(Z)-pent-2-enenitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study similar to recognised test guideline and sufficiently described for assessment.

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:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

standard acute oral  toxicity assay

GLP compliance:

no

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-pentene-2 nitrile commercial (C2PN COM)
- Physical state: clear liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: IFFA CREDO
- Age at study initiation: no data
- Weight at study initiation: 150-152 g (males), 150-156 g (females)
- Fasting period before study: yes, approximately 17h before test substance administration
- Housing: cage dimension 37.5 x 23.5 x 16 cm, 5 animals per cage
- Diet: IFFARAT, ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature: 22°C +/- 1°C
- Humidity: 50% +/- 10%
- Air changes: 8 per hr
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: No data

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: aqueous suspension of 10% arabic gum

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5 %
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: 8 mL/kg

- Rationale for the selection of the starting dose: A preliminary study was conducted. 5 groups (2M + 2F each) were exposed  to 100, 500, 1000, 2500 or 5000 mg/kg of 2-pentene nitrile, and observed  for 14 days. 

Doses:

0, 200, 300 and 400 mg/kg bw

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days (up to 45 days in the high dose group)
- Frequency of observations and weighing:
 * Clinical signs and mortality: immediately after exposure, then 1, 2 and 6 hours after administration of the test substance, and daily until day 14.       
* Body weight: on days 0, 1, 2, 4, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

The LD50 was calculated by the method of Litchfield and  Wilcoxon

Results and discussion

Preliminary study:

100 % mortality was observed at 500 mg/kg bw and above.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

304 mg/kg bw

Based on:

test mat.

95% CL:

>= 236 - <= 392

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

198 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Males are more sensitive than females

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

517 mg/kg bw

Based on:

test mat.

Mortality:

At equivalent dose level, mortality was more pronounced in males than in females. See detailed results in table 7.2.1/2.

Clinical signs:

other: Most of the animals showed an increased spontaneous activity, with a lack of coordination in the movements. Apathy, ptosis, piloerection, stumbing and unsteadiness were also observed in all treated animals. In the high dose group, these symptoms persist 

Gross pathology:

The autopsy of animals died during the test revealed:
- irritated and dilated stomac,
-hemorrhagic lungs,
-hemorrhagic digestive system,
- thickened peritoneum (hemorrhagic).
No macroscopic abnormalities were observed in the surviving animals.

Other findings:

No remarks

Any other information on results incl. tables

Table 7.2.1/2: Number of animals dead

 

Dose (mg/kg bw)	Mortality (n°dead/total)			Time range of deaths
	Male	Female	Combined
0	0/5	0/5	0/10	-
200	2/5	0/5	2/10	6 h
300	5/5	0/5	5/10	6 h (3 males), day 1 (2 males)
400	5/5	2/5	7/10	6 h ( all males), 1 d (1 female), 2 d (1 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 and based on the oral LD50 Males = 198 mg/kg bw, Cis-Pentene-2 Nitrile commercial is classified in Category 3 (H301:
Toxic if swallowed) according to the Regulation 1272/2008/EC and as toxic if swallowed (T, R25) according to the Directive 67/548/EEC.

Executive summary:

In an acute oral toxicity study performed similarly to the OECD test guideline No. 401, groups of fasted Sprague-Dawley rat (5/sex/group) were given a single oral dose of Cis-Pentene-2 Nitrile commercial in aqueous suspension of 10% arabic gum at doses of  0, 200, 300 or 400 mg/kg bw and observed for 14 days (up to 45 days in the high dose group). Most of the animals showed an increased spontaneous activity, with a lack of coordination in the movements. Apathy, ptosis, piloerection, stumbing and unsteadiness were also observed in all treated animals. In the high-dose group, these symptoms persist at day 14 and 45, no reversibility was observed.

Females of all the treated groups had significantly reduced bodyweights compared to controls.

The oral LD₅₀ are the following:

Oral LD₅₀ Combined = 304 mg/kg bw (236-392 mg/kg bw)

Oral LD₅₀ Males = 198 mg/kg bw

Oral LD₅₀ Females = 517 mg/kg bw

 At equivalent dose level, mortality was more pronounced in males than in females. Therefore the LD₅₀ identified in male rats was chosen for classification.

 Under the test conditions, Cis-Pentene-2 Nitrile commercial is classified in Category 3 (H301: Toxic if swallowed) according to the Regulation 1272/2008/EC and as toxic if swallowed (T; R25) according to the Directive 67/548/EEC.