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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:
1979-05-21 to 1979-06-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Non-GLP study conducted similarly to OECD Guideline 404 with deviations: no data about purity and no certificate of analysis of the test substance; no details on housing conditions of animals; observations not followed until the reversibility of the effects; different scoring system was followed in the study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
non-GLP study; no data about purity and no certificate of analysis of the test substance; no details on housing conditions of animals; observations not followed until the reversibility of the effects; different scoring system was followed in the study
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
impurity
Test material form:
other: liquid, may crystalize to white solid
Specific details on test material used for the study:
- Name of test material (as cited in study report): PM 343
- Source: PPL, UK
- Physical state: Clear liquid
- Date received: 29 March 1979

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Age at study initiation: 9-12 weeks

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100 %
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
Eight
Details on study design:
- Area of exposure: Dorsum
- % coverage: Test substance (0.5 mL) was applied under a semi-occlusive patch to the clipped skin and the patches were held in place with an adhesive tape.
- Type of wrap used: Animals were immobilised in a canvas body sleeve for 4 h after application of the patch.

REMOVAL OF TEST SUBSTANCE
- After the removal of the patches, the application site was wiped clean of excess material.

SCORING SYSTEM: Skin reactions were observed immediately after removal of the patch and after 24, 48 and 72 h and graded according to the following 8-point anchored ordinate scale:
1 = marginal / very slight
2 = slight
3 = fairly distinct
4 = quite distinct
6 = becoming well developed
8 = well developed
10 = becoming severe
12 = severe

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 8 animals
Time point:
other: average of 24, 48 and 72 h
Score:
3.4
Max. score:
12
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 8 animals
Time point:
other: average of 24, 48 and 72 h
Score:
2.8
Max. score:
12
Reversibility:
no data
Irritation parameter:
overall irritation score
Basis:
other: sum of scores observed in 8 animals
Time point:
other: 24, 48 and 72 h
Score:
225
Max. score:
1 152
Reversibility:
no data
Irritant / corrosive response data:
- At 24 h, generally fairly distinct to distinct erythema and oedema were noted in test animals.
- By 48 and 72 h, fairly distinct to distinct erythema and slight to fairly distinct oedema with marginal to slight cracking were noted in most animals.
- The response produced by PM 343 was greater than that produced by Diethyl Phthalate which produced a generally marginal to slight response in some animals, although one animal had distinct erythema and oedema at 24 h.
- The response produced by PM 343 was slightly less than that produced by the controls, Cyclamen Aldehyde and Geraniol, which produced similar responses showing fairly distinct to fairly well developed erythema and oedema at 24 h and fairly distinct to well-developed erythema and oedema with slight cracking in some animals by 48 and 72 h.
Other effects:
None

Any other information on results incl. tables

Table 7.3.1/1: Skin irritation data for individual rabbits

Rabbit number

Irritation scores*

24 h

48 h

72 h

Mean (24, 48 and 72 h)

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

1

3#

3

3#

2

3# α

2

3.0

2.3

2

4

3

4#

3

3#

2

3.7

2.7

3

4

3

3#

3

3#

2

3.3

2.7

4

2

2

3#

2

2#

1

2.3

1.7

5

4

3

4

4

4# α

4

4.0

3.7

6

4

4

4

3

3#

3

3.7

3.3

7

4# α

4

4# α

2

3# α

2

3.7

2.7

8

4

3

4

3

3#

3

3.7

3.0

Mean (all 8 animals)

3.4

2.8

*Reaction grades and scores:

1 = marginal / very slight

2 = slight

3 = fairly distinct

4 = quite distinct

6 = becoming well developed

8 = well developed

10 = becoming severe

12 = severe

#Very slight to fairly distinct cracking

αVery slight scaling

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Conclusions:
Under the test conditions, PM 343 is classified as ‘Category 2: Irritant’ according to the CLP Regulation and as ‘R38 Irritating to skin’ according to the Directive 67/548/EEC.
Executive summary:

In a primary dermal irritation study performed similarly to OECD Guideline 404, 0.5 mL of the test item, PM 343, was applied under a semi-occlusive patch to clipped dorsum of eight New Zealand White rabbits. After an exposure period of 4 h, the patches and the applied material were removed and skin reactions were scored immediately after removal of the patch and after 24, 48 and 72 h, according to the 8-point anchored ordinate scale ranging from very slight (score = 1) to severe reactions (score = 12).

At 24 h, generally fairly distinct to distinct erythema and oedema were noted in test animals. By 48 and 72 h, fairly distinct to distinct erythema and slight to fairly distinct oedema with marginal to slight cracking were noted in most animals. Very slight scaling was noted in 3/8 animals at 72 h. The calculated mean scores for each individual lesion for all animals within three scoring times (24, 48 and 72 h) on the 8-point anchored ordinate scale were 3.4 for erythema score and 2.8 for oedema score.

After comparing the scores with the scale in OECD Guideline, the calculated mean scores for all animals within three scoring times (24, 48 and 72 h) were as follows: 2 for erythema score and 2 for oedema score.

Under the test conditions, PM 343 is classified as ‘Category 2: Irritant’ according to the CLP Regulation and as ‘R38 Irritating to skin’ according to the Directive 67/548/EEC.