Registration Dossier

Administrative data

Description of key information

MON 13900 is not irritating to skin and eyes.  

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Feb 14, 1990 to Feb 17, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Six young adult New Zealand White rabbits (4 males, 2 females), obtained from Mohican Valley Rabbitry, Loundonville,Ohio, were used in this study. The animals were individually housed in suspended stainless steel cages in an environment-controlled room with a 12–h light/dark cycle. Agway Prolab rabbit ration and fresh water were provided to each animal ad libitum. The rabbits were individually identified using plastic ear tags and cage cards. All animals were allowed to acclimate to the laboratory environment for a minimum of 5 d prior to initiation of the study.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
0.5 g of the test substance (moistened with 0.5 mL of distilled water)
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 and 72 h
Number of animals:
6
Details on study design:
On the day prior to dosing, the fur was clipped from the dorsal area of the trunk of each animal using small animal clipper. Care was taken during clipping to avoid accidental abrasion to the skin. On the following day, the animals were weighed (animal weight ranged from 2.0-2.6kg) and two test sites measuring approx 1 inch x 1 inch were selected on the exposed skin of each rabbit. A dose of 0.5 g of the test substance (moistened with 0.5 mL of distilled water) was applied to the designated sites on each rabbit. Immediately after applying the test substance on each animal, a gauze patch was placed over the treated sites and secured to the adjacent skin, using nonirritating tape. A tubular stockinette sleeve (semi-occlusive binding) was then positioned around the trunk of the animal and this was positioned around the cut edges using tape. After an exposure period of 4 h, the stockinette sleeve and patches were removed from each animal. The test sites on each animal were then rinsed with distilled water to remove residual test substance. The test sites were examined for signs of erythema and edema at 1, 24, 48 and 72 h. All animals were sacrificed using T–61 euthanasia solution and discarded after completion of each animal’s final scoring interval.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 30-60 min, 24, 48 and 72 h
Score:
0.15
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: #1-6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1-6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Exposure to the test substance produced slight erythema on 7/12 test sites at the 1 h scoring interval. All dermal irritation resolved by 24 h post application.

Dermal irritation scores:

 

 

Time

 

Draize scores

Observation

(Hours)

Site

5459/M

5460/M

5463/M

5467/M

5479/F

5482/F

Erythema

1

1

0

1

0

1

0

1

 

 

2

0

1

1

1

0

1

 

24

1

0

0

0

0

0

0

 

 

2

0

0

0

0

0

0

 

48

1

0

0

0

0

0

0

 

 

2

0

0

0

0

0

0

 

72

1

0

0

0

0

0

0

 

 

2

0

0

0

0

0

0

Oedema

1

1

0

0

0

0

0

0

 

 

2

0

0

0

0

0

0

 

24

1

0

0

0

0

0

0

 

 

2

0

0

0

0

0

0

 

48

1

0

0

0

0

0

0

 

 

2

0

0

0

0

0

0

 

72

1

0

0

0

0

0

0

 

 

2

0

0

0

0

0

0

Overall mean scores

Erythema

Oedema

0.0

0.0

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this test, MON 13900 is considered a negligible irritant to the skin of the rabbit with a primary dermal index of 0.15.
Executive summary:

A study was conducted to assess the potential skin irritation and/or corrosion effects of MON 13900 in rabbits according to OECD Guideline 404, EPA OPP 81-5 and EU Method B.4 in compliance with GLP.

The test substance was applied as a 0.5 g dose (moistened with 0.5 mL distilled water) to two clipped dermal sites on six New Zealand white rabbits. The substance was held in place under a semi-occlusive dressing for 4 h, after which the dressing was removed. Any remaining test substance was wiped from the skin using gauze and distilled water. The test sites were examined and scored for dermal irritation at 1, 24, 48 and 72 h. Exposure to the test substance produced slight erythema in 4/6 rabbits at the 1 h time point. All dermal irritation had resolved by 24 h post-application.

