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Administrative data

Description of key information

The available data suggest that amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) is irritating to skin and highly irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
January to February 18 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD Guideline 404 in compliance with GLP.
Justification for data waiving:
other:
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
other: EU Method B.6 (Skin Sensitization)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
other: Kleinrusse Chbb
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HM/Fa. Thomae, Germany
- Average weight at study initiation: 2,192 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 hours
Observation period:
21 days
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.

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.

Other effects:
None

None

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Draize scoring system
Conclusions:
Under the test conditions, amides, C12-18(even-numbered) and C18(unsatd.), N,N-bis(hydroxyethyl) was considered to be irritating to rabbit skin.
Executive summary:

A study was conducted to assess the skin irritation potential of  amides, C12-18(even-numbered) and C18(unsatd.), N,N-bis(hydroxyethyl) to rabbit skin according to OECD Guideline 404 and EU Method B.6.

 

The shaved skin of 5 rabbits was exposed to the undiluted test substance using occlusive patches for 4 hours. The skin was then observed for effects (scoring according to the Draize system) for 21 d after patch removal. Exposure to undiluted amides, C12-18(even-numbered) and C18(unsatd.), N,N-bis(hydroxyethyl) caused light to moderate erythema and light oedema immediately after removal of the patch. The reactions intensified until the 72 hours 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 test conditions, amides, C12-18(even-numbered) and C18(unsatd.), N,N-bis(hydroxyethyl) was considered to be irritating to rabbit skin.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
October 31, 1986 to November 25, 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD Guideline 405 and EU Method B.5. in compliance with GLP
Justification for data waiving:
other:
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
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)).
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.
Other effects:
None

None

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, amides, C12-18(even-numbered) and C18(unsatd.), N,N-bis(hydroxyethyl) was considered to be highly irritating to the rabbit eye.
Executive summary:

A study was performed to assess the eye irritation potential of amides, C12-18(even-numbered) and C18(unsatd.), N,N-bis(hydroxyethyl) according to OECD 405 and EU guideline 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 test conditions, amides, C12-18(even-numbered) and C18(unsatd.), N,N-bis(hydroxyethyl) was considered to be highly irritating to the rabbit eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

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 structurally similar amides, C12-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl) to rabbit skin according to OECD guideline 404. The shaved skin of 5 rabbits was exposed to the undiluted test substance using occlusive patches for 4 hours. The skin was then observed for effects (scored according to the Draize system) for 21 days after patch removal. Exposure to undilutedtest substancecaused light to moderate erythema and light oedema immediately after removal of the patch. The reactions intensified until the 72 hours 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 days. The acute reactions were no longer visible after 14 days. Based on these results, amides, C12-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl)wasconsidered irritating to skin (Kästner, 1986).

A study conducted according to OECD guideline 404 was performed to assess the irritation potential of amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl)to rabbits. The test substance was applied undiluted to rabbit skin under an occlusive bandage for 4 hours, then washed with warm water. Animals were observed for 25 days. Strong erythema and oedema were observed in all animals. Slow recovery occurred, under thick scabs. After 25 days, 2/3 animals had fully recovered. In the third animal, scabs were falling away. The overall irritation index was 7 out of 8 which can be considered as highly irritating to rabbit skin (Mürmann P, 1990a).

Eye irritation

A study was performed to assess the eye irritation potential of the structurally similar amides, C12-18 (even-numbered) and C18 unsatd., N,N-bis(hydroxyethyl).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 hours, then 7, 10, 14, 17 and 21 days, eyes were analysed for reactions based on the Draize appraisal 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 day observation period. Amides, C12-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl) wasconsidered highly irritating to eyes (Kästner, 1987).

In another OECD guideline 405 study, the irritation potential of amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl)to rabbit eye was investigated. The test substance was applied neat to the left eye of three rabbits. Two out of three animals showed opacity of the cornea as well as slight corneal reddening and circumcorneal injection. These effects were reversible within 10 days. In all animals, moderate to strong erythema and slight swelling of the conjunctivae were noted. This was reversible within 13 days. The overall irritation index was 34.9/110. The results obtained in this study suggest thatamides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl)is a moderate eye irritant (Mürmann P, 1990b).

 


Justification for selection of skin irritation / corrosion endpoint:
Good quality KL2 study using a read-across test substance with higher purity

Justification for selection of eye irritation endpoint:
Good quality KL2 study using a read-across test substance with higher purity

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin

The key in vivo skin irritation study (reliable without restrictions ; GLP compliant and the appropriate number of animals used) conducted with the read-across substance amides, C12-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl) demonstrated that a 4 hour occlusive exposure was irritating to skin. A study conducted with the substance itself showed thatamides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) was highly irritating to skin, however this study was performed without GLP and the number of animals tested was lower than recommended by OECD guideline 404. On the basis of the key study, the substance was therefore classified as Xi;R38 according to EC criteria (67/548/EEC) and skin irritation category 2; H315 – causes skin irritation (hazard statement) according to CLP criteria (EC 1272/2008).

Eye

The available in vivo eye irritation studies suggest that amides, C12-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl) is highly irritating to eyes. The key study indicates irreversible eye effects in one animal. In the supporting study, positive responses (corneal opacity, conjunctival redness and oedema) were seen in 2/3 animals which reversed within 21 days. Since the effects seen in the key study (considered reliable without restrictions) were severe, Xi; R41 classification is warranted according to EC criteria (67/548/EEC) and classification as irreversible effects on the eye category 1; H318 – causes serious eye damage (hazard statement) is warranted according to CLP criteria (EC 1272/2008)