C16-18 (evennumbered, C18 unsaturated) alkyl bis(2-hydroxyethyl) amine oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 April 1990- 18 April 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to guideline and under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-(Z)-octadec-9-en-1-ylimino)bisethanol N-oxide

EC Number:

300-699-5

EC Name:

2,2'-(Z)-octadec-9-en-1-ylimino)bisethanol N-oxide

Cas Number:

93962-62-0

Molecular formula:

C22H45NO3

Details on test material:

Chemical name: Oleyl bis(2-hydroxyethyl)amine oxide
Description: Clear viscous liquid
Batch/Lot Number: RCD/HJ-173
Purity/Compostion: Amine oxide : 58.2% (from CoA)
Instructions for test substance storage: In the original container at room temperature in the dark.
Stability under storage conditions: stable
Expiry date: March 09, 1991

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: Approx. 8 weeks males, Approx. 11 weeks females
- Weight at study initiation: males: 199-251g, females: 163 - 197g
- Fasting period before study: Feed was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Group housed, five per sex to a cage, using polycarbonate cages containing purified sawdust as bedding material (Woody Clean supplied by Broekman Institute, Someren, The Netherlands).
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-75
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 4 April 1990- 18 April 1990

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
Group 1: 4.138 ml/kg body weight
Group 2: 2.365 ml/kg body weight
Group 3: 1.281 ml/kg body weight

Doses:

Group 1: 4200 mg/kg body weight
Group 2: 2400 mg/kg body weight
Group 3: 1300 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: animals were observed at periodic intervals on the day of dosing (day 1) and twice daily there after for 14 days. Animals were weighed on test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinicals igns were determined at periodic intervals on the day of dosing (day 1) and once daily there after for 14 days. All signs of reaction to treatment were recorded with particular attention paid to changes in the skin, fur , eyes and mucous membranes, as well as to behaviour pattern, tremors, convulsions, salivation , diarrhoea, lethargy, sleep and coma.

Statistics:

The LD50 values and the associated 95% confidence interval, the slope o f the dose mortality curve were calculated using the Maximum likelihood method (Finney, D.G. Probit Analyses, 3rd Edn., London, Cambridge, University Press, 1971).

Results and discussion

Preliminary study:

Initially a pilot study was conducted with three groups, each comprising 1 male and 1 female, with dose levels of 5000, 2000 or 200 mg/kg body weight, The female dosed at 5000 mg/kg body weight was found dead on day 3. Lethargy, piloerection, bloody eye encrustation and emaciation (body weight loss) was noted i n the male dosed at 5000 mg/kg body weight. This animal had not recovered by day 8 , the end of this pilot study. Lethargy and piloerection were noted i n the animals dosed at 2000 mg/kg body weight, while no symptoms of toxicity were noted i n the animals dosed at 200 mg,/kg body weight. Based on these results a full study with dose levels of 4200, 2400 and 1300 mg/kg body weight was performed.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 114 mg/kg bw

Remarks on result:

other: Corrected for 58.2 % active ingredient = 2394 mg/kg bw. Due to the mortality distribution only estimated LD50 values could be calculated.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

12 867 mg/kg bw

Remarks on result:

other: Corrected for 58.2 % active ingredient = 7489 mg/kg bw. Due to the mortality distribution only estimated LD50 values could be calculated.

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

2 932 mg/kg bw

Remarks on result:

other: Corrected for 58.2 % active ingredient = 1706 mg/kg bw. Due to the mortality distribution only estimated LD50 values could be calculated.

Mortality:

The incidence of mortality among the males form high to low dose group (4200, 2400 and 1300 mg/kg body weight) was 1/5, 0/5 and 0/5 and among the females was 5/5, 0/5 and 0/5. The deaths occured within days 3 and 9.

Clinical signs:

other: Lethargy, piloerection, emaciation, bloody eye and nose encrustion were noted among the animals dosed at 4200 mg/kg body.weight. The surviving animals of this treatment group had recovered by day 13. Piloerection was noted in one animal only dosed a t 130

Gross pathology:

Macroscopic post mortem examination revealed stomach enlargement and red colouration; irregular forestomach epithelium; forestomach covered with a grey/ white layer; gaseous accumulation in stomach; yellow intestine content; enlarged adrenals and small size and red colouration of thymus among animals that died during the study. At macroscopic post mortem examination of animals at termination, irregular areas or irregular grey/white areas on the forestomach epithelium were noted in all or some animals from all groups. The only other abnormality noted among these animals was the forestomach serosa adherent to the diaphragm in one male dosed at 4200 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The estimated LD50 for males and females combined is 4114 mg/kg bw (corrected for 58.2% active ingredient = 2394 mg/kg bw), for males alone 12867 mg/kg bw (corrected for 58.2% active ingredient = 7489 mg/kg bw ) and for females alone 2932 mg/kg bw corrected for 58.2% active ingredient = 1706 mg/kg bw ). Therfore under GHS the test substance is classified in category V.

Executive summary:

The study was carried out in accordance with OECD Guidelfne No. 401, "Acute Oral Toxicity" and EEC Directive 84/449/EEC, Part B.1, ''Acute Toxicity - Oral. The test item was administered to rats o f both sexes by oral gavage at 4200, 2400 and 1300 mg/kg body weight. Macroscopic examination was performed at the end of the experimental period. The incidence o f mortality for both sexes combined for the high, mid and low dose group was 6/10, 0/10 and 0/10, respectively. Lethargy, piloerection and emaciation were the major symptoms noted among the animals dosed at 4200 mg/kg body weight. All the surviving animals had recovered by day 13. The animals dosed at 2400 and 1300 mg/kg body weight showed no symptoms of toxicity during the study period, with the exception of one female dosed at 1300 mg/kg body weight. This animal showed piloerection on the day of dosing. The surviving animals dosed at 4200 mg/kg body weight showed large body weight loss in the first week of the study, but gained in the second week of the study. The animals dosed a t 2400 and 1300 mg/kg body weight generally showed body weight gain considered to be similar to that of untreated animals of the same age and strain, although weight gain by some females was lower than expected. The macroscopic post mortem examination mainly revealed stomach enlargement; red colouration of stomach and/or thymus and a small thymus among animals that died during the study. Macroscopic post mortem examination o f the surviving animals revealed mainly irregular grey/white areas in forestomach epithelium. Due to the mortality distribution only estimated LD50 values could be calculated. These amounted to 4114 mg/kg body weight for the sexes combined, 12867 mg/kg body weight for the males only and 2932 mg/kg body weight for the females only.

The estimated LD50 for males and females combined is 4114 mg/kg bw (corrected for 58.2% active ingredient = 2394 mg/kg bw), for males alone 12867 mg/kg bw (corrected for 58.2% active ingredient = 7489 mg/kg bw ) and for females alone 2932 mg/kg bw corrected for 58.2% active ingredient = 1706 mg/kg bw ). Therefore under GHS the test substance is classified in category V.