4-hydroxy-3,5-dimethoxybenzonitrile

Skin irritation / corrosion

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-hydroxy-3,5-dimethoxybenzonitrile

Cas Number:

72684-95-8

IUPAC Name:

4-hydroxy-3,5-dimethoxybenzonitrile

Test material form:

solid

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.

Test animals

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

> 0 <=

Remarks on result:

other: score was 1 at 66 minutes

Results 3

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.

Applicant's summary and conclusion

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.