Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because a study on acute toxicity by the inhalation route is available
Justification for type of information:
see cross-ref
Cross-reference
Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 20 to April 10 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Version / remarks:
1994
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Remarks:
strain: SPF Wistar/ Chbb :THOM
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeding facility : Dr . K . Thomae GmbH, Biberach, FRG
- Females (if applicable) nulliparous and non-pregnant: not mentioned
- Age at study initiation: approx. 8-9 weeks
- Weight at study initiation: male: 256 - 277 g
female: 194 -195 g
- Fasting period before study: no
- Housing: singly in cages type DK III of Becker, without bedding
- Diet: KLIBA rat/mouse/hamster laboratory diet 24-343-4 10 mm pellets, Klingentalmühle AG, Kaiseraugst, Switzerland, ad libitum during post-exposure observation period. The feed used in the study was assayed for chemical as well as for microbiological contaminants.
- Water: drinking water ad libitum during post-exposure observation period
- Acclimation period: not mentioned

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24'C
- Humidity (%): 30-70%
- Air changes (per hr): about 15 times
- Photoperiod (hrs dark / hrs light): light/dark rhythm of 12 hours .


Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Remarks:
Whole-body inhalation system : IKA 02 (glass-steel construction), BASF Aktiengesellschaft, Volume V= 200 l: the animals were kept singly in compartmentalized wire cages, and were exposed in the chamber
Vehicle:
air
Remarks:
By means of the continuous infusion pump amounts of the test substance per test group were supplied to the heated vaporizer . The vapors that developed were mixed with supply air and passed into the exposure system .
Remark on MMAD/GSD:
Test substance is a liquid
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure system: Whole-body inhalation system : IKA 02 (glass-steel construction), BASF Aktiengesellschaft, Volume: V= 200 l; the animals were kept singly in compartmentalized wire cages, and were exposed in the chamber .
The homogenous distribution of atmosphere in this inhalation system has been proven in technical tests with model vapors .
- Generation of the inhalation atmosphere
1. Substance preparation: The test substance was dosed unchanged
2. Technical equipment
- piston metering pump KP 2000 (Desaga)
- glass vaporizer with thermostat (BASF)
- glass mixing vessel (BASF )
3 . Procedure
A vapor was generated .
By means of the continuous infusion pump amounts of the test substance per test group were supplied to the heated vaporizer . The vapors that developed were mixed with supply air and passed into the exposure system .

EXPOSURE:
A supply air flow (conditioned air) of 3000 1/h was set for each test group .
An air change of about 15 times per hour can be calculated by dividing the supply air flow through the volume of the,inhalation system .
The supply air was conditioned via a central air-conditioning system .
The exposure system was placed in an air-conditioned laboratory .
By means of an exhaust air system the pressure ratios in the exposure system were adjusted in such a way that the amount of exhaust air was about 3% higher (pressure below atmospheric) . This ensured that no contamination of the laboratory occurred as result of leakages from the inhalation chamber.
The inhalation atmosphere was offered to the animals for inhalation for 4 hours .

ANALYTICAL INVESTIGATIONS
1. Nominal concentration
The nominal concentration was calculated from the amount of substance consumed and the air flow .
2. Sampling:
Equipment and.procedure :
- Sampling probe (diameter : 4 mm) 2 absorption vessels and a fritted glass flask, connected in series filled with sorption solvent.
- BASF sampling station (with vacuum pump, gas meter, impulse counter and automatic pump switch)
- Sampling position : immediately adjacent to the animals noses
- Sampling velocity : 1.25 m/ s
- Sampling frequency : 4 samples per concentration in about hourly intervals
- Sampling volumes : Test group 1: 5 l
Test group 2: 1.2 l
These volumes were adjusted to achieve comparabl e
amounts of the test substance in the samples of the different test groups in reference to the calibration point.
- Sorption solvent : Dimethy1formamide (DMF)
The first 2 absorptions vessels were analyzed for each sample . The fritted glass flask was used to control the effectiveness of the sorption for all samples of a test group and was analyzed separately at the end of the sampling campaign .

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.3 mg/l and 20 mg/l
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of the animals was determined just prior to exposure, after 7 days and at the end of the observation period . A check for overt clinical signs of toxicity or mortality as well as a check for feed and drinking water was made twice a day on workdays and once daily on weekends and public holidays .
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
Probit analysis
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.3 - < 20 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 5.3 - < 20 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
ca. 20 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
5.3 mg/l: no mortality
20 mg/l: Female: 3/5, male 5/5
Clinical signs:
In the low concentration clinical examination revealed the following signs of respiratory tract irritation : attempts to escape, eyelid closure, irregular, accelerated, intermittent and dragging respiration, nasal discharge and bloody crust formation as well as salivation . Furthermore piloerection and paleness occurred . No clinical sings could be detected from post exposure day 5 onward .
The high concentration resulted in virtually the same symptoms accomplished by signs of general anesthesia and reduced general state .
Body weight:
Body weight development in the low concentration animals was slightly depressed . The surviving female animals of the high concentration did not gain weight throughout the total post observation period .
Gross pathology:
Animals that died showed severe, diffuse dark red discoloration of all lung lobes . Lung histology revealed acute congestion, alveolar
and interstitial edema, diffuse alveolar histiocytosis
No macroscopic pathologic findings were noted in animals examined at the end-of the study period .
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The LC50 for male and female Wistar rats was estimated to be 5.3 < LC50 < 20 .0 mg/l in a study according to OECD guideline no. 403.
Executive summary:

For determination of the acute inhalation toxicity (single 4-hour-exposure) of Vinylpropionate as a vapor, a study in male and female Wistar rats was performed according to OECD-Guideline method 403, as well as EEC and EPA guidelines. The following concentrations were tested : 5.3 and 20 .0 mg/l . No mortality occurred at 5.3 mg/l. Three of five females and all male animals died at 20 .0 mg/l . The LC50 for male and female animals was estimated to be 5.3 < LC50 < 20 .0 mg/l .

In the low concentration clinical examination revealed the following signs of respiratory tract irritation: attempts to escape, eyelid closure, irregular, accelerated, intermittent and dragging respiration, nasal discharge and bloody crust formation as well as salivation . Furthermore piloerection and paleness occurred. No clinical sings could be detected from post exposure day 5 onward.

The high concentration resulted in virtually the same symptoms accomplished by signs of general anesthesia and reduced general state.

Body weight development in the low concentration animals was slightly depressed . The surviving female animals of the high concentration did not gain weight throughout the total post observation period.

During necropsy animals that died showed severe, diffuse dark red discoloration of all lung lobes. Lung histology revealed acute congestion, alveolar and interstitial edema, diffuse alveolar histiocytosis.

No macroscopic pathologic findings were noted in animals examined at the end-of the study period.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion