3-pyridyl dimethylcarbamate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-02-23 to 1999-07-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Adopted, 12 February 1999

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3-pyridyl dimethylcarbamate

EC Number:

257-297-7

EC Name:

3-pyridyl dimethylcarbamate

Cas Number:

51581-32-9

Molecular formula:

C8H10N2O2

IUPAC Name:

pyridin-3-yl N,N-dimethylcarbamate

Specific details on test material used for the study:

- CAS No.: 51581-32-9
- Batch No.: TMFP 304
- Purity: At least 99 %
- Solubility in water: Soluble
- Storage: In the refrigerator, in the dark
- Date of expiry: December 1999
- Appearance: Colorless liquid
- pH of the test substance: 7.29 (10 % solution in deionised water, v/v, determined with a pH-meter)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Supplier: J. Schitkovits, A-2620 Natschbach
- Justification for selection of the species: Recommended by the Directive / Guideline
- Number and sex: 3 females
- Body weight (at the start and at the termination of the test): Animal No. 11: 3.0 kg and 3.5 kg, Animal No. 12: 3.2 kg and 3.6 kg, Animal No. 13: 3.2 kg and 3.k - Housing: Individual caging in metal wire cages
- Diet (e.g. ad libitum): Yes
- Water (e.g. ad libitum): Yes
- Acclimation period: 10 days (animal no. 11) and 16 days (animal no. 12 and no. 13)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 53
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

The test substance was administered to the conjunctival sac of the right eye by gently pulling the lower lid away from the eyeball for instillation. The eye was held closed for about one second to prevent loss of test substance.

Observation period (in vivo):

Both eyes of the animals were examined within 24 hours before instillation and approximately 1, 24, 48 and 72 hours p.a.
Additional examinations were performed 6, 8, 10, 13, 15, 17 and 21 days after the instillation, ending individually for each animal.

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: The scoring terms of 24, 48 and 72 h after the instillation were used

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 13d

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21d

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6d

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 10d

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 6d

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 13d

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

not fully reversible within: 21d

Results 9

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8d

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8d

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

fully reversible within: 17d

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6d

Irritant / corrosive response data:

Ocular lesions were reversible in 2 / 3 animals within 17 days p.a. and were not reversible in 1 / 3 animals within 21 days

Other effects:

Other observations:
- Cornea: Diffuse areas of opacity (score "1") raised to easily discernible translucent areas with details of iris slightly obscured (score "2"). Most of the time the whole cornea was affected. White coverings on the sclera were noted in one animal 72 h p.a. and corneal lesions were still present 21 d p.a. In 2 / 3 animals, lesions were fully reversible. The corneae became normal again 6 d - 13 d p.a.
- Iris. In 2 / 3 animals mild changes (score "1") were noted from 24 h p.s. on and lasted until a maximum of 8 d p.a.
- Conjunctivae, redness: Injected blood vessels to diffuse beefy red colour were noted in all animals. The lesions were observed from 1 h p.a. to a maximum of 10 d p.a. in 2 / 3 animals and lasted until 21 d p.a. in the third animal. In 1/ 3 animals, a turbid ocular discharge from the instilled eye was seen 48 h p.a.
- Conjunctivae, chemosis: In all animals swelling in different degrees of severity were noted from 1 h onwards. The lesions then gradually returned to normal and 6, 8 and 17 d p.a. no swellings were detectable.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In this study, Pyridobase caused irreversible serious ocular lesions in 1 / 3 animals and was irritating to the eyes in 2 / 3 animals.

Executive summary:

In an in vivo eye irritation study conducted according to the OECD guideline 405, 0.1 mL of the test item was instilled to the conjunctival sac of one eye of each of 3 New Zealand White rabbits and the other eye was used as a control. The eyes were observed for body weights, general signs of toxicity and eye examinations. Irreversible ocular lesions in 1 / 3 animals and irritation in 2 / 3 animals was observed. Based on these results, the test substance is considered as an irritant under 'Category 1' according to the UN GHS Criteria.