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Acute Toxicity: inhalation

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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other: Comparable to guideline study, GLP-compliant, available as unpublished report, no restrictions, adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Terphenyl
EC Number:
247-477-3
EC Name:
Terphenyl
Cas Number:
26140-60-3
Molecular formula:
C18H14
IUPAC Name:
1,1':4',1''-terphenyl
Constituent 2
Reference substance name:
Therminol 75
IUPAC Name:
Therminol 75
Details on test material:
- Name of test material (as cited in study report): Therminol 75 (MCS 1980)
- Substance type: a mixture of terphenyls and quaterphenyls
- Physical state: An amber solid
- EHL Substance Identification Code: T830078
- Purity: mixture

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 Laboratory (Portage, Michigan)
- Age at study initiation: approximately 5 weeks
- Weight at study initiation: males weighing 160 to 186 grams and females 135 to 158 grams
- Housing: individually housed
- Diet (e.g. ad libitum): ad libitum; Purina Laboratory Certified Rodent Chow ®(5002), except during the exposure period
- Water (e.g. ad libitum): ad libitum; tap water (St. Louis City, MAO), except during the exposure period
- Acclimation period: eight days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-760F
- Humidity (%): 35-60% relative humidity
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The exposure atmosphere was generated by using a Laskin-type nebulizer utilizing double spray jets.
- Exposure chamber volume: The exposure chamber was a 0.3 m³ Rochester-type stainless steel chamber, with a pyramidal top and bottom and a glass window in the door
- Source and rate of air: Airflow through the chamber ranged from 20.0 to 22.9 liters/minute.
- Method of conditioning air: Test material (heated and melted) was placed in a 3-neck flask and a Laskin nebulizer was positioned in the liquid of the flask. Exposures were conducted under two sets of conditions: (a) test material heated and exposure chamber at ambient temperature and (b) both test material and exposure chamber heated. Control (room air) exposures were conducted at ambient and elevated chamber temperatures. A three-foot piece of heat tape was wrapped around the flask and connected to a 12UV variable autotransformer to neat the test material. The chamber atmosphere was heated by the use of two six-foot heat tapes attached to the outer chamber sides and controlled by a 120V variable autotransformer.
- Temperature, humidity, pressure in air chamber: The chamber atmosphere mean temperatures ranged from 23.3-24.7°c (ambient) and 38.0-39.0°c (heated). The relative humidity of the chamber, atmospheres ranged from 35-47%. Oxygen levels were measured using a Teledyne oxygen analyzer and were maintained at 20% or greater for all exposures.

TEST ATMOSPHERE
- Brief description of analytical method used: The analytical concentration of test material in iso-octane was determined by gas chromatography. The nominal concentration was calculated once for each exposure by determining the total amount of test material delivered by the nebulizer into the chamber and dividing this amount by the total air volume passing through the chamber during the exposure period. Particle-size analysis was performed using an Andersen cascade impactor (Andersen Samplers Inc., Atlanta, GA).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (Table 2)
- Particle size distribution: The percentage of particles, in the chamber, less than 10 microns ranged between 99.0 and 99.1.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD for the exposures was between 2.27 and 2.38 microns, with the geometric standard deviation between 1.83 and 1.90.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
3.6, 3.7, 3.8 mg/ml
No. of animals per sex per dose:
6 animals per sex per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were examined following exposure and gross signs of toxicity were recorded. During the 14-day post-exposure period, the animals were examined twice daily (morning and afternoon) and gross signs of toxicity were recorded except on weekends when only mortality checks were to be done. Body weights and toxicity observations were also obtained on post-exposure Days 2, 7, and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3.8 mg/L air
Exp. duration:
4 h
Mortality:
No deaths occurred (See Table 1).
Clinical signs:
other: During exposure observations in the 3.8 mg/l, 3.7 mg/l and heated control groups were salivation and red material around eyes (in 3.7 mg/l group only). Discharge from nose' was observed in the 3.6 mg/l group. Immediate post-exposure observations included
Body weight:
All groups gained body weight throughout the post-exposure period.
Gross pathology:
There were no gross pathology abnormalities observed in any of the animals during necropsy examinations.

Applicant's summary and conclusion

Conclusions:
The LD50 for Therminol 75 was determined to be above 3.8 mg/L air (males/females)
Executive summary:

To assess acute inhalation toxicity a test was set up according to the OECD 403 guideline, in which Therminol 75 was administered to Sprague Dawley rats via aerosol during 4 hours, after which the animals were observed for a period of 14 days. Exposure concentrations were 3.6, 3.7 and 3.8 mg/mL (two concentrations with heated chamber air and test material and one with ambient chamber air and heated test material). An LD50 (male/female) > 3.8 mg/L air was reported. Immediate post exposure observations included red encrustation around eyes and nose, labored breathing and salivation. On post-exposure days 7 and 14 these observations were no longer evident. No gross pathology abnormalities were observed in any of the animals during necropsy examinations.