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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report in agreement with OECD guideline 403-GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity liquid hydrocarbon

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sasco, Inc., Omaha, Nebraska
- Age at study initiation: young adults
- Weight at study initiation: approximately 200-300 grams
- Housing: individually
- Diet (e.g. ad libitum): Fresh Certified Rodent feed, ad llibitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week (7 days)

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-76 °F
- Humidity (%): 40 to 60 percent relative humidity
- Photoperiod (hrs dark / hrs light): 12hrs dark /12 hrs light

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Rats were exposed in to the test atmosphere in a Hazleton 1000 whole body inhalation chamber. The test atmosphere was generated by delivering the test article to a Sonimist nozzle (nebulizer) under pressure by compressed breathing air
- Volume: 1m3 (1000L)
- Temperature, pressure in air chamber: 23
- Air flow rate: 200 L/min (avg)

TEST ATMOSPHERE
- The test atmosphere shall be generated using an appropriate system selected according to the physical state and characteristics of the test article.
- Groups of individually caged rats will be exposed collectively to the test atmosphere under dynamic air flow conditions for four hours in an appropriate sized whole body chamber (50 in. x 48 in. x 25 in.).
- Air flow rate shall be monitored continuously and documented every thirty minutes
- An exposure environment of at least 19% oxygen shall be insured
-Temperature and humidity shall be monitored continuously and documented every thirty minutes
- Nominal concentrations of test article for each exposure shall be determined gravimetrically
- actual concentrations of airborn test article shall be measured near the breathing zone at one hour intervals during the test period
- particle size distribution measurements shall be made near the breathing zone during the exposed period
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
- nominal (gravimetric) concentration: 7630 +/- 900 mg/m³
- actual (miran) vapor concentration: 5610 +/- 300 mg/m³

No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
One group of ten rats (5 of each sex) will be collectively exposed to either 5.0 mg/l or the maximum attainable concentration (whichever is the lesser) of the test article. The sponsor representative shall be notified immediately if any deaths occur during the acute screening study. After obtaining the sponsor's representative's approval, groups of twenty rats (10 male, 10 female) will be collectively exposed. Exposure levels for this LC50 study shall be approved by the Sponsor Representative after reviewing the results of the screening study. On post dosing day 13, all surviving animals shall be sacrificed. All animals will undergo a complete gross necropsy.
Statistics:
-Mean and standard deviations shall be calculated for animal body weights at the following intervals: day 0, day 7 and termination.
-The ratio of vapor to aerosol phases generated shall be calculated for liquids
-Mean and standard deviations shall be calculated for air flow, temperature, test article concentration and humidity during the testing procedure
-If an LC50 study is performed, median lethal dose values shall be calculated for each sex by an accepted method such as Finney, D.J. (1971) Probit Analysis, 3rd Ed., Cambridge Univ. Press, London. A 95% confidence interval for the median lethal dose should be calculated.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 7 630 mg/m³ air (nominal)
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 610 mg/m³ air (analytical)
Mortality:
none
Clinical signs:
All animals survived to the scheduled sacrifice. There were no remarkable clinical signs noted during the course of treatment.
Body weight:
- male rats gained an average of 60 g (s.d. 9 g) with a range of 50-73 g over the two week period
- female rats gained an average of 18 g (s.d. 6 g) with a range of 11-27 g over the two week period
Gross pathology:
Three of the five male rats exhibited lungs with small round lesions. There were no other visible gross pathological lesions observed on any of the animals at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The inhalation LC50 of test article F-101 is greater than an average nominal (gravimetric) concentration of 7630 +/- 900 mg/m³ and an average actual (calculated by Miran) concentration of 5610 +/- 300 mg/m³. These findings do not warrant classification of the test article as an acute inhalation toxicant under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations. 
Executive summary:

Five male and five female rats were exposed to an average nominal (gravimetric) concentration of 7630 +/- 900 mg/m³ and an average actual (measured by Miran) vapor concentration of 5610 +/- 300 mg/m³ of test article F-101 for four consecutive hours. No in-life observation effects were observed during the 14 day observation period. At necropsy, three of the five male rats had lung lesions that may be test article related. None of the animals died during the 14 day observation period. Based on the parameters of this study, the inhalation LC50 of test article F-101 is greater than an average nominal (gravimetric) concentration of 7630 +/- 900 mg/m³ and an average actual (calculated by Miran) concentration of 5610 +/- 300 mg/m³. These findings do not warrant classification of the test article as an acute inhalation toxicant under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.