(Z)-pent-2-enenitrile

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-10-18 to 1991-05-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

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:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1150 (Acute inhalation toxicity)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(Z)-pent-2-enenitrile

EC Number:

247-323-5

EC Name:

(Z)-pent-2-enenitrile

Cas Number:

25899-50-7

Molecular formula:

C5H7N

IUPAC Name:

(2Z)-pent-2-enenitrile

Details on test material:

- Name of test material (as cited in study report): cis-2-Pentenenitrile
- Physical state: colorless liquid
- Stability under test conditions: the test material was assumed to be stable throughout the exposure phase of the study

Test animals

Species:

rat

Strain:

other: CRL: CD BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River breeding laboratories, Raleigh, North Carolina
- Age at study initiation: approximately 8 weeks old (7 weeks old upon arrival)
- Weight at study initiation: 240-299 g (males), 175-235 g (females)
- Fasting period before study: no
- Housing: singly or in pairs (sexes separate) in 8 x 14 x 8 suspended, stainless steel, wire mesh cages
- Diet: except during exposure, Purina certified rodent chow #5002 ad libitum
- Water: except during exposure, water from the Wilmington Suburban Water Corporation ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature: 23 +/- 2 °C
- Humidity: 50 +/- 10 %
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 1990-10-18 To: 1990-11-27

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose-only
- Exposure chamber volume: 29-L cylindrical glass
- Method of holding animals in test chamber: perforated, polycarbonate cylinders with conical nose pieces were inserted into the exposure chamber
- Source and rate of air: Brooks Sho-Rate rotameter, 35 L/min
- Method of conditioning air: chamber atmospheres were exhausted through a 1-L glass impinger containing sodium hydroxyde, a dry-ice cold trap, and a MSA particulate filter then discharged into the fume hood.
- Atmosphere generation: vaporization of the test material in a stream of filtered air heated to 100 °C. The test material was metered into a J-shaped glass tube containing 6 mm glass beads with a Harvard apparatus model 22 compact infusion pump. Chilled, filtered dilution air was added to the heated air/test material mixture. The generated train then fed into the exposure chamber with a baffle positioned in the airstream to aid in the distribution of the test material within the chamber.
- Temperature: 23-28 °C, measured continually with a Omega Type K thermocouple thermometers and recorded at least 7 times during each
exposure.
- Humidity: 21-58 %, measured once during each exposure with a Reuter-Stokes model RSS-230 Micro-psychrometer.
- Oxygen concentration: 21 % and measured with a Biosystems Model 3100R oxygen monitor 1 time during each exposure. Chamber relative
humidity and chamber temperatures were out of the targeted rang, these chamber conditions were not considered to have adversly affected the
validity of this study.


TEST ATMOSPHERE
- Brief description of analytical method used: approximately 3-liter samples of chamber tmospheres were drawn from the breathing zone of the rats through two glass, fritted midget impingers connected in tandem. The impingers were each filled with 10 mL of acetonitrile. The resulting solution obtained from the tandem impingers was analized by gas chromatography, using flame ionization as the method of detection. The atmospheric concentration of the cis-2-Pentenenitrile in these samples was determined by comparison of liquid standards prepared in acetonitrile. Prior to the test exposure, gravimetric samples were taken from the chamber in order to confirm that no aerosol had been created by the method of generation used in this study.
- Samples taken from breathing zone: yes
- Other: the chamber distribution of the vapor was characterized under a separate investigation by taking impinger samples from several different locations on the chamber face plate in the breathing zone of rats.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

18, 140, 650, 900 and 1200 ppm

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (18 ppm), 28 days (140, 650, 900 and 1200 ppm) due to the persistance of
clinical signs.
- Frequency of observations and weighing: immediately after they were removed from the restrainers, following exposure and then each day during
the 14- or 28-day post-exposure period
- Necropsy of survivors performed: no

Statistics:

Probit analysis was used for the determination of the EC50

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

850 ppm

95% CL:

>= 740 - <= 970

Exp. duration:

4 h

Remarks on result:

other: 2.82 mg/L (analytical concentration)

Mortality:

Mortality was 0/10, 0/10, 0/10, 8/10, and 9/10 at 18, 140, 650, 900, and 1200 ppm, respectively. The majority of the rats died within 1-2 days
following exposure, with the exception of one female rat exposed at 900 ppm that died 4 days following exposure. There were no sex-related
differences in the response of rats in this study based on the lethality. See Table 7.2.2/2.

