Hydrocarbons, C11-C12, isoalkanes, <2% aromatics

Acute Toxicity: inhalation

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Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2000/07/17-2000/07/31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 403: GLP.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2000/07/17-2000/07/31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 403: GLP.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 951 mg/m³ air (analytical)

Exp. duration:

4 h

Remarks on result:

other: maximum attainable vapor concentration

Mortality:

All rats survived to the end of the experimental observation.

Clinical signs:

other: All rats appeared normal during the exposure and during the 14 day post-exposure period.

Body weight:

No effects noted

Gross pathology:

All animals were free of any pathological symptoms at their postmortem examination.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LC50 for acute inhalation exposure to MRD-00-586 vapor is greater than the highest obtainable vapor concentration (4951 mg/m3). Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

This data is being read across from the source study that tested Hydrocarbons, C11-C13, isoalkanes, <2% aromatics based on analogue read across.

MRD-00-586 was administered via individual inhalation chambers for four hours to ten rats at the maximum attainable vapor concentration of 4951 mg/m³ for four hours to assess acute inhalation toxicity. There were no mortality or gross pathological alterations noted in any of the animals.  Based on the conditions of this study, the LC50 for acute inhalation exposure to MRD-00-586 vapor is greater than the highest obtainable vapor concentration (4951 mg/m³).  Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

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

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc.
- Age at study initiation: 9-10 weels
- Weight at study initiation: Males: 299-325 g; Females: 221-244g
- Fasting period before study:
- Housing: single housed
- Diet (e.g. ad libitum): PMI Feeds
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 64-72
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The animals were individually housed within a 150-liter stainless steel and acrylic whole body inhalation exposure chamber. The chamber operated under slight negative pressure to the room, at an airflow of approximately 30 liters per minute. The exposure period was 4 hours, plus time for equilibration (theoretical T99 = 23 minutes). Chamber airflow, temperature, and relative humidity were monitored continuously throughout the exposure and recorded approximately every 30 minutes.

The concentration of solvent in the test atmosphere was monitored continuously during the exposure by means of a high temperature total hydrocarbon analyzer. The instrument was calibrated using a gravimetric procedure.

Test Atmosphere Generation: The test material was volatilized at 160 deg C. The resulting vapors were drawn into the exposure chamber by the supply air moving countercurrent to the liquid flow.

Exposure Concentrations: Nominal concentrations were determined by subtracting the weight of the syringe from the weight of the syringe plus test material. Analytical concentrations were determined through the use of a calibrated infrared monitor. Chamber concentrations were recorded every 30 minutes. Uniformity of the test atmosphere was conducted by sampling the concentration of the four corners of the exposure chamber.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

4951 mg/m3; maximum attainable vapor

Duration of exposure:

4 h

Concentrations:

4951 mg/m3 (analytical); 5250 mg/m3 (nominal); maximum attainable vapor

No. of animals per sex per dose:

5 males; 5 females

Control animals:

no

Details on study design:

Experimental Evaluation
The animal population as a whole was observed for mortality and obvious signs of toxicity at approximately 1 5-minute intervals during the first hour of exposure and once each hour thereafter throughout the exposure. Detailed individual animal observations were recorded pre-exposure, post-exposure upon removal from the chamber, and once daily for 14 days post-exposure. Body weights were recorded prior to exposure (Day 0), and on Days 7 and 14 post-exposure.

Termination
After the Day 14 observations, all surviving animals were sacrificed by exsanguination from the abdominal aorta while under sodium pentobarbital anesthesia (administered intraperitoneal). A gross necropsy which included an examination of the external surface of the body, the cranial, thoracic, abdominal cavities and their contents, and complete examination of the respiratory tract (primarily the external surfaces) was performed on all animals.

Statistics:

Statistical analyses included the calculations of means and standard deviations for body weight and body weight change by sex (Snedecor and Cochran, 1989).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 951 mg/m³ air (analytical)

Exp. duration:

4 h

Remarks on result:

other: maximum attainable vapor concentration

Mortality:

All rats survived to the end of the experimental observation.

Clinical signs:

other: All rats appeared normal during the exposure and during the 14 day post-exposure period.

Body weight:

No effects noted

Gross pathology:

All animals were free of any pathological symptoms at their postmortem examination.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LC50 for acute inhalation exposure to MRD-00-586 vapor is greater than the highest obtainable vapor concentration (4951 mg/m3). Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

MRD-00-586 was administered via individual inhalation chambers for four hours to ten rats at the maximum attainable vapor concentration of 4951 mg/m³ for four hours to assess acute inhalation toxicity. There were no mortality or gross pathological alterations noted in any of the animals.  Based on the conditions of this study, the LC50 for acute inhalation exposure to MRD-00-586 vapor is greater than the highest obtainable vapor concentration (4951 mg/m³).  Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.