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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2014-10-16 To 2015-01-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

236-291-8

EC Name:

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

Cas Number:

13282-70-7

Molecular formula:

C23H48N2O.C2H4O2

IUPAC Name:

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

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

CRL The Crl:CD(SD) rat was selected based on consistently acceptable health status and on extensive experience with the strain at DuPont Haskell.

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: Charles River Laboratories International, Inc., Raleigh, North Carolina, U.S.A.
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Rationale for use of males (if applicable) n/a
- Age at study initiation: 9 weeks old.
- Weight at study initiation: n/a
- Fasting period before study: n/a
- Housing:housed individually in solid-bottom caging with bedding and appropriate species- specific enrichment.
- Historical data:n/a
- Diet (e.g. ad libitum): PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002, ad libitum,
- Water (e.g. ad libitum):tap water, ad libitum.
- Acclimation period:6-day quarantine period.
- Microbiological status when known:Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers.
- Method of randomisation in assigning animals to test and control groups:n/a

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26 °C
- Humidity (%): 30-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): artificially illuminated (fluorescent light) on an approximate 12-hour light/dark cycle.

IN-LIFE DATES: From: 2014-10-23 To: 2014-11-06

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

deionized water.

Details on dermal exposure:

TEST SITE
- Area of exposure: scapular to the lumbar region.37 square centimeters.
- % coverage: 5 cm x 7.4 cm.
- Type of wrap if used: 2-ply gauze patch, then wrapped with stretch gauze bandage and self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with paper towels soaked in soap and warm water, and the skin was dried.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/Kg bw.
- For solids, paste formed: yes

VEHICLE
The aliquot of test substance designated for an animal was moistened with approximately 4 mL of deionized water for male rats and 3 mL of deionized water for female rats to form a thick paste.

Duration of exposure:

24 hours

Doses:

- 5000 mg/kg bw; single dose.

No. of animals per sex per dose:

5 males and 5 females.

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:daily for clinical signs and toxicity, days 1, 8, and 15 for body weight.
- Necropsy of survivors performed: no
- Clinical signs including body weight: yes.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:examined to detect grossly observable evidence of organ or tissue damage.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no instances of mortality at 5000 mg/kg.

Gross pathology:

No gross lesions were present in the rats at necropsy.

Other findings:

On test days 2 and 3, one female exhibited ulceration on the treated area of skin, which was resolved by test day 4. Clinical signs of hyperkeratosis, desquamation, or epidermal scaling were observed in all animals between test days 3 and 8. The clinical observation of scabbing on the back of one female was present from test day 12-14. At final euthanasia, no clinical abnormalities were present.
At the beginning of the observation period (24 hours after exposure), on test day 2, edema was observed on 5/5 males and 4/5 females, with scores of 1 or 2. All edema was resolved by test day 3. Erythema was observed in all animals between test days 2 and 3, with scores of 1, 2, or 3. From tests 4-9, 1/5 females exhibited erythema scores of 1 or 2.
There were no overall (test day 1-15) body weight losses among any animals.

Any other information on results incl. tables

Individual Erythema Scores Males. Dose: 5000 mg/kg

 

Days relative to start date	2	3	4	5	6	7	8	9	12	13	14	15
N. animal
4975	3	1	0	0	0	0	0	0	0	0	0	0
4976	3	2	0	0	0	0	0	0	0	0	0	0
4977	3	1	0	0	0	0	0	0	0	0	0	0
4978	3	1	0	0	0	0	0	0	0	0	0	0
4979	3	2	0	0	0	0	0	0	0	0	0	0

 

 

 

Individual Erythema Scores Females. Dose: 5000 mg/kg

 

Days relative to start date	2	3	4	5	6	7	8	9	12	13	14	15
N. animal
4980	3	3	2	2	1	1	1	1	0	0	0	0
4981	1	1	0	0	0	0	0	0	0	0	0	0
4982	2	2	0	0	0	0	0	0	0	0	0	0
4983	2	0	0	0	0	0	0	0	0	0	0	0
4984	3	2	0	0	0	0	0	0	0	0	0	0

 

 

 

Individual Edema Scores Males. Dose: 5000 mg/kg

 

Days relative to start date	2	3	4	5	6	7	8	9	12	13	14	15
N. animal
4975	2	0	0	0	0	0	0	0	0	0	0	0
4976	2	0	0	0	0	0	0	0	0	0	0	0
4977	2	0	0	0	0	0	0	0	0	0	0	0
4978	2	0	0	0	0	0	0	0	0	0	0	0
4979	2	0	0	0	0	0	0	0	0	0	0	0

 

 

 

 

Individual Edema Scores Females. Dose: 5000 mg/kg

 

Days relative to start date	2	3	4	5	6	7	8	9	12	13	14	15
N. animal
4980	1	0	0	0	0	0	0	0	0	0	0	0
4981	0	0	0	0	0	0	0	0	0	0	0	0
4982	1	0	0	0	0	0	0	0	0	0	0	0
4983	1	0	0	0	0	0	0	0	0	0	0	0
4984	2	0	0	0	0	0	0	0	0	0	0	0

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the dermal LD50 for H-31339 was greater than 5000 mg/kg of body weight when applied to the skin of male and female rats for 24 hours.
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, classification is not required.

Executive summary:

A single dose of H-31339 was applied to the shaved, intact skin of 5 male and 5 female rats at a dose level of 5000 mg/kg of body weight. The application site was covered with a semi-occlusive dressing for 24 hours, after which the test substance was removed. The rats were observed for 14 days following application. The rats were necropsied to detect grossly observable evidence of organ or tissue damage at the end of the 15-day test period.

There were no instances of mortality.

On test days 2 and 3, one female exhibited ulceration on the treated area of skin, which was resolved by test day 4. Clinical signs of hyperkeratosis, desquamation, or epidermal scaling were observed in all animals between test days 3 and 8. The clinical observation of scabbing on the back of one female was present from test day 12-14. At final euthanasia, no clinical abnormalities were present.

At the beginning of the observation period (24 hours after exposure), on test day 2, edema was observed on 5/5 males and 4/5 females, with scores of 1 or 2. All edema was resolved by test day 3. Erythema was observed in all animals between test days 2 and 3, with scores of 1, 2, or 3. From tests 4-9, 1/5 females exhibited erythema scores of 1 or 2.

There were no overall (test day 1-15) body weight losses among any animals. No gross lesions were present in the rats at necropsy.

Under the conditions of this study, the dermal LD50 for H-31339 was greater than 5000 mg/kg of body weight when applied to the skin of male and female rats for 24 hours.

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, classification is not required.