Reaction mass of N,N-dimethyldecan-1-amide and N,N-dimethyloctanamide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

June 5, 2012 to August 9, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Full reliable study according to actual protocols and guidelinies conducted under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethyloctanamide

EC Number:

214-272-5

EC Name:

N,N-dimethyloctanamide

Cas Number:

1118-92-9

Molecular formula:

C10H21NO

IUPAC Name:

N,N-dimethyloctanamide

Details on test material:

- Name of test material (as cited in study report): Octanamide, N,N-dimethyl-
- Physical state: Liquid
- Analytical purity: 97.0 corr. area-% determined by GC-FID
- Impurities (identity and concentrations): see analytical report 12L00166
- Composition of test material, percentage of components: see analytical report 12L00166
- Lot/batch No.:Z773320002
- Expiration date of the lot/batch: November 29, 2013
- Stability under test conditions: stable
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Weight at study initiation: 228-234g
- Housing: Single housing, Makrolon cage, type III
- Diet (e.g. ad libitum): ad libitum VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +- 3°C
- Humidity (%): 30 – 70% for relative humidity
- Air changes (per hr): Approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 40cm2
- % coverage: 10%
- Type of wrap if used: semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing of the application site with warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):2.29ml/kg bw
- Concentration (if solution): unchanged
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

2000mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weight determination:
Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
Clinical observations:
Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
Scoring of skin findings:
Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times (see results) until the last day of observation.
Mortality:
A check for any dead or moribund animals was made at least once each workday, these records are archived by Bioassay.
Pathology:
Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.

Statistics:

none

Results and discussion

Preliminary study:

no

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality observed

Mortality:

No mortality occurred

Clinical signs:

other: Male animal clinical signs Systemic effects In two animals impaired general state, dyspnoea and piloerection were observed at hour 4 and/or 5 and persisted in one animal until study day 1. In this animal impaired general state, dyspnoea, piloerection and

Gross pathology:

In one female and one male animal the following findings were examined on the last day of observation: dark red discoloration of the liver, no content in the stomach, red discoloration of the glandular stomach and red discoloration of the small intestine and its content. These two animals showed weight reduction during the observation period.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information EU GHS Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of Octanamide, N,N-dimethyl- after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), according to OECD guideline 402, young adult Wistar rats(5 males and 5 females)were dermally exposed to a single dose of 2000 mg/kg bw of Octanamide, N,N-dimethyl-,

one of the two main constituents of the registered substance,

 to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

The following test item-related clinical observations were recorded during the course of the study:

• No mortality occurred
• Impaired general state in seven animals
• Poor general state in one animals
• Dyspnoea in six animals
• Piloerection in six animals
• Exsiccosis in two animals
• Exophthalmos in one animal
• Lacrimation in one animal
• Lateral position in one animal
• Diarrhea in one animal
  

The following test item-related local effects were recorded during the course of the study:

• Slight to well-defined erythema (grade 1 to 2)

 The mean body weights of the male and female animals increased as expected in four animals in each group but distinctly decreased in one male and female animal during the observation period.

 Macroscopic pathological findings in the animals examined on the last day of observation (findings in the male and female animal, which showed weight reduction):

o  Dark red discoloration of the liver

o  No content in stomach

o  Red discoloration of the glandular stomach

o  Red discoloration of the small intestine and its content

 There were no macroscopic pathological findings in the other 4 males and females.    

Accordingly, the acute dermal median lethal dose (LD₅₀) was determined to be

 

LD₅₀, dermal, rat > 2000 mg/kg bw