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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:
supporting study
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no GLP, 24h application period (guideline 4h), no individual scores reported

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1976

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Draize test: the procedure involves applying 0.5 ml of the test substance to intact or abraded skin of rabbits for 24h. The degree of irritation/corrosion is read and scored at 24h, 48h and 72h. The experiment included histopathological examinations of the induced lesions.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-methyl-m-phenylene diisocyanate
EC Number:
209-544-5
EC Name:
4-methyl-m-phenylene diisocyanate
Cas Number:
584-84-9
Molecular formula:
C9H6N2O2
IUPAC Name:
2,4-diisocyanato-1-methylbenzene
Details on test material:
- Name of test material (as cited in study report): 2,4-TDI (Merck - Schuchardt)
- purity: around 97 %

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
female animals,
body weight 2.4 -3.1 kg

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: intact or abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:
24 hours
Observation period:
3 weeks (24h, 48h, 72h, 10days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: the treated area was covered with a gauze patch, which was held in contact with the skin by means of a suitable semi-occlusive, sterile cotton-dressing for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE: no data

SCORING SYSTEM: Scores obtained at 24h and 72h were used to calculate a primary dermal irritation index.

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24h and 72h
Score:
3.6
Max. score:
8
Reversibility:
fully reversible within: 3 weeks
Irritant / corrosive response data:
Macroscopic evaluation at 24 hours:
- Erythema: slight 2/6, moderate 3/6, severe 1/6
- Oedema: very slight 3/6, moderate 3/6.
Lesions on abraded skin seem slightly more severe than on intact skin.
Slight regression by 72 h.
Primary cutaneous irritation index of 3.6 on a 0-8 scale.
(0-2 equals slight, 2-5 medium and 5-8 severe irritation.)
Resolution in 3 weeks.

Any other information on results incl. tables

Macroscopic and microscopic observation of induced lesions (rabbit skin)

I- Macroscopic lesions assays within 3 day periods

A polymerisation reaction was described, when the TDI came into contact with the water emitted by the skin surface. As a consequence the application pad adhered to the skin.

After 24 hours treated sites (intact and abraded) were whitely, scaly-like (product rests) and furry, underneath the whole patch surface. The observed lesions were delimitated by a fine reddish borderline and appeared deep-rooted compared to the adjacent skin. The treated sites felt hard by contact, probably (no certitude) due to polymer deposition or to superficial necrosis.

- Slight erythema in 2/6 animals              - Very slight edema in 3/6 animals

- Moderate erythema in 3/6 animals       - Moderate edema in 3/6 animals

- Important erythema in 1/6 animals       - Casually moderate at abraded sites

 

NB: the lesions were slightly more severe at abraded test sites

 

c) During the following 2 days the lesions were stable or slightly decreasing.

 

II- Microscopic lesions on day 3 (identical for intact and abraded sites)

- Epidermic atrophy with exulceration overlapping a reactive dermis (congestion of superficial dermal vessels containing inflammatory polymorphic infiltrate)

- Or necrosis of epidermis / superficial dermis, accompanied by granular tissue formation under which neoepidermis was emerging; polymorphic infiltrate in mid and deep dermis layers.

Temporary lesions were also observed.

 

III- Macroscopic and microscopic evolution of the observed lesions

At day 10 the lesions observed in intact sites were more severe than those at abraded sites.

Subcutaneous scar formation was observed in one animal.

In 3 animals brilliant scar with eschar formation wer observed at abraded sites; and moderate erythema with necrotic areas sometime with hemorrhage and moderate (mid) edema at intact sites.

 

All reversible within 3 weeks.

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The 2,4-TDI was considered to be a skin irritant. This substance is classified irritant according to EU criteria and the GHS.
Executive summary:

In a primary dermal irritation study (Duprat et al., 1976), six albino female rabbits were dermally exposed to 0.5 ml of 2,4-TDI (97 % of purity) for 24 hours. Test sites (abraded or intact) were covered with a semi-occlusive dressing. Animals then where observed for 3 weeks. The skin reactions were assessed at 24, 48 and 72 hours, as well as, 10 days and 3 weeks after removal of the dressing. Slight to severe erythema and very slight to moderate oedema were observed at 24 hours. Results obtained on abraded skin seemed more severe at 24 hours. At day 3, microscopic observations did not revealed any difference between intact or abraded treated skin. The primary dermal irritation index (based on scores obtained at 24 and 72 hours) was 3.6 on 0-8 scale. Skin effects were reversible within 3 weeks. In the conditions of this test, Toluene diisocyanate (isomer 2,4) is a skin irritant.

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