Valeronitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: the study was performed according to OECD-/EU-testing guidelines, but not under GLP; therefore the study was considered to have Klimisch 2

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Dir. 79/831/EEC, Annex V

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Valeronitrile

EC Number:

203-781-8

EC Name:

Valeronitrile

Cas Number:

110-59-8

Molecular formula:

C5H9N

IUPAC Name:

pentanenitrile

Details on test material:

- Physical state: Colourless liquid
- Density: 0.804
- Quantity of test sample: ca. 200 g
- Date of receipt: 7 February 1983

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Centre d'élevage d'IFFA CREDO, 69210 Saint-Germain sur l'Arbresle
- Age at study initiation: 7 weeks old
- Weight at study initiation: 210-220 g males; 160-170 g females
- Housing: in groups à 2 or 5 animals in plastic cages
- Diet (e.g. ad libitum): Souriffarat food ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Fasting period: 18 hours before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 1.5°C
- Humidity (%): 55% +/- 15%
- Air changes (per hr): 10 renewals/hr
- Photoperiod (hrs dark / hrs light): not indicated

IN-LIFE DATES: From 09 feb 1983 To 10 march 1983

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Hydrogel Gum Arabic 10%

Doses:

MAIN TEST:
- Dose groups males: 0; 250; 325; 420; 550; 715 mg/kg
- Dose groups females: 0; 650; 715; 785; 865; 950 mg/kg

No. of animals per sex per dose:

MAIN TEST:
- Ten animals per sex and dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation, daily. Weighing at D0, D1, D2, D4, D7 and D14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Statistics:

Litchfield and Wilcoxon method

Results and discussion

Preliminary study:

PRETEST:
- Two animals per sex and dose
- Dose groups: 100; 250; 500; 1000; 1005; 2500; 5000 mg/kg

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

332 mg/kg bw

Based on:

test mat.

95% CL:

252 - 437

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

705 mg/kg bw

Based on:

test mat.

95% CL:

576 - 863

Mortality:

Details are given in the table below.

Clinical signs:

other: The following clinical symptoms were observed in one or more animals per dose groups, fifteen minutes or later after treatment: MALES: - 250 mg/kg: depression, ptosis - 325 - 715 mg/kg: depression, ptosis, prostration, piloerection, salivation, hyperexci

Gross pathology:

Surviving animals showed no abnormalites at necropsy. Animals that died during the study, all showed a peritoneum aspect edematous, and thickening of the glandular part of the stomach. In some animals, liver and spleen were discolored, and thymic involution greater or lesser degree was observed.

Any other information on results incl. tables

Males

Dose Level (mg/kg)	No. of deaths
0	0/10
250	1/10
325	7/10
420	7/10
550	9/10
715	9/10

 

Females

Dose Level (mg/kg)	No. of deaths
0	0/10
650	4/10
715	6/10
785	5/10
865	7/10
950	7/10

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity LD50 on Sprague-Dawley rats was determined to be 332 mg/kg for males and 705 mg/kg for females.

Executive summary:

The study was performed in 1983 according to EU-testing guideline B.1, but not in conformity with GLP-principles. The appropriate dose levels were determined in a preliminary test with a reduced number of animals. The main test was conducted with dose groups of 0-715 mg/kg for males and dose groups of 0-950 mg/kg for females. Most of treated animals expressed clinical symptoms, mortality was noted in all dose groups except the control group.

In this study, the acute oral toxicity LD50 on Sprague-Dawley rats was determined to be 332 mg/kg for males and 705 mg/kg for females.