Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Study Type  Species Findings  Guideline Reliability 
Skin Rabbit  No irritation  

OECD 404, OPPTS 870.2500

 1 
Skin Rabbit  No irritation OECD 404, EPA 81-5 1
Skin Rabbit No irritation OECD 404, EPA 81-5 1
Eye Rabbit Slight irritation cleared by 72 hours OECD 405, OPPTS 870.2400 1
Eye Rabbit Moderate irritation cleared by 7 days No guideline 2
Eye Rabbit Mild irritation No guideline 2

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin 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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Ministry of Agriculture, Forestry and Fisheries of Japan 12-Nouan-8147
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Substance name: Methomyl Technical
- Substance ID: DPX-X1179
- Lot#: X1179-599
- Purity: 99.6%
Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Robinson Services, Inc. Clemmons, North Carolina
- Age at study initiation: Young adult
- Weight at study initiation: 2449-2596 g
- Housing: One animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 or 13 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-21°C
- Humidity: 35-63%
- Photoperiod: 12 hour light/dark cycle
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: distilled water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.71 g
Duration of treatment / exposure:
4 hours
Observation period:
Immediately following patch removal, at approximately 30-60 minutes, 24, 48, and 72 hours after patch removal
Number of animals:
1 male and 2 female animals
Details on study design:
TEST SITE
- Area of exposure: Dorsal area and the trunk
- Coverage: 6-cm²
- Type of wrap if used: Semi-occlusive 3-inch Micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing: Test sites were gently cleansed
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Immediately following patch removal and at approximately 30-60 minutes after each patch removal, and 24, 48, and 72 hours after patch removal.

SCORING SYSTEM:
- Method of calculation: Draize scoring system (1944)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema 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 edema observed at any treated dose site during the study. Very slight erythema (score of 1) was noted for all three treated dose sites. All animals were free from dermal irritation by 48 hours.
Other effects:
All animals appeared active and healthy and gained body weight during the study. Apart from the very slight erythema, there were no other signs of gross toxicity, adverse clinical signs, or abnormal behavior.
Interpretation of results:
GHS criteria not met
Conclusions:
Not irritating in rabbits
Executive summary:

A primary skin irritation test was conducted with rabbits to determine the potential for the test substance to produce irritation after a single topical application. The study was conducted according to OECD guideline 404 and OPPTS 870.2500.

The study was conducted in a stepwise manner using a single patch applied initially to one rabbit for 4 hours. Five-tenths of a gram of the test substance was moistened with distilled water and then applied to the skin of one healthy rabbit for 4 hours. The dose site was evaluated for dermal irritation by Draize method. immediately following patch removal, and at 30-60 minutes and at 24, 48, and 72 hours after patch removal. Since only minimal dermal irritation was observed in this animal, the test was completed on two additional animals, as described above.

There was no edema observed at any treated dose site during the study. Very slight erythema (score of 1) was noted for all three treated dose sites. All animals were free from dermal irritation by 48 hours.

All animals appeared active and healthy and gained body weight during the study. Apart from the very slight erythema, there were no other signs of gross toxicity, adverse clinical signs, or abnormal behavior.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Ministry of Agriculture, Forestry and Fisheries of Japan, 59 NohSan No. 4200
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Substance name: Methomyl (technical)
- Substance ID: DPX-X1179-394
- Lot#: T00620-06
- Purity: 98.35%
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: deionized water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Approximately 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours
Number of animals:
6 male animals
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Not irritating in rabbits
Executive summary:

The test substance was evaluated for acute skin irritation potential in 6 young adult male New Zealand White rabbits following OECD guideline 404 and U.S. EPA 81-5. A 0.5 g aliquot was administered to a localized test site on the back of each animal. Each test site was covered with a semi-occlusive dressing to ensure contact between the skin and test substance and the animals were exposed to the test substance for 4 hours.

The test sites were evaluated and scored according to a numerical scale, 1, 24, 48, and 72 hours after the end of the 4-hour exposure period. Since there was no evidence of dermal irritation at 72 hours, further evaluations to assess reversibility were not made.

The test substance produced no dermal irritation in any of the rabbits during the study. Therefore, mean values calculated from the quantitative evaluation of the two dermal lesions (erythema and edema) observed in all rabbits at 24, 48, and 72 hours following exposure were 0. The overall average of means (EEC) was also 0.

