4-mesyl-2-nitrotoluene

Endpoint summary

Description of key information

Skin: not irritating, OECD 404 (Draize criteria), Lees 1999
Eye: not irritating, OECD 405 (modified Kay and Calandra system), Lees 1999

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:

11 September - 28 September 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, no restrictions, fully adequate for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adults
- Weight at study initiation: 2414-3283 g
- Housing: individually, in cages suitable for rabbits of this strain and weight range expected during the course of the study
- Diet: STANRAB SQC ad libitum
- Water: mains water ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17±2°C
- Humidity: 40-70%
- Air changes: approximately 25 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 13 September 1995 To: 28 September 1995

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Remarks:

corn oil

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approximately 500 mg
- The test substance was moistened to a dry paste with approximately 0.5 mL corn oil

VEHICLE
- Amount(s) applied (volume or weight with unit): the test substance was moistened with approximately 0.5 mL corn oil to a dry paste

Duration of treatment / exposure:

4 hours

Observation period:

4 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approximately 2.5 cm x 2.5 cm of the left flank
- % coverage: not reported
- Type of wrap if used: the treated area was covered with a piece of 8-ply surgical gauze which was secured by two strips of surgical tape. This was covered by a piece of impermeable rubber sheeting wrapped once around the trunk of the animal and secured with adhesive impermeable polyethylene tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the application site was cleansed free of any residual test material using clean swabs of absorbent cotton wool and clean warm water, then dried with clean tissue paper.
- Time after start of exposure: approximately 4 hours

SCORING SYSTEM
- The Draize scale (Draize JH (1959) Third printing, 1975. 'Dermal Toxicity' in 'Appraisal of the safety of chemicals in food, drugs and cosmetics'. Association of Food and Drug Officials of the US, pp46-59) was used to assess the degree of erythema and oedema approximately 30 minutes and 1, 2, 3 and (for one animal) 4 days after removal of the dressings. Any other signs of skin irritation were also noted.

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3

Time point:

other: 30 minutes after decontamination

Score:

1

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

no changes at any timepoint

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

other: 30 minutes after decontamination

Score:

1

Reversibility:

fully reversible within: 4 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

no changes at any timepoint

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

no changes at any timepoint

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 48 hours

Table1: Individual and mean skin irritation scores according to the Draize scheme

Time	Erythema			Oedema
Animal number	2	10	11	2	10	11
after 1 hour	1	1	1	1	1	1
after 24 hours	1	0	1	0	0	1
after 48 hours	1	0	1	0	0	0
after 72 hours	1	0	0	0	0	0
mean score 24-72 hours	1	0	0.7	0	0	0.3

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

This test substance is a slight irritant following a single four-hour application to rabbit skin. The substance does not meet the criteria for classification.

Executive summary:

A group of 3 female rabbits received a single four-hour application of 500 mg of the test substance to the shorn flank. The animals were assessed for up to 4 days for any signs of skin irritation.

Very slight erythema was seen in all three animals approximately 1 hour after decontamination and in two animals for the following 2 or 3 days. Very slight oedema was seen in all three animals approximately 1 hour after decontamination and in one animal for 1 day. All signs of irritation had completely resolved 4 days after application.

The test substance is a slight irritant following a single four-hour application to rabbit 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:

11 September - 28 September 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, no restrictions, fully adequate for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adults
- Weight at study initiation: 2553-3045 g
- Housing: individually, in cages suitable for rabbits of this strain and weight range expected during the course of the study
- Diet: STANRAB SQC ad libitum
- Water: mains water ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17±2°C
- Humidity: 40-81%
- Air changes: approximately 25-30 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 13 September 1995 To: 28 September 1995

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Approximately 100 mg

Duration of treatment / exposure:

Single dose

Observation period (in vivo):

4 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eyes were not washed.

SCORING SYSTEM: an assessment of initial pain was made using a six-point scale. The Draize scale (Draize JH (1959) Third printing, 1975. 'Dermal Toxicity' in 'Appraisal of the safety of chemicals in food, drugs and cosmetics'. Association of Food and Drug Officials of the US, pp46-59) was used to assess the grade of ocular reaction approximately one hour and 1, 2, 3 and (for one animal) 4 days after application.

TOOL USED TO ASSESS SCORE: fluorescein staining was used at all readings from day 1 after application.

A modified form of the Kay and Calandra system (Kay JH and Calandra JC 1962, Interpretation of eye irritation tests. J Soc Cosmet Chem 13, pp281-289) was used to interpret and classify the numerical scores.

