N,N-bis(2-hydroxyethyl)undec-10-enamide

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From April 05, 2017 to April 07, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Remarks:

artificial three-dimensional model of human skin

Source species:

human

Cell type:

non-transformed keratinocytes

Justification for test system used:

This test method provides an in vitro procedure that, depending on information requirements, may allow determining the cytotoxic potency and skin irritancy of test substances as a stand-alone replacement test within a testing strategy, in a weight of evidence approach.

Vehicle:

unchanged (no vehicle)

Details on test system:

Three tissues were used for each treatment and concurrent control groups. The optical density (OD) was determined by using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Thiazolyl blue) reduction assay and expressed as relative percentage of viability of the negative control-treated tissues.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

The test substance was applied as liquid test substance topically undiluted to the model skin surface.

Duration of treatment / exposure:

60 min

Duration of post-treatment incubation (if applicable):

42 h

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Remarks:

cells

Run / experiment:

MTT test (mean viablility compared to the negative control - %)

Value:

6.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: prediction of irritation

Other effects / acceptance of results:

- The mean viability of cells exposed to the test substance was 6.5% of the negative controls and, hence, was below the cut-off percentage cell viability value that distinguishes irritant from non-irritant test substances of ≤50%. The test substance was considered to be cytotoxic and predicted to be irritant to skin in accordance with UN GHS category 1 or 2 (H314 or H315).
- The mean optical density (OD) of 3 negative control tissues was 1.314 and was well within the acceptable range of ≥ 1.0 to ≤ 2.5. The viability of cells treated with the positive reference substance, 5% SDS, was 6.9% of the negative control and fulfilled the acceptance criterion of ≤20%.
- The standard deviation of all triplicates determined was below the limit of acceptance of 18%. Hence, all acceptance criteria were fulfilled.

None.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the study conditions, the test substance was predicted to be a skin irritant.

Executive summary:

A study was conducted to determine the in vitro skin irritation potential of the test substance, C11-unsatd. DEA, according to OECD Guideline 439 and EU Method B.46 (three-dimensional reconstructed human epidermis model EpiDermTM), in compliance with GLP. The test substance was applied for 60 min in liquid form topically, undiluted, to the model skin surface (3 replicates). This was followed by a 42 h post incubation period. The optical density (OD) was determined by using the MTT reduction assay and expressed as relative percentage of viability of the negative control-treated tissues. The mean viability of cells exposed to the test substance was 6.5% of the negative controls and, hence, was below the cut-off percentage cell viability value that distinguishes irritant from non-irritant test substances of ≤50%. The test substance was considered to be cytotoxic and predicted to be irritant to skin in accordance with UN GHS classification. The mean optical density (OD) of 3 negative control tissues was 1.314 and well within the acceptable range of ≥1.0 to ≤2.5. The viability of cells treated with the positive reference substance, 5% SDS, was 6.9% of the negative control and fulfilled the acceptance criterion of ≤ 20%. The standard deviation of all triplicates determined was below the limit of acceptance of 18%. Hence, all acceptance criteria were fulfilled. Under the study conditions, the test substance was predicted to be a skin irritant (Spruth, 2017).

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From May 22, 2017 to May 31, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Remarks:

three-dimensional model of human skin EpiDerm

Source species:

human

Cell type:

non-transformed keratinocytes

Vehicle:

unchanged (no vehicle)

Details on test system:

Model used: EpiDerm™ (EPI-200-SCT, Lot no. 25815) MatTek In Vitro Life Science Laboratories, Bratislava, Slovak Republic.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

50 μL of the supplied test substance were applied to the skin model with a surface area of 0.63 cm2 to uniformly cover the skin surface.

Duration of treatment / exposure:

The test substance and the reference substance were applied to the skin model surface at two exposure periods of 3 minutes or 1 hour.

Number of replicates:

Two tissues were used for each treatment and concurrent control groups.

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 min

Value:

88.9

Negative controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1 h

Value:

32

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

The mean optical density (OD) of the negative control of 2 tissues was 1.304 (3 min exposure) or 1.472 (1 h exposure) and therefore well within the acceptable range of ≥ 0.8 to ≤ 2.8. The viability of cells treated with the positive control 8 N KOH was 5.3 or 4.4% (3 min or 1 h exposure, respectively) of the negative control and, hence well below the 15% cut-off value at the 1 h exposure. The difference of viability between the two tissue replicates (at 20 – 100% viability) was below the limit of acceptance of 30%. Hence, all acceptance criteria were fulfilled.

None.

Conclusions:

Under the study conditions, the test substance was determiend to be non-corrosive to the skin.