All values for both erythema and edema derived at 1, 24, 48, and 72 hours were summed and divided by 4, for each of 6 rabbits, to obtain primary dermal irritation scores. The Primary Irritation Index (EPA) or average of these 6 scores is 0.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Ministry of Agriculture, Forestry and Fisheries of Japan, 59 NohSan No. 4200
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Substance name: Methomyl (technical)
- Substance ID: DPX-X1179-394
- Lot#: T00620-06
- Purity: 98.35%
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: deionized water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Approximately 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours
Number of animals:
6 female animals
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Not irritating in rabbits
Executive summary:

The test substance was evaluated for acute skin irritation potential in 6 New Zealand White rabbits following OECD guideline 404 and U.S. EPA 81-5. Approximately 0.5 g was administered to a localized test site on the back of each animal. The test sites were covered with a semi-occlusive dressing to ensure contact between the skin and test substance. The animals were exposed to the test substance for 4 hours.

The test sites were evaluated and scored according to a numerical scale, 1, 24, 48, and 72 hours after the end of the 4-hour exposure period.

Mean values were calculated from the quantitative evaluation of the two dermal lesions (erythema and edema) observed in all rabbits at 24, 48, and 72 hours following exposure. An overall average of means (EEC) were also calculated.

24, 48, and 72 hours mean erythema and edema score for all the animals is found to be 0. On the basis of the absence of any dermal irritation, the test substance was non-irritant when tested in rabbits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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
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
Specific details on test material used for the study:
- Substance name: Methomyl Technical
- Substance ID: DPX-X1179
- Lot#: X1179-599
- Purity: 99.6%
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
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)
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.
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.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
A dose of 10 mg of test substance was placed into the right conjunctival sac of six albino rabbits. Two other rabbits were similarly treated using an equivalent amount of test substance dissolved in propylene glycol. Twenty seconds after contact three eyes exposed to solid test substance and one eye exposed to solution were washed with tap water for one minute; the remaining four exposed eyes were not washed. In all cases, the left eyes served as untreated controls. Observations were made with a hand slit lamp at 15 minutes, 1, 2, 3, and 4 hours and at 1, 2, 3, and 7 days; one unwashed eye dosed with solid test substance was also observed at 14 days. Pupillary diameters were estimated at each eye observation with a mm-scale. A biomicroscope and 5% fluorescein stain were used at examinations after the day of treatment.
GLP compliance:
no
Specific details on test material used for the study:
- Substance name: S-Methyl N-[(methylcarbamoyl)oxy]thioacetimidate (syn form)
- Substance ID: INB-1884-1
- Purity: Not reported
Species:
rabbit
Strain:
other: albino
Vehicle:
other: propylene glycol (for 2 rabbits); dosed as recieved (for 6 rabbits)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
10 mg of powder or 0.1 mL of 10% solution of test substance in propylene glycol
Duration of treatment / exposure:
20 seconds
Observation period (in vivo):
15 minutes, 1, 2, 3, and 4 hours and at 1, 2, 3, and 7 days
Number of animals or in vitro replicates:
8
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks on result:
other: Microscopically, localized surface sheen and thickening at 1 day, then decreasing - only minimal sheen at 7 days
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks on result:
other: Localized mild injury at 1 day; only microscopic surface thickening 2-3 days
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks on result:
other: Moderate damage 1-2 days; only microscopic surface thickening at 3 days
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
other: pupil
Basis:
animal #1
Remarks on result:
other: Mild constriction at 15 mins, questionable at 1-2 hours
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
other: pupil
Basis:
animal #2
Remarks on result:
other: Mild constriction at 15 mins, questionable at 1-2 hours
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
other: pupil
Basis:
animal #3
Remarks on result:
other: Moderate constriction at 15 mins, mild to questionable at 1-4 hours
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
iris score
Basis:
animal #1
Remarks on result:
other: Minimal or mild congestion at 2-4 hours
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
iris score
Basis:
animal #2
Remarks on result:
other: Minimal or mild congestion at 3-4 hours
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
iris score
Basis:
animal #3
Remarks on result:
other: Minimal or mild congestion at 15 mins
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
other: conjunctival discharge, redness and swelling
Basis:
animal #2
Remarks on result:
other: Moderate discharge at 3-4 hours
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
other: conjunctival discharge, redness and swelling
Basis:
animal #3
Remarks on result:
other: Copious or moderate discharge at 15 mins-2 days; otherwise, mild or minimal irritation in 3/3. Normal in 3 to 7 days.
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
cornea opacity score
Basis:
animal #4
Remarks on result:
no indication of irritation
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
cornea opacity score
Basis:
animal #5
Remarks on result:
other: Moderate injury at 1 day, then decreasing - only minute area of microscopic sheen at 7 days
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
cornea opacity score
Basis:
animal #6
Remarks on result:
other: Moderate injury at 1 day, then decreasing - microscopic surface thickening with localized vascularization at 7 days; receding changes at 14 days
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
other: pupil
Basis:
animal #4
Remarks on result:
other: Questionable constriction 15 mins-2 hours
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
other: pupil
Basis:
animal #5
Remarks on result:
other: Moderate constriction at 15 mins, then mild or questionable through 3 or 4 hours
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
other: pupil
Basis:
animal #6
Remarks on result:
other: Moderate constriction at 15 mins, then mild or questionable through 3 or 4 hours
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
iris score
Basis:
animal #4
Remarks on result:
other: Minimal or mild congestion in all animals, 15 mins-4 hours
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
iris score
Basis:
animal #5
Remarks on result:
other: Minimal or mild congestion in all animals, 15 mins-4 hours
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
iris score
Basis:
animal #6
Remarks on result:
other: Minimal or mild congestion in all animals, 15 mins-4 hours
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
other: conjunctival discharge, redness and swelling
Basis:
animal #4
Remarks on result:
other: mild or minimal irritation
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
other: conjunctival discharge, redness and swelling
Basis:
animal #5
Remarks on result:
other: Copious discharge at 15 mins-4 hours; otherwise, mild or minimal irritation in all three animals. Normal in 3-7 days
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
other: conjunctival discharge, redness and swelling
Basis:
animal #6
Remarks on result:
other: Copious discharge at 15 mins-4 hours; otherwise, mild or minimal irritation in all three animals. Normal in 3-7 days
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
cornea opacity score
Basis:
animal: #7
Remarks on result:
no indication of irritation
Remarks:
0.1 mL 10% solution (eye washed)
Irritation parameter:
cornea opacity score
Basis:
animal: #8
Remarks on result:
no indication of irritation
Remarks:
0.1 mL 10% solution (eye not washed)
Irritation parameter:
other: pupil
Basis:
animal: #7
Remarks on result:
other: Questionable constriction at 15 mins-1 hour
Remarks:
0.1 mL 10% solution (eye washed)
Irritation parameter:
other: pupil
Basis:
animal: #8
Remarks on result:
other: Questionable constriction at 15 mins
Remarks:
0.1 mL 10% solution (eye not washed)
Irritation parameter:
iris score
Basis:
animal: #7 and 8
Remarks on result:
no indication of irritation
Remarks:
0.1 mL 10% solution (eye washed for animal #7 and not washed for animal #8)
Irritation parameter:
other: conjunctival discharge, redness and swelling
Basis:
animal: #7
Remarks on result:
other: Mild or minimal. Normal in 2 days.
Remarks:
0.1 mL 10% solution (eye washed)
Irritation parameter:
other: conjunctival discharge, redness and swelling
Basis:
animal: #8
Remarks on result:
other: Mild or minimal. Normal in 3 days
Remarks:
0.1 mL 10% solution (eye not washed)
Interpretation of results:
study cannot be used for classification
Conclusions:
The test substance produced moderate corneal injury in 2 out of 3 rabbit eyes
Executive summary:

