Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent
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 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).