Acetonitrile

Endpoint summary

Description of key information

Acetonitrile is not irritating to rabbit skin, but is irritating to the rabbit eye under standard test conditions.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

This study was conducted in accordance with Standard Operating Procedures, Good Laboratory Practice Standards as set forth by the EPA in 40 CFR Part 160 (FIFRA) and 40 CFR Part 792 (TSCA), JMAFF in NohSan No. 3850, and OECD in (C(81)30(Final)Annex 2), and the Protocol as approved by the Sponsor. Procedures pertinent to this study are described in this report.

GLP compliance:

yes

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products, Inc., Kalamazoo, Michigan.
- Age at study initiation: 7.5 months of age
- Weight at study initiation: The body weight range on the day of dosing was 3283-3519 grams.
- Housing: housed in individual stainless steel slatted floor cages in an animal room
- Diet: Certified Rabbit Chow® # 5322, PMI Feeds, Inc., St. Louis, Missouri was available up to 125 g/day.
- Water: ad libitum
- Acclimation period: The animals were maintained in accordance with the recommendations contained in the D.H.H.S. Publication entitled "Guide for the Care and Use of Laboratory Animals" and conditioned for a period of 114 days prior to dosing.

ENVIRONMENTAL CONDITIONS
- Temperature: 66-68°F
- Humidity: 56-66%
- Photoperiod: 12 hours light and 12 hours dark

IN-LIFE DATES: From: May 12,1997 To: September 8, 1997

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

72 hours after bandage removal

Number of animals:

6 male

Details on study design:

Each rabbit was identified by a Monel® metal ear tag bearing the individual animal number.

TEST SITE
- Area of exposure: 1 intact skin site on the back of each rabbit. Dorsal area
- Type of wrap if used: The test sites were then wrapped with 8-ply gauze bandaging and overwrapped with Denniform® tape. A collar (E-Jay Saf-T-Shield) was placed on each rabbit to prevent them from disturbing the application site and wrapping.

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

SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The test sites were evaluated for dermal irritation approximately 0.5-1, 24, 48, and 72 hours following patch removal and scored based on the Draize method. All scores at each observation interval were 0 for each animal.

Other effects:

No signs of ill health or test article-related effects were observed during the study.

The overall irritation score was 0.0

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study, Acetonitrile (HPLC Grade) is non-irritating to the skin of rabbits.

Executive summary:

In a guideline (OECD 404 equivalent) and GLP study, Acetonitrile (HPLC Grade) was found to be non-irritating to the skin of rabbits (4 -hour exposure). All scores at each observation interval were 0.0 for each animal. No other signs of ill health or test article-related effects were observed during the study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Each rabbit was identified by Monel® metal ear tag bearing the individual animal number.

TEST ANIMALS
- Source: Covance Research Products, Inc., Kalamazoo, MI.
- Age at study initiation: approximately 8 months of age.
- Weight at study initiation: 3393 - 3623g
- Housing: animals were housed in individual stainless steel slatted floor cages
- Diet: Certified Rabbit Chow® #5322, PMI Feeds, Inc., St. Louis, Missouri, was limited upon arrival and then available up to 125 g/day.
- Water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature: 66-70 °C
- Humidity: 55-70%
- Photoperiod: 12 hours light and 12 hours dark

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL.

Duration of treatment / exposure:

The test article was administered into the cupped conjunctival sac of the right (test) eye of each rabbit and the eyelid was then gently held together for 1 second before release.

Observation period (in vivo):

Scoring was conducted according at 1, 24, 48, and 72 hours after dosing, as well as 4, 7, 14, and 21 days after dosing.

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes remained unwashed.

SCORING SYSTEM: Draize Scoring Method at 1, 24, 48, and 72 hours after dosing, as well as 4, 7, 14 and 21 days after dosing (study days 5, 8, 15, and 22, respectively). A sodium fluorescein examination was conducted after scoring at the 24 hour, 72 hour, and day 7, 14, and 21 post-dose intervals.

