4-hydroxy-3,5-dimethoxybenzonitrile

Endpoint summary

Description of key information

Primary dermal irritation study in rabbits showed that the test substance, 4-hydroxy-3,5-dimethoxybenzonitrile, is "slightly irritating" to the skin.

Primary Eye Irritation/Corrosion Study in the Rabbits showed that the test substance is "mildly irritating" to the eyes.

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:

2008-12-09 to 2008-12-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Composition of test material, percentage of components: syringonitrile 99.8%
- Expiration date of the lot/batch: May 2010
-Physical description: pale yellow powder
-solubility: soluble in water
-stability: test substance was expected to be stable for the duration of the testing.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: received from Robinson Services, Inc. Clemmons, NC on Dec. 03, 2008
- Age at study initiation: young adult
-Sex: female, non pregnant
- Housing: singly housed in a suspended stainless steel caging
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
-Animal room temp. and relative humidity: 18-22°C and 32-64% respectively
-Photoperiod: 12 hr light/dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

dorsal area and trunk

Vehicle:

water

Controls:

no

Amount / concentration applied:

Test substance was applied as a dry paste (65% w/w mixture with distilled water) to achieve dry paste. Five-tenths of a gram of the test substance was placed on a gauze pad (0.77 grams of the mixture paste) and applied to the dose site.

Duration of treatment / exposure:

4 hrs

Observation period:

72 hrs (time points at 66 min, 24 hr, 48 hr, and 72 hr) after the gauze pad removal.

Number of animals:

3

Details on study design:

TEST SITE
-1 inch x 1 inch, 4 ply gauze was applied to 6 cm x 6 cm intact dose site on each animal. The gauze and the entire trunk were wrapped with semiocclusive 3-inch micropore tape to avoid dislocation of the gauze. Elizabethan collars were placed on each rabbit and returned to their designated cages.
REMOVAL OF TEST SUBSTANCE
After 4 hrs, the gauzes and the collars were removed and the site was gently cleaned of any residual test substance with a paper towel.
SCORING SYSTEM:
Individual site was scored according to the Draize scoring system at 66 min, 24 hr, 48 hr, and 72 hrs after the gauze removal.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

> 0 <=

Remarks on result:

other: score was 1 at 66 minutes

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: score was 0 at 66 minutes

Irritant / corrosive response data:

All animals appeared active and healthy during the study. No edema observed at any of the treated sites during the study. Within one hour of gauze removal, all three treated sites exhibited very slight erythema. All animals were free of dermal irritation by 24 hrs.

Other effects:

No signs of gross toxicity, adverse pharmacologic effects, or abnormal behaviour.

Interpretation of results:

other: not classified based on EU CLP criteria

Conclusions:

Test substance is slightly irritating to the skin.

Executive summary:

This study was conducted to assess the local irritant effect of Mediator SNP (syringonitrile, 4-hydroxy-3,5-dimethoxybenzonitrile). The test substance was applied as a dry paste (65% w/w mixture in distilled water). Five-tenths of a gram of the test substance was placed on a gauze pad and applied to one 6-cm2 intact dose-site on the dorsal area of three rabbits. The pad and entire trunk of each animal were then wrapped and Elizabethan collars were placed on each rabbit to prevent accidental ingestion of Mediator SNP. After 4 hours of exposure, the pads and collars were removed. Individual dose sites were scored according to the Draize’s scoring system at 1, 24, 48 and 72 hours after patch removal.

No deaths or overt signs of toxicity were observed in this study. No effects on feed consumption and weight gain were recorded. Slight erythema was noted at the 1-hour application with clearing by 24 hours. The primary irritation score for erythema was 0.4. All animals appeared healthy and active during the study. There was no edema observed at any treated site. Slight erythema was noted at the 1-hour scoring period but returned to normal at the 24-hour scoring period. The Primary Dermal Irritation Index for Mediator SNP is 0.3 out of a possible 8.0. On the basis of the results obtained in this study, Mediator SNP is classified as slightly irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

2008-12-15 to 2008-12-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Composition of test material, percentage of components: syringonitrile 99.8%
- Expiration date of the lot/batch: May 2010
-Physical description: pale yellow powder
-solubility: soluble in water
-stability: test substance was expected to be stable for the duration of the testing.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Received from Robinson Services, Inc, Clemmons, NC, on Dec. 10, 2008
- Age at study initiation: young adult
- Housing: singly housed in suspended stainless steel cage
- Diet (e.g. ad libitum): pelleted Purina Rabbit Chow
- Water (e.g. ad libitum): filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 38-44%
- Photoperiod (hrs dark / hrs light): 12 hr light/dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

One-tenth of a mililiter (0.06 grams) of the test substance was instilled to the right eye.

Duration of treatment / exposure:

After the instillation, the upper and lower lids were gently held together for about one second before releasing to minimize loss of the test substance.