A dose of 10 mg of test substance was placed into the right conjunctival sac of six albino rabbits. Two other rabbits were similarly treated using an equivalent amount of test substance dissolved in propylene glycol. Twenty seconds after contact three eyes exposed to solid test substance and one eye exposed to solution were washed with tap water for one minute; the remaining four exposed eyes were not washed. In all cases, the left eyes served as untreated controls. Observations were made with a hand slit lamp at 15 minutes, 1, 2, 3, and 4 hours and at 1, 2, 3, and 7 days; one unwashed eye dosed with solid test substance was also observed at 14 days. Pupillary diameters were estimated at each eye observation with a mm-scale. A biomicroscope and 5% fluorescein stain were used at examinations after the day of treatment.

The test substance produced moderate corneal injury in two of three rabbit eyes in which the solid test substance was permitted to retain. Residual effect was noted through either seven or 14 days. The thrid eye exposed to solid test substance and also another similarly treated with a comparable dose in propylene glycol solution showed no corneal changes.

In general, prompt washing appeared to be only slightly effective in reducing ocular lesions. Moderate or mild but temporary corneal injuries were observed in two eyes exposed to solid test substance and promptly washed; a third eye similarly treated showed a minor corneal irritation which was still minimally present at seven days. No corneal changes were seen in a washed eye exposed to propylene glycol solution.

