Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

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:
other: 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:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

Test animals

Species:
mouse
Strain:
other: Crl:CD-1 (ICR) BR
Sex:
male/female
Details on test animals 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
469 mg/kg bw
95% CL:
>= 163 - <= 699
Sex:
female
Dose descriptor:
LD50
Effect level:
765 mg/kg bw
95% CL:
>= 539 - <= 1 104
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:
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.
Body weight:
Body weight gains for survivors were similar for both sexes. The 300 and 500 mg/kg groups were the only groups with survivors from both sexes. Body weight gains were 2-3 grams for each sex.

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

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.