TOOL USED TO ASSESS SCORE:
- Sodium fluorescein examinations were conducted after scoring at the 24 hour, 72 hour, and 7,
14, and 21 day post-dose intervals.
- The treated (right) eyes and control (left) eyes of all animals were examined with the aid of a penlight.

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

> 2 - <= 3

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 5

Max. score:

5

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 5

Max. score:

5

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 5

Max. score:

5

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

> 0 - <= 5

Max. score:

5

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

> 0 - <= 5

Max. score:

5

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

ca. 5

Max. score:

5

Reversibility:

fully reversible

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

> 36.7 - <= 46

Max. score:

46

Reversibility:

not fully reversible within: 21 days

Remarks on result:

probability of severe irritation

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

ca. 20

Max. score:

20

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

> 15 - <= 20

Max. score:

20

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

> 20 - <= 30

Max. score:

30

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

> 15 - <= 30

Max. score:

30

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 20

Max. score:

20

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 10 - < 40

Max. score:

40

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

All animals displayed ocular irritation at 1 hour post-dose, continuing to day 21 post-dose in 4 of 6 animals, with the eyes of 2 animals returning to normal by day 14 or 21 post-dose. Diffuse beefy red conjunctival color was observed in all animals, with obvious swelling, partially everted lids, and considerable discharge around the eye. Blanching and petechiae was observed in all animals. The conjunctivae of 2 animals returned to normal by day 7 or 14 post-dose, while the remaining animals continued to exhibit slight to diffuse redness, slight swelling, and slight discharge at study termination.

Diffuse to easily discernable corneal opacity, covering more than ¾ of the area in some animals, was observed in all animals. Corneal opacity cleared in 3 animals by day 7 or 14 post-dose, but diffuse opacity continued to day 21 post-dose in the remaining animals. Corneal vascularization was observed in 3 of 6 animals. Slight iris irritation was observed in all animals, clearing by 48 hours (1 animal) and 7 or 14 days post-dose.

Other effects:

No other signs of toxicity or ill health were observed.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Based on the results of this study, Acetonitrile (HPLC Grade) is severely irritating to the eyes of rabbits.

Executive summary:

In a guideline (OECD 405 equivalent) and GLP study, Acetonitrile (HPLC Grade) was found to be severely irritating to the eyes of rabbits, with a maximum group average ocular Draize irritation score of 46.0 occurring at 24 hours postdose. Considerable ocular irritation was observed in all animals, including easily discemable corneal opacity, slight iris injection, diffuse beefy red conjunctivae, obvious swelling, partial lid eversion, and considerable discharge. Some ocular irritation was present in 4 of 6 animals at study termination 21 Days after dosing. No other signs of ill health or toxicity were observed during the study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

In a guideline (OECD 404 equivalent) and GLP study, exposure to acetonitrile was found to be non-irritating to the skin of rabbits (MPI Research, 1997). Earlier work published by Zeller et al (1969) and Smyth & Carpenter (1948) support these findings.

Eye irritation

In a guideline (OECD 405 equivalent) and GLP study, acetonitrile was found to be severely irritating to the eyes of rabbits, with a maximum group average ocular Draize irritation score of 46.0 occurring at 24 hours (MPI Research, 1997).

Some ocular irritation was present in 4 of 6 animals after 21 days. Earlier work published by Zeller et al (1969) and Carpenter & Smyth (1946) support the eye irritation potential of acetonitrile.

Justification for selection of skin irritation / corrosion endpoint:

Guideline-comparable study

Justification for selection of eye irritation endpoint:

Guideline-comparable study

Effects on eye irritation: irritating

Justification for classification or non-classification

Acetonitrile has a harmonised CLP classification for Eye Irritation Cat. 2 (H319). No change is proposed to this classification based on the data available. No classification for skin irritation is triggered by the available data.