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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:
June 16, 1992 - June 30, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with OECD 404 and GLP (no deviations). Batch number and purity not given.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): XDI: 1,3-BENZENEBIS(METHYL ISOCYANATE)
- Appearance: clear colourless liquid
- Storage condition of test material: room temperature under N2 in brown glass bottles

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, United Kingdom
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.70 - 2.78 kg
- Housing: the animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum (Spillers Rabbit diet, Dalgety Agriculture Ltd., Almondsbury, Bristol, United Kingdom)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: a minimum period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23 °C
- Humidity (%): 50 - 69%
- Air changes (per hr): approximately 15 changes per hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: on the day before the substance was applied, the animals were clipped free of fur from the dorsal flank area using veterinary clippers.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

VEHICLE: not applicable
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
2 males and 1 female
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm (6.25 cm^2)
- Type of wrap if used: gauze patch, secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 x 4.0 cm) to prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to OECD 404 (2002)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
other: mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72h after patch removal
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days (in all 3 animals)
Remarks on result:
other: Individual mean scores: 2-2-2
Irritation parameter:
edema score
Basis:
other: mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72h after patch removal
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days (in 2 of the 3 animals)
Remarks on result:
other: Individual mean scores: 4-4-4

Any other information on results incl. tables

- At all treated skin sites well-defined (score 2) to severe erythema (score 3) was noted at the 7 day observation (average of the 3 animals: 2.67)

- Well-defined and very slight oedema were noted at 2 treated skin sites at the 14 day observation (averages of the 3 animals: 1.33 (erythema) and 0.67 (oedema)).

- The oedema extended ventrally below all treated skin sites at the 1 hr to 72 hrs observations

- Fissuring was noted at 1 treated skin site at the 7 day observation.

- Adverse reactions prevented accurate evaluation of oedema at all treated skin sites at the 7 day observation

- Crust formation, glossy skin and/or reduced re-growth of fur were noted at all treated skin sites at the 14 day observation. Reactions extended up to 5 cm beyond all treatment sites.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on an in vivo skin irritation study (OECD 404), the substance is classified as irritating to the skin (Category 2).
Executive summary:

In an in vivo skin irritation study in rabbits, conducted in accordance with OECD 404 and GLP, 2 male and 1 female rabbits were semi-occlusively exposed for 4 hours to 0.5 mL of the undiluted substance. Well-defined erythema and severe oedema were noted at all treated skin sites 1 hr after patch removal and at the 24, 48 and 72 hour observations with well-defined to severe erythema at the 7 day observation. Erythema was not fully reversible within 14 days in all 3 animals and oedema in 2 of the 3 animals. In accordance with the CLP Regulation the substance is classified as irritating to the skin (Category 2) as the mean value for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal is ≥ 2.3.