(Z)-pent-2-enenitrile

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

occlusive dressing

Principles of method if other than guideline:

Not applicable

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: 169-179 g (males), 163-165 g (females)
- Fasting period before study: no data
- Housing: cage dimension 37.5 x 17 x 15 cm, 1 animal 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: No data


IN-LIFE DATES: No data

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: on the back
- % coverage: no data
- Type of wrap if used: aluminium and sparadrap


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No


TEST MATERIAL
- Amount(s) applied: 0.98, 1.22 or 1.46 ml/kg
- Constant volume or concentration used: no

Duration of exposure:

24 hours

Doses:

0, 800, 1000, 1200 mg/kg bw

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

yes, concurrent no treatment

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:         
Clinical signs and mortality: immediately after exposure, then 1, 2, 6h after administration of the test substance, and then daily until day 14
Body weight: at 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:

A preliminary study was conducted. Three groups (2M + 2F each) were exposed  in the same conditions (except the use of an aqueous dispersion of 10%  arabic gum as vehicle for 100 and 500 mg/kg bw) to 100, 500 and 1000 mg/kg of 2-pentene nitrile,  and observed for 14 days. At 100 mg/kg, no mortality was observed. At 500 mg/kg, 2/2 males and 0/2 females died. At 1000 mg/kg, 2/2 males and 1/2 females died.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

833 mg/kg bw

Based on:

test mat.

95% CL:

>= 671 - <= 1 034

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

< 800 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Males are more sensitive than females. At 800 mg/kg bw all male rats died.

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1 039 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 7.2.3/2

Clinical signs:

other: One and six hours after exposure, reduced spontaneous activity, ptosis, apathy and tremor were noted in animals. Then, during the first day after  administration, some animals showed a reduced spontaneous activity and tremor. No local effect was observed 

Gross pathology:

The autopsy of animals died during the test revealed:
- haemorrhagic lungs,
- pale and mottled liver,
- thickened peritoneum,
- haemorrhagic patch on the skin.
No macroscopic abnormalities were observed in the surviving animals.

Other findings:

No other fingings.

Any other information on results incl. tables

Table 7.2.3/2: Number of animals dead

Dose (mg/kg bw)	Volume (mL/kg)	Mortality (# dead/total)			Time range of deaths
		Male	Female	Combined
0	-	0/5	0/5	0/10	-
800	0.98	5/5	0/5	5/10	6 h (2M); 1 d (3M)
1000	1.22	3/5	3/5	6/10	1 d (all animals)
1200	1.46	5/5	4/5	9/10	6 h (4M+3F); 1 d (1M+1F)

M = Males; F = Females

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 Male LD50, Cis-Pentene-2 Nitrile commercial is classified in Category 3 (H311) according to the
Regulation 1272/2008/EC and as toxic in contact with skin (T; R24) according to the Directive 67/548/EEC.

Executive summary:

In an acute dermal toxicity study performed similarly to the OECD test guideline No. 402, groups of Sprague-Dawley rats (5/sex/group) were exposed to Cis-Pentene-2 Nitrile commercial undiluted for 24 hours at doses of 0, 800, 1000 and 1200 mg/kg bw.  Animals then were observed for 14 days. A preliminary study was conducted. In this study, 3 groups (2M + 2F) were exposed to 100, 500 and 1000 mg/kg of 2-pentene nitrile and observed for 14 days. At 100 mg/kg, no mortality was observed. At 500 mg/kg, 2/2 males and 0/2 females died. At 1000 mg/kg, 2/2 males and 1/2 females died.

 In the main study, during the first day after administration, some animals showed a reduced spontaneous activity and trembling. No local effect was observed at the application site.

The autopsy of the animals died during the test revealed haemorrhagic lungs, pale and mottled livers, thickened peritoneum and haemorrhagic patch on the skin.

In the main study, the dermal LD₅₀are the following

Dermal LD₅₀Combined = 833 mg/kg bw (671-1034 mg/kg bw)

Dermal LD₅₀Males < 800 mg/kg bw (lowest dose tested) (all the male rats died)

Dermal LD₅₀Females = 1039 mg/kg bw

At equivalent dose level, mortality was more pronounced in males than in females.

 

Under the test conditions, based on LD₅₀in males and based on the fact that all male rats died at 500 mg/kg in the preliminary study, Cis-Pentene-2 Nitrile commercial is classified in a conservative way as Category 3 (H311) according o the Regulation 1272/2008/EC and as

toxic in contact with skin (T; R24) according to the Directive 67/548/EEC.