Irritation parameter:

other: initial pain

Basis:

mean

Time point:

other: immediately after application

Remarks on result:

other: none or slight initial pain (class 0-2 on a 0-5 scale)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1.2 hrs, 1, 2, 3 and (for one animal) 4 days

Score:

0

Max. score:

80

Remarks on result:

other: no corneal effects in any animal

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1.2 hrs, 1, 2, 3 and (for one animal) 4 days

Score:

0

Max. score:

10

Remarks on result:

other: no effects in the iris in any animal

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1.2 hrs

Score:

9.3

Max. score:

20

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: day 1

Score:

2

Max. score:

20

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: day 2

Score:

2

Max. score:

20

Reversibility:

fully reversible within: 3 days

Irritation parameter:

cornea opacity score

Basis:

animal: #15

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

no change at any timepoint

Irritation parameter:

cornea opacity score

Basis:

animal: #12

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

no change at any timepoint

Irritation parameter:

cornea opacity score

Basis:

animal: #13

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

No change at any timepoint

Irritation parameter:

iris score

Basis:

animal: #15

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

no change at any timepoint

Irritation parameter:

iris score

Basis:

animal: #12

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

No change at any timepoint

Irritation parameter:

iris score

Basis:

animal: #13

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

No change at any timepoint

Irritation parameter:

conjunctivae score

Basis:

animal: #15

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal: #12

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal: #13

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal: #15

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

No change at any timepoint

Irritation parameter:

chemosis score

Basis:

animal: #12

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

No change at any timepoint

Irritation parameter:

chemosis score

Basis:

animal: #13

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks:

No change at any timepoint

Approximately 1/3 or 1/2 of the test substance was displaced from the conjunctival sac of two animals immediately after application.

Application into the eye caused no or slight pain (class 0 -2 on a 0 -5 scale). There were no corneal or iridial effects. Conjunctival effects, in all animals for up to 2 days, consisted of slight or moderate redness, slight or mild chemosis and a slight or moderate discharge. In addition, two animals had a slight mucoid discharge. All signs of irritation had completely resolved 3 days after application.

Eye irritation scores of according to the Draize scheme

Time		Cornea			Iris			Conjunctiva
								Redness			Chemosis
Animal number		15	12	13	15	12	13	15	12	13	15	12	13
after 1 hour		0	0	0	0	0	0	2	1	2	1	1	2
after 24 hours		0	0	0	0	0	0	1	1	1	0	0	0
after 48 hours		0	0	0	0	0	0	1	1	1	0	0	0
after 72 hours		0	0	0	0	0	0	0	0	0	0	0	0
mean scores 24-72 hours		0	0	0	0	0	0	0.7	0.7	0.7	0	0	0

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance is a mild irritant (class 4 on a 1-8 scale) to the rabbit eye. The substance does not meet the criteria for classification.

Executive summary:

The test substance (100 mg) was applied into one eye of each of three rabbits and an assessment of initial pain was made. The eyes were examined for up to 4 days, to assess the grade of ocular reaction.

Application into the eye caused no or slight pain (class 0 -2 on a 0 -5 scale). There were no corneal or iridial effects. Conjunctival effects were seen in all animals for up to 2 days. All signs of irritation had completely resolved 3 days after application.

The test substance is a mild irritant (class 4 on a 1-8 scale) to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

A group of 3 female rabbits received a single four-hour application of 500 mg of the test substance to the shorn flank. The animals were assessed for up to 4 days for any signs of skin irritation. Very slight erythema was seen in all three animals approximately 1 hour after decontamination and in two animals for the following 2 or 3 days. Very slight oedema was seen in all three animals approximately 1 hour after decontamination and in one animal for 1 day. All signs of irritation had completely resolved 4 days after application. The test substance is a slight irritant following a single four-hour application to rabbit skin.

Eye Irritation

The test substance (100 mg) was applied into one eye of each of three rabbits and an assessment of initial pain was made. The eyes were examined for up to 4 days, to assess the grade of ocular reaction. Application into the eye caused no or slight pain (class 0 -2 on a 0 -5 scale). There were no corneal or iridial effects. Conjunctival effects were seen in all animals for up to 2 days. All signs of irritation had completely resolved 3 days after application.The test substance is a mild irritant (class 4 on a 1-8 scale) to the rabbit eye.

Justification for selection of skin irritation / corrosion endpoint:
Only one study was available for skin irritation. The available data are considered to be relevant, reliable and adequate for risk assessment, classification and labelling of the substance.

Justification for selection of eye irritation endpoint:
Only one study was available for eye irritation. The available data are considered to be relevant, reliable and adequate for risk assessment, classification and labelling of the substance.

Justification for classification or non-classification

Skin irritation/corrosion

In an OECD 404 compliant study the substance is slightly irritating when assessed according to the Draize scheme. It does not meet the criteria for classification as irritating to the skin according to Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.2.2

Eye irritation

In an OECD 405 compliant study the substance is a mild irritant when assessed using a modified form of the Kay and Calandra system. It does not meet the criteria for classification as irritant to the eye according to Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.2