[3aR-(3aα,5aβ,9aα,9bβ)]-dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]furan

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

June 1979

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1979

Reference 2

Reference Type:

other company data

Title:

Unnamed

Year:

1979

Materials and methods

Principles of method if other than guideline:

2-hour whole body exposure

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[3aR-(3aα,5aβ,9aα,9bβ)]-dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]furan

EC Number:

229-861-2

EC Name:

[3aR-(3aα,5aβ,9aα,9bβ)]-dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]furan

Cas Number:

6790-58-5

Molecular formula:

C16H28O

IUPAC Name:

(3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyl-dodecahydronaphtho[2,1-b]furan

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): 8α,-12-Oxido-13,14,15,16-tetranorlabdan / Ambroxan
- Physical state: liquid (supplied as a solution in the vehicle)
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Züchter Winkelmann GmbH, D Borchen
- Age at study initiation: adult
- Weight at study initiation: 130 -150 g
- Fasting period before study: no, but food and water were withdrawn during exposure
- Housing: Makrolon tyoe 3
- Diet (e.g. ad libitum): Altromin maintenance diet Nr. 1324
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 50
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: Ethanol (40%)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates/aerosols: the substance solution is nebulized with an atomizer and spray mist is introduced into the experimental animal room. The effluent air stream is passed through a gas meter after filtering and the flow rate is measured
No other data

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

2 h

Concentrations:

1 %

No. of animals per sex per dose:

5 males / dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes, trachea and lung were removed for histological examinations (3 animals per group)

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

> 1 other: % (nominal)

Based on:

test mat.

Exp. duration:

2 h

Mortality:

None

Clinical signs:

other: Fast passing decrease of the general well-being after the end of the exposure constituted the sole symptom.

Body weight:

No data

Gross pathology:

A mild subacute to chronic tracheitis was present in the air-tubes of all animals (i.e. treated and control). The lungs had moderate to severe interstitial pneumonia usually focal, which was also associated with subacute to chronic bronchitis and / or bronchopneumonia. No compound-specific alterations of the target organs (respiratory tract) were observed.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

LC 50 (2h) > 1 % (nominal)

Executive summary:

In an acute inhalation toxicity study adult Wistar rats (5 males/group) were exposed by inhalation route to Ambroxan in Ethanol (40%) for 2 hours to whole body at concentrations of 1 %. Animals then were observed for 14 days.

LC50 Males > 1 % (nominal)

Fast passing decrease of the general well-being after the end of the exposure constituted the sole symptom.

No compound-specific alterations of the target organs (respiratory tract) were observed.

Due to the general lack of details included the study report, this study is not considered as self-sufficient to satisfy the requirement for acute inhalation toxicity endpoint