3-pyridyl dimethylcarbamate

Endpoint summary

Description of key information

In vivo GLP guideline studies are available for effect to the skin and the eyes, according to OECD 404 and OECD 405, respectively.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-02-23 to 1999-07-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted on 17 July, 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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: 7.29

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: J. Schitkovits, A-2620 Natschbach
- Weight (at study initiation and termination) : Animal no. 1: 2.9 kg and 3.1 kg, Animal no. 2: 2.7 kg and 2.9 kg, Animal 3: 2.8 kg and 2.8 kg
- Housing: Individual caging in metal wire cages
- Diet (e.g. ad libitum): Yes
- Water (e.g. ad libitum): Yes
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 53
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 h after patch removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm X 2.5 cm

OBSERVATION TIME POINTS : 1, 24, 48 and 72 h
(indicate if minutes, hours or days)

SCORING SYSTEM:
- Method of calculation: Scoring terms of 24, 48 and 72 h after the patch removal were used

Irritation parameter:

erythema score

Basis:

animal: 1, 2 and 3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal: 1, 2 and 3

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

All areas treated with the test substance and all control areas were normal before the application and at each observation time

Other effects:

- Other adverse local effects: None
- Other adverse systemic effects: None

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, the test substance is considered non-corrosive or a non-irritant to the skin.

Executive summary:

In an in vivo skin irritation study conducted according to the OECD guideline 404, 0.5 mL of the test item was spread on cellulose patches in a size of about 2.5 cm X 2.5 cm and were applied to test sites on each of 3 New Zealand White rabbits for 4 hours. The patches were then removed and the skin was examined for erythema / eschar and oedema as well as other local signs approximately 1, 24, 48 and 72 hours after patch removal. No general toxic effects were observed. All areas treated with test substance and all control areas were normal before the application and at each observation time. Based on these results, the test substance is considered as a non-irritant to the skin under the UN GHS Criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

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)

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)

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

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

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

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

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6d

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 10d

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 6d

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

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

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

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8d

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

fully reversible within: 17d

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on irreversible ocular lesions in 1 out of 3 animals, the test substance is considered to cause serious eye damage. Classification as Eye Damage 1 is warranted under CLP.