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Toxicological information

Acute Toxicity: dermal

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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-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 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

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: 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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
833 mg/kg bw
Based on:
test mat.
95% CL:
>= 671 - <= 1 034
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.
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:
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 at the site of application of the test 
substance.
Body weight:
No specific effect was noted.
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.