Pent-3-enenitrile

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1970

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment, no details provided. Only one dose of 3-PN was tested.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well conducted study although some information are missing.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Six ChR-cd male rats were exposed to the test material in a 16 L bell jar for 4 hours. The test substance was metered at a uniform rate into a heated stainless steel T-tube by a syringe drive and vaporized under prepurified nitrogen. The test material vapors were mixed with oxygen and carried into the bell jar. Houseline air was used as diluent to give the desired atmospheric concentration. Gross and histopathologic examinations were performedon two rats each at 1, 2, 7 and 14 days post exposure. The other survivors were sacrified 14 days post-exposure.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

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 g
- Fasting period before study: no data
- Housing: no data
- 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

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Male rats were exposed to the test material in a 16 L bell jar for 4 hours. The test substance was metered at a uniform rate into a heated stainless steel T-tube by a syringe drive and vaporized under prepurified nitrogen. The test material vapors were mixed with oxygen and carried into the bell jar.
Houseline air was used as diluent to give the desired atmospheric concentration.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gas samples were taken periodically from the chamber exit and analyzed by gas chromatography.

Duration of exposure:

4 h

Concentrations:

338, 359, 447, 538, and 692 ppm

No. of animals per sex per dose:

6 animals per dose

Control animals:

not specified

Details on study design:

Gross and histopathologic examinations were performed on 2 rats each at 1, 2, 7, and 14 days post- exposure. Tissues examined included lungs, liver, spleen, kidney, testes, and thymus. The other survivors were sacrificed 14 days post-exposure.

Statistics:

Litchfield and Wilcoxin (1949)

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

420 ppm

Based on:

test mat.

95% CL:

>= 362 - <= 478

Exp. duration:

4 h

Remarks on result:

other: 1.391 mg/L air (1.2-1.58)

Mortality:

No data.

Clinical signs:

other: At lethal concentration: irregular respiration, hyperemia, red discharge around eyes, tremors, salivation, pale ears and first death within 150 min were observed during exposure. Death overnight and hypersensitivity were noted after exposure. At non-letha

Body weight:

Initial weight loss followed by normal weight gain.

Gross pathology:

No anatomical evidence of primary injury.

It was apparent that inhalation of 3 -Pentene nitrile exerted some sort of stress on the animals, but the nature of this effect was not revealed by microscopic examination of the tissues that were examined.

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Under the test conditions, 3-Pentene Nitrile is classified in Category 2 (H330: fatal if inhaled) according to the CLP Regulation 1272/2008/EC and as toxic by inhalation (T; R23) according to the Directive 67/548/EEC.

Executive summary:

In an acute inhalation toxicity study, groups of ChR-CD rats (6 males) were exposed to 338, 359, 447, 538 and 692 ppm of 3-Pentene nitrile vapors in a 16-liter bell jar for 4 hours.Gross and histopathologic examinations were performed on 2 rats eachat 1,2, 7, and 14 days post- exposure. Tissues examined included lungs, liver, spleen, kidney, testes, and thymus.The other survivors were sacrificed 14 days post-exposure

 

 LC₅₀Males = 1.391 mg/L (420 ppm) (1.2 -1.58 mg/L)

 

At lethal concentration, irregular respiration, hyperemia, red discharge around eyes, tremors, salivation, pale ears and hypersensitivity were observed during and after exposure. Death occurred from 2.5 hours to overnight.

At non-lethal concentration, irregular respiration, incoordination, red discharge from nose, hindleg tremors and incontinence were observed during and after exposure.

 Under the test conditions, 3-Pentene Nitrile is classified in Category 2 (H330: Fatal if inhaled) according to the CLP Regulation 1272/2008/EC and as toxic by inhalation (T; R23) according to the Directive 67/548/EEC.

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:

The subacute exposure procedure was the same than described in (Acute Inh. tox. V2 1970 JAPP). Six rats 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. Three control and three test rats were sacrified after the tenth exposure; the remaining three control and three rats were sacrificed following a 14-day recovery period.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pent-3-enenitrile

EC Number:

225-060-7

EC Name:

Pent-3-enenitrile

Cas Number:

4635-87-4

Molecular formula:

C5H7N

IUPAC Name:

(3E)-pent-3-enenitrile

Details on test material:

- Name of test material (as cited in study report): 3-Pentene nitrile

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 g
- Fasting period before study: no data
- Housing: no data
- 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

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: No data

Details on inhalation exposure:

Male rats were exposed to the test material in a 16 L bell jar for 4 hours. The test substance was metered at a uniform rate into a heated stainless steel T-tube by a syringe drive and vaporized under prepurified nitrogen. The test material vapors were mixed with oxygen and carried into the bell jar.
Houseline air was used as diluent to give the desired atmospheric concentration.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Gas samples were taken periodically from the chamber exit and analyzed by gas chromatography.

Duration of treatment / exposure:

2 weeks

Frequency of treatment:

4 hours/day (total of 10 exposures)

Doses / concentrations

Dose / conc.:

55 ppm

Remarks:

Basis: analytical conc.

No. of animals per sex per dose:

6 males/doses

Control animals:

other: Other: control rats were exposed to oxygen and nitrogen.

Details on study design:

No data

Positive control:

No

Examinations

Observations and examinations performed and frequency:

Gross and histopathologic examinations were performed on 3 control and 3 test rats after the tenth exposure.
Tissues examined included lungs, liver, spleen, kidney, testes, and thymus.

Sacrifice and pathology:

The remaining 3 control and 3 test rats were sacrificed following a 14-day recovery period.

Statistics:

No

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 examined

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:

no effects observed

Details on results:

Mild hyperemia and red discharge around eyes were observed during exposure.
Gross and histopatologic examinations showed no evidence of primary injury.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Only mild hyperemia and red discharge around eyes were observed during exposure at the only dose tested (55 ppm). Exposure did not give any clinical or pathological indication of accumulation in exposed rats. Gross and histopatologic examinations showed no evidence of primary injury.

Executive summary:

In a subacute inhalation toxicity study, 3-Pentene nitrile was administered to male ChR-CD rats (6/dose) by dynamic whole body exposure at concentrations of 0 and 0.18 mg/L (55 ppm) for 4 hours per day, 6 days/week for a total of 10 exposures. 3PN was metered at a uniform rate into a stainless steel T-tube by a syringe drive and vaporized under prepurified nitrogen in a 16-liter bell jar.

Gross and histopathologic examinations were performed on 3 control and 3 test rats after the tenth exposure. Tissues examined included lungs, liver, spleen, kidney, testes, and thymus. The remaining 3 control and 3 test rats were sacrificed following a 14 -day recovery period.

 

Only mild hyperemia and red discharge around eyes were observed during exposure at 55 ppm (0.18 mg/L). Exposure did not give any clinical or pathological indication of accumulation in exposed rats. Gross and histopatologic examinations showed no evidence of primary injury.