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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997
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:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
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): 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:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Inc. Kalamazoo, MI.
- Age at study initiation: 3.5 months of age.
- Weight at study initiation: 2721 - 3035g (m); 2477 - 2884g (f)
- Housing: Individually in stainless-steel cages.
- Diet: Certified Rabbit Chow® # 5322 ad libitum
- Water: Ad libitum
- Acclimation period: 8 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 66 - 70°F
- Humidity: 46 - 80%
- Photoperiod: 12 hours a day light

IN-LIFE DATES: From: August 11, 1997 To: September 18, 1997

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: The test article was applied to the shaven intact skin on the back of each rabbit.
- % coverage: approximately 15% of body surface.
- Type of wrap if used: The trunk of each rabbit was wrapped with gauze bandaging and secured with Dermiform® tape.

REMOVAL OF TEST SUBSTANCE
- Following the exposure period, the bandaging materials and collars were removed and the test sites wiped with disposable toweling moistened with water to remove any residual material.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The dosage volume was 2.6 mL/kg based on a test article density of 0.777 g/mL.
Duration of exposure:
24 hours.
Doses:
Single 2000 mg/kg dose.
No. of animals per sex per dose:
5 males and 5 females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes. A gross necropsy was performed on all animals at study termination (study day 15). Euthanasia was by an overdose injection of sodium pentobarbital.
Statistics:
No data were analyzed statistically.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All animals survived to study termination.
Clinical signs:
No signs of toxicity or ill health were observed in the males during the conduct of this study. With the exception of decreased defection observed in 3 females for 1 day during the 14-day observation period ( which was described as a probable test article-related change), no other signs of ill health or toxicity were observed in the females during the study.
Body weight:
Mean group body weights for each sex increased at each observation interval. All animals gained weight at each observation interval with the exceptions of 1 male that lost 23 grams at study day 8 and another that lost 2 grams at study termination.
Gross pathology:
At necropsy, no visible abnormalities were observed at the application site or in other tissues.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, the acute dermal LD50 value of Acetonitrile (HPLC Grade) is greater than 2000 mg/kg for male and female rabbits.
Executive summary:

In a guideline (OECD 402 equivalent) and GLP study by MPI Research (1998), the acute dermal LDLo (24 -hour exposure) of Acetonitrile (HPLC Grade) was found to be greater than 2000 mg/kg for male and female rabbits. No signs of toxicity or ill health were observed in the males during the conduct of this study. With the exception of decreased defection observed in 3 females for 1 day during the 14-day observation period (which was described as a probable test article-related change), no other signs of ill health or toxicity were observed in the females during the study.