HDI oligomers, allophanate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Klimisch reliability of study is 1 (GLP guideline study); according to ECHA Practical Guide 6 rel. 2 is selected from the IUCLID pick-list as this should be the maximum score for read-across.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(2002)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

197393-84-3

Cas Number:

197393-84-3

IUPAC Name:

197393-84-3

Constituent 2

Reference substance name:

900-066-9

EC Number:

900-066-9

IUPAC Name:

900-066-9

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: New Zealand White A1077 INRA (SPF)
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: About 5 months
- Weight at study initiation: 3.08 - 3.39 kg
- Housing: Single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm²
- Diet: Kliba-Labordiät, Provimi Kliba SA, Kaiseraugst, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated skin sites of the same animal.

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

- Clipping of the fur: At least 24 hours before the beginning of the study clipping of the dorsolateral part of the trunk of the animal(s).
- Body weight determination: Just before application of the test substance and after the last reading.
- Route of application: The test substance was applied in a single dose to the intact untreated skin The test patch was secured in position with a semiocclusive dressing. The test substance was removed at the end of the exposure period with Lutrol and Lutrol/water (1 : 1).
- Readings: lmmediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals up to day 14.
- Illumination used for reading: Daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)
- Check for dead animals or moribund: Twice each workday (beginning and end) and once on Saturdays, Sundays and on public holidays.
- Evaluation of results: For evaluation, the calculation of the mean values of erythema and edema for readings 24, 48 and 72 hours were quoted. Additionally, the reversibility of the observed findings was taken into account.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 2 - <= 3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: mean score after 72h: 2.3

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

>= 1 - <= 3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: mean score after 72 h: 2

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 4

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: mean score after 72 h: 0.3

Irritant / corrosive response data:

- Moderate erythema (grade 2), observed in all animals immediately and 1 hour after removal of the patch, increased to marked (grade 3) in all animals after 24 hours and decreased to slight or moderate (grade 1 or 2) in one or two animals after 48 and 72 hours. In one animal marked erythema persisted up to 72 hours, decreased to slight after day 7 and persisted up to study termination on day 14.
- Slight edema (grade 1) was noted in all animals immediately after removal of the patch up to 24 hours.
- Additionally erythema was extended beyond the area of exposure in all animals after 24 hours up to 72 hours. Moreover scaling and dryness of the skin was noted. The cutaneous reactions were reversible in two animals within 7 days, while in one animal slight erythema and scaling was still present up to study termination on day 14. Mean scores over 24, 48 and 72 hours for each animal were 2.3, 2.0 and 3.0 for erythema and 0.3 for edema.

Any other information on results incl. tables

For assessing skin irritation in vivo a read across from a substance with a very similar chemical composition (comparable allophanate-type HDI oligomerisation product, EC 900 -066 -9, CAS 197393 -84 -3) is applied. The read across is based on physicochemical and toxicological similarity of the two substances. Especially a recently conducted comparative pulmonary irritant potency study based on the recommendations of TRGS 430 (Technical Rule for Hazardous Substances 430, published by the German Federal Ministry of Labour and Social Affairs, last update 2009), confirmed for both allophanat-type HDI oligomerisation products the same toxicological mode of action and a nearly identical potency (both NOAEL at 3.4 mg/m³). For further justification of the grouping and read-across according to regulation (EC) No 1907/2006, Annex XI, 1.5 see document attached to chapter "Assessment Reports".

 

Applicant's summary and conclusion

Executive summary:

An Acute Skin Irritation/Corrosion test according to OECD 404 was conducted with the test substance. Slight to marked erythema, partly extending beyond the area of exposure and slight edema were observed in the animals during the course of the study. Additionally dryness of the skin and scaling were noted during the observation period. The cutaneous reactions were reversible in two animals within 7 days, while in one animal slight erythema and scaling was still present up to study termination on day 14. The average scores (24, 48, and 72 hours) were for erythema 2, 2.3, 3 and for edema 0.3, 0.3, 0.3.