Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(hydroxyethyl) derivs.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July-August 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well reported and carried out study according to guidelines/standards of 1996 instead of 2001 using class 200 mg/kg rather than 300 mg/kg.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

version of 1996 rather than 2001 used

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amines, N-(C16-18 (even numbered) and C18-unsatd. alkyl) trimethylenedi-, ethoxylated(NLP)

EC Number:

800-029-6

Cas Number:

1290049-56-7

Molecular formula:

Not applicable

IUPAC Name:

Amines, N-(C16-18 (even numbered) and C18-unsatd. alkyl) trimethylenedi-, ethoxylated(NLP)

Test material form:

liquid: viscous

Details on test material:

Name: DINORAMOX S3
Batch no.: 6751
Appearance: thick brown liquid
Date of receipt: 20 June 2003
Storage: room temperature
Purity: 99.76%
Expiry date: June 2004

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 6 weeks
- Weight at study initiation: 192 ± 5 g (males), 162 ± 10 g (females)
- Fasting period before study: overnight (ca. 18 h) until ca. 4 h after dosing
- Housing: in polycarbonate cages, 3 rats/per sex
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30-70
- Air changes (per hr): ca. 12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 23 July To: 19 August 2003

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not indicated
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: no info
- Lot/batch no. (if required): 122K0131
- Purity: not indcated


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


DOSAGE PREPARATION (if unusual): fresh every morning


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: for animal welfare reasons, because no info on toxicity was available, the starting dose was chosen to be 200 mg/kg bw.

Doses:

1. 200 mg/kg (males)
2. 2000 mg/kg (males)
3. 200 mg/kg (females)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequently on the day of dosing, at least once a day thereafter; bw weekly
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

Not required

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Remarks on result:

other: 0/3 females and 1/3 males died at 200 mg/kg, 3/3 males died at 2000 mg/kg

Mortality:

See at clinical signs

Clinical signs:

other: At the 200 mg/kg dose-level, one male was found dead on day 14; hypoactivity, piloerection and hypersalivation were observed in this animal on days 1 and 2, but no clinical signs were noted from day 3. In both surviving males, hypoactivity, piloerection

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The oral LD50 of the test item DINORAMOX S3 (batch No. 6751) is comprised between 200 and 2000 mg/kg in male rats. Toxicity is comparable in females. Because only 1 male out of 3 male and 3 female rats dosed at 200 mg/kg died on day 14, it is expected that the LD50 value is higher than 300 mg/kg bw but lower than 2000 mg/kg with LD50 cut-off 500 mg/kg; therefore classification in GHS Category IV is warranted.

Executive summary:

At the request of CECA SA, Paris-la-Défense, France, the acute oral toxicity of the test item DINORAMOX S3 (batch No. 6751) was evaluated in rats according to OECD (No. 423, 22 March 1996) and EC (96/54/EC, B.1 ter, 30 July 1996) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. The test item was prepared in corn oil and was administered by oral route (gavage), at a volume of 10 mL/kg, to groups of fasted Sprague-Dawley rats. The study design was as follows: 3 males 200 mg/kg, 3 males 2000 mg/kg, 3 females 200 mg/kg. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item. All animals were subjected to necropsy. At the 200 mg/kg dose-level, one male was found dead on day 14; hypoactivity, piloerection and hypersalivation were observed in this animal on days 1 and 2, but no clinical signs were noted from day 3. In both surviving males, hypoactivity, piloerection and hypersalivation were recorded on days 1 and 2, and recovery was complete on day 3. In females, no mortality occurred. Hypoactivity and piloerection, together with dyspnea on day 2, were observed in all animals on days 1 and 2. Then dyspnea, together with swollen abdomen on days 3 and 4 or noisy breathing between days 12 and 14, was noted in 1/3 females from day 3 to day 5 and from day 12 to day 14. At the 2000 mg/kg, the three males were found dead on day 2; hypoactivity, piloerection and dyspnea were recorded prior to death. When compared to historical control animals, a slightly reduced body weight gain was seen in 2/3 females given 200 mg/kg during the first or second week of the study. The overall body weight gain of both surviving males given 200 mg/kg was not affected by treatment with the test item. At necropsy, no apparent abnormalities were observed. Based on these results, the oral LD50 of the test item DINORAMOX S3 (batch No. 6751) is comprised between 200 and 2000 mg/kg in male rats. Toxicity is comparable in females. Because only 1 male out of 3 male and 3 female rats dosed at 200 mg/kg died on day 14, it is expected that the LD50 value is higher than 300 mg/kg bw but lower than 2000 mg/kg, and according to OECD 423 (2001) the LD50 cut-off = 500 mg/kgbw; therefore classification in GHS-OECD Category IV is warranted.