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Toxicological information

Acute Toxicity: oral

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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-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
304 mg/kg bw
Based on:
test mat.
95% CL:
>= 236 - <= 392
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
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:
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 day 45  (autopsy was delayed for this group). No reversibility was observed.
Body weight:
In male rats, no significant difference was observed between the treated and the control groups.
In female rats of all treated groups, the mean body weight was significantly lower when compared to the control group.
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.