Amines, N-(3-aminopropyl)-N'-C12-18-alkyltrimethylenedi-, reaction products with N-C12-18-alkyltrimethylenediamines and formic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2002-07-31 to 2002-11-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

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 401 (Acute Oral Toxicity)

Version / remarks:

Reliability scoring based on 1987 guideline for test n°401

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Amines, tallow alkyl[3-(tetrahydropyrimidinyl)propyl]

EC Number:

296-557-4

EC Name:

Amines, tallow alkyl[3-(tetrahydropyrimidinyl)propyl]

Cas Number:

92797-22-3

IUPAC Name:

92797-22-3

Constituent 2

Reference substance name:

Amines, suifalkyl [(tetrahydropyrimidinyl)3-propyl]

IUPAC Name:

Amines, suifalkyl [(tetrahydropyrimidinyl)3-propyl]

Details on test material:

- Name of test material (as cited in study report): POLYRAM L200
- Chemical name : Amines, suifalkyl [(tetrahydropyrimidinyl)3-propyl]
- CAS number : 92797-22-3
- Physical state: clear brown liquid
- Analytical purity: > 95% expressed in amines content
- Purity test date: 2002-06-20
- Lot/batch No.: 94052206
- Expiration date of the lot/batch: July 2003.
- Storage condition of test material: in dark and at room temperature

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: 194 ± 7 g for the males and 172 ± 8 g for the females.
- Fasting period before study: overnight, ca. 18 hours before dosing
- Housing: five rats of the same sex and group per cage.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): ca. 12 cycles/hour of filtered, non-recycled
- Photoperiod (hrs dark / hrs light): 12/12
:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: undiluted at the dose-level of 2000 mg/kg, water as vehicle for the 500 and the 1000 mg/kg bw dose groups.

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
Undiluted at the dose-level of 2000 mg/kg bw but taking into consideration that the specific gravity of the test item was 0.916 g/ml. the volume administered was then 2.19 ml/kg.
Diluted with water at concentrations of 50 and 100 mg/mL for the 500 and the 1000 mg/kg bw dose groups respectively.
- Amount of vehicle (if gavage): 10 mL/kg bw for the 500 and the 1000 mg/kg bw dose groups
- Justification for choice of vehicle: solubility, water is recommended as vehicle by the guideline
- Lot/batch no. (if required): not applicable

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

500, 1000 and 2000 mg/kg bw

No. of animals per sex per dose:

5 per sex at 2000 mg/kg bw, 5 females for the 500 and the 1000 mg/kg bw dose groups

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 - 16 days
- Frequency of observations and weighing: once daily and weighing at 1, 8 and 15 days after exposure (day 1 = day of exposure)
- Necropsy of survivors performed: yes

Statistics:

- LD50: Probit-Analysis (Weber (1972) and Bliss (1938)).
- The 70 to 95% confidence interval limits were calculated statistically according to Fieller's method (1944).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

704 mg/kg bw

Based on:

test mat.

95% CL:

283 - 1 312

Mortality:

- At the 2000 mg/kg bw dose-level, all males and females died on day 1 or during the night between day 1 and day 2,
- At the 1000 mg/kg bw dose-level, 4/5 females died on day 1 within the 5 hours following treatment
- At the 500 mg/kg bw dose-level, 1/5 females died on day 17.

Clinical signs:

other: - At the 2000 mg/kg bw dose-level, hypoactivity, piloerection, dyspnea, and hypersalivation were observed prior to death. - At the 1000 mg/kg bw dose-level, sedation, tremors and dyspnea were noted in 1 female prior to death. In the surviving animal, hypo

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

other: Toxicity category 4 / Harmful

Remarks:

Criteria used for interpretation of results: other: CLP (Reg. 1272/2008/EC) and Directive 67/548/EEC

Conclusions:

Under these experimental conditions, the oral LD50 of the test item POLYRAM L200 was 704 (283 - 1312) mg/kg bw in female rats with 95% confidence interval limits. Toxicity was comparable in males. In accordance, with ethic and scientific recommandations concerning LD50, a more precise determination was not conducted.

Executive summary:

The acute oral toxicity of the test item was evaluated in rats according to OECD (No. 401, 24th february 1987) and Commission Regulation (EC) (No. 92/69/EEC, B.1, 31st july 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was administered by oral route (gavage) to groups of five male and/or five female fasted Sprague-Dawley rats. In the first instance, the test item was administered undiluted, at the dose-level of 2000 mg/kg bw, taking into consideration that its specific gravity was 0.916 g/mL. As more than 50% mortality occurred in this limit test, the test item was then prepared in purified water and administered to the animals at the lower doses of 1000 and 500 mg/kg bw, under a volume of 10 mL/kg.

Clinical signs, mortality and body weight were checked for a period of up to 16 days following the single administration of the test item. All animals were subjected to necropsy. The LD50 was calculated according to Probit's method.

At the 2000 mg/kg bw dose-level, the 5 females and the 5 males died on day 1 or during the night between day 1 and day 2. Hypoactivity, piloerection, dyspnea, and hypersalivation were observed prior to death.

At the 1000 mg/kg bw dose-level, 4/5 females died on day 1 within the 5 hours following the treatment. Sedation, tremors and dyspnea were noted in one female prior to death. In the surviving animal, hypoactivity or sedation, piloerection and dyspnea were observed from day 1 up to day 3.

At the 500 mg/kg bw dose-level, clinical signs sush as hypoactivity, piloerection and dyspnea were noted in all animals from day 1 up to day 4. From day 5 up to day 11, no clinical signs were recorded. Dyspnea, swollen abdomen, piloerection and hypoactivity were then recorded in 1/5 females, from day 12; it was found dead on day 17.

The body weight gain of the surviving animals given 500 or 1000 mg/kg bw was not affected by treatment with the test item. No apparent abnormalities were observed at necropsy in any animal.

Under these experimental conditions, the oral LD50 of the test item was 704 (283 - 1312) mg/kg bw in female rats with 95% confidence interval limits. Toxicity was comparable in males.