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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:
31. May 2005 - 21. Sep 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): N-VINYLFORMAMIDE
- Analytical purity: 99.1 area-% (
- Lot/batch No.: Pr. Nr. 71500
- Stability under test conditions: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility .

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland.
- Age at study initiation: Young adult animals (female animals approx. 8- 12 weeks).
- Weight at study initiation: 179 g (mean)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, FRG).
- Diet: Kliba-Labordiät (Maus / Ratte Haltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12 / 12 (6.00 a .m. - 6 .00 p.m. / 6 .00 p.m. - 6.00 a .m.)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.93 ml/kg

Doses:
1000 and 2000 mg/kg bw
No. of animals per sex per dose:
6 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study . Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 1. Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals. A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
1 000 - 2 000 mg/kg bw
Mortality:
Four animals of the 2000 mg/kg administration groups and one animal of the 1000 mg/kg administration groups were found dead on study days 1 and 2, respectively.
Clinical signs:
Clinical observation in the 2000 mg/kg administration groups revealed impaired and poor general state, dyspnoea, lateral position, staggering, piloerection, salivation and lacrimation and were observed from hour 0 until including study day 6 after administration.
Clinical observation in the 1,000 mg/kg administration groups revealed impaired general state, dyspnoea, staggering, piloerection, salivation and lacrimation and were observed from hour 0 until including study day 5 after administration.

Body weight:
The mean body weights of the surviving animals of the administration groups increased throughout the study period .
Gross pathology:
The following macroscopic pathologic findings were observed in the animals that died:
- Few (2-5) or several (6-10), black erosions/ulcers in the glandular stomach, diameter 1 mm or up to 4 mm (2,000 mg/kg: 4 females).
- Slight red or red discoloration of contents of the small intestine (2,000 mg/kg: 2 females).
- Many (>10), black erosions/ulcers in the glandular stomach, diameter 1 mm; dark red discoloration of contents of the large intestine; red discoloration of the small intestine; beige discoloration of the liver (1,000 mg/kg: 1 female).

No macroscopic pathologic abnormalities were noted in the animals examined at termination of the study (2,000 mg/kg: 2 females; 1,000 mg/kg: 5 females).

Any other information on results incl. tables

Mortality:

Dose (mg/kg bw)

1000

2000

Administration

1

2

1

2

No. of animals

3

3

3

3

 

after

 

 

 

 

day 1

0

0

0

2

day 2

0

1

1

3

day 14

0

1

1

 

Mortality

1 / 6

4 / 6

 

Maximum incidence (and maximum duration) of clinical findings:

Dose (mg/kg bw)

1000

2000

Administration

1

2

1

2

No. of animals

3

3

3

3

 

Impaired general state

3

(h0-d1)

3

(h0-d5)

3

(h0-d6)

3

(h0-h4)

Poor general state

-

 

-

 

-

 

1

(d1)

Dyspnoea

3

(h0-d1)

3

(h0-d5)

3

(h0-d6)

3

(h0-d1)

Lateral position

-

 

-

 

-

 

1

(d1)

Staggering

3

(h2-d1)

2

(h3-d1)

1

(h1-d1)

3

(h0-h4)

Piloerection

3

(d1)

1

(d1-d2)

3

(d1-d6)

-

Salivation

3

(h1-h3)

2

(h0-h2)

3

(h0-h4)

3

(h0-d1)

Lacrimation

2

(h1-h2)

3

(h1-d1)

3

(h0-h3)

3

(h0-d1)

 

Individual body weights:

Dose 1000 mg/kg bw, Administration 1

Weightday

0

7

14

at death

Animal 994

181

196

211

 

Animal 995

183

191

205

 

Animal 996

179

182

217

 

 

Dose 1000 mg/kg bw, Administration 2

Weightday

0

7

14

at death

Animal 118

180

 

 

169 (d2)

Animal 119

182

193

215

 

Animal 120

183

204

217

 

 

Dose 2000 mg/kg bw, Administration 1

Weightday

0

7

14

at death

Animal 010

174

 

 

163 (d2)

Animal 011

170

175

194

 

Animal 012

171

187

201

 

 

Dose 2000 mg/kg bw, Administration 2

Weightday

0

7

14

at death

Animal 043

180

 

 

175 (d2)

Animal 044

179

 

 

177 (d1)

Animal 045

181

 

 

168 (d1)

 

 

 

 

 

 

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information criteria for interpretation: EU/GHS
Conclusions:
Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 1000 mg/kg bw and less than 2000 mg/kg bw in rats.
Executive summary:

The study is reliable without restriction (GLP-study according to OECD guideline 423).

Single doses of 2000 and 1000 mg/kg bw of the unchanged test material were given to four administration groups of three fasted female Wistar rats, each, by gavage in a sequential manner. After administration a 14 -day observation period followed.

Four animals of the 2000 mg/kg administration groups and one animal of the 1000 mg/kg administration groups were found dead from study day 1 until including study day 2.

Clinical observation in the 2000 mg/kg administration groups revealed impaired and poor general state, dyspnoea, lateral position, staggering, piloerection, salivation and lacrimation. Findings were observed from hour 0 until including study day 6 after administration. Clinical observation in the 1000 mg/kg administration groups revealed impaired general state, dyspnoea, staggering, piloerection, salivation and lacrimation. Findings were observed from hour 0 until including study day 5 after administration.

The mean body weights of the surviving animals of the administration groups increased throughout the study period.

During necropsy findings in the animals that died in the 2000 mg/kg and 1000 mg/kg administration groups comprised few, several or many black erosions/ulcers in the glandular stomach and red or slight red discoloration of contents of the small intestine. In addition one animal of the 1000 mg/kg administration group that died showed dark red discoloration of contents of the large intestine and beige discoloration of the liver. No macroscopic pathologic abnormalities were noted in the surviving animals of the 2000 mg/kg and 1000 mg/kg administration groups examined at the end of the observation period.

Conclusion: Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 1000 mg/kg bw and less than 2000 mg/kg bw in rats.