N-[3-(dimethylamino)propyl]stearamide monoacetate

Endpoint summary

Description of key information

Two valid studies are available for the test item NDPSa (Cas n.: 13282-70-7,other identifier: H-31339). 

 

GHS Cat. 1; primary eye irritation test on rabbits; OECD TG 405; D. Merrill (2014)

 

Not-classified; primary skin irritation in rabbits; OECD TG 404; D. Merrill (2014)

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:

From : 2014-10-28 To: 2014-12-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Received from Robinson Services, Inc. Mocksville, NC on November 5 and November 12, 2014.
- Age at study initiation: Young adult (10 weeks)
- Weight at study initiation: 2383-2702 grams at experimental start.
- Housing:stainless steel caging.
- Diet (e.g. ad libitum): Harlan Teklad Global High Fiber Rabbit Diet® #2031. A designated amount of the diet was available to each rabbit (approximately 150 grams/day).
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum.
- Acclimation period:6 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 40-50%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle.

IN-LIFE DATES: From: To:

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Five-tenths of a gram of the test substance

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : 30-60 minutes and 24, 48 and 72 hours.

Irritation parameter:

erythema score

Basis:

animal: 3501

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 3501

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal: 3502

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 3502

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal: 3503

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 3503

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

There was no skin irritation observed at any treated site during this study.

Individual Skin Irritation Scores

Erythema/Edema 

			Time After Patch Removal
Animal n.	Sex	Immediately after patch removal	30-60 min	24 hrs	48 hrs	72 hrs
3501	F	0/0	0/0	0/0	0/0	0/0
3502	F	n/a	0/0	0/0	0/0	0/0
3503	F	n/a	0/0	0/0	0/0	0/0

N/A – Not Applicable

Interpretation of results:

GHS criteria not met

Conclusions:

In accordance with the provisions of Directive 67/548/EEC amended by COMMISSION DIRECTIVE 2001/59/EC of 6 August 2001, Annex VI, classification is not required.
According to the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Fifth revised edition 2013 under the conditions of this study, classification is not required.

Executive summary:

A primary skin irritation test was conducted with rabbits to determine the potential for H-31339 to produce irritation after a single topical application.

At the request of the Sponsor, the study was conducted in a stepwise manner using a single patch applied initially to one rabbit for 4 hours. Five-tenths of a gram of the test substance was moistened with distilled water and applied to the skin of one healthy rabbit for 4 hours. The dose site was evaluated for dermal irritation by the method of Draize et al.1 (see Table 4) immediately after patch removal and at 30-60 minutes and 24, 48, and 72 hours after patch removal. Since there was no dermal irritation noted at the dose site of this animal, the test was completed on two additional animals, as described above, except the dose sites were not evaluated immediately after patch removal.

There was no skin irritation observed at any treated site during this study.

In accordance with the provisions of Directive 67/548/EEC amended by COMMISSION DIRECTIVE 2001/59/EC of 6 August 2001, Annex VI, classification is not required based on the results of this study.

According to the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Fifth revised edition 2013 under the conditions of this study, classification is not required.

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:

From: 2014-10-28 To: 2014-12-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

The protocol states that all animals will be examined using ophthalmic fluorescein sodium and scored at the 24-hour interval. Due to the severity of opacity and other irritation observed with a white light source, fluorescein was not applied to the eye.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Received from Robinson Services, Inc. Mocksville, NC on November 12, 2014.
- Age at study initiation: Young adult (10 weeks)
- Weight at study initiation: 2235 grams
- Housing: stainless steel caging
- Diet (e.g. ad libitum): Harlan Teklad Global High Fiber Rabbit Diet® 2031. A designated amount of the diet (approximately 150 grams/day) and a Premium Timothy CubeTM (Ontario Dehy Inc.) were available to the rabbit.
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum.
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 41-42
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

IN-LIFE DATES: From: 17 November 2014 To: 18 November 2014

Amount / concentration applied:

TEST MATERIAL

- Concentration (if solution):One-tenth of a milliliter

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

24 hours

Number of animals or in vitro replicates:

1 animal

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): n/a
- Time after start of exposure: 1 hour

TOOL USED TO ASSESS SCORE: white lamp and fluorescein

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hour

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

other: Red Discharge

Basis:

animal #1

Time point:

other: 1 hour

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Remarks:

Study terminated

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Remarks:

Study terminated

Irritation parameter:

conjunctivae score

Remarks:

Chemosis and Discharge

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Remarks:

Study terminated

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Remarks:

Study terminated

Irritant / corrosive response data:

Within one hour following test substance instillation, the treated eye of the animal exhibited conjunctival redness (score of 1), chemosis (score of 3), and discharge (score of 3). By 24 hours, iritis and corneal opacity also developed.

