Acetonitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Acetonitrile

EC Number:

200-835-2

EC Name:

Acetonitrile

Cas Number:

75-05-8

Molecular formula:

C2H3N

IUPAC Name:

acetonitrile

Details on test material:

- Name of test material (as cited in study report): Acetonitrile HPLC Grade
- Physical state: Clear liquid
- Analytical purity: 99.9%
- Impurities (identity and concentrations): Water: 0.002%
- Lot/batch No.: 973432
- Storage condition of test material: Room temperature
- Supplier: Fisher Chemicals, Fair Lawn, New Jersey

Specific details on test material used for the study:

- Name of test material (as cited in study report): Acetonitrile HPLC Grade
- Physical state: Clear liquid
- Analytical purity: 99.9%
- Impurities (identity and concentrations): Water: 0.002%
- Lot/batch No.: 973432
- Storage condition of test material: Room temperature
- Supplier: Fisher Chemicals, Fair Lawn, New Jersey

Test animals

Species:

mouse

Strain:

other: Crl:CD-1 (ICR) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, MI.
- Age at study initiation: 6-8 weeks of age.
- Weight at study initiation: 24-33g (m); 19-28g (f)
- Housing: The animals were housed 3-4 per cage for the first few days of the acclimation period in order to become accustomed to the automatic watering system, then were housed individually in stainless-steel cages.
- Diet: Certified Rodent Chow® #5002, PMI Feeds, Inc., St. Louis, Missouri was available ad libitum, except during designated fasting periods (3-4 hours prior to dosing and 1-2 hours after dosing).
- Water: Water was available ad libitum.
- Acclimation period: 8-19 days

ENVIRONMENTAL CONDITIONS
- Temperature: 66-77°F
- Humidity: 34-73%
- Photoperiod: 12 hours flourscent light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

- Rationale for the selection of the starting dose: The 2000 mg/kg dose is specified by regulatory agencies for the limit test. The other doses were selected to produce partial mortalities in order to calculate an LD50.

Doses:

Single dose 300, 500, 650, 900, 1200, 2000 mg/kg.

No. of animals per sex per dose:

6 groups of 5 males and 5 females each.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed approximately 1, 2, and 4 hours after dosing on the day of test article administration (study day 1). They were then observed twice daily (morning and afternoon) for 13 additional days and once on the day of necropsy. Individual body weights were obtained just prior to test article administration, on study day 8, at study termination (study day 15), or when an animal was found dead.
- Necropsy of survivors performed: yes, A gross necropsy was performed on all animals dying on study as well as those surviving until study termination (study day 15). For animals surviving until study termination, euthanasia was by carbon dioxide inhalation followed by exsanguination from the abdominal aorta. External abnormalities including palpable masses were examined. Subcutaneous masses were identified and correlated with antemortem findings. Organs were removed and examined and the tissues and carcasses discarded.

Statistics:

The median lethal dose (LD50) and its 95% confidence limits were calculated by the method of Bliss, CI (1938), The determination of the dosage-mortality curve from small numbers. Quarterly Journal of Pharmacy and Pharmacology, 11: 192-216.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

469 mg/kg bw

95% CL:

>= 163 - <= 699

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

765 mg/kg bw

95% CL:

>= 539 - <= 1 104

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

617 mg/kg bw

95% CL:

>= 450 - <= 787

Mortality:

Test article-related combined sex mortalities were 10, 30, 60, 80, 90, and 90% for dose levels 300, 500, 650, 900, 1200, and 2000 mg/kg of Acetonitrile (HPLC Grade), respectively. With the exception of the 650 mg/kg group, mortalities were approximately equal for both sexes. No mortalities occurred after study day 2 for any group.

Clinical signs:

other: Significant clinical signs observed during the study included death, tremors, prostration, decreased activity, impaired righting reflex, labored breathing, convulsions, gasping, and increased salivation. All surviving animals were judged normal by study d

Gross pathology:

At necropsy, there were no test article-related findings in any animal.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of this study, the oral LD50 of Acetonitrile (HPLC Grade) was calculated to be 617 mg/kg for male and female mice combined (with 95% confidence limits of 450-787 mg/kg).

Executive summary:

In a guideline (OECD 401 equivalent) and GLP study by MPI Research (1998), the acute oral LD50 of Acetonitrile (HPLC Grade) was calculated to be 617 mg/kg for male and female mice combined (with 95% confidence limits of 450-787 mg/kg). Significant clinical signs observed during the study included death, tremors, prostration, decreased activity, impaired righting reflex, labored breathing, convulsions, gasping, and increased salivation. All surviving animals were judged normal by study day 4, with the exception of a single 300 mg/kg group animal that exhibited increased salivation on study day 8.