Observation period (in vivo):

72 hrs

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
-At the 24-hour scoring period, one drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit and the eyes were rinsed with physiological saline and then evaluated for corneal opacity with an UV-light.

SCORING SYSTEM:
Kay and Calandra scheme for classifying eye irritants
Ocular irritation evaluated in accordance with Draize et al.

TOOL USED TO ASSESS SCORE: Ocular irritation was evaluated using a high-intensity white light (Mag Lite). Corneal opacity evaluated with an UV-light.

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24/48/72 h

Score:

17

Max. score:

17

Remarks on result:

other: includes score for 1-hour reading

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: includes score for 1-hour reading

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: score of 1 for 1-hour reading

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: score of 1 for 1-hour reading

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: score of 1 for 1-hour reading

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: score of 1 for 1-hour reading

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: score of 1 for 1-hour reading

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 0 - <= 2

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: score of 2 for 1-hour reading

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: score of 2 for 1-hour reading

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: score of 1 for 1-hour reading

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: score of 1 for 1-hour reading

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: score of 1 for 1-hour reading

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: score of 0 for 1-hour reading

Irritant / corrosive response data:

One hour after the instillation, two treated eyes exhibited corneal opacity and all three treated eyes exhibited iritis and conjunctivitis. The overall incidence and severity of irritation decreased gradually with time. All animals were free of ocular irritation within 72 hrs.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Under the conditions of this study, the test substance is mildly irritating to the eye.

Executive summary:

The objective of this study was to assess the ocular irritation potential of Mediator SNP (4-hydroxy-3,5-dimethoxybenzonitrile). One-tenth of a milliliter (0.1 mL) of Mediator SNP was instilled into the right eye of three rabbits. The left eye remained untreated and served as control. Ocular irritation was evaluated using a high-intensity white light (Mag Lite) at 1, 24, 48 and 72 hours post-instillation. At the 24-hour scoring period, one drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit and the eyes were rinsed with physiological saline and then evaluated for corneal opacity with an UV-light.

All animals appeared healthy and active during the study. One hour after Mediator SNP instillation, corneal opacity was noted in 2 out of 3 rabbits and iritis and conjunctivitis were recorded in all three animals. The overall incidence and severity of irritation decreased gradually with time and no ocular irritation was noted at the 72-hour scoring period. The maximum mean score of Mediator SNP was 17.0 out of a possible 110. Using the Kay and Calandra scheme for classifying eye irritants, Mediator SNP is classified as “mildly irritating” to the eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

IRRITATION/CORROSION OF 4 -HYDROXY-3,5 -DIMETHOXYBENZONITRILE

Primary dermal irritation study in rabbits The objective of this study was to assess the local irritant effect of Mediator SNP (4-hydroxy-3,5-dimethoxybenzonitrile). The test substance was applied as a dry paste (65% w/w mixture in distilled water). Five-tenths of a gram of the test substance was placed on a gauze pad and applied to one 6-cm2 intact dose-site on the dorsal area of three rabbits. The pad and entire trunk of each animal were then wrapped and Elizabethan collars were placed on each rabbit to prevent accidental ingestion of Mediator SNP. After 4 hours of exposure, the pads and collars were removed. Individual dose sites were scored according to the Draize’s scoring system at 1, 24, 48 and 72 hours after patch removal.

All animals appeared healthy and active during the study. There was no oedema observed at any treated site. Slight erythema was noted at the 1-hour scoring period but returned to normal at the 24-hour scoring period. The Primary Dermal Irritation Index for Mediator SNP is 0.3 out of a possible 8.0. On the basis of the results obtained in this study, Mediator SNP is classified as slightly irritating to the skin.

 

Primary Eye Irritation/Corrosion Study in the Rabbit

The objective of this study was to assess the ocular irritation potential of Mediator SNP (4-hydroxy-3,5-dimethoxybenzonitrile). One-tenth of a milliliter (0.1 mL) of Mediator SNP was instilled into the right eye of three rabbits. The left eye remained untreated and served as control. Ocular irritation was evaluated using a high-intensity white light (Mag Lite) at 1, 24, 48 and 72 hours post-instillation. At the 24-hour scoring period, one drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit and the eyes were rinsed with physiological saline and then evaluated for corneal opacity with an UV-light.

The maximum mean score of Mediator SNP was 17.0 out of a possible 110. Using the Kay and Calandra scheme for classifying eye irritants, Mediator SNP is classified as “mildly irritating” to the eyes.

Justification for classification or non-classification

Although the test substance produced some irritation to the skin of rabbits, the irritation did not meet the criteria for classification acconring to CLP. Based on the effects observed in the eye irritation study, the test substance is classified for eye irritation as Cat 2 (H319: Causes serious eye irritation) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.