Registration Dossier

Diss Factsheets

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 the assessment.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
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:
EU Method B.3 (Acute Toxicity (Dermal))
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

Constituent 1
Chemical structure
Reference substance name:
Pent-3-enenitrile
EC Number:
225-060-7
EC Name:
Pent-3-enenitrile
Cas Number:
4635-87-4
Molecular formula:
C5H7N
IUPAC Name:
(3E)-pent-3-enenitrile
Details on test material:
- Name of test material (as cited in study report): Trans-pentene-3 nitrile (T3PN)
- 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: 157-174 (males), 168-174 (females)
- Fasting period before study: no
- Housing: 1 animal per cage (37.5 x 17 x 15 cm)
- Diet: IFFARAT, ad libitum
- Water: ad libitum
- Acclimation period: no data


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


IN-LIFE DATES: no data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: aqueous dispersion of arabic gum 10%
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: no data
- Type of wrap if used: aluminium + adhesive tape


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


TEST MATERIAL
- Amount(s) applied: 1 to 5 mL/kg
- Concentration: 20 %
- Constant volume or concentration used: no


VEHICLE
- Amount(s) applied (volume or weight with unit): aqueous dispersion of arabic gum 10%
Duration of exposure:
24 h
Doses:
0, 200, 400, 600, 800, 1000 mg/kg
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
   body weight: days 0, 1, 2, 4, 7 and 14
Behaviour and mortality: at 1, 2, 6 h and daily until day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Probit, Litchfield & Wilcoxon, Arcsinus

Results and discussion

Preliminary study:
3 groups of 4 animals (2 males, 2 females) were given once a dose of 100,  500 or 1000 mg/kg. The animals were then observed during 14 days. At 100 mg/kg, no animals died. At 500 mg/kg, 2/4 animals died (the 2  males). At 1000 mg/kg, all the animals died.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
369 mg/kg bw
Based on:
test mat.
95% CL:
>= 264 - <= 515
Sex:
male
Dose descriptor:
LD50
Effect level:
259.45 mg/kg bw
Based on:
test mat.
95% CL:
>= 78.7 - <= 383.1
Remarks on result:
other: Males are more sensitive than females.
Sex:
female
Dose descriptor:
LD50
Effect level:
524.6 mg/kg bw
Based on:
test mat.
95% CL:
>= 305.7 - <= 753.4
Mortality:
See Table 7.2.3/2
Clinical signs:
Reduced activity, apathy, ptosis. No signs of  irritation was observed at all the tested doses.
Body weight:
See table 2 in the attached document
Gross pathology:
Haemorrhagic lungs, congestioned derma and thickening of the peritoneum were observed in the animals died during the study. No abnormalities 
were noted in the animals sacrificed at the end of the study.
Other findings:
No data

Any other information on results incl. tables

Table 7.2.3/2: Number of animals dead

Dose
(mg/kg bw)

Mortality (# 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 (M)

400

3/5

3/5

6/10

Day 1 (M+F)

600

5/5

1/5

6/10

Day 1 (M+F)

800

5/5

4/5

9/10

2 h (3M), 6 h (2M), day 1 (4F)

1000

5/5

5/5

10/10

2 h (3M), 6 h (2M+1F), day 1 (3F), day 4 (1F)

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 dermal LD50 calculated in male rats, trans-pentene-3 nitrile is classified in Category 3 (H311, toxic in
contact with skin) according to the CLP 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, groups of Sprague-Dawley rats (5/sex) were exposed to trans-pentene-3 nitrile (purity unknown) in an aqueous dispersion of arabic gum 10% for 24 hours at doses of 0, 400, 600, 800 and 1000 mg/kg bw.  Animals then were observed for 14 days. Reduced activity, apathy and ptosis were observed during the study. However, no sign of skin irritation was noted.

 

Dermal LD50Combined = 369 mg/kg bw (264-515 mg/kg bw)

LD50 males = 259.4 mg/kg bw

LD50 females = 524.6 mg/kg bw.

 

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

 

Under the test conditions,trans-pentene-3 nitrile is classified in Category 3 (H311, Toxic in contact with skin) according to the CLP Regulation 1272/2008/EC and as toxic in contact with skin (T; R24) according to the Directive 67/548/EEC.