Isopropenyl acetate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-09-30 to 2000-06-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD Guideline Study report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Isopropenyl acetate

EC Number:

203-562-7

EC Name:

Isopropenyl acetate

Cas Number:

108-22-5

Molecular formula:

C5H8O2

IUPAC Name:

isopropenyl acetate

Details on test material:

Test Substance: 2-Acetoxypropene (Essigsaureisopropenylester)
Date of production: unknown
Physical state / appearance: liquid / colourless
Storage conditions: room temperature
CAS No.: 108-22-5

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Wistar rats (strain: Rj : WI (SPF Han)) supplied by Elevage Janvier, Route des Chenes Secs, B.P. 5, F-53940 Le Genest St Isle were used for the investigations. Only animals free from clinical signs of disease were used for the study. The females were nulliparous and non-pregnant. The animals were subjected to an acclimatization period of at least 1 week in which they were adapted to the surroundings. Age of the animals at the beginning of the study was approx. 8 - 9 weeks. Weight: Males 309.92 +/- 5.11 g, Females 207.00 +/- 3.88 g.
The animals were offered KLIBA rat/mouse/hamster laboratory diet 10 mm pellets, Provimi
Kliba SA, Kaiseraugst, Switzerland, and drinking water ad libitum during the post-exposure
observation period.
The feed used in the study was assayed for chemical as well as for microbiological contaminants.
In view of the aim and duration of the study, the contaminants occurring in
commercial feed might not influence the results.
The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the Technical SeNices of BASF -Aktiengesellschaft as well as for the presence of germs by a contract laboratory. In view of the aim and duration of the study, there are no special requirements exceeding the specification of drinking water. The animals were kept in fully air-conditioned rooms in which temperatures in the range of 20 - 24°C and relative humidities in the range of 30 - 70°J!c> were regulated by means of a central air-conditioning system.
They were housed singly in cages type DK III (Seeker, Germany) without bedding, with a light/dark cycle of 12 hours (6 a.m. - 6 p.m. light on, 6 p.m. - 6 a.m. light off).

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Whole-body inhalation system: IKA 02 (glass-steel construction), BASF Aktiengesellschaft, volume V ~ 200 I: the animals were kept singly in compartmentalized wire cages, and were exposed in the chamber. The homogenous distribution of atmospheres in this inhalation system has been proven in technical tests with model vapors.
Technical equipment
• piston metering pump KP 2000 (Desaga)
• vaporizer with thermostat (glass, BASF)
• glass mixing stage (BASF)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gas Chromatography

Duration of exposure:

4

Concentrations:

22 mg/l

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

The vapor was generated by supplying amounts of the test substance to the heated vaporizer by means of the piston metering pump. The vapors that developed were taken up by the supply air and passed into the exposure system.
The exposure system was located inside an exhaust cabin in an air-conditioned laboratory. A supply air flow (conditioned air (from a central air-conditioning system)) of 3.0 m3/h was used for the test group. The exhaust air flow was 3.3 m3/h. An air change of about 15 times per hour can be calculated by dividing the supply air flow by the volume of the inhalation system. The higher amount of exhaust air, which was adjusted by means of a separate exhaust air system, achieved a negativ pressure inside the exposure system. This ensured that no contamination of the laboratory occurred as result of possible leakage from the inhalation chamber. The animals were exposed to the inhalation atmosphere for 4 hours plus equilibration time of the inhalation systems (tgg about 20 min ).

Statistics:

The statistical evaluation of the concentration-response relationship was carried out using a computer program: Depending on the data of the concentration-response relationship obtained by way of experiment, this program is used to estimate the LC50 or to perform a Probit analysis (4). Estimation of the LC50 will produce types "LC50 greater than", "LC50 approx.", or "LC50 smaller than". If the results are type "LC50 greater than" or "LC50 smaller than", an additional binomial test is carried out (5), in order to verify these statements statistically.

Results and discussion

Preliminary study:

not reported

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 22 mg/L air

Exp. duration:

4 h

Remarks on result:

other: none

Mortality:

not observed in the dose groups

Clinical signs:

other: eyelid closure, visually accelerated respiration, nasal discharge and crust formation as well as apathy, squatting posture, reduced general state, smeared fur and piloerection

Body weight:

no effect

Gross pathology:

no effect

Other findings:

not reported

Applicant's summary and conclusion

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Substance is not harmful to rats under conditions used after vapor inhalation.

Executive summary:

For determination of the acute inhalation toxicity (single 4-hour-exposure) of 2-Acetoxypropene (Isopropenyl acetate, Essigsäureisopropenylester) 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. No mortality occurred at the analytically determined concentration of 22 mg/l (Limit test). The LC50 for male and female animals (5 animals/group) therefore is > 22 mg/l (> 5300 ppm). Clinical examination reveal edeyelid closure, visually accelerated respiration, nasal discharge and crust formation as well as apathy, squatting posture, reduced general state, smeared fur and piloerection . No clinical signs could be detected from post exposure day 7 onward. Body weight development of the male animals was slightly depressed in the first post exposure week but recovered in the second. The female animals did not gain weight throughout the post exposure observation period. During necropsy no macroscopic pathologic findings were noted in the animals examined at the end of the study.