In both washed and unwashed eyes, moderate to questionable pupillary constriction and mild to minimal iritic congestion were noted on the day of treatment. Initial copious or moderate discharge was sometimes noted, but otherwise conjunctival irritation was mild or minimal, and in all cases it was reversible within seven days.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
10 mg of powder or 0.1 mL of a 10% solution of the test material in propylene glycol was instilled into the conjunctival sacs of two pairs of rabbit eyes, respectively. 20 seconds after instillation, one eye of each pair was washed with water for one minute; the other eye was not washed. Examinations were made at 1, 2, 3, 4, and 6 hours on the day of treatment and 1, 2, 3, and 6 days thereafter with the hand slit lamp. Fluorescein stain was used after the day of treatment.
GLP compliance:
no
Specific details on test material used for the study:
- Substance name: Methylcarbamic acid ester with thiolacetohydroxamic acid, S-methyl ester
- Substance ID: INX-1179-1
- Purity: Not reported
Species:
rabbit
Strain:
not specified
Vehicle:
other: dosed as recieved (one eye); propylene glycol (second eye)
Controls:
no
Amount / concentration applied:
10 mg of powder or 0.1 mL of 10% solution of test substance in propylene glycol
Duration of treatment / exposure:
20 seconds
Observation period (in vivo):
1, 2, 3, 4, and 6 hours, and at 1, 2, 3, and 6 days
Number of animals or in vitro replicates:
2
Irritation parameter:
cornea opacity score
Remarks on result:
no indication of irritation
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
cornea opacity score
Remarks on result:
no indication of irritation
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
cornea opacity score
Remarks on result:
no indication of irritation
Remarks:
washed eye (10% solution)
Irritation parameter:
cornea opacity score
Remarks on result:
no indication of irritation
Remarks:
eye not washed (10% solution)
Irritation parameter:
iris score
Remarks on result:
other: Injection of blood vessels on day of treatment
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
iris score
Remarks on result:
no indication of irritation
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
iris score
Remarks on result:
no indication of irritation
Remarks:
washed eye (10% solution)
Irritation parameter:
iris score
Remarks on result:
other: Injection of blood vessels on day of treatment
Remarks:
eye not washed (10% solution)
Irritation parameter:
other: pupil
Remarks on result:
other: Marked constriction at 1 hour, decreasing to slight at 6 hours
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
other: pupil
Remarks on result:
other: Marked constriction at 1 hour, decreasing to slight at 6 hours
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
other: pupil
Remarks on result:
other: Marked constriction at 1 hour, decreasing to slight at 6 hours
Remarks:
washed eye (10% solution)
Irritation parameter:
other: pupil
Remarks on result:
other: Marked constriction at 1 hour, decreasing to slight at 4 hours
Remarks:
eye not washed (10% solution)
Irritation parameter:
conjunctivae score
Remarks on result:
other: Mild inflammation on the day of treatment
Remarks:
washed eye (10 mg test substance)
Irritation parameter:
conjunctivae score
Remarks on result:
other: Mild inflammation on the day of treatment
Remarks:
eye not washed (10 mg test substance)
Irritation parameter:
conjunctivae score
Remarks on result:
other: Mild inflammation on the day of treatment; slight fibrinous discharge at 1 day
Remarks:
washed eye (10% solution)
Irritation parameter:
conjunctivae score
Remarks on result:
other: Mild inflammation on the day of treatment
Remarks:
eye not washed (10% solution)
Interpretation of results:
study cannot be used for classification
Conclusions:
In rabbit, as a powder or suspension in propylene glycol, test substance caused mild conjunctivitis and injection of iritic blood vessels on day of treatment; no corneal injury; marked papillary constriction occurred.
Executive summary:

10 mg of powder or 0.1 mL of a 10% solution of the test material in propylene glycol was instilled into the conjunctival sacs of two pairs of rabbit eyes, respectively. 20 seconds after instillation, one eye of each pair was washed with water for one minute; the other eye was not washed. Examinations were made at 1, 2, 3, 4, and 6 hours on the day of treatment and 1, 2, 3, and 6 days thereafter with the hand slit lamp. Fluorescein stain was used after the day of treatment.

The test substance, either as a powder or as a suspension in propylene glycol, caused mild conjunctivitis and injection of iritic blood vessels on the day of treatment. There was no corneal injury at any time. Marked pupillary constriction occurred and is consistent with the effects produced by this class of compounds.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In three acute dermal irritation studies in rabbits conducted according to OECD guideline 404, no dermal irritation was noted. 

An eye irritation study in rabbits was conducted according to OECD 405 and OPPTS 870.2400, in a step-wise fashion. The rabbit administered 0.08 grams of the test substance died 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 rabbit dosed with 0.009 g of the test substance had irritation which cleared by 48 hours and thus two additional rabbits were tested at this dose level. 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.

Justification for classification or non-classification

The test substance produced no skin irritation and, therefore, does not need to be classified for skin irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. The substance also does not need to be classified for eye irritation acording to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. In the study conducted according to OECD guidelines, t

here 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. Mild to moderate irritation was observed in two other rabbit studies; however, these studies were older studies not conducting according to OECD guidelines or utilizing the Draize scoring system.