Amides, C8-18 (even numbered) and C18-unsatd., N,N-bis(hydroxyethyl)

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

January to February 18, 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Please refer to Section 13 of the dataset for the read across justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EU Method B.6 (Skin Sensitization)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: Kleinrusse Chbb

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HM/Fa. Thomae, Germany
- Average weight at study initiation: 2192 g

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Undiluted

Duration of treatment / exposure:

4 h

Observation period:

21 d

Number of animals:

5

Details on study design:

24 h before test start, the right flank of the rabbits was shaved and the skin inspected for intactness. Only rabbits with intact skin were used for the study. 0.5 mL of the undiluted test substance were applied to a 2.5 x 2.5 cm patch and placed onto the shaved skin, then securely fastened with a larger plastic sheet to provide an occlusive dressing. After 4 h, the dressing was removed and the skin was scored for reddening (erythema) and swelling (oedema) after 1, 24, 48 and 72 h, then 7, 10, 14, 17 and 21 d according to the Draize system.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.8

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.6

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.8

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3.6

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3.8

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

erythema score

Basis:

animal: 1-5

Time point:

7 d

Score:

>= 1 - <= 4

Max. score:

4

Reversibility:

fully reversible within: 21 d

Irritation parameter:

erythema score

Basis:

animal: 1-5

Time point:

21 d

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 21 d

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.16

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3.16

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

animal: 1-5

Time point:

7 d

Score:

>= 1 - <= 2

Max. score:

4

Reversibility:

fully reversible within: 21 d

Irritation parameter:

edema score

Basis:

animal: 1-5

Time point:

21 d

Score:

0

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritant / corrosive response data:

Light to moderate erythema and light oedema were observed on the treated skin after removal of the patch. The reactions intensified until the 72 h observation time point when strong erythema and moderate to strong oedema, as well as eschar formation were seen. No or only traces of the eschar were left in 1/5 and 4/5 animals, respectively, after 21 d. The acute reactions were no longer visible after 14 d.

None.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the study conditions, the test substance was considered to be irritating to rabbit skin.

Executive summary:

A study was conducted to assess the skin irritation potential of the read across substance, C12-18 and C18-unsatd. DEA, to rabbit skin according to OECD Guideline 404 and EU Method B.6, in compliance with GLP. The shaved skin of 5 rabbits was exposed to the undiluted test substance using occlusive patches for 4 h. The skin was then observed for effects (scoring according to the Draize system) for 21 d after patch removal. Exposure to undiluted test substance caused light to moderate erythema and light oedema immediately after removal of the patch. The reactions intensified until the 72 h observation time point when strong erythema and moderate to strong oedema, as well as eschar formation were seen. No or only traces of the eschar were left in 1/5 and 4/5 animals, respectively, after 21 d. The acute reactions were no longer visible after 14 d. Under the study conditions, the test substance was considered to be irritating to rabbit skin (Kästner, 1986).

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

October 31, 1986 to November 25, 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Refer to the section 13 for details on the category justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: Kleinrusse chbb

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- 4 males
- Source: HM/Fa. Thomae, Germany
- Average bodyweight at test start: 2,630 g

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.01 ml (low volume method)

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

21 d

Number of animals or in vitro replicates:

4

Details on study design:

0.01 mL test substance carefully applied in undiluted form into the lower lid of the right eye of the test animals. The other eye remained untreated. After 1, 6, 24, 48 and 72 h, then 7, 10, 14, 17 and 21 d, eyes were analysed for reaction based on the Draize appraisal method (J.H. Draize, Appraisal of the safety of chemicals in foods, drugs and cosmetics. Ass. of Food and Drug Officials of the US, pp 49-52 (1959)).

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 21 days

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 21 days

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 21 days

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

other: exudation

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

other: exudation

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

other: exudation

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

other: exudation

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

On the cornea, slight to moderate opacity was observed in all treated eyes. The reaction was irreversible. Irreversible effects were also noted in the iris of one animal. Finally, all animals presented moderate to severe redness, chemosis, and/or exudation (sometimes infiltrated with blood) of the conjunctivae, which did not entirely disappear by the end of the 21 d observation period.

None.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Under the study conditions, the test substance was highly irritating to the rabbit eye.

Executive summary:

A study was performed to assess the eye irritation potential of the read across substance, C12 -18 and C18 -unsatd. DEA, according to OECD Guideline 405 and EU Method B.5, in compliance with GLP. Four rabbits received 0.01 mL of an undiluted solution in one eye. The other eye remained untreated. After 1, 6, 24, 48 and 72 h, then 7, 10, 14, 17 and 21 d, eyes were analysed for reaction based on the Draize scoring method. On the cornea, slight to moderate opacity was observed in all treated eyes. The reaction was irreversible. Irreversible effects were also noted in the iris of one animal. Finally, all animals presented moderate to severe redness, chemosis, and/or exudation (sometimes infiltrated with blood) of the conjunctivae, which did not entirely disappear by the end of the 21 d observation period. Under the study conditions, the test substance was highly irritating to the rabbit eye (Kästner, 1987).

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

A study was conducted to assess the skin irritation potential of the read across substance, C12-18 and C18-unsatd. DEA, to rabbit skin according to OECD Guideline 404 and EU Method B.6, in compliance with GLP. The shaved skin of 5 rabbits was exposed to the undiluted test substance using occlusive patches for 4 h. The skin was then observed for effects (scoring according to the Draize system) for 21 d after patch removal. Exposure to undiluted test substance caused light to moderate erythema and light oedema immediately after removal of the patch. The reactions intensified until the 72 h observation time point when strong erythema and moderate to strong oedema, as well as eschar formation were seen. No or only traces of the eschar were left in 1/5 and 4/5 animals, respectively, after 21 d. The acute reactions were no longer visible after 14 d. Under the study conditions, the test substance was considered to be irritating to rabbit skin (Kästner, 1986).

Eye

A study was performed to assess the eye irritation potential of read across substance, C12-18 and C18-unsatd. DEA, according to OECD Guideline 405 and EU Method B.5, in compliance with GLP. Four rabbits received 0.01 mL of an undiluted solution in one eye. The other eye remained untreated. After 1, 6, 24, 48 and 72 h, then 7, 10, 14, 17 and 21 d, eyes were analysed for reaction based on the Draize scoring method. On the cornea, slight to moderate opacity was observed in all treated eyes. The reaction was irreversible. Irreversible effects were also noted in the iris of one animal. Finally, all animals presented moderate to severe redness, chemosis, and/or exudation (sometimes infiltrated with blood) of the conjunctivae, which did not entirely disappear by the end of the 21 d observation period. Under the study conditions, the test substance was highly irritating to the rabbit eye (Kästner, 1987).

Justification for classification or non-classification

Skin

The key in vivo skin irritation study conducted with the read-across substance, C12-18 and C18-unsatd. DEA, demonstrated that a 4 h occlusive exposure was irritating to skin. On the basis of this study, the substance was classified as Skin Irrit. 2 - H315 (causes skin irritation) according to CLP (EC 1272/2008) criteria.

Eye

The key in vivo eye irritation study suggests that the read across substance, C12-18 and C18-unsatd. DEA, is highly irritating to eyes, with irreversible eye effects in one animal. Since the effects seen in this study were severe, the substance was classified as Eye Damage 1 - H318 (causes serious eye damage) according to CLP (EC 1272/2008) criteria.