2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

Endpoint summary

Description of key information

The key studies provided were conducted to recognised testing guidelines and with GLP certification.

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:

1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2180 - 2390 g
- Housing: individually
- Diet (e.g. ad libitum): Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours / 12 hours

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: The substance was water moistened before application.

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: gauze patch loosely held in place by adhesive but non irritating tape (ISOPLAST AG, CH-5200 Brugg)

SCORING SYSTEM: OECD Draize Scoring System

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: One animal showed very slight erythema after one hour.

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: One animal showed very slight oedema after one hour.

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Other effects:

The body weight development was not affected by the application of the test article.
No other reactions to treatment were recorded during the whole observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material failed to induce a dermal irritation response in rabbits under the conditions of the test.

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:

1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2320 - 2680 g
- Housing: individually
- Diet (e.g. ad libitum): Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/- 3
- Humidity (%): 30-70
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and served as the control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

The test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: OECD Scoring System

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Remarks on result:

other: Slightly irritative reactions after one hour in one animal.

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: No effects observed.

Remarks on result:

other: Irritative effects were observed after one hour in one animal.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Irritation was observed after one hour

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Irritation was observed after one hour

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Remarks on result:

other: Slight swelling was observed after one hour

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Other effects:

In one animal the body weight decreased during the test period.
No other reactions to treatment were recorded during the whole observation period.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: GHS EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A GLP in vivo study was performed to assess the acute dermal irritation or corrosion potential of the test substance in White New Zealand rabbits according to the OECD guideline 404. 0.5 g of the test substance (purity: > 98 weight-%) was applied topical once on the intact skin of three female rabbits, using a patch of 6 cm2 for 4 hours. The application site was dressed semi-occlusively. The average score (24 to 72 hours) for irritation was calculated to be 0 for erythema and 0 for edema. Considering the described skin reactions, the test substance does not show a skin irritation potential under the test conditions chosen.

A supporting study to assess the acute dermal irritation or corrosion potential of the test substance was performed on 3 male and 3 female adult White New Zealand rabbits based on the proposed guidelines of the US EPA with a stringent design, namely: exposure under 24 h, occlusive conditions. An amount of 0.5 g of the test substance was applied topically once to the abraded skin of 6 rabbits. The application site was covered with an occlusive dressing for a period of 24 hours. The calculated primary irritation index was 0.05. Under the conditions of the present experiment the test substance was found to cause no irritation when applied to intact and abraded rabbit skin.

 

To assess the acute eye irritation potential of the test substance in vivo a GLP eye irritation test in White New Zealand rabbits was performed according to the method described in OECD guideline 405. An amount of 0.1 g of the test substance (purity: > 98 weight-%) was applied once to the eyes of three rabbits. The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity and iris, 0.33, 1 and 1.33 for conjunctivae redness in the three animals and 0, 0.33 and 0.33 for chemosis in the three animals. The findings were reversible in all animals within not later than 7 days after application. Under the test conditions chosen and considering the described findings the test substance does not give indication of an irritant property to the eye.

A supporting study to assess the acute eye irritation or corrosion potential of the test substance was performed on 3 male and 3 female White New Zealand rabbits based on the proposed guidelines of the US EPA.The test material (0.1 g) was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. Eye irritation was appraised with a slit-lamp on days 1, 2, 3, 4 and 7 and scored for each rabbit. The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity and iris, 0.3 for conjunctivae redness and 0 for chemosis. Under the conditions of this experiment, the test material does not give indication of an irritant property to the eye.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008.