N,N-bis(2-hydroxyethyl)dodecanamide

Endpoint summary

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:

March 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

other: the U.S. Code of Federal Hazardous Substance Act (U. S. Federal Register, 1973, Vol. 38, No. 187, Section 1500:41 and revised annually in the U.S. Code of Federal Regulations, Title 16, Part 1500, Subchapter C-Federal Hazardous Substances Act Regulations)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: From recognized breeders whose standards were acceptable to the animal welfare department of toxicology laboratories
- Housing: Grid bottomed metal cages
- Diet (e.g. ad libitum): Antibiotic free pelleted rabbit diet (Product Ref. 680 Dalgety Spillers Limited), ad limitum
- Water (e.g. ad libitum): From holding tanks were available ad limitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 9-18 °C
- Humidity (%): 60-80%
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h day

Type of coverage:

occlusive

Preparation of test site:

other: abraded and intact

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL aliquots of the undiluted test substance.

Duration of treatment / exposure:

24 h

Observation period:

24 and 72 h from dosing.

Number of animals:

Six

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm square; the dorsal surfaces of the trunk were clipped free of hair using an Oster Model A2 clipper with Angra blade. Immediately before dosing the left flank of the animals' back was lightly abraded in a criss-cross pattern using the point of a 25 x 0.6mm sterile disposable hypodermic needle. The abrasions were sufficiently deep to damage the stratum corneum but not to penetrate the dermis. The skin of the right flank remained intact.

- Type of wrap if used: Yes, 2.5 cm square surgical lint pads (2.5 cm square) attached to a length of 5 cm wide ‘sleek’ plastic adhesive wrapping was placed on the intact and abraded skin. Then the trunk of the animal was encircled with a length of 'elastoplast' elastic adhesive bandage 7.5 cm wide.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, by gentle wiping with cotton wool soaked in warm water.
- Time after start of exposure: 24 h

SCORING SYSTEM: Erythema, eschar formation and oedema were evaluated numerically as described in the attached background document. The derived primary irritation scores were then evaluated as per the definitions provided in the U.S. Federal hazardous substances act as well as the Draize system of classification.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 h and 72 h (abraded + intact)

Score:

2

Max. score:

8

Reversibility:

not reversible

Remarks:

at 72 h

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

ca. 0.5

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 0.33

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

ca. 1.67 - ca. 1.83

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 1.33 - ca. 1.5

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Well defined erythema of the skin was observed at five abraded sites and four intact skin sites after 24 hour dosing period. The remaining abraded sites and two intact sites exhibited very slight erythema. Slight oedema was also observed at this time at both skin sites in one rabbit and very slight oedema at both skin sites in another rabbit. The severity of this irritant response showed some decline with time (but not reversible within 72 h) and the numerical values given to the irritation observed during the course of the study, when averaged for the group of six rabbits, were 6.3 for erythema and 1.7 for oedema giving a primary irritation score of 2.0 (max. 8). For further details on results, refer to the table under the ' attached backgroud material'.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the study conditions, the test substance was a mild to moderate irritant according to Draize classification system and non irritating according to the U.S. Federal hazardous substances act. It is considered to be Category 2 irritant according to EU CLP classification as the mean average erythema and/or edema score was ≥2.3.

Executive summary:

A study was conducted to assess the skin irritation potential of the test substance, C12 DEA, in New Zealand White rabbits according to the U.S. Code of Federal Hazardous Substance Act, in compliance with GLP. The substance was applied undiluted to shaved rabbit dorsal abraded and intact skin under an occlusive bandage for 24 h. Well-defined erythema of the skin was observed at five abraded sites and four intact skin sites 24 h after treatment. The remaining abraded site and two intact sites exhibited slight erythema. Slight oedema was also observed at this time at both skin sites in one rabbit and slight oedema at both skin sites in another rabbit. The severity of response declined somewhat over time (but was not reversible within 72 h of treatment). The average numerical scores for the group of six rabbits were 6.3 for erythema and 1.7 for oedema, giving a primary irritation score of 2.0 (max. 8). Under the study conditions, the test substance was irritating to rabbit skin according to the Draize classification system (Nicholson, 1985).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

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:

mean

Time point:

24/48/72 h

Score:

ca. 1.25

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0.25

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.58

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.17

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.92

Max. score:

3

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 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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A study was conducted to assess the skin irritation potential of the test substance, C12 DEA, in New Zealand White rabbits according to the U.S. Code of Federal Hazardous Substance Act, in compliance with GLP. The substance was applied undiluted to shaved rabbit dorsal abraded and intact skin under an occlusive bandage for 24 h. Well-defined erythema of the skin was observed at five abraded sites and four intact skin sites 24 h after treatment. The remaining abraded site and two intact sites exhibited slight erythema. Slight oedema was also observed at this time at both skin sites in one rabbit and slight oedema at both skin sites in another rabbit. The severity of response declined somewhat over time (but was not reversible within 72 h of treatment). The average numerical scores for the group of six rabbits were 6.3 for erythema and 1.7 for oedema, giving a primary irritation score of 2.0 (max. 8). Under the study conditions, the test substance was irritating to rabbit skin according to the Draize classification system (Nicholson, 1985).

Eye irritation

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 produced irreversible damage to the rabbit eye (Kästner, 1987).

Justification for classification or non-classification

Skin

The available in vivo skin irritation studies, demonstrated a clear irritation response following occlusive exposure to C12 DEA for 4 or 24 hours. The data support a classification 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 is classified as Eye Damage 1 - H318 (causes serious eye damage) according to CLP (EC 1272/2008) criteria.