Isobutyryl chloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isobutyryl chloride

EC Number:

201-194-1

EC Name:

Isobutyryl chloride

Cas Number:

79-30-1

Molecular formula:

C4H7ClO

IUPAC Name:

2-methylpropanoyl chloride

Details on test material:

- Name of test material (as cited in study report): Isobuttersäurechlorid
- Analytical purity: >99%
- Physical state: liquid colourless to light yellowish
- Lot/batch No.: 121/K
- Product number: 72468
- Stability under test conditions: stability was ensured for at least the study period
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeding facility: Dr. K. Thomae GmbH, D-7950 Biberach, FRG
- Age at study initiation: approximately 8-9 weeks
- Weight at study initiation: male mean body weight: 258 ± 10.1 g; female mean body weight: 193 ± 4.3 g
- Animal identification: colour marking on the tail
- Diet: KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets, Klingentalmuhle AG, CH-4303 Kaiseraugst, Switzerland, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20-24 °C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: whole-body inhalation system IKA 02 (glass-steel construction)
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: compartmentalized wire cages
- Method of conditioning air: a vapour air mixture was generated by means of a continuous infusion pump UNITA I (B. Braun) in the test group 1, a continuous infusion pump INFU 362 (INDIGEL/Switzerland) in the test group 2 and a glass vapourized with thermostat (BASF). By means of the continuous infusion pumps amounts of the test substance per test group were supplied to the heated vapourizer. The vapours that developed were mixed with supply air and passed into the inhalation system. The supply air was conditioned via a central air-conditioning system. The exposure system was placed in an airconditioned laboratory.
- Treatment of exhaust air: By means of an exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of axhaust air was about 8% higher (pressure below atmospheric). This ensured that no contamination of the laboratory occurred as result of leakages from the inhalation chamber.
- Temperature in air chamber: 19-25 °C

TEST ATMOSPHERE
- Brief description of analytical method used: The nominal concentration was calculated from the amount of substance consumed and the air flow. 2 absorption vessels and a fritted glass flask, connected in series filled with sorption solvent (propanol-2). The absorption vessels were analysed 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. Sampling velocity: 1.25 m/s; sampling amount: 10-20 L; sampling position: immediately adjacent to the animals noses; sampling probe diameter: 4 mm; sampling frequency: 1 sample per concentration group about hourly. For the quantitative determination of the vapour concentration a gas chromatographical method was used (GC HP 5840 A, Hewlet Packard). The obtained samples were taken up in 50 mL 2-propanol in a 50-mL calibrated flask. An internal standard was added using a pipette and the flask was filled up to the calibration mark. The following gaschromatographical conditions were used:
- column: metal
- length: 3 m
- int. diam.: 2 mm
- separation phase: 20% UCCW 982
- support material: Chromosorb W/HP
- size: 80/100 mesh
- carrier gas: helium
- carrier gas flow rate: 36.2 mL/min.;
- hydrogen: 30 mL/min.
- air: 246 mL/min.
- furnace temp.: 110 °C
- detector temp.: 200 °C
- injector temp.: 200 °C
- internal standard (i. st.): CgKW
- calibr. retention time i. st.: 7.1 min.
- calibr. retention time sample: 3.7 min.

A calibration curve was prepared in the solvent with the test substance to be investigated. The curve was calculated with a Hewlett Packerd Computer program SD 03A curve adjustment; linear regression). From the analytically determined mass values and the sample volumes of the inhalation atmosphere the concentrations were calculated in mg/L.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC analysis

Duration of exposure:

4 h

Concentrations:

0.47 and 1.95 mg/L (analytical concentrations)

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: Clinical examinations: several times during exposure and at least once on each workday in the observation period; Body weight: before the beginning of the test, after 7 days and at the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

The statistical evaluation of the dose-response relationship was carried out using FORTRAN program AKPROZ. Depending on the data of the dose-reponse relationship obtained by way of experiment, this program is used to estimate the LC50 or to perform a probit-analysis. Estimation of the LC50 will produce types LC50-greater, LC50-about, or LC50-smaller. If the results are type LC50-greater or -smaller, an additional binominal test will be carried out to verify these statements statistically, if necessary.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.47 - 1.95 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 0.7 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 1.3 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

1/10 animals died after exposure to 0.47 mg/L
9/10 animals died after exposure to 1.95 mg/L
Deaths occurred on the day of exposure or on day 1 of the observation period.

Clinical signs:

other: During exposure: 0.47 mg/L test group: <1h: accelerated respiration, apathy, restlessness; 1-4 hours after exposure: accelerated respiration, intermittent respiration, eyelid closure, nasal discharge, apathy, restlessness, squatting posture, ruffled fur.

Body weight:

0.47 mg/L test group:
- after 7 days: male mean weight: 257 g (4 animals); female mean weight: 192 g (5 animals)
- after 14 days: male mean weight: 300 g (4 animals); female mean weight: 211 g (5 animals)

1.95 mg/L test group:
- after 7 days: male mean weight: all animals dead; female weight: 174 g (1 animal)
- after 14 days: male mean weight: all animals dead; female weight: 215 g (1 animal)

Gross pathology:

Animals that died during the test: general congestion, intensified focal hyperaemia in the lungs of some animals.
Animals sacrificed at the end of the observation period: no pathological abnormalities.