Isovaleraldehyde

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Determination of RD50 values from measurement of the decrease in respiratory rate of mice caused by inhalation exposure to graduate doses of different aldehydes

GLP compliance:

no

Type of method:

in vivo

Endpoint addressed:

respiratory irritation

Test material

Test material information

Constituent 1

Reference substance name:

Isovaleraldehyde

EC Number:

209-691-5

EC Name:

Isovaleraldehyde

Cas Number:

590-86-3

Molecular formula:

C5H10O

IUPAC Name:

3-methylbutanal

Details on test material:

- Name of test material (as cited in study report): isovaleraldehyde (obtained from Aldrich Chemical Company, Milwaukee, WI, USA) )
- Analytical purity: laboratory grade (between 85 to 99% depending on the specific aldehyde)
- Impurities (identity and concentrations): water (being the balance to aldehyde content)
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

mouse

Strain:

other: two strains used: B6C3F1 and Swiss-Wbster

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Labs Inc., Kingston, NY, USA)
- Age at study initiation: no data
- Weight at study initiation: B6C3F1: mean 23 g (19 - 27 g); Swiss-Webster: mean 27 g (20 - 32 g)
- Housing: polycarbonate cages (Thoren double mouse cage, Thoren Caging System, Hazleton, PA, USA) with hardwood chip bedding
- Diet (e.g. ad libitum): NIH-07, Zeigler Bros. Inc., Gardners, PA, USA; ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 45 - 60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12-hr on/off light cycle

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 2.7 l head only exposure chamber
- Method of holding animals in test chamber: animals were held in airtight body plethysmographic tubes attached to the head only exposure chamber
- Source and rate of air: no data on source; air flow rate was adjusted between 25 and 220 L/min depending on the desired exposure chamber aldehyde concentration
- Method of conditioning air: no data
- System of generating vapors: a stream of nitrogen was passed over the test aldehyde in a 100 mL glass impinger. Vaporization rates were controlled by varying the nitrogen flow rates from 100 to 900 mL/min and/or submerging the impinger in a constant-temperatiure water bath which ranged from 22 to 95°C depending on the aldehyde. The teflon tubing for leading the aldehyde vapors to the exposure champer air supply inlet was heated to ca. 90°C, if necessary, to prevent condensation of the vaporized aldehyde.
- Temperature, humidity, pressure in air chamber: no data
- Air flow rate: between 25 and 220 L/min depending on the desired exposure chamber test substance concentration
- Air change rate: no data
- Method of particle size determination: determination not conducted (only vapor generated)
- Treatment of exhaust air: no data

TEST ATMOSPHERE
- Brief description of analytical method used: aldehyde concentrations in test atmosphere were continously analyzed with an infrared analyzer (Miran Model 1A, Foxborow Analytical, Norwalk, CT, USA)
- Samples taken from breathing zone: no data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Aldehyde concentrations in test atmosphere were continously analyzed with an infrared analyzer (Miran Model 1A, Foxborow Analytical, Norwalk, CT, USA)

Duration of treatment / exposure:

10 min

Frequency of treatment:

single exposure

Post exposure period:

5 min (recovery period)

Doses / concentrations

Remarks:

Doses / Concentrations:
five graduate concentrations; individual concentrations not reported
Basis:
no data

No. of animals per sex per dose:

4

Control animals:

other: pre-exposure control period (respiratory rate = 100%)

Details on study design:

Test animals were allowed to acclimate in the test apparatus for ca. 10 min. Then during a 5 min pre-exposure control period, respiratory rates were recorded (respiratory rate = 100%). The 10 min exposure period was followed by a 5 min recovery period. The average maximum decrease in respiratory rate for 1 min (during exposure) was computed from the response of each group of animals. RD50 were calculated from resulting concentration-response curves.

Results and discussion

Details on results:

B6C3F1 mice: RD50 = 757 ppm (95% CL 672 - 868 ppm); regression line equation: y = 76.15 (log x) - 169.26
Swiss-Webster mice: RD50 = 1008 ppm (95% CL 754 - 1720 ppm); regression line equation: y = 57.65 (log x) - 123.14

Applicant's summary and conclusion

Conclusions:

Inhalation of isovaleraldehyde vapor reduces the respiratory rate of mice as indication of respiratory irritation. RD50 values (concentrations which cause the decrease of respiratory rate by 50%) were determined to be 757 and 1008 ppm for B6C3F1 mice and Swiss-Webster mice, respectively.

Executive summary:

B6C3F1 mice and Swiss-Webster mice were exposed head only in groups of 4 to 5 graduate concentrations of isovaleraldehyde vapor. Prior to exposure (5 min, control period), and during exposure (10 min) followed by a recovery period (5 min), respiratory rates were recorded by means of a body plethysmograph. The average maximum decrease in respiratory rate for 1 min was computed from the response of each group of animals. The RD50 value was calculated from the resulting concentration-response curve.

 

RD50 values of 757 ppm and 1008 ppm were determined for B6C3F1 and Swiss-Webster mice, respectively (Steinhagen 1984).