Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to OECD TG and was conducted in accordance with the Principles of GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): DOWANOL PM Glycol Ether
- Substance type: liquid
- Physical state: clear, colourless liquid
- Analytical purity: 97.49%
- Impurities (identity and concentrations): not specified in the report
- Composition of test material, percentage of components: 1-methoxy-2-propanol: 97.49% and 2-methoxy-1-propanol: 2.46%
- Isomers composition: same as above
- Purity test date: not specified in the report
- Lot/batch No.: Lot # QP-901011-25S1
- Expiration date of the lot/batch: not specified in the report
- Stability under test conditions: not specified in the report
- Storage condition of test material: not specified in the report

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: approximately 8-9 weeks
- Weight at study initiation: not specified in the report
- Fasting period before study: not specified in the report
- Housing: two/cage in stainless steel wire cages
- Diet (e.g. ad libitum): Purina certified Rodent Chow #5002 available ad libitum, except during exposure
- Water (e.g. ad libitum): Municipal tap water available ad libitum, except during exposure
- Acclimation period: one week prior to exposure


ENVIRONMENTAL CONDITIONS
- Temperature (°C): standard conditions
- Humidity (%): standard conditions
- Air changes (per hr): standard conditions
- Photoperiod (hrs dark / hrs light): standard conditions

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel and glass Rochester-type inhalation chamber (50 x 50 x50 cm) with a pyramidal top, under dynamic conditions
- Exposure chamber volume: 157 liter stainless steel
- Method of holding animals in test chamber: whole-body exposure
- Source and rate of air: ambient
- Method of conditioning air: not specified in the report
- Treatment of exhaust air: not specified in the report
- Temperature, humidity, pressure in air chamber: 22 °C and 50%


TEST ATMOSPHERE
- Brief description of analytical method used: The analytical concentration of DOWANOL PM in the breathing zone of the animals was determined continuously with a Miran 1A infrared (IR) spectrophotometer at a wavelength of 8.9 microns. The IR was calibrated and a standard curve compiled, prior to start of the study, with air standards of DOWANOL PM, prepared by vaporizing measured volumes of DOWANOL PM into Saran fim bags containing metered volumes of dry, compressed air. The analytical concentration during each exposure was interpolated from a standard curve. The analytical system was checked prior to each exposure with at least one standard of known concentration. The nominal concentration of the test material in the chamber was calculated based on the amount of test material used and the total amount of air passed through the chamber during the exposure period.
- Samples taken from breathing zone: not specified in the report
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
6 h
Concentrations:
6000 ppm nominal (6038 ppm analytical), 7000 ppm nominal (7559 ppm analytical)
No. of animals per sex per dose:
5 male + 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation and animals weighed on days 1, 2, 4, 8, 11 and 15
- Necropsy of survivors performed: yes
Statistics:
Descriptive statistics - means and standard deviations of body weights, chamber concentration (time-weighted average, only), temperatures, relative humidity and air-flows were calculated

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 7 000 ppm
Exp. duration:
6 h
Remarks on result:
other: 7559 ppm (analytical)
Mortality:
No mortalities observed
Clinical signs:
6000 ppm: All rats were generally unresponsive to noise with only staggered movement the last three and one half hours of the exposure. Upon removal from the chamber, all rats were laterally recumbent with sporadic, staggered movement. By day 2, all male rats appeared normal, however, three of five females were still inactive with some staggered movement. All rats appeared normal by day 3 and survived the 2-week post-exposure period
7000 ppm: All rats were mostly inactive and unresponsive to noise the last three and one half hours of the exposure. Upon removal from the chamber, all male and female rats were laterally recumbent, motionless and unresponsive to noise or touch. By day 2, all male rats were alert but weak with little movement. Female rats, however, were laterally recumbent and motionless on day 2 but did not respond to touch. All male and female rats appeared visibly normal by day 3.
Body weight:
6000 ppm: Body weights of both the sexes were decreased 11%, from pre-exposure values, on the day of exposure, but had exceeded pre-exposure weights within a week.
7000 ppm: Male body weights were decreased 10% from pre-exposure values, on the day after exposure, but had exceeded pre-exposure weights within a week. Female body weights on day 4 were decreased 11% from pre-exposure values and did not exceed pre-exposure values until day 11
Gross pathology:
6000 ppm: Gross examination of all animals after the two-week post-exposure period only found a unilateral corneal opacity in one female and there were no effects attributable to DOWANOL PM exposure.
7000 ppm: Gross examination of all animals after the two-week post-exposure period did not find any effects attributable to DOWANOL PM exposure

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In summary, female rats seemed to be affected to a greater degree as they required a longer period of time than males before returning to normal. There were no mortality or lesions in male or female Fischer 344 rats attributable to exposure to either 6000 ppm nominal (6038 ppm analytical) and 7000 ppm nominal (7559 ppm analytical) DOWANOL PM. The LC50 of DOWANOL PM to male and female Fischer 344 rats is in excess of 7000 ppm nominal (7559 ppm analytical)
Executive summary:

Groups of five male and five female Fischer 344 rats were exposed for six hours to nominal concentrations of 6000 ppm and 7000 ppm (analytical concentrations of 6038 ppm and 7559 ppm) of DOWANOL PM. Animals were observed daily, weighed two to three times per week and survivors were necropsied two weeks after exposure.

All rats survived the exposure to 6038 ppm and the two -week post-exposure period. All rats were laterally recumbent and generally unresponsive to noise during most of the exposure to 6038 ppm and did not appear normal until day 2 (males and two females) or day 3 (remaining females). For exposure to 7559 ppm, all rats appeared normal on day 3. Mean body weights of both sexes for either exposure were decreased to 10 -11%, from pre-exposure levels, on the day after exposure, but exceeded pre-exposure values generally within a week. There were no exposure-related, grossly visible lesions noted in any animal necropsied fourteen days after exposure to the test material.

Based on the results of the study, the six-hour LC50 for DOWANOL PM to male and female Fischer 344 rats is greater than 7000 ppm nominal (analytical 7559 ppm).