Condensation products of tetramethylenediamine with hydrogenated fatty acids of castor-oil

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

of 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

of 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

of 2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries. Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sprague Dawley rats, strain: Crl:CD(SD) with appropriate range of bodyweight at study start.
- Source: Charles River (UK) Ltd.
- Age at study start (day of dosing): 8 to 12 weeks.
- Weight at start (day of dosing): Females: minimum 232 g, maximum 255 g.
- Fasting period: Overnight immediately prior to dosing until ca. 4 hours post administration.
- Housing: In groups of 3 by sex in solid bottomed polycarbonate cages inside a barriered rodent facility.
- Bedding material: Autoclaved wood flake bedding
- Cage enrichment: Soft white chew block and plastic shelter (chew block removed during fasting).
- Diet: Standard rodent diet (Rat and Mouse No. 1 Maintenance Diet)
containing no added antibiotic, chemotherapeutic or prophylactic agent.
- Drinking water (ad libitum): Pottable drinking water from the public supply
- Acclimation period: At least 6 days before dosing.

Routine analysis of the batch of diet used, water and chew blocks did not provide evidence of contamination that might have prejudiced the study.

ENVIRONMENTAL CONDITIONS

Air conditioned room kept at positve pressure without re-circulation of the filtered fresh air supplied to the room.
Controlled environment, environmental conditions were set at:
- Temperature (°C): 21 ± 2°C
- Relative Humidity (%): 40 to 70%
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night
- Rate of air exchange: Ca. 15 changes/h

There were no deviations from these ranges, which compromised the quality, integrity or outcome of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous methylcellulose

Details on oral exposure:

DOSE FORMULATION AND DOSE VOLUME:

- Concentration of test material in vehicle: 200 mg/mL
- Amount (dose volume by gavage): 10 mL/kg bw

Preparation of the test material formulation was on the day of dosing. Formulations were stirred before and throughout the dosing procedure.

ACUTE TOXIC CLASS METHOD - Rationale for the selection of the starting dose:

The starting dose of 2000 mg/kg was chosen based on information provided by the Sponsor.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (females only)

Control animals:

no

Details on study design:

- Duration of observation period following administration on Day 1: 14 days (Days 1 to 15)
- Frequency of observations and weighing:
Mortality checks: At least twice daily.
Observation of clinical signs: Ca. 3 minutes post dosing and at frequent intervals thereafter on Day 1; subsequently twice daily and on Day 15 in the morning
Weighing of each animal: Day 1 prior to dosing and on Days 8 and 15.
- Necropsy performed: Yes, of all animals.

Statistics:

Not applicable, as there were no deaths and only one dose group. In addition, the acute toxic class method is not intended for the calculation of a precise LD50 value.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths at 2000 mg/kg bw

Mortality:

Dose level Mortality
2000 mg/kg 0/3 (f)
2000 mg/kg 0/3 (f)

Clinical signs:

Clinical signs were not evident.

Body weight:

No adverse effects on body weight.

Gross pathology:

Necropsy of each animal at the end of the 14-day post treatment observation period (Day 15) did not reveal any macroscopic pathology abnormalities.

Applicant's summary and conclusion

Conclusions:

In view of the oral LD50 > 2000 mg/kg bodyweight attained in the present study, its outcome does not necessitate any labelling regarding acute oral toxicity according to EU regulations (REGULATION (EC) 1272/2008).