2,2'-[(4-methylphenyl)imino]bisethanol

Endpoint summary

Description of key information

Skin irritation (in vivo): not irritant

Eye irritation (in vivo): severe eye damage

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:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16. Section 1500.41

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Lippische Versuchstierzucht, Germany
- Weight at study initiation: 2.4 kg
- Housing: Animals were individually housed.
- Diet: Mümmel z (ssniff, Soest, Germany), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 7 -14 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Remarks:

left flank of each animal was intact; right flank of each animal was abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

24 h
Reading time points: approximately 30 min after removal of the test substance (24-h reading time point) and 48 (72-h reading time point) and 72 h after start of the experiment

Observation period:

8 d

Number of animals:

6 males

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap: The treated skin was covered with a gauze, held in place with a PVC foil and Leukoflex® adhesive plaster. The whole body of the animal was wrapped with elastic Eloflex® during the exposure period.

SCORING SYSTEM:
- Method of calculation: Draize Scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

individual score of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal: #2, #3 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal: #5 and #6

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritant / corrosive response data:

The dermal application of the test substance did not result in erythema in any of the animals tested at any observation time point. Thus, the erythema score for all animals was 0 over 24, 48 and 72 h, respectively. 1/6 animals showed a slight edema 24 h (grade 2) and 72 h (grade 1) after the test substance application, respectively, which was fully reversible within 8 days, resulting in an edema score of 1.66 over 24, 48 and 72 h, respectively. 2/6 animals showed slight edema (grade 1) at the 24-h reading time point. At the 72-h reading time point the dermal effect was completely reversible, resulting in an edema score of 0.66 for both animals over 24, 48 and 72 h, respectively. In 3/6 animals the dermal application of the test substance did not result in edema in at any observation time point.

Table 1. Results of skin irritation study

Observation time	Rabbit no.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
24 h	0	2	0	0	0	0	0	0	0	1	0	1
48 h	No experimental data available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption)
72 h	0	1	0	0	0	0	0	0	0	0	0	0

Table 2. Calculation of mean scores

	Rabbit no.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
Mean value 24 + 48 + 72 h*	0,00	1,67	0,00	0,00	0,00	0,00	0,00	0,00	0	0,67	0,00	0,67

*No 48 h data are available: for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h).

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

Based on the results of this study, no skin irritating properties were determined in rabbits after dermal application of the test substance.

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:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 1500.42

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 2017

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Lippische Versuchstierzucht, Germany
- Weight at study initiation: 2.4 kg
- Housing: Animals were individually housed.
- Diet: Mümmel z (ssniff, Soest, Germany), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 7 -14 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:

72 h

Observation period (in vivo):

8 d
Reading time points: 24, 48 and 72 h and 8 d

Number of animals or in vitro replicates:

6 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No washing was performed

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3, #4 and #5

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

animal: #1, #2, #5 and #6

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

animal: #3 and #4

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

not fully reversible within: 8 days in animal #2

Irritation parameter:

conjunctivae score

Basis:

animal: #4 and #5

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 8 days in animal #2

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal: #4 and #5

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritant / corrosive response data:

24 h after exposure, chemosis (grade 1 or 2) was observed in all animals, which did not disappear in 5/6 animals up to the end of the observation period. The chemosis scores were 1.0 (2/6 animals), 1.3 (1/6 animals), 1.7 (2/6 animals) and 2.0 (1/6 animals) over 24, 48 and 72 h, respectively. All 6 animals showed redness of the conjunctivae (grade 1 or 2), which did not disappear in 5/6 animals up to the end of the observation period. The conjunctivae scores were 1.0 (3/6 animals), 1.7 (2/6 animals) and 2.0 (1/6 animals) over 24, 48 and 72 h, respectively. Adverse effects on the cornea (score 1 or 2) and the iris (score 1 or 2) were observed in all animals, which were not completely reversible up to the end of the observation period. The cornea opacity score of 1.0 and 1.3 was determined for 5/6 and 1/6 animals over 24, 48 and 72 h, respectively. The iris score was 1.3 for 4/6 animals and 1.0 for 2/6 animals over 24, 48 and 72 h, respectively.

