Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

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

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
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
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 / tissue source

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

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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.

Applicant's summary and conclusion

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.