Registration Dossier

Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conducted under OECD guidelines, OECD Good Laboratory Practices

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: granular
Details on test material:
- purity: 99.75 %

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
-General information: Three male animals approximately 7-9 months of age with initial body weights of 2.3-2.4 kg were used.
-Diet: Ad libitum before and after the exposure period. Standard rabbit diet of Altromin 2023 (ALTROMIN GmbH, D-32791 Lage/Lippe). Food was analysed at least twice per year for contaminants.
-Drinking water: Water was offered ad libitum before and after the exposure period. Water samples were analysed twice per year for contaminants and once per year for a bacteriological investigation.
-Housing: Before the exposure period and 8 hours after the exposure period, animals were kept singly in cages measuring 425 mm x 600 mm x 380 mm (manufacturer: Dipl. Ing. W. EHRET GmbH, D-16352 Schonwalde). During the exposure period and for 8 hours afterwards, animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn and wiping of the eyes by the paws and excluded irritation of the eye by excrement and urine.
-Acclimation period: At least 20 days.

ENVIRONMENTAL CONDITIONS
-Temperature: 17-23 degrees C
-Humidity: 30-70%
-Photoperiod: 12 hours light (150 lux at approximately 1.5 meter room height)/12 hours dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
The test material was ground to a fine dust and 100 mg was used per animal.
Duration of treatment / exposure:
Single instillation into the conjunctival sac, after which the lids were gently held together for one second.
Observation period (in vivo):
28 days.
Number of animals or in vitro replicates:
Three males.
Details on study design:
Three male Himalayan rabbits were treated with 100 mg BPA by a single instillation into the conjunctival sac of the right eye. The eye lids were then gently held together for one second to prevent loss of the material. The left eye, which remained untreated, served as a control. The eyes of the animals were not rinsed. The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, and 72 hours and 4 to 28 days after administration. The eye reactions were observed and registered. At 24 hours, 7, 14, and 28 days after administration, the eyes were treated with Fluorescein SE Thilo eye drops (Alcon Pharma GmbH, D-79108, Freiburg, Germany) and examined.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
other: all 3 animals
Time point:
other: 1 hour to 9 days
Score:
1
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #2
Time point:
other: until 13 days
Score:
1
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #3
Time point:
other: until 28 days
Score:
1
Irritation parameter:
iris score
Basis:
other: all 3 animals
Time point:
other: 1 hour to 9 days
Score:
1
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: until 11 days
Score:
1
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: until 28 days
Score:
1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
other: all 3 animals
Time point:
other: 1 to 24 hours
Score:
1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: until 4 days
Score:
1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: until 6 days
Score:
1
Irritation parameter:
chemosis score
Basis:
other: animal #1 and animal #2
Time point:
other: 24 hours
Score:
1
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 1 hour to 4 days
Score:
2
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 5 and 6 days
Score:
1
Irritant / corrosive response data:
Corneal opacity (grade 1) was observed in all three animals 1 hour to 9 days after instillation; in animal #2 until 13 days; and in animal #3 until 28 days after instillation. The fluorescein test performed after 24 hours revealed corneal staining in all 3 rabbits (whole surface). The fluorescein test performed after 7 days revealed corneal staining in animal #1 and animal #2 (3/4 of the corneal surface) and in animal #3 (whole surface). The fluorescein tests performed after 14 and 21 days revealed corneal staining in animal #3 (1/2 of the corneal surface). An irritation of the iris (grade 1) was observed in all three animals one hour to 9 days after instillation, and in animal #2 until 11 days and in animal #3 until 28 days after instillation. Conjunctival redness (grade 1) was observed in all animals one to 24 hours after instillation, in animal #2 until 4 days and in animal #3 until 6 days after instillation. Conjunctival chemosis (grade 1) was observed in animal #1 and animal #2 24 hours after instillation and in animal #3 one hour to 4 days (grade 2) and 5 and 6 days (grade 1) after instillation. Whitish deposits in the conjunctival sac (probably pus) were observed in animal #2 and animal #3 from 72 hours to 5 days after instillation.
Other effects:
There were no systemic intolerance reactions.

Applicant's summary and conclusion

Conclusions:
The authors concluded that BPA induced grade 1 corneal opacity, corneal staining, grade 1 iris irritation, grade 1 conjunctival redness, and grades 1 and 2 conjunctival chemosis.
Executive summary:

Three male Himalayan rabbits were treated with 100 mg BPA by a single instillation into the conjunctival sac of the right eye. The eye lids were then gently held together for one second to prevent loss of the material. The left eye, which remained untreated, served as a control. The eyes of the animals were not rinsed. The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, and 72 hours and 4 to 28 days after administration. The eye reactions were observed and registered. At 24 hours, 7, 14, and 28 days after administration, the eyes were treated with Fluorescein SE Thilo eye drops (Alcon Pharma GmbH, D-79108, Freiburg, Germany) and examined. Corneal opacity (grade 1) was observed in all three animals 1 hour to 9 days after instillation; in animal #2 until 13 days; and in animal #3 until 28 days after instillation. The fluorescein test performed after 24 hours revealed corneal staining in all 3 rabbits (whole surface). The fluorescein test performed after 7 days revealed corneal staining in animal #1 and animal #2 (3/4 of the corneal surface) and in animal #3 (whole surface). The fluorescein tests performed after 14 and 21 days revealed corneal staining in animal #3 (1/2 of the corneal surface). An irritation of the iris (grade 1) was observed in all three animals one hour to 9 days after instillation, and in animal #2 until 11 days and in animal #3 until 28 days after instillation. Conjunctival redness (grade 1) was observed in all animals one to 24 hours after instillation, in animal #2 until 4 days and in animal #3 until 6 days after instillation. Conjunctival chemosis (grade 1) was observed in animal #1 and animal #2 24 hours after instillation and in animal #3 one hour to 4 days (grade 2) and 5 and 6 days (grade 1) after instillation. Whitish deposits in the conjunctival sac (probably pus) were observed in animal #2 and animal #3 from 72 hours to 5 days after instillation.