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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was not conducted in compliance with GLP regulations but is well documented and scientifically acceptable. The study was performed according to OECD Guideline 423.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): C4-AMIN
- Substance type: Mono-constituent
- Physical state: Liquid
- Analytical purity: 98%
- Purity test date: No reported
- Lot/batch No.: P 5756
- Expiration date of the lot/batch: 1-APR-2002
- Storage condition of test material: At room temperature (17-23 C)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division
- Age at study initiation: Males: 8 weeks, Females: 10 weeks
- Weight at study initiation: Male average: 192.2 g, Female average: 181.1 g
- Fasting period before study: 16-20 hours
- Housing: In groups of three per sex in Makrolon type-4 cages with wire mesh tops and standardized softwood bedding.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kilba 3433 rat maintenance diet (batch no. 71/01) ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 6 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 15 June, 2001 To: 04 July, 2001

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): All animals were dosed at a volume of 10 mL/kg
- Justification for choice of vehicle: Solubility of the test material.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
200 and 2,000 mg/kg
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: Rats were observed at 1, 2, 3 and 5 hours post-dose, and once daily for 14 days for clinical signs of toxicity. Body weights were recorded on Day 1 (prior to administration) and on Days 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
All animals (3 females) dosed at 2,000 mg/kg were found dead 5 or 7 hours after treatment. All animals dosed at 200 mg/kg survived throughout the end of the observation period.
Clinical signs:
None of the animals dosed at 200 mg/kg had abnormal clinical signs throughout the study.
Body weight:
The body weight gain of the animals in the 200 mg/kg group was within the range commonly recorded for this strain and age.
Gross pathology:
Black-brown contents in the stomach, duodenum and jejunum were noted in all females at 2000 mg/kg. All other animals were without macroscopic findings.
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the test, the oral LD50 of the test article is > 200 mg/kg body weight (LD0) and < 2,000 mg/kg body weight (LD100).
Executive summary:

The acute oral toxicity potential of the test article was evaluated in male and female rats. The test was not intended to comply with GLP guidelines. The test method was based on EEC Guidelines B.1 (1996) and OECD 423 (1996). Male and female rats (Wistar, 3/sex/group) received 200 mg/kg test article suspended in bi-distilled water via single oral gavage at a dose volume of 10 mL/kg. Three additional female rats received 2,000 mg/kg test article in the same manner. Rats were observed at 1, 2, 3 and 5 hours post-dose, and once daily for 14 days for clinical signs of toxicity. Body weights were recorded on Day 1 (prior to administration) and on Days 8 and 15. All animals were examined via necropsy at termination. All animals (3 females) dosed at 2,000 mg/kg were found dead 5 or 7 hours after treatment. Ruffled fur, hunched posture, lateral recumbency, tremors and half closed lids were noted in the female rats dosed at 2000 mg/kg prior to death. The animals dosed at 200 mg/kg survived through the end of the observation period and had no abnormal clinical signs. Black-brown contents in the stomach, duodenum and jejunum were noted in all females dosed with 2000 mg/kg test article upon necropsy. All other animals were without macroscopic findings. The body weight gain of the animals in the 200 mg/kg group was within the range commonly recorded for this strain and age. Based on the results of the test, the oral LD50 of the test article is > 200 mg/kg body weight (LD0) and < 2,000 mg/kg body weight (LD100).