m-(1-cyanoethyl)benzoic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 17 December 1993 to 15 June 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study under international guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

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:

other: E.E.C. 92/69 - Annex V - method 81 (1992) - 93/21 (1993)

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

m-(1-cyanoethyl)benzoic acid

EC Number:

226-897-0

EC Name:

m-(1-cyanoethyl)benzoic acid

Cas Number:

5537-71-3

Molecular formula:

C10H9NO2

IUPAC Name:

3-(1-cyanoethyl)benzoic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

. Identification : Carboxyphenyl propionitrile (CAPRIL)
. Identification for the study : 07651 A4 009
. Presentation : fine brown-yellow powder
. Purity : 85.9 %
. Batch number (reference) : 9318400
. Packaging : brown glass container
. Quantity received : about 50 g
. Date of receipt : 4 January 1994
. Storage : room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Number and sex :
. minimum of 6 males. 6 females (preliminary study) ;
. 5 males. 5 females (limit test study) ;
. 20 to 30 males, 20 to 30 females (main study).

- Age at initiation of treatment : adult 5 to 7 weeks old.
- Body weight range at initiation of treatment :
males : 130 to 230 g
females : 120 to 180 g

ENVIRONMENT AND HUSBANDRY
- Housing: in on air-conditioned building (building L2) :
.Temperature : 19 to 25°C (target values),
. Relative humidity: 30 to 70% R.H. (target values),
. Air changes : minimum 8 air changes per hour.
. lighting cycle: 12 hours light (artificial)/12 hours dark.

- Caging : animals housed in groups of 5 (or of 2 for preliminary study) of the some sex and dose goup In polycarbonate cages type FI (305 x 180 x 184 mm) for the preliminary study and type MI (365 x 225 x 180 mm) for the main study.
- Bedding : dust-free sawdust made from spruce tree wood, analysed twice a year for chemical and bacterial contaminants.

DIET AND WATER
- Diet : pelleted complete Diet, ad libitum (rat-mouse Diet reference AO4 C10, Usine d'Alimentation Rationnelle. Villemoisson s/Orge, France), sterilised by irradiation and analysed for the absence of chemical and bacteriological contaminants. Animals will be fasted overnight (15 to 20 hours) before the treatment. Animals will be given food 3 to 4 hours after Intubation.
- Water : filtered (0.2 µm) mains drinking water, ad libitum analysed twice a year for chemical and bacterial contamination (Service d'Hygiene et de Sante de la ville de Lyon France).
- Contaminants : no contaminants are known to be present in the diet or water at levels which might interfere with achieving the objective of the study.

PRE-TREATMENT PROCEDURES
- Animal health procedure : clinical Inspection for ill-health on arrival and then just before the beginning of treatment.
- Acclimatisation period: 5 days minimum between animal arrival and start of treatment.
- Allocation to treatment group : if appropriate, performed during the acclimatisation period, using a body weight range procedure.
Mean body weights of each group will not be statistically significantly different from each other (Student't test), each sex being considered separately.
- Weight variation not to exceed for each sex ± 20 % of the mean weight.
- Identification of the animals : ear notches.
- Identification of the cages : colour coded label with study number, group number, sex and animal numbers, code number of the test article, the starting date of the test.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1 % (W/V) aqueous dispersion of carboxymethylcellulose

Details on oral exposure:

Vehicule used:
. pH = 7.3 (vehicle of the main study)
Conditions of measurement: the measurement was carried out under magnetic stirring.
T = 17.7 °C

Doses:

. Preliminary study : test article as a 2.5 - 5.0 and 10.0 % (W/V) suspension in the vehicle.
. Main study : test article as a 10 % (W/V) suspension in the vehicle.

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

yes

Details on study design:

PRELIMINARY STUDY:
The animals will be observed for 7 days. Only mortality will be expressed. Necropsy will not be performed.

MAIN STUDY:
- Mortality: Animals observed 15 minutes after administration of the test article, then at 1, 2 and 4 hours, and daily for the 14 day study period. After the 14 day observation period if abnormal clinical signs persist, these examinations will be continued.
- Body weight: The day before treatment (day -1), immediately before treatment (day 1), on days 8 ond 15 and at death from day 2 onwards.
- Necropsy: At day 15, all surviving animals will be euthanatized by carbon dioxide inhalation and necropsied.
All animals (including found dead/moribund animals) will be submitted to full necropsy procedure including on examination of :
the external surface, all orifices and the thoracic, abdominal and pelvic cavities ond viscera .
- Organ/tissue preservation and histopathology: For all the animals surviving for 24 hours or more after administration of the test article, organs with macroscopic lesions could be kept in fixative (10 % formalin), and with the agreement of the sponsor, will be examined by a pathologist.

Statistics:

Data from concurrent controls and historical data from control rats will be used to assess effects.
Statistical analysis will be performed where appropriate using the following currently accepted methods :
. body weights : analysis of variance ond Student t test (LD 50),
. mortality rate will be calculated (as a percentage) to determine the innocuity or degree of toxicity of the test article,
. calculation of the LD50 expressed in mg of the test article per kg of body weight, with a 95 % confidence limit interval evaluated according to Bliss ond Litchtield & Wilcoxon's methods.

Results and discussion

Preliminary study:

Doses: 500, 1000, 2000 mg/kg
2 animals per sex per doses
No mortality observed

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: All the animals showed subdued behaviour 2 hours after administration of the test article. All animals were normal on Day 2 onwards.

Gross pathology:

There were no macroscopic findings that could be associated with treatment.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD 50, by the oral route, in the rat (male and female) > 2000 mg/kg.