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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
Study period:
19NOV2012 to 10DEC2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
July 2010
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
March 2003
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): TMAC
- Physical state: white, crystalline powder
- Expiration date of the lot/batch: 27 July 2013 (allocated by WIL Research Europe B.V., 1 year after receipt of the test substance)
- Storage condition of test material: At room temperature in the dark, in well-sealed container
- pH: 6-8

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Charles River Deutschland, Kisslegg, Germany.
- Age at study initiation: Animals were at least 6 weeks old.
- Weight at study initiation: Body weights were between 1646 and 2284 g.
- Housing: Individually housed in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimatization period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 19NOV2012 to 10DEC2012

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each animal remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL- Amount applied (weight with unit): 49.8 mg (range 49.6 – 50.3 mg), a volume of approximately 0.1 mL.
Duration of treatment / exposure:
Single instillation on Day 1.
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance.
Number of animals or in vitro replicates:
3 males.
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 14 days later, after considering the degree of eye irritation observed in the first animal.

TREATMENT
Animals were treated by instillation of the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.

Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS (beschrijf beperkt)
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Prior to instillation and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded. The irritation was assessed according to OECD 405.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hrs.
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hrs.
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hrs.
Score:
1.1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hrs.
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Instillation of approximately 50 mg (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in corneal injury consisting of slight dulling of the normal luster, noted in one animal on Day 1. Treatment of the eye with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage in any of the rabbits. Iridial irritation grade 1 was observed in one animal and resolved within 24 hours. Irritation of the conjunctivae was seen in all animals and consisted of redness, this had completely resolved in all animals within 7 days. All animals showed chemosis and discharge at 24 hrs after instillation, this had resolved after 48 hours.
Other effects:
No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.
No changes in body weight gain occurred.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an eye irritation study with rabbits, performed according to OECD/EC test guidelines, limited irritation was observed, not sufficient for classification.
Executive summary:

An eye irritation study was performed according to OECD/EC test guidelines and GLP principles. Approximately 50 mg (a volume of approximately 0.1 mL) was instilled into one eye of each of three rabbits. In one animal on Day 1, the corneal injury consisted of slight dulling of the normal luster. Redness of conjunctivae and chemosis was noted for all animals (mean 1.1 and 0.3 resp. at 24, 48 and 72 hrs), which had completely resolved after 7 days. Treatment of the eye with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage. No systemic toxicity, changes in body weight gain or mortaliy occurred.

According to these data, the test substance is not irritating to the eyes and is not classified for eye irritation.