Clinical signs:

other: Clinical signs of toxicity could not be assessed during exposure because the method of restraint prevented clear visual observation of the rats. During exposures, tapping on the chamber elicited a response from all rats. Upon removal of the rats from re

Body weight:

By the first day following exposure, most rats exhibited weight loss. Male rats exposed to 18 ppm cis-2-pentenenitrile lost from 2-4% of their initial body weight, while females lost from 0.3-4% of their initial body weight. At higher concentrations (exposures >=140 ppm), male rats lost from 10-17% and females lost 4-14% of their initial body weight. Generally, all rats gained weight over the recovery period, but surviving rats exposed at all levels experienced some periods of transient body weight loss throughout the recovery period.

Gross pathology:

Not applicable

Other findings:

A number of clinical signs that were observed were suggestive of central nervous system effects. These included abnormal gait and mobility, ataxia, hyperreactivity, hypersensitivity, tremors, forward circling, backward circling, splaying of the feet, bobbing of the head, vocalizations, chattering of the teeth, rolling behavior, wobbling behavior, and walking backward. Effects such as abnormal gait, ataxia, circling behavior, head bobbing movement, vocalizations, and tremors were noted in non-lethal levels as low as 140 ppm. Many of these effects appeared reversible within 1-4 days following exposure. However, abnormal gait and mobility, circling behaviors, splaying of the feet, and head bobbing movement were observed throughout the 28-day recovery period in rats exposed at concentrations of 650 ppm or greater. These clinical signs, when present in rats exposed at 140 ppm, were not as persistent as in rats exposed at levels greater than 140 ppm. Other clinical signs noted during the recovery period included alopecia, lung noise, weakness, and stained perineum.

Any other information on results incl. tables

Table 7.2.2/2: Number of animals dead and time range within which mortality occurred

Analytical concetration (ppm)	Mortality (# dead/total)			Time range of deaths
	Male	Female	Combined
18	0/5	0/5	0/10	-
140	0/5	0/5	0/10	-
650	0/5	0/5	0/10	-
900	5/5	3/5	8/10	1 d (3M), 2 d (2M, 2F), 4 d (1F)
1200	4/5	5/5	9/10	1 d (4M, 4F), 2 d (1F)

M = male

F = female

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions,cis-2-Pentenenitrile is classified in Category 3 (H331; Toxic if inhaled) according to the CLP Regulation (1272/2008) and as harmful by inhalation (Xn; R20) according to the Directive 67/548/EEC.

Executive summary:

In an acute inhalation toxicity study performed similarly to the OECD test guideline No. 403 (1981) and in compliance with EPA GLP, groups of 8-weeks old Crl:CD®BR rats (5/sex) were exposed by nose-only inhalation to vapors of cis-2-Pentenenitrile (98.6 % pure) for 4 hours at concentrations of 0.06, 0.46, 2.16, 2.99 or 3.98 mg/L (18, 140, 650, 900 or 1200 ppm) . Animals were then observed for 14 or 28 days due to the persistence of clinical signs.

 

Mortality occurred at 2.99 and 3.98 mg/L. There were no sex-related differences in the response of rats in this study based on the lethality.

 

LC₅₀Combined = 2.82 mg/L (2.45 -3.22 mg/L)

 

The clinical observations made during the recovery period in rats exposed at a level of 0.46 mg/L or greater were indicative of central nervous system effects. These observations included abnormal gait and mobility, hyperreactivity, hypersensitivity, muscle fasciculations, tremors and chattering of the teeth. Many of these clinical signs were absent within 1 to 4 days of their initial observation. However, other observations such as circling behavior, splaying of the feet, and head bobbing movement were observed throughout much of the recovery period.

 

Under the test conditions,cis-2-Pentenenitrile is classified in Category 3 (H331; Toxic if inhaled) according to the CLP Regulation (1272/2008) and as harmful by inhalation (Xn; R20) according to the Directive 67/548/EEC.