Table 1. Results of eye irritation study

Rabbit #	Time	conjunctivae		iris	cornea
		redness	swelling
1	24 h	1	1	2	1
	48 h	1	1	1	1
	72 h	1	1	1	1
	average 24/48/72 h	1	1	1.3	1
	8 days	0	0	1	1
2	24 h	1	1	2	1
	48 h	1	1	1	1
	72 h	1	1	1	1
	average 24/48/72 h	1	1	1.3	1
	8 days	1	1	1	1
3	24 h	1	2	1	1
	48 h	1	1	1	1
	72 h	1	1	1	1
	average 24/48/72 h	1	1.3	1	1
	8 days	0	1	1	1
4	24 h	2	2	1	1
	48 h	2	2	1	1
	72 h	1	1	1	1
	average 24/48/72 h	1.7	1.7	1	1
	8 days	1	1	1	1
5	24 h	2	2	1	1
	48 h	2	2	1	1
	72 h	1	1	1	1
	average 24/48/72 h	1.7	1.7	1	1
	8 days	1	1	1	1
6	24 h	2	2	1	2
	48 h	2	2	1	1
	72 h	2	2	1	1
	average 24/48/72 h	2	2	1	1.3
	8 days	1	1	1	1
	Time [h]	conjunctivae		iris	cornea
		redness	swelling
Mean of 6 animals	24	1.5	1.67	1.33	1.17
	48	1.5	1.5	1	1
	72	1.17	1.17	1	1
	24+48+72	1.39	1.44	1.11	1.06

Interpretation of results:

other: CLP/EU GHS Category 1, H318 according to Regulation (EC) No. 1272/2008.

Conclusions:

The observation period in the conducted study was shorter than recommended in the recent OECD 405. Since the observed effects were not completely reversible up to the end of the observation period of 8 days, the test substance was considered to have a corrosive potential towards the eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

An in vivo skin irritation study according to Code of Federal Regulations, Title 16, Section 1500.41 was available and used to assess the skin irritation potential of the target substance N,N-Dihydroxyethyl-p-toluidine (CAS 3077-12-1) (Fraunhofer Institut, 1981a). In this study 0.5 mL of the unchanged test substance was applied on the dorsal back each of 6 NZW rabbits under occlusive conditions for 24 h. The animals were observed approximately 30 min after removal of the test substance (24-h reading time point) and 48 (72-h reading time point) and 72 h after start of the experiment. Scoring of skin findings was done according to the Draize scorring system. The dermal application of the test substance did not result in erythema in any of the animals tested at any observation time point. Thus, the erythema score for all animals was 0 over 24, 48 and 72 h, respectively. 1/6 animals showed a slight edema 24 h (grade 2) and 72 h (grade 1) after the test substance application, respectively, which was fully reversible within 8 days, resulting in an edema score of 1.66 over 24, 48 and 72 h, respectively. 2/6 animals showed slight edema (grade 1) at the 24-h reading time point. At the 72-h reading time point the dermal effect was completely reversible, resulting in an edema score of 0.66 for both animals over 24, 48 and 72 h, respectively. In 3/6 animals the dermal application of the test substance did not result in edema in at any observation time point. Based on these results, the test substance was not considered to show an irritation potential to the skin.

Eye

To evaluate the irritation potential towards the eyes of N,N-Dihydroxyethyl-p-toluidine (CAS 3077-12-1), an in vivo study performed according to Code of Federal Regulations, Title 16, Section 1500.42 was evaluated. In this study, 0.1 mL (unchanged) of the test substance (CAS 3077-12-1) was instilled into the eyes of 6 male white rabbits (NZW) (Fraunhofer Institut, 1981b). The treated eyes remained unwashed and were observed 24, 48 and 72 h and 8 d after treatment. Scoring of eye findings was done according to the Draize scoring system. 24 h after exposure, chemosis (grade 1 or 2) was observed in all animals, which did not disappear in 5/6 animals up to the end of the observation period. The chemosis scores were 1.0 (2/6 animals), 1.3 (1/6 animals), 1.7 (2/6 animals) and 2.0 (1/6 animals) over 24, 48 and 72 h, respectively. All 6 animals showed redness of the conjunctivae (grade 1 or 2), which did not disappear in 5/6 animals up to the end of the observation period. The conjunctivae scores were 1.0 (3/6 animals), 1.7 (2/6 animals) and 2.0 (1/6 animals) over 24, 48 and 72 h, respectively. Adverse effects on the cornea (score 1 or 2) and the iris (score 1 or 2) were observed in all animals, which were not completely reversible up to the end of the observation period. The cornea opacity score of 1.0 and 1.3 was determined for 5/6 and 1/6 animals over 24, 48 and 72 h, respectively. The iris score was 1.3 for 4/6 animals and 1.0 for 2/6 animals over 24, 48 and 72 h, respectively. Based on the results of the conducted study, N,N-Dihydroxyethyl-p-toluidine (CAS 3077-12-1) is considered to reveal severe eye damage.

The available data with the registration substance regarding skin irritation/corrosion do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification. However, the available data regarding eye irritation meet the classification criteria for Eye Damage 1, H318 according to Regulation (EC) 1272/2008.

Justification for classification or non-classification

The available target substance data regarding skin irritation/corrosion do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification. The available target substance data regarding eye irritation meet the classification criteria for Eye Damage 1, H318 according to Regulation (EC) 1272/2008.