N,N-dimethyldecylamine N-oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-11-28 to 2012-02-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethyldecylamine N-oxide

EC Number:

220-020-5

EC Name:

N,N-dimethyldecylamine N-oxide

Cas Number:

2605-79-0

Molecular formula:

C12H27NO

IUPAC Name:

decyl(dimethyl)amine oxide

Test material form:

other: Aqueous solution

Details on test material:

- Name of test material (as cited in study report): N,N-dimethyldecylamine-N-oxide (solution)
- Substance type: colourless to yellowish liquid
- Analytical purity: 40.5% active (aqueous solution)
- Impurities (identity and concentrations): peroxide: 0.01%, free amine: < 0.5%
- Purity test date: 2011-11-14
- Lot/batch No.: 1108042301
- Expiration date of the lot/batch:2 years in original closed packaging
- Storage condition of test material: 10 - 25°C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River Laboratories Research Models and Services Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany.
- Age at study initiation: ca. 8 weeks
- Weight at study initiation: 160-194 g
- Fasting period before study: yes, ca. 16 hours before start
- Housing: MAKROLON cages (type III plus) with granulated textured wood as bedding.
- Diet (e.g. ad libitum): ad libitum prior to fasting period and in recovery period
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 15%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 2011-11-28 To: 2011-12-29

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5.09 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on toxicity information from study sponsor.

Doses:

300 and 2000 mg AO/kg bw

No. of animals per sex per dose:

6 animals at 300 mg AO/kg bw
3 animals at 2000 mg AO/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days.
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity, as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on mortality were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study and at death. Changes in weight were calculated and recorded.

- Necropsy of survivors performed: yes

Statistics:

No applicable

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

300 mg AO/kg bw: No animal died prematurely.
2000 mg AO/kg bw: Two of 3 animals died prematurely within 6 hours after administration.

Clinical signs:

other: Under the present test conditions, a single oral administration of 300 mg N,N-dimethyldecylamine-N-oxide/kg b.w. to female rats revealed slight salivation in 4 of 6 animals. A single oral administration of 2000 mg N,N-dimethyldecylamine-N-oxide/kg b.w. to

Gross pathology:

No pathological changes were observed at necropsy.

Any other information on results incl. tables

Table 1: Summary of results

Symptoms/criteria	300 mg AO/kg bw		2000 mg AO/kg bw
	Females (n = 3) First step	Females (n = 3) Second step	Females (n = 3) First step
Clinical signs: salivation	+ 15’ (3)	+ 5’-15’ (1)	+ 15’ (3)
Mortality: Within 6h Within 24h Within 7d Within 14d
	0	0	2
	0	0	2
	0	0	2
	0	0	2
Mean bodyweight (g) Start After 7d After 14 d
	169.0	171.0	185.0
	195.0 (+15.5)	198.7 (+16.3)	241.0 (+24.1)
	212.7 (+25.9)	220.0 (+28.8)	273.0 (+40.7)
Inhibition of bodyweight gain	none	none	none
Necropsy findings	none	none	none

In brackets:      clinical signs: no of animals affected

                        Bodyweight: bodyweight gain in %, compared to start value

+ = slight

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral (gavage) LD50 is in the range 300 - 2000 mg AO/kg bw.

Executive summary:

Test Guideline

OECD Guideline 423 and EC Method B1 tris (acute toxic class)

Method and material

In a first step 3 female Sprague-Dawley rats were dosed by oral gavage with 300 mg/kg of the test material as supplied (corrected for active content). As no animals died a further three female rats were dosed at the same dose level. No animals died. Three female rats were then dosed by oral gavage at 2000 mg/kg. Animals were observed for 14 days after dosing for mortalities, bodyweight gain and clinical signs of toxicity. All surviving animals under went necropsy at study termination.

Results

300 mg AO/kg bw: No animal died prematurely.

2000 mg AO/kg bw: Two of 3 animals died prematurely within 6 hours after administration.

Salivation was noted in animals in both dose groups after dose administration. There was no effect on bodyweight gain. There were no macroscopic treatment related effects noted at necropsy.

The acute oral (gavage) LD50 is in the range 300 - 2000 mg AO/kg bw.

Conclusion

In accordance with CLP Regulation (EC) No 1272/2008 the substance is classified as Acute category 4 for oral toxicity.