N-vinylformamide

Acute Toxicity: oral

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

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-vinylformamide

EC Number:

236-102-9

EC Name:

N-vinylformamide

Cas Number:

13162-05-5

Molecular formula:

C3H5NO

IUPAC Name:

N-vinylformamide

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 or test system 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- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.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:

other: 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 adminis

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.