Executive summary:

A study was conducted to determine the skin corrosion potential of the test substance, C11-unsatd. DEA (90.6% active), according to OECD Guideline 431 and EU Method B.40-tris using an artificial three-dimensional model of human skin, in compliance with GLP. Two tissues were used for each treatment and concurrent control groups. The optical density (OD) was determined by using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, thiazolyl blue) reduction assay and expressed as relative percentage of viability of the negative control-treated tissues. 50 μL of the supplied test substance were applied to the skin model with a surface area of 0.63 cm2 to uniformly cover the skin surface. Sterile deionised water was used as the negative control. 8 N KOH was used as the positive reference substance. The test substance and the reference substance were applied to the skin model surface at two exposure periods of 3 min or 1 h. All the acceptance criteria for the test were fulfilled. In comparison to the negative controls, the mean viability of cells exposed to the test substance was 88.9% after a 3 min exposure period and 32.0% after a 1 hour exposure and hence, both values were above the cut-off percentage cell viability distinguishing corrosive from non-corrosive test substances (≥50 and ≥15%, respectively). Under the study conditions, the test substance was determiend to be non-corrosive to the skin (Spruth, 2017).

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:

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.

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 (>95% active), 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). Based on the result of the read across study, the test substance is also expected to have similar eye irritation potential.

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 determine the skin corrosion potential of the test substance, C11-unsatd. DEA (90.6% active), according to OECD Guideline 431 and EU Method B.40-tris using an artificial three-dimensional model of human skin, in compliance with GLP. Two tissues were used for each treatment and concurrent control groups. The optical density (OD) was determined by using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, thiazolyl blue) reduction assay and expressed as relative percentage of viability of the negative control-treated tissues. 50 μL of the supplied test substance were applied to the skin model with a surface area of 0.63 cm2 to uniformly cover the skin surface. Sterile deionised water was used as the negative control. 8 N KOH was used as the positive reference substance. The test substance and the reference substance were applied to the skin model surface at two exposure periods of 3 min or 1 h. All the acceptance criteria for the test were fulfilled. In comparison to the negative controls, the mean viability of cells exposed to the test substance was 88.9% after a 3 min exposure period and 32.0% after a 1 hour exposure and hence, both values were above the cut-off percentage cell viability distinguishing corrosive from non-corrosive test substances (≥50 and ≥15%, respectively). Under the study conditions, the test substance was determiend to be non-corrosive to the skin (Spruth, 2017).

A study was conducted to determine the in vitro skin irritation potential of the test substance, C11-unsatd. DEA, according to OECD Guideline 439 and EU Method B.46 (three-dimensional reconstructed human epidermis model EpiDermTM), in compliance with GLP. The test substance was applied for 60 min in liquid form topically, undiluted, to the model skin surface (3 replicates). This was followed by a 42 h post incubation period. The optical density (OD) was determined by using the MTT reduction assay and expressed as relative percentage of viability of the negative control-treated tissues. The mean viability of cells exposed to the test substance was 6.5% of the negative controls and, hence, was below the cut-off percentage cell viability value that distinguishes irritant from non-irritant test substances of ≤50%. The test substance was considered to be cytotoxic and predicted to be irritant to skin in accordance with UN GHS classification. The mean optical density (OD) of 3 negative control tissues was 1.314 and well within the acceptable range of ≥1.0 to ≤2.5. The viability of cells treated with the positive reference substance, 5% SDS, was 6.9% of the negative control and fulfilled the acceptance criterion of ≤ 20%. The standard deviation of all triplicates determined was below the limit of acceptance of 18%. Hence, all acceptance criteria were fulfilled. Under the study conditions, the test substance was predicted to be a skin irritant (Spruth, 2017).

Eye irritation

A study was performed to assess the eye irritation potential of read across substance, C12-18 and C18-unsatd. DEA (>95% active), 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). Based on the result of the read across study, the test substance is also expected to have similar eye irritation potential.

Justification for classification or non-classification

Skin

Based on the results of the in vitro skin corrosion (OECD 431) and skin irritation (OECD 439) study conducted with C11-unsatd. DEA, the substance warrants classification Skin Irrit. 2 - H315 (causes skin irritation) according to CLP (EC 1272/2008) criteria. 

Eye 

The key in vivo eye irritation study with the read-across substance with C12-18 and C18-unsatd. DEA suggests that the test substance is highly irritating to eyes, with irreversible eye effects in one animal. Since the effects seen in this study were severe, C11-unsatd. DEA was classified as Eye Damage 1 - H318 (causes serious eye damage) according to CLP (EC 1272/2008) criteria.