2-hydroxy-4-(methylthio)butyronitrile

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 18 August 1998 to 28 August 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 404)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-4-(methylthio)butyronitrile

EC Number:

241-756-3

EC Name:

2-hydroxy-4-(methylthio)butyronitrile

Cas Number:

17773-41-0

Molecular formula:

C5H9NOS

IUPAC Name:

2-hydroxy-4-(methylsulfanyl)butanenitrile

Details on test material:

- Name of test material (as cited in study report): 2-hydroxy-4-méthylthiobutyronitrile
- Physical state: pale yellow liquid
- Analytical purity: 75.77% (TOS) / 74.5 % (HPLC)
- Purity test date: no data
- Lot/batch No.: MO69
- Expiration date of the lot/batch: no data
- Storage condition of test material: at room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
- Age at study initiation: no data
- Weight at study initiation: the animals had a mean body weight of 2.5 +/- 0.2 kg.
- Housing: individually in polystyrene cages
- Diet : ad libitum, 112 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France)
- Water : ad libitum, water filtered by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3
- Humidity (%): 30 to 70
- Air changes (per hr): 12
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 18 August 1998 To: 28 August 1998

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

3 minutes and 4 hours

Observation period:

72 hours (when no evidence of dermal irritation)
Examination time points: 1 hour, 24, 48 and 72 hours after removal of the dressing.
14 days (when persistent cutaneous irritation)

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: right flank (application for 4 hours), left flank (application for 3 minutes)
- Type of wrap if used: dry gauze pad


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No residual test substance was observed on removal of the dressing.
- Time after start of exposure: 3 minutes and 4 hours


SCORING SYSTEM:
Irritation evaluated for each animal according to the grading scale originally proposed by Draize and adopted by OECD test guideline 404.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.77

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritant / corrosive response data:

After a 3-minute exposure (one animal): a well-defined erythema (grade 2) was recorded on day 1. No other cutaneous reactions were observed.
After a 4-hour exposure (three animals): a very slight or well-defined erythema (grade 1 or 2) was recorded on day 1 in all animals; it persisted up to day 3 (in one animal) or 8 (in another animal). No other cutaneous reactions were observed.

Other effects:

None

Any other information on results incl. tables

Table: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point/ Reversibility	Erythema Max. score: 4	Edema Max. score: 4
60 min	2/2/1	0/0/0
24 h	0/2/2	0/0/0
48 h	0/1/1	0/0/0
72 h	0/0/1	0/0/0
Mean scores over 24, 48 and 72 hours for each animal	0/1/1.33	0/0/0
Average 24h, 48h, 72h calculated over all the animal tested	1	0
Reversibility*)	c.	-

*) Reversibility: c.=completely reversible; n.c.= not completely reversible; n= not reversible

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP and EU

Conclusions:

Under the experimental conditions, the test substance 2-hydroxy-4-methylthiobutyronitrile is slightly irritant when applied topically to rabbits.

Executive summary:

In an acute dermal irritation study (CIT, 1998), the potential of the test substance 2 -hydroxy-4-methylthiobutyronitrile to induce skin irritation was evaluated in three male New Zealand White rabbits according to OECD 404 guideline. The test substance (0,5 ml) was applied (undiluted) for 4 hours to an area of approximately 6 cm² of the right flank. Test sites were covered with a semi-occlusive dressing. Animals then were observed for 3 to 14 days. Irritation was scored by the method of Draize adopted by OECD test guideline 404. In one animal, after a 3-minute exposure, a well-defined erythema was recorded on day 1. No other cutaneous reactions were observed. After a 4-hour exposure (3 animals), a very slight or well-defined erythema was recorded on day 1 in all animals. It persisted up to day 3 (in one animal) or 8 (in another animal). No other cutaneous reactions were observed.The mean value of the scores at each of the reading times (24, 48 and 72 hours) for erythema and edema calculated over all the animals tested was 0.77 and 0, respectively. Under the experimental conditions, the test substance 2-hydroxy-4-methylthiobutyronitrile is slightly irritant when applied topically to rabbits. In conclusion, according to the classification criteria laid down in Directive 67/548/EEC and CLP regulation, te test substance 2 -hydroxy-4 -methylthiobutyronitrile should not be classified as irritating to the skin.