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:
August 2002-December 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-documented and corresponded to the requirements of the recommended Annex V Test Guidelines
Justification for data waiving:
other:

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): PEBETAL dibasic lead phthalate
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state: fine, white powder
- Analytical purity: 74.15% Pb = 97.6% Pebetal
- Impurities (identity and concentrations):
- Composition of test material, percentage of components: ash: 79.3%; water: 0.2%
- Isomers composition:
- Purity test date:
- Lot/batch No.: D1/4296
- Expiration date of the lot/batch: July 31,2004
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material: At room temperature; shelf life - at least one year after dispatch
- Other:

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann
- Age at study initiation:
- Weight at study initiation: 3.11, 3.25, and 3.27 kg
- Housing: Cage size of 100 x 45 x 40 cm (L x B x H), equipped with a paper diposal system.
- Diet (e.g. ad libitum): Teklad Global Rabbit Diet ad libitum
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking nipples
- Acclimation period: Animals used in the test were housed at the testing facility and acclimatised for 27 days or several months


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 degrees Centigrade
- Humidity (%): between 30-70%
- Air changes (per hr): 16/hr and filtered adequately
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light with light on at 7:00 AM


IN-LIFE DATES: From: To:

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated left eye served as the control.
Amount / concentration applied:
0.1 g of the solid test article
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours - 7 days
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
Three male rabbits used in the test were acclimatised to laboratory conditions for 27 days or several months. Twenty four hours before treatment, the eyes of all animals were examined for potential ocular lesions. Since the animals did not show ocular abnormalities, they were allocated to the test.

The solid test article was used as supplied +by the sponsor. One of the animals was treated in advance in order to assess ocular reactions to the test articles. The animal was treated with 0.1 g of the solid test article, which was introduced into the conjunctival sac of the right eye after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about 1 sec in order to limit loss of the test article. The untreated left eye served as control. Since there was no remarkable response to the instillation of the test article within a few days, the further two animals were treated subsequently in the same manner. Ocular reactions were assessed 1,24,48, and 72 hours after instillation and thereafter once daily up to day 7 according to the "Grades for ocular lesions." In addition to the examination of the eyes, general clinical observation was conducted. Ocular reactions were classified on the basis of calculated mean grades at 24,48 and 72 hours after treatment according to the EEC Directive 2001/59/EEC of 6 August
2001 and Gefahrstoffverordnung (GefStoffV) 0f 15 November 1999 (BGB1. I, p.2233).
+

Results and discussion

In vivo

Results
Irritation parameter:
conjunctivae score
Basis:
mean
Reversibility:
fully reversible within: 7days after instillation
Irritant / corrosive response data:
Moderate redness of the conjunctivae (grade 2) was observed in all three animals at 1 hour after instillation. This finding was still apparent at 24 and 48 hours after instillation in animals no.1 and 2 or up to day 6 after instillation in animal no.3, evaluated with grade 3 at 24 hours after treatment. Discharge (grade 1 or 2) was seen in the animals at 1 hour after instillation and was still observed in animal no.3, evaluated with grade 3 at 24 hours
after treatment. Discharge (grade 1111 or 2) was seen in animals at 1 hour after instillation and was still observed in animal no.3 at 24 hours after instillation. Additionally, bloody vessels of the eyeball were seen in animal no.3 at 24 hours up to day 5 adter instillation. In all animals, no ocular findings were seen at day 7 after instillation.
Other effects:
No general toxic effects were observed. The observed ocular findings were fully reversible within 7 days after instillation.

Any other information on results incl. tables

 

Mean values of ocular reactions at 24, 48 and 72 hours after treatment (test eye) R

 Cornea  Iris  Conjunctivae Redness  Conjunctivae Chemosis
 Rabbit 1 0.00 0.00 1.00 0.67
 Rabbit 2 0.00 0.00  1.00 0.33 
 Rabbit 3 0.00  0.00   2.33 2.00 

Key:

Conjunctivae redness 1.00 - Some blood vessels definitely hyperaemic

2.00- Diffuse, Crimson colour, individual vessels not easily discernible

Conjunctivae chemosis 0 -No swelling; 1.00 Any swelling above normal; 2.00 Obvious swelling with partial eversion of lids

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: OECD 405
Conclusions:
The mean grades of ocular reactions at 24, 48 and 72 hours after instillation were lower than the value classified as irritant by the EEC Directive 2001/59/EEC of 6 August 2001 and the Gefahrstoffverordnung (GefffStoffV) of 15 November 1`999 (BGB1. I, p,2233). When administered to the eye, the test article "PEBETAL dibasic lead pthalate" may be classified as "non-irritant."
Executive summary:

The potential toxicity of "PEBETAL dibasic lead phthalate" was assessed in an acute eye irritation/corrosion test on 3 albino rabbits. In each animal, 0.1 g of the test article was introduced into the conjunctival sac of the right eye, the untreated left eye served as control. Both eyes were examined at 1, 24, 48, and 72 hours post applicationem.

The following results were obtained;

Redness and chemosis of the conjunctivae, grade 2, were observed in the animals 1 hour after instillation and in one rabbit up to day 5 or 6 after instillation. Moderate discharge was observed in all animals at 1 hour after instillation and was seen in one out of three animals also at 24 hours after instillation. Additionally, bloody vessels of the eyeball were seen in one animal between 24 hours and day 6 after instillation.

No general toxic effects were observed.

The observed ocular findings were fully reversible within 7 days after instilllation in all animals.

The mean grades of findings were 1.00, 1.00, and 2.33 for redness of the conjunctivae and 0.67, 0.33 and 2.00 for chemosis of the conjunctivae

The mean grades of ocular reactions at 24,48 and 72 hours after instillation were lower than the value classified as irritant by the EEC Directive 2001/59/EEC of 6 August 2001 and the Gefahrstofffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p.2233) When administered to the eye, the test article "PEBETAL dibasic lead phthalate" may be classified as "non-irritant."