Exo-1-methyl-4-(1-methylethyl)-7-oxabicyclo[2.2.1]heptan-2-ol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1985-06-21 to 1985-07-05

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:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Exposure duration less than 4 hours

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(1S,2S)-1-methyl-4-(propan-2-yl)-7-oxabicyclo[2.2.1]heptan-2-ol

Cas Number:

87172-89-2

IUPAC Name:

(1S,2S)-1-methyl-4-(propan-2-yl)-7-oxabicyclo[2.2.1]heptan-2-ol

Test material form:

solid

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, Inc., Wilmington, Massachusetts
- Age at study initiation: Young adult
- Weight at study initiation: Males: 219 ± 6; Females: 233 ± 5
- Housing: The animals were individually housed in wire-mesh cages during the exposure.
- Diet: Food (NIH Open Formula 07, certified rodent diet, Zeigler Brothers, Inc., Gardners, PA) was supplied ad libitum before the test and during the post-exposure phases. The animals received no food during the exposure period.
- Water: Tap water was supplied ad libitum before the test and during the post-exposure phases. The animals received no water during the exposure period.
- Acclimation period: Yes, at least 5 days.

ENVIRONMENTAL CONDITIONS
- Airflow rate: 10 L/minute
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The exposure was performed in a 123 L acrylic (plexiglass) chamber.
- Source and rate of air: The total airflow through the chamber was maintained at a rate of 30 L/minute using a transvector jet (Model 901, Vortec Corporation, Cincinnati, OH) and monitored using a prestandardized pressure gauge attached to the transvector jet.
- Method of conditioning air: The test atmosphere was vented via an air treatment system (Charles Spengler and Associates, Cincinnati, OH) constructed of a glass fiber pre-filter, Micretain® HEPA filter and an activated charcoal bank. The test substance was heated and maintained between 65 and 69 °C. Airflow rate of 10 L/minute was passed through the heated test substance. The resultant vapor/air mixture was delivered into the exposure chamber at an air inlet port, which allows the test article and incoming air to mix evenly within the chamber at the top before being drawn down over the animals.
- Airflow rate: 10 L/minute
- Total airflow through system: 2400 L
- Temperature in air chamber: 23-27 °C
- Humidity in air chamber: 53-58 %

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

80 min

Remarks on duration:

Twenty minutes were added to the 60 minutes exposure period in order to allow the test system to reach 99 percent of the desired concentration (point of equilibration).

Concentrations:

12.8 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animal observations for pharmacotoxic signs and mortality were recorded periodically during exposure, subsequent to exposure on day one and twice daily thereafter. Individual body weight data were recorded on day 1 (just prior to exposure), 8 and 15.
- Necropsy of survivors performed: Not specified

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 12.8 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

80 min

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.27 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: The exposure period was extrapolated to 4 h using the modified Haber's Law.

Mortality:

No mortality or signs of toxicity were noted in any animal during the 14 day post-exposure period.

Clinical signs:

other: None.

Body weight:

The test substance exposure did not exhibit an adverse effect upon body weight gain in either sex.

Any other information on results incl. tables

The classification criteria for acute inhalation toxicity relate to a 4 hour experimental exposure period. But, under the conditions of this test, the test animas were exposed to the test substance for only 1.3 h. If data for a 4 -hour period are not available then extrapolation of the results to 4 hours can be achieved using the modified Haber's Law according to ECHA Guidance document Chapter R7a: Endpoint specific guidance (July 2017).

 

Extrapolation of the results to 4 hours using the modified Haber's Law:

 

C1ⁿ* t1 = K = C2 * t2

C2 = C1ⁿ* t1 / t2

C2 = 12.8 mg*h/L * 1.3 h / 4 h = 4.27 mg/L

 

C1 = 12.8 mg/L

t1= 1.3

t2 = 4 h

n = 1 (default value for extrapolation to longer duration)