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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: Guideline study conducted in compliance with GLP regulations
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-phenoxypropan-2-ol
EC Number:
212-222-7
EC Name:
1-phenoxypropan-2-ol
Cas Number:
770-35-4
Molecular formula:
C9H12O2
IUPAC Name:
1-phenoxypropan-2-ol
Constituent 2
Reference substance name:
1-phenylpropan-2-ol
EC Number:
211-821-0
EC Name:
1-phenylpropan-2-ol
Cas Number:
698-87-3
IUPAC Name:
1-phenylpropan-2-ol
Details on test material:
- Name of test material (as cited in study report): Protectol PP (CAS No 770-04-4)
- Physical state: liquid (solution)/colourless
- Composition of test material, percentage of components: 84.8% 1-phenoxy-propan-2-ol and 14.7% 2-phenoxy-propan-1-ol
- Lot/batch No.: P. 70-1840
- Stability under test conditions: verified by reanalysis
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: SPF Wistar/Chbb: THOM ; breeding facility: Dr. K. Thomae GmbH, D-W7950 Biberach, FRG
- Age at study initiation: 8- 9 weeks
- Weight at study initiation: see below
- Housing: singly in cages type DK III of Becker, without bedding
- Diet: KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets, Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland; ad libitum
- Water: drinking 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: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: compressed air
Details on inhalation exposure:
Animals (5/sex) were assigned to the test group. Rats were exposed to Protectol PP (PPh) by nose-only inhalation exposure for 4 hours using a head-nose inhalation system INA 20 (glass-steel construction) with their snouts projected into the inhalation chamber. The test atmosphere was sampled from the breathing zone of the animals at regular intervals to determine concentration and particle size.
Aerosols were generated using a two-component Schlick Model 970 atomizer by mixing pure Protectol PP with air. This test material was aspirated into the atomizer using a motorized continuous infusion pump INFU 362 (INDIGEL/Switzerland) and the resulting aerosol was injected into a mixing vessel. Air-conditioned external air (1,500 liter/hr) was mixed with the aerosol inside the chamber to achieve the desired concentration. Chamber airflow was monitored at the beginning of exposures and at approximately 60-minute intervals after equilibration over the 4-hour aerosol exposure. The chamber to which the nose-only tubes attached had a volume of 55 liters. Venting and disposal of the aerosol atmosphere was not described. The airflow rate, measured at ~60 minute intervals, was 25 liters/minute, resulting in ~27 air changes per hour and sufficient to provide adequate oxygen. The time to t99 (equilibration time to reach 99% of target concentration) was not specified.
The nominal concentration was calculated by dividing the amount of test material used per unit time, by the airflow rate. To determine actual concentrations, the test atmosphere was sampled near the breathing zone of the subjects using a sampling probe connected to a flask containing a sorption solvent (isopropanol). Five liters of test atmosphere was drawn through the sampling probe (7 mm diameter) at a sampling velocity of 1.25 m/s at approximately 1-hour intervals. The sorption solvent was analyzed for the test substance using a Hewlett Packard gas chromatograph (Model GC HP 5840 A) equipped with a flame ionization detector.
To measure particle size, a sample of the chamber atmosphere (taken once during the exposure period at least 30 minutes after commencement of exposure) was drawn through an Anderson Mark III stack cascade impactor. This cascade impactor was comprised of seven stages with each stage holding a glass fiber filter of progressively smaller pore size, each designed to collect particles of a specific range of aerodynamic diameter (up to 9 micrometers). Rather than measure the net weight increase of each filter, test material was eluted from each filter stage using isopropanol as a sorption solvent. The solvent was measured for test material content using a gas chromatograph.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
nominal concentration: 28 mg/l
analytical concentration: 5.41 ± 0.08 mg/l
No. of animals per sex per dose:
5 rats/sex
Control animals:
not specified
Details on study design:
Animals (5/sex) were assigned to the test group. Rats were exposed to Protectol PP (PPh) by nose-only inhalation exposure for 4 hours using a head-nose inhalation system INA 20 (glass-steel construction) with their snouts projected into the inhalation chamber. The test atmosphere was sampled from the breathing zone of the animals at regular intervals to determine concentration and particle size. Subjects were observed for signs of toxicity during exposure, immediately upon removal from the chambers after exposure, repeatedly on the day of exposure, and daily thereafter for 14 days. After 14 days of observation, all animals were terminated and a necropsy was performed.
Statistics:
no data

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.4 mg/L air
Exp. duration:
4 h
Remarks on result:
other: (5400 mg/m3)
Mortality:
no mortalities observed
Clinical signs:
other: Clinical abnormalities were noted in the test subjects on the first day of exposure but not thereafter. These included breathing difficulties during the 4-hour exposure period in all subjects
Body weight:
Body weight gains were not affected by exposure
Gross pathology:
No adverse findings attributable to Protectol PP were reported when animals were necropsied at the end of the 14-day observation period
Other findings:
not applicable

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, Protectol PP (i.e. 86% CAS# 770-35-4, 14% CAS No. 4169-04-4), administered as a liquid aerosol by inhalation to rats, the 4-hour inhalation LC50 (combined sexes) was greater than 5.4 mg/l (or 5400 mg/m3) as no deaths occurred in 5 males or 5 females at this exposure level. Hence Protectol PP was not classified according to the EU classification
Executive summary:

In this study, rats (5/sex) were exposed to Protectol PP (PPh) by nose-only inhalation exposure for 4 hours using a head-nose inhalation system INA 20 (glass-steel construction) with their snouts projected into the inhalation chamber. The test atmosphere was sampled from the breathing zone of the animals at regular intervals to determine concentration and particle size. Subjects were observed for signs of toxicity during exposure, immediately upon removal from the chambers after exposure, repeatedly on the day of exposure, and daily thereafter for 14 days. After 14 days of observation, all animals were terminated and a necropsy was performed.

Clinical abnormalities were noted in the test subjects on the first day of exposure but not thereafter. These included breathing difficulties during the 4-hour exposure period in all subjects. Body weight gains were not affected by exposure. No adverse findings attributable to Protectol PP were reported when animals were necropsied at the end of the 14-day observation period.

Under the conditions of the study, Protectol PP (i.e. 86% CAS# 770-35-4, 14% CAS No. 4169-04-4), administered as a liquid aerosol by inhalation to rats, the 4-hour inhalation LC50 (combined sexes) was greater than 5.4 mg/l (or 5400 mg/m3) as no deaths occurred in 5 males or 5 females at this exposure level. Hence Protectol PP was not classified according to the EU classification.

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