour(s) / 0.5 mL
Observation period:
21 days in total
Number of animals:
12
Details on study design:
The test was carried out according to the OECD Guideline no. 404, acute dermal irritation/corrosion, adopted by the OECD Council on May 12, 1981. After an acclimatization period of six days, i.e. one day prior to the start of the experiment, the hair was removed from the back and flanks of the animals, using electric clippers in a way as to avoid abrasions.
Six rabbits were treated on the intact skin and on the abraded skin. The abrasions were minor incisionsi of the stratum corneum, but not suf- ficiently deep to disturb the underlying derma or to produce bleeding. An araount of 0.5 ml of the tesit material was brought onto the intact and the abraded skin under a surgical patch measuring l inch x l inch. The patches were fixed to the application site by means of adhesive tape and the entire trunk of the rabbits was wrapped with an impervious material to maintain the test patches in position and to retard evaporation of
volatile substances. After an exposure period of 4 hours the patches and the material applied were removed and the resulting skin reactions were evaluated by the method of Draize et al. (J. Pharmacol. exptl. Therap. 82 (1944) 377-390). A transcript of the grading system by Draize et al. is given in an appendix to this report. Further readings were made after 28, 52 and 76 hours and after 7 and 21 days.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 4h
Score:
5.8
Max. score:
8
Irritation parameter:
overall irritation score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 28h
Score:
5.5
Max. score:
8
Irritation parameter:
overall irritation score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 52h
Score:
3.8
Max. score:
8
Irritation parameter:
overall irritation score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 76h
Score:
3.7
Max. score:
8
Irritation parameter:
erythema score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 4h
Score:
3.7
Max. score:
4
Irritation parameter:
erythema score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 28h
Score:
3.7
Max. score:
4
Irritation parameter:
erythema score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 52h
Score:
3.7
Max. score:
4
Irritation parameter:
erythema score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 76h
Score:
3.7
Max. score:
4
Irritation parameter:
edema score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 4h
Score:
2.2
Max. score:
4
Irritation parameter:
edema score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 28h
Score:
1.8
Max. score:
4
Irritation parameter:
edema score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 52h
Score:
0.2
Max. score:
4
Irritation parameter:
edema score
Remarks:
Intact skin
Basis:
mean
Time point:
other: 76h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
Intact skin
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
Other time points measured
Irritation parameter:
edema score
Remarks:
Intact skin
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
Other time points measured
Irritant / corrosive response data:
See table 1 in the section "Any other information on results incl. tables".

Any other information on results incl. tables

After 4 hours the dermal effects generally observed in all rabbits consisted of very slight to slight ischemic necrosis, moderate to severe haemorrhages and slight or moderate oedema.

After 28 hours the dermal effects observed generally consisted of very slight to slight ischemic necrosis, moderate haemorrhages, slight or moderate incrustation and slight: oedema.

During the course of the following two days ischemic necrosis, haemorrhages and oedema were no longer observed. The application sites generally became crater-shaped with a central sunken area which was moderately or severely encrusted, and a surrounding, raised border of non-necrotic skin showing well-defined erythema.

After 7 days this picture had hardly changed, apart from the clearance of erythema. The central sunken areas of the application sites generally showed moderate to severe incrustation. At the end of the observation period, after 3 weeks, some signs of healing were observed at the edges of the encrusted skin areas which had been in contact with the test material. In the new skin visible under the crust edges coming off from the treated skin, formation of scar tissue

could be observed whereas hair growth was absent. There were no distinct differences between reactions of the intact skin and those of the abraded skin.

On the basis of observations in earlier experiments with comparable results, performed at the performing laboratory, the authors state that it is expected that the old necrotic skin will be ejected and that: the formation of scar tissue will be continued. This scar tissue forned already or yet to be formed is not considered a reversible skin alteration.

Table 1: INDIVIDUAL AND AVERAGE SKIN IRRITATION SCORES OF LACTIC ACID (88%), AFTER 4, 28, 52 AND 76 HOURS

Rabbit no.

Intact skin

4 h

28 h

52 h

76 h

A

B

A

B

A

B

A

B

3231

4

2

4

2

4

0

4

0

3232

4

2

4

2

4

0

4

0

3233

4

3

4

2

4

0

4

0

3234

4

3

4

2

4

0

4

0

3235

2

1

2

1

2

1

2

0

3236

4

2

4

2

4

0

4

0

 

 

 

 

 

 

 

 

 

average (A+B)

5.8

5.5

3.8

3.7

Rabbit no.

Abraded skin

4 h

28 h

52 h

76 h

A

B

A

B

A

B

A

B

3231

4

2

4

2

4

0

4

0

3232

4

2

4

2

4

0

4

0

3233

4

3

4

2

4

0

4

0

3234

4

2

4

2

4

0

4

0

3235

4

2

4

2

4

0

4

0

3236

4

2

4

2

4

0

4

0

 

 

 

 

 

 

 

 

 

average (A+B)

6.2

6.0

4.0

4.0

A = erythema

B = oedema

Evaluation of skin reactions (Draize) Value

A. Erythema and eschar formation

No erythema                                                                0

Very slight erythema (barely perceptible)                    l

Well-defined erythema                                                2

Moderate to severe erythema                                     3

Severe erythema (beet redness) to slight eschar       

formation (injuries in depth)                                         4

Maximum possible: 4

B. Oedema formation

No oedema                                                         0

Very slight oedema (barely perceptible)            1

Slight oedema (edges of area well defined by

definite raising)                                                  2

Moderate oedema

(raised approximately l millimeter)                     3

Severe oedema

(raised more than 1 millimeter and

extending beyond the area of exposure)            4

Maximum possible: 4

Total maximum possible score for primary irritation: 8 (4+4).

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Classification: irritating
Executive summary:

A sample of lactic acid (88%) was examined for acute dermal irritating/corrosive properties in an experiment with six albino rabbits. The test sample caused very slight to slight ischemic necrosis, moder- ate to severe haemorrhages, slight to moderate oedema, and moderate to severe incrustation. Three weeks after treatment moderate to severe incrustation, formation of scar tissue and absence of hair growth were observed. On the basis of the results obtained it was concluded that:

- lactic acid (885)is severely irritating to the skin of albino rabbits

- lactic acid (88%) is corrosive to the skin of albino rabbit