Propan-1-ol

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity

Remarks:

other: in vitro

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Relative Acute Neurotoxicity of Solvents : Isoeffective Air Concentrations of 48 Compounds Evaluated in Rats and Mice

Author:

Frantik E., Hornychovà M., Horváth M.

Year:

1994

Bibliographic source:

Environ. Res. 66, 173-185

Materials and methods

Principles of method if other than guideline:

Effect-air concentration regressions of 48 common solvents (aromatic, aliphatic, and chlorinated hydrocarbons, alcohols, ketones, acetates) were determined for 4-hr inhalation exposures in male rats. Inhibition of propagation and E maintenance of the electrically evoked seizure discharge was used as a criterion of the acute neurotropic effect. The isoeffective concentrations in air were estimated by interpolation on the level of one-third of the maximum effect (ECC).

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Propan-1-ol

EC Number:

200-746-9

EC Name:

Propan-1-ol

Cas Number:

71-23-8

Molecular formula:

C3H8O

IUPAC Name:

propan-1-ol

Specific details on test material used for the study:

The test substance was described as analytically pure.

Test animals

Species:

rat

Strain:

other: Wistar albino SPF

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: 0.5-1yr
- Housing: 1/cage
- Diet: pelleted DOS2b with a supraoptimal concentrations of vitamins (maximum of 12g/d)


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

other: inhalation: vapour (whole body)

Vehicle:

other: air

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Whole body exposures were carried out in 80-liter glass chambers operated under dynamic conditions. The experimental subjects (1 rat) were placed into small plastic boxes ventilated through diffusion tubes permitting almost instant stabilization of the air concentration in the respiration zone. The exposure started after an approx 30 min habituation and lasted 4h.


TEST ATMOSPHERE
- Brief description of analytical method used: GC
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Methode: gas chromatography

Duration of treatment / exposure:

4h

Frequency of treatment:

intervals between exposures being at least 3 weeks .

Doses / concentrations

Remarks:

Doses / Concentrations:

Basis:
nominal conc.

No. of animals per sex per dose:

Test group: 4 /dose
Control: 4

Control animals:

yes, sham-exposed

Examinations

Neurobehavioural examinations performed and frequency:

Each compound was tested in at least two independent experiments on two samples of animals exposure box. A short electrical impulse (0 .2 sec, 50 Hz, 180 V in rats) was through ear electrodes. The duration of tonic extentions of hind limbs in rats was measured. All animals were given three control tests at weekly intervals before the first exposure. Measuring of the biological effect always started less than 1 min after removal. The median of individual control values was subtracted from the values observed after exposure. Group means of differences were corrected for the difference in the simultaneously tested control group and converted to relative values i.e percentages of the arbitrary maximum values, which for rats was 8 sec

Statistics:

All data (including zero concentration group) were processed using linear reregression analysis. If the component for nonlinearity was significant, then the highest and/or the zero concentration groups were omitted, but the number of exposure levels was not allowed to drop below three. The effect in the lower lower third of the linear part of the dose-response function was chosen as the critical level, i .e ., shortening of the tonic extension of hindlimbs by 3 sec in rats. Isoeffective concentrations, corresponding to the critical level of effect (ECC), interpolated on all regression lines and 90% confidence intervals computed. The lowest effective concentration (EC10) was interpolated-or extrapolated in cases when the zero concentration group was omitted-on a level of the maximum possible effect

Results and discussion

Results of examinations

Details on results:

- The saturated vapour concentration at 37°C was derived from the values given in the publication to be 70000 ppm (178.8 mg/ml)

Effect levels

Dose descriptor:

other: Isoeffective concentration (EEC)

Effect level:

32.2 mg/L air

Sex:

male

Basis for effect level:

other: 95% confidence limits (26.6 - 37.8). Concentration effecting a 30% depression in the duration of tonic extension of hindlimb of the rat

Remarks on result:

other: Generation not applicable