3-Morpholinone, 4-[4-[(5S)-5-(aminomethyl)-2-oxo-3-oxazolidinyl]phenyl]-, hydrochloride (1:1)

Endpoint summary

Description of key information

Skin irritation in vivo (Rabbit-NZW, GLP, OECD TG 404, EU Method B.4, OPPTS 870.2500): not irritating to the skin
[Bayer AG, Report No. PH-33322, 2004-06-03]

Eye irritation in vivo (Rabbit-NZW, GLP, OECD TG 405, EU Method B.5, OPPTS 870.2400): not irritating to the eye
[Bayer AG, Report No. PH-33338, 2004-06-14]

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:

Apr 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch BXR2B06
purity: 100%

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 88353 Kißlegg, Germany, 69592
- Age at study initiation: young adult animals
- Weight at study initiation: 2.518 kg — 2.560 kg
- Housing: The animals were housed individually in cage units Metall/Noryl by EBECO. Excrement trays below the cages contained low dust wood granulate bedding (J. Rettenmaier & Söhne, 73494 Rosenberg, Germany).
- Diet (e.g. ad libitum): The animals received the standard diet “SsniffK-Z” 4mm (manufacturer: Ssniff Spezialdiäten GmbH, 59494 Soest, Germany), approximately 100 g per animal per day
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 50±25
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

pulverized test item moistened with water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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

Duration of treatment / exposure:

one animal: first patch removed after 3 minutes, second patch (because no serious skin reactions were observed after the first patch) removed after 1 hour and third patch removed after 4 hours
two more animals: exposed for 4 hours

Observation period:

72 hours

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: 0.5 g of the pulverized test substance moistened with Aqua p.i. (to ensure good contact with the skin) was applied to the skin of the animal under a gauze patch. The patch was placed on the dorso-lateral areas of the trunk of each animal and was held in place with non-irritating tape for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The exposed skin area was carefully washed with water without altering the existing response, or the integrity of the epidermis.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1, 24, 48, 72 h

SCORING SYSTEM: The degree of erythema/eschar formation and oedema formation was recorded as specified by DRAIZE

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

There were no systemic intolerance reactions.

Results of the study:

	Irritant Effects (Scores)
	24 h		48 h		72 h		Mean scores
animal	erythema	edema	erythema	edema	erythema	edema	erythema	edema
1	0	0	0	0	0	0	0	0
2	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

the test item is not irritating to skin

Executive summary:

500 mg of the test substance was semi-occlusively applied to the shaved intact skin of 3 female rabbits for an exposure period of 4 h. Evaluation of skin irritation was made according to Draize.

In this skin irritation study (S)-Oxamin Hydrochlorid was not irritating to the skin.

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:

Apr 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch BXR2B06
purity: 100%

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, 88353 Kißlegg, Germany, 69592
- Age at study initiation: young adult animals
- Weight at study initiation: 3.085 kg — 3.530 kg
- Housing: The animals were housed individually in cage units Metall/Noryl by EBECO. Excrement trays below the cages contained low dust wood granulate bedding (J. Rettenmaier & Söhne, 73494 Rosenberg, Germany).
- Diet (e.g. ad libitum): The animals received the standard diet “SsniffK-Z” 4mm (manufacturer: Ssniff Spezialdiäten GmbH, 59494 Soest, Germany), approximately 100 g per animal per day
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 50±25
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other:

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,1 g

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 1h

SCORING SYSTEM: According to DRAIZE

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: not reported

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

There were no systemic intolerance reactions.

Results of the study

		Irritant Effects (Score)
Animal		24 h	48 h	72 h	Mean scores
1	Corneal Opacity	0	0	0	0.0
	Iritis	0	0	0	0.0
	Redness conjunctivae	1	0	0	0.3
	Chemosis conjunctivae	0	0	0	0.0
2	Corneal Opacity	0	0	0	0.0
	Iritis	0	0	0	0.0
	Redness conjunctivae	1	0	0	0.3
	Chemosis conjunctivae	0	0	0	0.0
3	Corneal Opacity	0	0	0	0.0
	Iritis	0	0	0	0.0
	Redness conjunctivae	0	0	0	0.0
	Chemosis conjunctivae	0	0	0	0.0

All animals showed reddening of the conjunctivae (grade 2), chemosis (grade 1) and lacrimation (grade 1) 1 h after administration.

Interpretation of results:

GHS criteria not met

Conclusions:

the test item is not an irritant to eyes

Executive summary:

0.1 g of the test substance was administered into the conjunctival sac of in each case one rabbit eye of 3 females and after 1 h the treated eyes were washed.

Evaluation of eye irritation was made according to Draize.

According to the classification criteria (S)-Oxamin Hydrochlorid is not irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the skin irritation test in all 3 animals no signs of skin irritation could be observed. There were no systemic intolerance reactions.

In the eye irritation test all animals showed reddening of the conjunctivae (grade 2), chemosis (grade 1) and lacrimation (grade 1) 1 h after instillation. Only 2 of them had slight irritation signs at the conjunctivae (grade 1) after 24 h. All effects were fully reversible within 2 days. There were no systemic intolerance reactions.

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008 (CLP) is not required.