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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Ministry of Agriculture, Forestry and Fisheries of Japan 12-Nouan-8147
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Methomyl
EC Number:
240-815-0
EC Name:
Methomyl
Cas Number:
16752-77-5
Molecular formula:
C5H10N2O2S
IUPAC Name:
(E)-[1-(methylsulfanyl)ethylidene]amino N-methylcarbamate
Test material form:
solid: crystalline
Specific details on test material used for the study:
- Substance name: Methomyl Technical
- Substance ID: DPX-X1179
- Lot#: X1179-599
- Purity: 99.6%

Test animals / tissue source

Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Robinson Services, Inc. Clemmons, North Carolina
- Age at study initiation: Young adult
- Weight at study initiation: 2930-3150 g
- Housing: One animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6-19 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-21°C
- Humidity: 26-59%
- Photoperiod: 12 hour light/dark cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Initial: 0.08 g
Amount/concentration reduced to 0.009 g
Duration of treatment / exposure:
The test substance was instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance.
Observation period (in vivo):
1, 24, 48, and 72 hours
Number of animals or in vitro replicates:
4 males and 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Unwashed

SCORING SYSTEM: Draize method

TOOL USED TO ASSESS SCORE: High-intensity white light (Mag Lite)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
There was no corneal opacity or iritis noted for any treated eye during the study. At the one hour scoring interval, the pupil of the treated eye of two of the three rabbits was constricted and the pupil of the treated eye of one of these rabbits did not respond to light. At 24 hours after instillation, the constriction/non-response to light of the pupils was not observed. Conjunctival redness (score of 1) was observed in the treated eye of three rabbits and discharge (score of 1) was observed in the treated eye of two rabbits. All animals were free of ocular irritation by 72 hours.
Other effects:
The rabbit dosed with one-tenth of a milliliter (0.08 grams) test substance was found dead within one hour of dosing. One of the rabbits dosed with 0.009 grams test substance was found dead within 24 hours of dosing. No clinical signs of systemic toxicity were observed in the decedents. White ocular discharge and clear oral discharge were observed in both decedents at gross necropsy. All surviving animals appeared active and healthy. No biologically relevant weight loss occurred in any of the surviving rabbits.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
There was no corneal opacity or iritis noted. Conjunctival redness (score of 1) was observed in the treated eye of three rabbits and discharge (score of 1) was observed in the treated eye of two rabbits. All animals were free of ocular irritation by 72 hours.
Executive summary:

A primary eye irritation test was conducted with rabbits to determine the potential for the test substance to produce irritation from a single instillation via the ocular route. The study was conducted according to OECD guideline 405 and U.S. EPA OPPTS 870.2400.

The study was conducted in a stepwise fashion. Initially, one-tenth of a milliliter (0.08 grams) of the ground test substance was instilled into the conjunctival sac of the right eye of one healthy rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The left eye remained untreated and served as a control.

This rabbit was found dead within one hour of dosing. No clinical signs of systemic toxicity were observed. White ocular discharge and clear oral discharge were observed at gross necropsy.

Due to the mortality of this animal at the 0.1 mL dose level, subsequent testing was conducted using a lower dose amount.

A quantity of 0.009 g of the ground test substance was instilled into the conjunctival sac of the right eye of one healthy rabbit using the same procedures as above. Ocular irritation was evaluated by Draize method. Since irritation cleared by 48 hours and there was no significant irritation or adverse clinical signs observed in this animal, two additional animals were treated as described above. One of these animals died prior to the 24-hour scoring interval. No clinical signs of systemic toxicity were observed in the decedent. White ocular discharge and clear oral discharge were observed at gross necropsy. The rabbit that died was replaced and the replacement animal was dosed with 0.009 g of test substance.

There was no corneal opacity or iritis noted in the treated eye of the three surviving rabbits. At the one hour scoring interval, the pupil of the treated eye of two of the three rabbits was constricted and the pupil of the treated eye of one of these rabbits did not respond to light. At 24 hours after instillation, the constriction/non-response to light of the pupils was not observed. Conjunctival redness (score of 1) was observed in the treated eye of three rabbits and discharge (score of 1) was observed in the treated eye of two rabbits. All animals were free of ocular irritation by 72 hours.