Salicylonitrile

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 29 2011 - May 14 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to a national guideline method, essentially equivalent to a OECD TG 404 (1981 edition). Although not conducted under GLP (OECD), the study was conducted under a similar national quality assurance system. Adequately documented study, purity data available separately for test batch.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Guidelines for the testing of chemicals: Test No. 404: Acute dermal irritation/corrosion test (Minestry of Environmental Protection People's Republic of China)

Deviations:

not specified

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981 edition

Deviations:

yes

Remarks:

Scoring at 30/60min not reported.

GLP compliance:

no

Remarks:

The study was conducted in compliance with a national quality assurance system, with similar objectives to GLP (OECD).

Test material

Test material information

Constituent 1

Reference substance name:

Salicylonitrile

EC Number:

210-259-3

EC Name:

Salicylonitrile

Cas Number:

611-20-1

Molecular formula:

C7H5NO

IUPAC Name:

2-hydroxybenzonitrile

Details on test material:

- Name of test material (as cited in study report): 2-cyanophenol
- Substance type: powder
- Physical state: solid
- Purity test date: not reported
- Expiration date of the lot/batch: not reported
- Storage condition of test material: not reported

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: not reported
- Weight at study initiation: ca. 2kg
- Housing: Suspended, wire bottom, stainless steel, 1 animal per cage
- Diet: ad libitum (Statement that contaminents in feed and water effecting study outcome not expected)
- Water: ad libitum (Municipal water supply, analyzed by City Water Quality Monitoring Center of Zhejiang Province)
- Acclimation period: 5 days
- Sex: male and female, nulliparous & non-pregnant

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: not reported

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

distilled

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: total dose 0.5g
- Concentration: not reported

VEHICLE
- Amount: not reported

Duration of treatment / exposure:

4 hours

Observation period:

Observations were made at 24h, 48h, 72h, or until "reversibility was observed" up to 14 days. The study reported observations to at least 72h (guideline minimum), possibly to 14 days (as tabulated).

Number of animals:

4

Details on study design:

TEST SITE
- Area of exposure: 3x3cm clipped free of hair; 2x3cm 4 ply surgical gauze patch, secured with non-irritating adhesive tape.
- % coverage:
- Type of wrap if used: trunk of each animal wrapped in orthopedic stockinette to prevent possible ingestion of test substance.

REMOVAL OF TEST SUBSTANCE
- Washing: Washed gently with room temperature tap water without altering the existing response, or the integrity of the epidermis.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
- According to the Guidelines for the testing of chemicals: Test No. 404: Acute dermal irritation/corrosion test (Minestry of Environmental Protection People's Republic of China). For each animal, all of the erythema and edema scores were added, and the sum was divided by 4 to obtain an individual irritation score. The primary irritation index was determined by calculating the mean of the irritation scores for all the animals and was used to obtain a rating for the test substance.

Erythema Formation Score
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) and eschar formation 4

Edema Formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) 4

Classification of Test Substance
Non-irritating 0.0-0.4
Mildly Irritating 0.5-1.9
Moderately Irritating 2.0-5.9
Severely Irritating 6.0-8.0
The primary irritation index is calculated using only the observation scheduled through 72h.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 6

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 7

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 8

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 9

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 10

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 11

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 12

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 13

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 14

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 15

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 16

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Signs of dermal irritation or defects are presented in Table 1. Very slight erythema and no edema in the skin of New Zealand white rabbits was observed after the patch removal. Therefore, the maximum primary irritation index of the test substance was calculated to be 1.00.

Other effects:

None reported.

Any other information on results incl. tables

Table 1: Acute dermal irritation in rabbits

Animal number	Start weight (kg)	Final weight (kg)	Effect	Score time point
				24h	48h	72h	4d	5d	6d	7d	8d	9d	10d	11d	12d	13d	14d
1	2.41	2.49	Erythema	1	1	0	0	0	0	0	0	0	0	0	0	0	0
			Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2	2.52	2.60	Erythema	1	1	0	0	0	0	0	0	0	0	0	0	0	0
			Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
3	2.80	2.89	Erythema	1	1	0	0	0	0	0	0	0	0	0	0	0	0
			Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
4	2.13	2.22	Erythema	1	1	0	0	0	0	0	0	0	0	0	0	0	0
			Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Primary irritation scores				1.0	1.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

Descriptive rating: mildly irritating

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The current OECD and EU guidelines deviate from the 1981 OECD guideline primarily with respect to numbers of animals, staggered and successive testing, and the preliminary consideration of weight-of-evidence and in vitro data. The report is thus considered to be adequate for classification and risk assessment purposes.

Executive summary:

In a primary dermal irritation study, male or female New Zealand white rabbits (4 animals) were dermally exposed to 0.5g of 2-cyanophenol in distilled water for 4 hours with a 2x3cm patch. Animals were then observed for up to 14 days. Very slight erythema and no edema in the skin of New Zealand white rabbits was observed after the patch removal in all animals, and was fully reversible within 72h. In this study, 2-cyanophenol was found to be mildly irritating according to Guidelines for the testing of chemicals: Test No. 404: Acute skin irritation/corrosion test (Ministry of Environmental Protection of the People's Republic of China, 2004).