Oligomerisation products of beta-pinene

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:

other: Guideline study performed under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Nu-Film-17

IUPAC Name:

Nu-Film-17

Constituent 2

Reference substance name:

Oligomerisation products of beta-pinene

EC Number:

701-246-8

Molecular formula:

Variable (dimer = C20-H34)

IUPAC Name:

Oligomerisation products of beta-pinene

Details on test material:

Pinene oligomers content 91.1% w/v

Test animals

Species:

rat

Strain:

other: Sprague Dawley, strain Crl: CD(SD) IGS-BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: Young adults
- Weight at study initiation: 200 - 300 g
- Housing: Animals housed individually in steel cages with a bedding of wood shavings
- Diet: Rat-Mouse Ganave (supplied by Distribuidora Horacio Izaguirre) ad libitum
- Water: tap water (dechlorinated by passage though activated charcoal) ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod: 12 hours light / 12 hours dark

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

A 2.7L 'only nasal' chamber was used as the inhalation chamber. A Respirex professional ultrasonic nebulizer was used to generate the liquid aerosol which was connected to the inhalation chamber by plastic tubing to generate 12 air changes per hour. The air from the chamber is extracted and fed through a treatment system containing carbon tetrachloride solution. The inhalation chamber was maintained under negative pressure throughout the exposure period using a vacuum pump (ECAM Aspirex) and an air flux meter to regulate the air litres/minute.

A group of 10 rats (5 male and 5 female) were exposed to an aerosol concentration of the test substance over a period of 4 hours. After exposure, residual test substance was removed from the facial area of each animal and were returned to their corresponding cages with food and water provided ad libitum. The aerosol particle size was determined though drop measurement, obtained from emulsifying the cloud generated in the inhalation chamber, in vaseline. The nominal concentration of the test substance was determined by dividing the total amount of the nebulized test substance (mg) by the total amount of air flowing through the chamber (litres).

The median aerodynamic diameter of the particles was determined to be 4.1 um and the standard deviation 1.60 um.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

by IR analysis

Duration of exposure:

4 h

Concentrations:

A nominal concentration of 4.64 mg/l was used (maximum achievable concentration, due to the physical-chemical properties of the test substance).

No. of animals per sex per dose:

10 animals in total (5 male, 5 female)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observations were conducted (these included any change to the skin and/or fur, eyes, mucous, respiratory, circulatory and autonomous and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed towards observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleepiness and coma). Animals were weighed prior to exposure to test substance and then at weekly intervals and at time of death or at test termination.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.43 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.64 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities were observed in this study.

Clinical signs:

other: No signs of toxicity were observed in this study

Body weight:

No significant changes to body weight were observed

Gross pathology:

No abnormalities were observed

Any other information on results incl. tables

Table 1. Measured concentrations of test substance (determined by IR analysis)

Sample	Time (min)	Concentration (mg/l)
1	20	4.12
2	60	4.52
3	120	4.4
4	180	4.56
5	240	4.55

Median analytical concentration: 4.43 mg/l

Standard deviation: 0.18 mg/l

Applicant's summary and conclusion

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of this study, the inhalation LC50 in rats was determined to be >4.43 mg/l (measured concentration).