Other effects:

Due to the severity of irritation in the treated eye, the animal was euthanized for humane reasons.

Individual Scores for ocular irritation.

 

Irritation	Score	Hour
	1	24
I.Cornea
Opacity	0	4
Area	4	4
II. Iris
Values	0	2
III. Conjunctivae
Redness	1	2
Chemosis	3	4
Discharge	3	4

Interpretation of results:

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

Conclusions:

In accordance with the provisions of Directive 67/548/EEC amended by COMMISSION DIRECTIVE 2001/59/EC of 6 August 2001, Annex VI, classified as Corrosive.
According to the United Nations Globally Harmonized System of Classification and Labeling of Chemicals (GHS) Fifth revised edition 2013, H-31339 is classified in Category 1.

Executive summary:

A primary eye irritation test was conducted with rabbits to determine the potential for H-31339 to produce irritation from a single instillation via the ocular route.

At the request of the Sponsor, the study was conducted in a stepwise fashion. One-tenth of a milliliter of the test substance was instilled into the conjunctival sac of the right eye of one healthy rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize et al.1 (see Table 4). Due to the severity of irritation noted in the treated eye, the animal was euthanized for humane reasons and the study was terminated.

Within one hour following test substance instillation, the treated eye of the animal exhibited conjunctival redness (score of 1), chemosis (score of 3), and discharge (score of 3). By 24 hours, iritis and corneal opacity also developed. Due to the severity of irritation in the treated eye, the animal was euthanized for humane reasons.

In accordance with the provisions of Directive 67/548/EEC amended by COMMISSION DIRECTIVE 2001/59/EC of 6 August 2001, Annex VI, classified as Corrosive.

According to the United Nations Globally Harmonized System of Classification and Labeling of Chemicals (GHS) Fifth revised edition 2013, H-31339 is classified in Category 1.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Primary Eye Irritation in Rabbit:

 

A primary eye irritation test was conducted with rabbits to determine the potential for H-31339 to produce irritation from a single instillation via the ocular route.

At the request of the Sponsor, the study was conducted in a stepwise fashion. One-tenth of a milliliter of the test substance was instilled into the conjunctival sac of the right eye of one healthy rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize et al.1 (see Table 4). Due to the severity of irritation noted in the treated eye, the animal was euthanized for humane reasons and the study was terminated.

Within one hour following test substance instillation, the treated eye of the animal exhibited conjunctival redness (score of 1), chemosis (score of 3), and discharge (score of 3). By 24 hours, iritis and corneal opacity also developed. Due to the severity of irritation in the treated eye, the animal was euthanized for humane reasons.

In accordance with the provisions of Directive 67/548/EEC amended by COMMISSION DIRECTIVE 2001/59/EC of 6 August 2001, Annex VI, classified as Corrosive.

According to the United Nations Globally Harmonized System of Classification and Labeling of Chemicals (GHS) Fifth revised edition 2013, H-31339 is classified in Category 1.

 

Harmonised classification:

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP). 

 

Self-classification:

Based on the available information on test item, self-classification is proposed according to the CLP or GHS.

GHS 1.

 

Primary Skin Irritation Test:

A primary skin irritation test was conducted with rabbits to determine the potential for H-31339 to produce irritation after a single topical application.

At the request of the Sponsor, the study was conducted in a stepwise manner using a single patch applied initially to one rabbit for 4 hours. Five-tenths of a gram of the test substance was moistened with distilled water and applied to the skin of one healthy rabbit for 4 hours. The dose site was evaluated for dermal irritation by the method of Draize et al.1 (see Table 4) immediately after patch removal and at 30-60 minutes and 24, 48, and 72 hours after patch removal. Since there was no dermal irritation noted at the dose site of this animal, the test was completed on two additional animals, as described above, except the dose sites were not evaluated immediately after patch removal.

There was no skin irritation observed at any treated site during this study.

In accordance with the provisions of Directive 67/548/EEC amended by COMMISSION DIRECTIVE 2001/59/EC of 6 August 2001, Annex VI, classification is not required based on the results of this study.

According to the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Fifth revised edition 2013 under the conditions of this study, classification is not required.

 

Harmonised classification:

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP). 

 

Self-classification:

Based on the available information on test item, no self-classification is proposed according to the CLP or GHS.

 

Justification for selection of irritation toxicity endpoint -
two key 1 studies used 

Justification for classification or non-classification

Due to the results of the in vivo primary eye irritation study, with a conclusive outcome of being irritating, a classification is  justified.

This classification has been selected on the adverse effects outcome of the key 1 study report.

GHS Category 1

 

The test item is not classified for skin irritation endpoint.