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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study report which meets basic scientific principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Principles of method if other than guideline:
Standardized test method (BASF test) to study the acute inhalative toxicity in rats after 4 hours of exposure.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
aerosol dispenser: not specified
Remarks:
migrated information: aerosol
Details on test material:
- Name of test material (as cited in study report): Vinylpyrrolidon
- Physical state: clear, liquid
- Analytical purity: >99%
- Impurities (identity and concentrations): 10 ppm N-N'-Di-2-butyl-p-phenylendiamin (stabilisator)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WIGA, Sulzfeld, D (SPF)
- Mean weight per group at study initiation: males: 182 - 219.5 g; females: 176 - 206 g
- Diet: Herilan MRH, H. Eggersmann KG, Rinteln, D; ad libitum
- Water: tap water ad libitum

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: permanent infusion pump (UNITA I, Braun, Melsungen, D)

TEST ATMOSPHERE
- Brief description of analytical method used: GC HP 5840 A; determination of the test substance in toluol
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
analytical: 0.8, 2.0, 2.8, 5.2 and 5.63 mg/L (mean of 4 measurements)
nominal: 9.4, 18.8, 28.2, 37.6 and 46.4 mg/L
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing was performed on day 0 before treatment, day 7 and day 14; clinical signs were observed daily
- Necropsy of survivors performed: yes
Statistics:
Probit analysis according to Finney, 1971

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
3.07 mg/L air (analytical)
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
2.87 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
3.32 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
0.8 mg/L: 0/10 males and 0/10 females
2.0 mg/L: 2/10 males and 3/10 females
2.8 mg/L: 7/10 males and 5/10 females
5.2 mg/L: 5/10 males and 8/10 females
5.63 mg/L: 8/10 males and 9/10 females
Mortality appeared 2 to 4 days after treatment
Clinical signs:
In all treatment groups, accelerated and intermittent respiration, disturbance of equilibrium to narcosis, bloody secretion of the eyes and nose were observed. In the 2.8 mg/L group, bloody urine was observed. Survivors were free from symptoms after 5-8 days.
Body weight:
Mean weight at day 0, day 7 and day 14 in g (total bw gain in brackets), based on data of the living animals at any one time

Males
Control: 182.0 - 203.6 - 250.0 (68)
0.8 mg/L: 219.5 - 247.0 - 273.0 (53.5)
2.0 mg/L: 203.8 - 232.0 - 278.0 (74.2)
2.8 mg/L: 208.0 - 223.0 - 225.0 (17.0)
5.2 mg/L: 197.0 - 203.0 - 252.0 (55.0)
5.63 mg/L: 183.0 - 186.0 - 227.0 (44.0)
During the first week, the body weight gain was parallel in all groups. In the second week, the body weight gain of the survivors of the 2.8 and the 5.63 mg/L group were lower than the other groups including control.
Females
Control: 176.0 - 186.2 - 202.0 (26.0)
0.8 mg/L: 193.5 - 201.0 - 217.0 (23.5)
2.0 mg/L: 188.1 - 177.0 - 214.0 (25.9)
2.8 mg/L: 206.0 - 217.0 - 227.0 (19.0)
5.2 mg/L: 206.0 - 218.0 - 232.0 (26.0)
5.63 mg/L: 176.0 - 190.0.0 - 206.0 (30.0)
All treatment groups gained body weight comparably to the control. Females of the 2.0 g/L group lost weight in the first week of observation, but recovered completely in terms of weight gain
Gross pathology:
Animals that died: acute dilatation of the atria; lung with acute congestion hyperemia, partially edematic; liver muddy-grey due to broadened lobe circumference; stomach: bloody ulcerations; intestine: hematinised content; kidneys: slightly lighter coloured

Surviving animals: nothing abnormal found

Applicant's summary and conclusion