2,6-diisopropylnaphthalene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 1981

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(isopropyl)naphthalene

EC Number:

254-052-6

EC Name:

Bis(isopropyl)naphthalene

Cas Number:

38640-62-9

Molecular formula:

C16H20

IUPAC Name:

1,2-bis(propan-2-yl)naphthalene

Details on test material:

- Name of test material (as cited in study report): KMC

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland
- Age at study initiation: males 11 weeks, females 13 weeks
- Weight at study initiation: males 237.5 - 255.6 g, females 218.3 - 239.7 g
- Housing: 5 per cage in makrolon cages, type IV, with standard softwood bedding
- Diet: pelleted standard Kliba 343 rat maintenance diet (Klingenthalmuehle AG. Kaiseraugst, Switzerland), ad libitum
- Water: community tap water from Geneva, ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 09.11.1987 To: 01.12.1987

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: exposure chamber according to Sachsse et al (1973, 1976): The breathing atmosphere (aerosol) is passed through a central cylindrical tube vertically positioned to which animal confinement chambers are radially attached. From the internal active exposure chamber, small tubes lead to the breathing zone of the attached confinement chambers. Surplus breathing air and exhaled air are discharged through an outer cylindrical tube positioned around the internal active chamber.
- Exposure chamber volume: volume of the internal active chamber: 1 L
- Method of holding animals in test chamber: Macrolon restraint tubes of suitable size and shape vertically attached to the exposure chamber
- System of generating particulates/aerosols: The test atmosphere was generated by a constant volume reservoir feeding a Hospitak No. 950 nebulizer following dissolution with water. Following the nebulizer, a dilution system was used to dilute the test article output of the nebulizer with clean air to the concentration required for the study. The aerosol generating system was designed to create an aerosol with a mass median diameter of 3 µm or less. Following aerosolization, the test article was discharged into the exposure chamber.
- Method of particle size determination: Separation of particles using a Mercer 7 stage cascade impactor. The sampling air flow was 1.0 L/min and the mass content of the different stages of the impactor was assessed gravimetrically.
- Temperature, humidity, pressure in air chamber: 21°C, 12% (relative humidity), slight positive pressure in inner chamber and slight negative pressure in outer chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: The test substance was sampled by passing test atmosphere through three in line gas washing bottles containing ice-cold acetonitrile as solvent. Aliquots of this solution were analyzed by HPLC (solvent acetonitrile/water 70/30, column RP-18). KMC was used as external standard for calibration.
- Samples taken from breathing zone: yes

VEHICLE
- no

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 36.3% ≤4.6 and >3.0 µm, 23.3% ≤3.0 and >2.13 µm, 40.4% ≤2.13 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see above

Duration of exposure:

4 h

Concentrations:

5.64 mg/l (Limit test; mean analytical exposure concentration)

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: once per hour during exposure, once after exposure on test day 1 and twice daily thereafter, body weight measurements at days 1 (day of exposure), 8, and 15 of test
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight; lungs from all animals were collected at necropsy and fixed in a neutral phosphate buffered 4% formaldehyde solution.

Statistics:

No statistics

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.64 mg/L air

Based on:

test mat.

Remarks:

aerosol

Exp. duration:

4 h

Mortality:

2/5 females died at day 14 post exposure; no deaths among males.

Clinical signs:

other: Please refer to 'Any other information on results incl. tables'

Body weight:

Males: Mean body weight decreased from test day 1 to day 8. Until test day 15, mean body weight increased again, but the starting value was not reached.
Females: Mean body weight decreased continuously over day 8 up to day 15 (only 3 animals at day 15).

Gross pathology:

red spots in the lung

Any other information on results incl. tables

Clinical signs:

During exposure: slight to moderate nose bleeding (epistaxis), no other significant signs.

After exposure: slight to moderate signs of discomfort and physiological distress: hunched posture, piloerection, distended abdomen, tremor, impaired breathing, salivation and rhinorrhea. Impaired breathing and piloerection continued until the end of the observation period. Rales were observed starting at day 2 and continued into week 2 of observation. Symptoms were more pronounced in females than in males.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

In an acute inhalation toxicity test (limit test), 5 rats/sex were exposed to the test substance as aerosol for 4 h. The LC50 for acute inhalation toxicity was determined to be > 5.64 mg/L air.