Under the conditions of the study, the test substance produced only minor irritation to skin, with a primary dermal index (PDII) of 0.15.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Feb 19, 1990 to Feb 26, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Six adult New Zealand White rabbits (1 male, 5 females) obtained from Mohican Valley Rabbitry, Loudonville, Ohio, were used in this study. The animals were individually housed in suspended stainless steel cages in an environment-controlled room with a 12–h light/dark cycle. Agway Prolab rabbit ration and fresh water were provided to each animal ad libitum. The rabbits were individually identified using plastic ear tags and cage cards. All animals were acclimated to the laboratory environment for a minimum of 5 d prior to initiation of the study.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.047 g (0.1 mL equivalent)
Duration of treatment / exposure:
Once
Observation period (in vivo):
1, 24, 48 and 72 h and up to Day 7
Number of animals or in vitro replicates:
6
Details on study design:
Animals were weighed prior to the initiation of the study (body weights ranged from 2.3-2.6 kg). Within 24 h prior to the start of the study, both eyes of each animal provisionally selected for testing were examined macroscopically for ocular irritation with the aid of an auxillary light source. In addition, the corneal surface was examined using fluorescein sodium dye. Fluorescein dye was instilled into each eye. Following a 15 sec exposure, the eyes were thoroughly rinsed with physiological saline. The corneal surface was then examined for dye retention under a long-wave UV light source. Only those animals which showed no signs of eye irritation, ocular defects or pre-existing corneal lesions were used. A dose of 0.047 g (0.1 mL equivalent) of the test substance was instilled into the conjunctival sac of the right eye of each animal. Immediately after dosing, the eyelids were gently held together for approx 1 sec. The contralateral eye of each rabbit remained untreated and served as the control for that animal. Both eyes of each animal were examined for signs of irritation at 1, 24, 48 and 72 h and up to Day 7 after dosing using the ocular irritation grading system. Following macroscopic observations at the 24 h scoring interval, the fluorescein examination procedure was repeated on all test and control eyes. If positive fluorescein dye retention was noted at 24 h (other than normal background retention or mechanical abrasions), a fluorescein exam was conducted on the affected eyes at each subsequent interval until a negative response was obtained.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1, 2 and 6
Time point:
other: 24, 48 and 72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal: #4 and 5
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal: #1, 5 and 6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritant / corrosive response data:
Exposure to the test substance produced iritis in 6/6 test eyes at the 1 h scoring interval. The iridal irritation resolved in all animals by 24 h postdose. Conjunctivitis (redness, discharge and/or swelling) was noted in 6/6 test eyes at the 1 h scoring interval. The conjunctival irritation diminished over the test period and resolved in all animals by study Day 7.

Refer to the attached document under 'attached background material'.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this test, MON 13900 is considered to be a mild irritant to the ocular tissue of the rabbit.
Executive summary:

The potential eye irritation and/or corrosion effects of MON 13900 were evaluated in New Zealand White rabbits according to the EU Method B.5, EPA OPP 81-4 and OECD Guideline 405 in compliance with GLP.

Each of six animals received a 0.047 g dose (0.1 mL equivalent) of the test substance in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Exposure to the test substance produced iritis in 6/6 eyes at the 1 h scoring interval. The iridal irritation resolved by 24 h post-dose. Conjunctivitis (redness, discharge and/or swelling) was noted in 6/6 eyes at the 1 h scoring interval. The conjunctival irritation diminished over the test period and resolved in all animals by study Day 7.

Under the conditions of this study, the test substance is considered to be a mild irritant to the ocular tissue of rabbit.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A study was conducted to assess the potential skin irritation and/or corrosion effects of MON 13900 in rabbits according to OECD Guideline 404, EPA OPP 81-5 and EU Method B.4 in compliance with GLP. The test substance was applied as a 0.5 g dose (moistened with 0.5 mL distilled water) to two clipped dermal sites on six New Zealand white rabbits. The substance was held in place under a semi-occlusive dressing for 4 h, after which the dressing was removed. Any remaining test substance was wiped from the skin using gauze and distilled water. The test sites were examined and scored for dermal irritation at 1, 24, 48 and 72 h. Exposure to the test substance produced slight erythema in 4/6 rabbits at the 1 h time point. All dermal irritation had resolved by 24 h post-application. Under the conditions of the study, the test substance produced only minor irritation to skin, with a primary dermal index (PDII) of 0.15.

The potential eye irritation and/or corrosion effects of MON 13900 were evaluated in New Zealand White rabbits according to the EU Method B.5, EPA OPP 81-4 and OECD Guideline 405 in compliance with GLP. Each of six animals received a 0.047 g dose (0.1 mL equivalent) of the test substance in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Exposure to the test substance produced iritis in 6/6 eyes at the 1 h scoring interval. The iridal irritation resolved by 24 h post-dose. Conjunctivitis (redness, discharge and/or swelling) was noted in 6/6 eyes at the 1 h scoring interval. The conjunctival irritation diminished over the test period and resolved in all animals by study Day 7. Under the conditions of this study, the test substance is considered to be a mild irritant to the ocular tissue of rabbit.

Justification for selection of skin irritation / corrosion endpoint:

Only one relevant guideline compliant study was available.

Justification for selection of eye irritation endpoint:

Only one relevant guideline compliant study was available.

Justification for classification or non-classification

In an in vivo skin irritation study, MON 13900 produced slight erythema which resolved by 24 h post-application. Hence, it was not considered to warrant skin irritation classification according to Regulation (EC) 1272/2008. In an in vivo eye irritation study, MON 13900 was considered to be a negligible irritant to the ocular tissue of the rabbit, therefore also not qualifying for classification for eye irritation classification according to Regulation (EC) 1272/2008.