Valeryl 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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

current version, adopted 7 Sep 2009

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Valeryl chloride

EC Number:

211-330-1

EC Name:

Valeryl chloride

Cas Number:

638-29-9

Molecular formula:

C5H9ClO

IUPAC Name:

pentanoyl chloride

Details on test material:

- Physical state / appearance: liquid / colourless, clear
- Batch number: 51/L
- Analytical purity: 98.7%
- Appearance: liquid, colourless, clear

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source/strain: SPF Wistar/Chbb:THOM; breeding facility: Dr. K. Thomae GmbH, D-7950 Biberach, FRG
- Age at study initiation: approx. 8 - 9 weeks
- Weight at study initiation: male animals 281 ± 19.7 g, female animals 193 ± 9.7 g
- Fasting period before study:
- Housing: the animals were housed in groups of five in cages type D III of Becker, without bedding
- Diet: KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets (Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland) ad libitum
during the post-exposure observation period.
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- 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: IKA 02 (glass-steel construction)
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: the animals were kept singly in compartmentalized wire cages, and were exposed in the chamber.
- Source and rate of air: compressed air at 3000 L/h
- Method of conditioning air: a vapor/air mixture was generated by means of a continuous infusion pump INFU 362 (INDIGEL/Switzerland) (test groups 1 and 2), a piston metering pump KP 2000 (Desaga) (test group 3) and a glass vaporizer with thermostat (BASF). By means of the metering 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 inhalation system.

TEST ATMOSPHERE
- Brief description of analytical method used: 2 absorption vessels and a fritted glass flask, connected in series filled with sorption solvent. The absorption 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 and a BASF sampling station (with gas meter, impulse counter and automatic pump switch). The sorption solvent was 2-propanol (BASF WAre). The sampling amount was 5 to 20 L. One sample per concentration group was taken about hourly. For the quantitative determination of the vapor concentration a gas chromatographical method was used. The obtained samples were taken up in ~ 40 ml 2-Propanol in a 50-ml calibrated flask. An internal standard (C11KW with a retention time of 9.3 min) was added using a pipette and the flask was filled up to the calibration mark. A GC HP 5840 A (Hewlett Packard) was used with a 2 m glass column (i.d. = 2 mm). The separation phase used was 15% Ucon LB 550X with Chromosorb W AW DMCS/HP as the support material with a 80/100 mesh. Helium was used as the carrier gas with a flow rate of 30 ml/min. The flow rate of hydrogen and air was 32 and 240 ml/min, respectively. The furnace temperature was 100 ºC, the temperature of both the FID and the injector was 200 ºC. The retention time of the sample was 5.3 min.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC analysis

Duration of exposure:

4 h

Concentrations:

0.35, 2.02 and 4.86 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
- Clinical examinations: The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were recorded several times during exposure and at least once on each workday in the observation period. A check for dead animals was made daily.
- Necropsy: At the end of the 14-day observation period the surviving animals were sacrificed and were subjected to gross-pathological examination like all other animals which had died before.

Statistics:

The statistical evaluation of the dose-response relationship was carried out using FORTRAN program AKPROZ. Depending on the data of the dose-response relationship obtained by way of experiment, this program is used to estimate the LC50 or to perform a Probit analysis.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.07 mg/L air

Based on:

test mat.

95% CL:

0.74 - 3.19

Exp. duration:

4 h

Mortality:

0.35 mg/L: none of the animals died after 14 days
2.02 mg/L: 3/5 males and 2/5 females after 14 days
4.86 mg/L: 4/5 males and 5/5 females after 14 days

Clinical signs:

other: During exposure Irregular and accelerated respiration, eyelid closure, eye discharge, restlessness at all exposure levels; additionally: eyelid discharge at the mid and high concentration and intermittent respiration, salivation, nasal discharge, stretche

Body weight:

The body weight gain of male and female rats in all test groups compared with a historical control collective, was reduced in the first week of the observation period and adjusted to normal in the second week of the observation period, except the body weight gain of female rats in test group 3, which could not be determined because all animals had died.

Gross pathology:

Animals which died during the study:
General congestion in all animals, focal hyperemia with emphysema in the lungs (2.02 mg/L) and focal hyperemia with emphysema and edema in the lungs (4.86 mg/L).

Sacrificed animals:
No abnormalities were noted.