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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-compliant OECD guideline study, available as unpublished report, no restrictions, adequate for assessment.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3GO / Triethylene Glycol Di-2-Ethylhexanoate
- Physical state: straw colored liquid
- Purity: 98.3%
- Impurities (identity and concentrations): not provided
- Stability under test conditions: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed.

Test animals

Species:
rat
Strain:
other: Crl:CD®(SD)IGS BR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina
- Age at study initiation: approximately 7 weeks old on the day of arrival
- Housing: Except during exposure, animals were housed singly
- Diet (e.g. ad libitum): ad libitum except during exposure (PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002)
- Water (e.g. ad libitum): ad libitum except during exposure (tap water)
- Acclimation period: Rats were quarantined after arrival for 6 days prior to testing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Relative humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): approximate 12-hour light/dark cycle

IN-LIFE DATES: From: January 18, 2005 To: February 21, 2005

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 and exposure chamber volume: The exposure chamber was constructed of glass (cylindrical) with a nominal internal volume of 34 L. A polycarbonate baffle inside the chamber promoted uniform chamber distribution of the test atmosphere.
- Method of holding animals in test chamber: During exposure, animals were individually restrained in perforated stainless steel cylinders with conical nose pieces. The restrainers were inserted into a polymethylmethacrylate faceplate attached to the exposure chamber so that the nose of each animal extended into the exposure chamber.
- System of generating particulates/aerosols: Chamber atmospheres were generated by aerosolization of the test substance in air with a Spraying Systems nebulizer. The test substance was metered into the nebulizer with a Harvard Apparatus model 22 syringe infusion pump. Filtered, high-pressure air, metered into the nebulizer by a Brooks model 0154E mass flow controller, carried the resulting atmosphere into the exposure chamber. Chamber concentrations of test substance were controlled by varying the rate of the infusion pump.
- Treatment of exhaust air: Test atmospheres were exhausted through a dry-ice cold trap followed by an MSA charcoal/HEPA filter cartridge prior to discharge into the fume hood.
- Temperature, humidity, pressure in air chamber: Chamber temperature was 24°C, relative humidity ranged from 46 - 50%, airflow was 16.0 L/min and the oxygen concentration was 21.0%.

TEST ATMOSPHERE
- Brief description of analytical method used: During each exposure the atmospheric concentration of the test substance was determined by gravimetric analysis at approximately 30-minute intervals in the test chamber. Known volumes of chamber atmosphere were drawn from the sampling port through a 25 mm filter cassette containing a pre-weighed glass fiber (Type A/E) filter. The filters were weighed on a Cahn model C-31 Microbalance®. The atmospheric concentration of the test substance was calculated from the difference between the pre- and postsampling filter weights divided by the volume of chamber atmosphere sampled.

TEST ATMOSPHERE
- Particle size distribution: See Tables below
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The atmosphere generated in this study was considered to be respirable in rats, the mass median aerodynamic diameter was 2.0 μm ± 2.0 (MMAD ± GSD), with 97% of the aerosol being less than 10 μm MMAD.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2000 ± 560 mg/m³
No. of animals per sex per dose:
5 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily cage-site examination – all animals
- Body weight: twice weekly – all animals

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
other: ALC (approximate lethal concentration)
Effect level:
> 2 000 mg/m³ air
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
> 2 000 mg/m³ air
Exp. duration:
4 h
Mortality:
No animals died following the single acute 3G8 exposure.
Clinical signs:
other: No notable clinical signs of toxicity were observed during this study.
Body weight:
All animals demonstrated a normal weight gains (approximately 5-10 g/day) except for one rat that lost 3g and subsequently demonstrated weight gain by 2 days post-exposure.

Any other information on results incl. tables

Chamber Concentrations of 3GO (Acute Lethal Concentration Study)

MEASURED CONCENTRATION (mg/m³)*

MEAN

S.D.

RANGE

n

2000

560

1100 - 2600

8

* Represents the mean, standard deviation (S.D.), and range for the exposure, based on n samples.

 

Particle Size Distribution of 3GO (Acute Lethal Concentration Study)

MEASURED

CONCENTRATION

MASS MEDIAN

AERODYNAMIC

GEOMETRIC

STANDARD

% PARTICLES

BY MASS

(mg/m³)

DIAMETER (μm)

DEVIATION

<1 μm

<3 μm

<10 μm

2000

2.0

2.0

15

73

97

 

Chamber Environmental Conditions (Acute Lethal Concentration Study)

MEASURED

CONCENTRATION

TEMPERATURE

(°C)*

RELATIVE

HUMIDITY (%)*

AIRFLOW

(L/min)*

(mg/m³)

RANGE

n

RANGE

n

RANGE

n

2000

24

3

46 - 50

3

16

4

* Values represent the range for all samples obtained from n samples.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
LC50 > 2000 mg/m³ air
ALC (approximate lethal concentration) > 2000 mg/m³ air
Executive summary:

One group of Crl:CD®(SD)IGS BR rats was subject to a 4-hour nose-only exposure to 2000+560 mg/m³ (mean+SD) 3G8. No notable clinical signs of toxicity were observed in animals immediately following exposure and no animals died. Under the conditions of exposure, the approximate lethal concentration (ALC) for 3G8 is greater than 2000 mg/m³ and the median lethal concentration is greater than 2000 mg/m³ air. According to the Haskel Laboratory toxicity classification, 3G8 is considered to be of very low toxicity (ALC greater than 2000 mg/m³ air) in rats.