Registration Dossier

Administrative data

Endpoint:
eye irritation, other
Remarks:
An adequate in vivo study was conducted on the test article prior to the requirement for in vitro data.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 March 2007 to 02 May 2007 (In-life phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Manual temp recording and no monitoring for humidity was done on 06 April 2007.It is expected the relative humidity remained within 30-70% based on data during time period from adjacent rooms. Study integrity not adversely affected by the deviations.
Qualifier:
according to
Guideline:
other: EC, Council Directive 67/548/EEC, An. V, B.5, (2004) "Acute Toxicity: Eye Irritation/Corrosion"
Deviations:
yes
Remarks:
Manual temp recording and no monitoring for humidity was done on 06 April 2007.It is expected the relative humidity remained within 30-70% based on data during time period from adjacent rooms. Study integrity not adversely affected by the deviations.
Qualifier:
according to
Guideline:
other: EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"
Deviations:
yes
Remarks:
Manual temp recording and no monitoring for humidity was done on 06 April 2007.It is expected the relative humidity remained within 30-70% based on data during time period from adjacent rooms. Study integrity not adversely affected by the deviations.
Qualifier:
according to
Guideline:
other: JMAFF guidelines (2000); including the most recent partial revisions.
Deviations:
yes
Remarks:
Manual temp recording and no monitoring for humidity was done on 06 April 2007.It is expected the relative humidity remained within 30-70% based on data during time period from adjacent rooms. Study integrity not adversely affected by the deviations.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid (30% active ingredient in water)
Details on test material:
- Name of test material (as cited in study report): MTDID 6675
- Substance type: Clear colorless liquid
- Physical state: Liquid
- Analytical purity: 30% active ingredient in water
- Purity test date: 12/20/2005
- Lot/batch no.: 140499-19/10
- Expiration date of the lot/batch: 01 December 2008
- Storage condition of test material: At room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
other: New Zealand White, (SPF-Quality)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan, Horst, The Netherlands.
- Age at study initiation: At least 6 weeks old
- Weight at study initiation: At least 1.0 kg
- Housing: Individually in labeled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits (K-H from SSNIFF Spezialdiaten GmbH, Soest, Germany) approx. 100 g. per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least three times a week.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: At least 5 days before start of treatment.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8-22.9 degrees Celsius
- Humidity (%):31-66%
- Air changes (per hr): No Data
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 12 March 2007 To: 02 May 2007

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Second eye of animal remained untreated and served as the reference control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test substance
- Concentration (if solution): 30% active ingredient in water
Duration of treatment / exposure:
Test substance was instilled into one eye and observed for 21 days.
Observation period (in vivo):
Tested eye was observed for 21 days
Number of animals or in vitro replicates:
3 males were tested
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not done
TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: Observations at 1, 24, 48, 72 hours, and days 7, 14, and 21.
Score:
ca. 0 - ca. 3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: Individual eye irritation scores are below in Table 1.
Irritant / corrosive response data:
Corneal injury consisted of opacity (maximum grade 1) and epithelial damage (maximum 75% of the corneal area in one animal and 50% in the other two animals). As a result of the corneal injury, in two animals pannus (neovascularisation of the cornea) was apparent 7 and 14 days after instillation. The corneal injury had resolved within 7 days in one animals and within 21 days in the other two animals. Iridial irriation grade 1 was observed and had resolved within 7 days in all animals. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 21 days in one animal and within 14 days in the other two animals.

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of the study, the test substance caused severe eye irritation which was fully reversible within 21 days. Based on these results the test substance should be classified as irritating to eyes (Category 2A according to GHS criteria and R36 according to EC criteria).
Executive summary:

The purpose of this study was to assess the acute eye irritancy/corrosivity of the test substance in rabbits according to OECD Test Guideline 405. Single samples of 0.1 ml of the test substance were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation. Instillation of the test substance resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity (maximum grade 1) and epithelial damage (50-75% of the corneal area). As a result of the corneal injury, pannus (neovascularisation of the cornea) was apparent 7 and 14 days after instillation in two animals. The corneal injury had resolved within 7 days in one animal and within 21 days in the other two animals. lridial irritation grade 1 was observed and had resolved within 7 days in all animals. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 21 days in one animal and within 14 days in the other two animals. Under the conditions of the study, the test substance caused severe eye irritation which was fully reversible within 21 days. Based on these results the test substance should be classified as irritating to eyes (Category 2A according to GHS criteria and R36 according to EC criteria).