HDI oligomers, allophanate

Eye irritation

Administrative data

Endpoint:

eye 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 405 (Acute Eye 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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues 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 6 - 7 months
- Weight at study initiation: 3.52 - 3.82 kg
- Housing: Single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm²
- Diet: Kliba-Labordiät, Provimi Kuba 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

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated left eye

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

24 hours. The test substance was applied in a single dose to the conjunctival sac of the right eyelid. About 24 hours after application of the liquid test substance the treated eye of the animal(s) was rinsed with 3 to 6 ml of hand warm tap water tor 1 to 2 minutes using a syringe with a blunt probe.

Observation period (in vivo):

Animals were monitored approx. 1, 24, 48 and 72 h after application and then in weekly intervals maximally up to day 28.

Number of animals or in vitro replicates:

1 female, 2 males

Details on study design:

- Body weight determination: Just before application of the test substance and after the last reading.
- Route of application: The test substance 0.1 mL (undiluted) was applied in a single dose to the conjunctival sac of the right eyelid.
- Rinsing of the eye: About 24 hours after application of the liquid test substance the treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water tor 1 to 2 minutes using a syringe with a blunt probe.
- Readings: Approx. 1, 24, 48 and 72 h after application.
- Illumination used tor reading: Daylight tubes ‹Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)
- Check for dead or moribund Twice each workday (beginning and end) and once animais: on Saturdays, Sundays and on public holidays.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: mean score after 72h: 0.3

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal: #2, #3

Time point:

24/48/72 h

Score:

>= 0 - <= 2

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: mean score after 72h: 1.3

Results 5

Irritation parameter:

chemosis score

Basis:

animal: #1, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

chemosis score

Basis:

animal #2

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 72h: 0.3

Irritant / corrosive response data:

- Slight conjunctival redness (grade 1) was observed in one animal 1 hour after application up to 24 hours. Two animals showed moderate conjunctival redness (grade 2) from 1 hour until 48 hours after application. Slight conjunctival chemosis (grade 1) was noted in one animal 24 hours after application only. Slight discharge (grade 1) was observed in two animals 1 hour after application. Severe discharge (grade 3), noted in one animal after 1 hour, decreased to slight at the 24 hour-reading.
- No other ocular reactions were observed during the study.
- The ocular reactions were reversible in one animal within 48 hours and in two animals within 72 hours after application.
- Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0 for corneal opacity and for iris lesions, 0.3, 1.3 and 1.3 for redness of the conjunctiva and 0.0, 0.3 and 0.0 for chemosis.

Any other information on results incl. tables

For assessing eye 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 allophante-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 Eye Irritation/ Corrosion test according to OECD TG 405 was conducted with the test substance. Slight or moderate conjunctival redness and slight or severe discharge were observed in the animals during the course of the study. Slight conjunctival chemosis was noted in one animal 24 hours after application only.

The ocular reactions were reversible in all animals within 72 hours after application at the latest. The average scores (24, 48 and 72 hours) were for conjunctivae (redness) 0.3, 1.3, 1.3 and for chemosis 0.0, 0.3 and 0.0. No effects were observed on corneal opacity or iris.