2-methyl-1-phenylpropan-2-ol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 10th 1980 to 14th July 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl-4-phenylbutan-2-ol

EC Number:

203-074-4

EC Name:

2-methyl-4-phenylbutan-2-ol

Cas Number:

103-05-9

Molecular formula:

C11H16O

IUPAC Name:

2-Methyl-4-phenyl-2-butanol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source of test material: Research. Institute for Fragrance Materials, Englewood Cliffs, NJ.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories Ltd., Wilmington, Mass, USA.
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 175 to 225 g
- Fasting period before study:
- Housing: Housed individually in stainless steel, wire meshed-bottom cages
- Diet: Certified Purina Laboratory Rat Chow ad libitum
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS (in inhalation chamber room)
- Temperature (°C): 22.3±0.29°C
- Humidity (%): 38.5±0.58%

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

1.08 µm

Geometric standard deviation (GSD):

0.05

Details on inhalation exposure:

Inhalation Exposure Equipment
A 27" cube (400 liter volume) stainless steel whole body exposure chamber was utilized. A complete group of rats (5 males and 5 females) was housed in the chamber during treatment in a stainless steel wire mesh compartmentalized cage with each compartment being 7" X 3" X 4". Temperature and relative humidity in the inhalation chamber were. monitored hourly by means of remote sensors (YSI model 705 Temperature Probe and 91HC Dew Point Hygrometer) located inside the chamber. Air flow rate through the chamber was set at 45 L/min and was measured in the exhaust line by means of an orifice plate and Magnehelic differential pressure gauge. ' This arrangement in turn had been calibrated against a conventional balltype flow meter. The negative pressure within the chamber with respect to the room atmosphere was set at less than 0. 5 inches of water. Decontamination of chamber air was accomplished by passing the air through ~ HEPA filter, an activated charcoal filter arid a liquid scrubber prior to eliminating it from the facility.

Generation of Test Atmospheres
An aerosol of the test article was generated using a Thermo Systems Inc. six jet atomizer. The atomizer was used at a pressure of 9 psig with two jets in operation.

Exposure Procedure
After loading into the chamber the test animals were exposed to an aerosol of the test article for a single period of four hours. Nominal chamber concentrations were calculated from the weight loss from the atomizer and total airflow through.the chamber during the exposure period.

Measurement of Chamber Concentration and Particle Size Distribution
Hourly air samples for measurement of chamber concentration were drawn from the chamber, at a rate of 5 L/min for two minutes, through a preweighed Gelman glass fibre filtet paper in a Gelman in-line filter holder. Chamber concentration was calculated from the increase in weight of the filter and volume of air sample. Hourly air samples from the inhalation chamber for particle size analysis were withdrawn and passed through a Casella Cascade Impactor. The distribution and size of particles which deposited on each of the four stages of the Impactor were determined by light microscopy. The method was originally described in Cascade Impactor Casella leaflet 3018/RT and was modified in this laboratory (see Bio Standard Operating Procedures No. I AC 01, 02 and 04) to include the following procedures:

1) Circular cover-slips upon which the aerosol had been impacted were mounted on a slide and examined microscopically.
2) A representative region of eaqh slide was selected for analysis.
3) An observing field of 0.47 mm X 0.47 mm (square grid) under 400 X magnification was superimposed on 'the region selected.
4) All particles falling within this grid were observed with a calibrated filar micrometer eyepiece and the numbers falling into various size ranges were recorded.
5) The numbers of particles in each size range were plotted against particle size on log probability graph paper. The line of best fit was drawn and the geometric mean particle size and its standard deviation calculated.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal concentration of 4.63 mg/L
Measured chamber concentration of 1.38 mg/L ±0.19

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: All animals were observed closely during and immediately after exposure, and at least twice daily during the 14 day recovery period.
- Frequency of observations and weighing: Each animal was weighed on the_ day of exposure and on days 2, 3, 4, 7 and 14 of the study.
- Necropsy of survivors performed: Yes. All animals were killed 14 days. after exposure by intraperitoneal injection of Hoechst T-61 euthanasia solution and examined macroscopically. Liver and kidneys were preserved in 10% buffered formalin solution. Lungs were preserved by perfusion with the fixative. Bronchial lymph nodes were examined macroscopically but not retained·for histological assessment. All other macroscopically abnormal tissues were preserved.
- Histopathology: Samples of lung, liver, kidney and any macroscopic abnormality, from all animals were fixed in formalin for at least 48 hours, routinely processsed, embedded in paraffin wax stained with haematoxylin and eosin and examined microscopically.

Statistics:

Mean and standard deviatl6n will be determined for chamber temperature and humidity. In addition, animal. body weight will also be tabula.ted.
Clinical findings and gross and histopathological observations will be summarized in incidence tables.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.63 mg/L air (nominal)

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.38 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

There were no deaths.

Clinical signs:

other: There were no clinical changes of possible toxicological importance.

Body weight:

Although small body weight losses occurred on the days following exposure the losses were generally made good by day 7 of the study. Body weight gains during the second week of the observation period were considered to be satisfactory.

Gross pathology:

Focal grey-green areas observed grossly on the lungs were characterized histologically by aggregates of mononuclear leucocytes mainly about blood vassels· and air passages and occasionally extending to alveolar walls., some interstitial fibrosis and infiltration by foamy macrophages. These lesions were considered to be spontaneous and caused as a result of mild infection with murine respiratory mycoplasmosis. Pulmonary edema and mild congestion revealed in 3 rats could be attributed to euthanasia.

Other findings:

- Histopathology: There were no treatment related changes.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute inhalation study in Sprague-Dawley rats, the LC50 fro PEA was >4.63 mg/L (nominal concentration).

Executive summary:

In an acute inhalation toxicity study (5692-07/14), a group of young adult Sprague Dawley strain rats (5/sex) were exposed to a test atmosphere of PEA for 4 hours (whole body) at a target concentration of 4.63 mg/L. Animals were then observed for 14 days.

LC50 male/female = > 4.63 mg/L (nominal concentration)

The mean achieved concentration was 1.38 ±0.19 mg/L (MMAD: 1.08 µm; GSD: 0.05). There were no deaths and no clinical changes of possible toxicological importance. Although small body weight losses occurred on the days following exposure the losses were generally made good by day 7 of the study. Focal grey-green areas observed grossly on the lungs were characterized histologically by aggregates of mononuclear leucocytes mainly about blood vessels and air passages and occasionally extending to alveolar walls., some interstitial fibrosis and infiltration by foamy macrophages. These lesions were considered to be spontaneous and caused as a result of mild infection with murine respiratory mycoplasmosis. Pulmonary edema and mild congestion revealed in 3 rats could be attributed to euthanasia.

This acute inhalation toxicity test in rats is acceptable and satisfies the guideline requirement for an OECD 403 study.