2-methyl-3-butenenitrile

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

No data

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Only one dose was tested. The purity is not indicated. Few data are available. No conclusion can be made.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1970

Report date:

1970

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Six ChR-CD male rats were exposed to the test substance an a 16-liter bell jar for four hours. The animals were exposed for four hours each day for two weeks (total of ten exposures). Control rats were exposed to oxygen and nitrogen for the same amount of time. The test substance was administered at a uniform rate into a jeated (140-165 °C ) stainless steel T-tube by a syringue drive and vaporized under prepurified nitrogen. The test substance vapors were mixed with oxygen and carried into the bell jar; houseline air was used as diluent to give the desired atmospheric concentration.
For analysis, gas samples were taken periodically from the chamber exit and analyzed by a gaz chromatographic method.
Three control and three test rats were sacrified after the tenth exposure; the remaining three control and three test rats were sacrified following a 14-day recovery period. Gross and histopathologic examinations were performed.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl-3-butenenitrile

EC Number:

240-596-1

EC Name:

2-methyl-3-butenenitrile

Cas Number:

16529-56-9

Molecular formula:

C5H7N

IUPAC Name:

2-methylbut-3-enenitrile

Details on test material:

- Name of test material (as cited in study report): 2-methyl-3-butenenitrile (2M3BN)
- Substance type: No data
- Physical state: No data
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: No data

- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: No data
- Other: No data

Test animals

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 250-289 grams
- Fasting period before study: No data
- Housing: in cages
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
No data


IN-LIFE DATES: No data

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Remarks:

houseline air

Vehicle:

other:

Remarks on MMAD:

MMAD / GSD: No data

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
No data


TEST ATMOSPHERE
- Brief description of analytical method used: No data
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable): houseline air was used as diluent to give the desired atmospheric concentration
- Concentration of test material in vehicle (if applicable): houseline air was used as diluent to give the desired atmospheric concentration
- Justification of choice of vehicle: the test substance was mixed with oxygen and houseline air was used as diluent to give the desired atmospheric concentration
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

For analysis, gas samples were taken periodically from the chamber exit and analyzed by a gaz chromatographic method.

Duration of treatment / exposure:

Two weeks (total of ten exposures).

Frequency of treatment:

For four hours daily

Doses / concentrations

Remarks:

Doses / Concentrations:
560 ppm
Basis:
analytical conc.

No. of animals per sex per dose:

6

Control animals:

yes

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data


BODY WEIGHT: Yes


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data


WATER CONSUMPTION: No data
- Time schedule for examinations: No data


OPHTHALMOSCOPIC EXAMINATION: No data


HAEMATOLOGY: No data


CLINICAL CHEMISTRY: No data


URINALYSIS: No data


NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not specified

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY
Irregular respiration, hyper-sensitivity, red discharge around eyes, salivation, pale ears, pilo-erection during 5th, 6th and 8th exposures.
No mortality.
Normal gain weight gain post-exposure.


BODY WEIGHT AND WEIGHT GAIN
No weight gain during test period


GROSS PATHOLOGY
No evidence of primary injury by 2-methyl-3-butenenitrile.

HISTOPATHOLOGY: NON-NEOPLASTIC
No histological evidence of primary injury by 2-methyl-3-butenenitrile in any of the tissues (lungs, liver, spleen, kidney, testes and thymus) that were examined.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No additional data

Applicant's summary and conclusion

Executive summary:

In a repeated dose toxicity, Six ChR-CD male rats were exposed to 2 -methyl-3 -butenenitrile for four hours each day for two weeks (total of ten exposures) at 560 ppm. Control rats were exposed to oxygen and nitrogen for the same amount of time. Three control and three test rats were sacrified after the tenth exposure; the remaining three control and three test rats were sacrified following a 14-day recovery period. Gross and histopathologic examinations were performed.

No clinical or pathologic indication of accumulation in exposed rats was observed. There were no histological evidence of primary injury by 2 -methyl-3 -butenenitrile, in any of the tissues examined. No mortality was observed.

Only one dose was tested, few data are available. Therefore non conclusion can be established.