Orthosulfamuron

Endpoint summary

Description of key information

IR5878 was moistened with about 1 mL of water and then applied to a small area (approximately 6 cm²) of skin of New Zealand White rabbits (4 males and 2 females). 0.5 mg of IR5878 were applied to the skin of each animal and covered with a gauze patch, which was loosely held in contact with the skin by means of a suitable semi-occlusive dressing for the duration of the exposure periods: 3 minutes, 1 hour (first animal only) and 4 hours. IR5878 when administrated to rabbits by dermal route is to be considered as NON IRRITANT to the rabbit skin.

IR5878 as such was placed into the conjunctival sac of the right eye of New Zealand White rabbits (4 males and 2 females). 0.1 mg of IR5878 was applied to the eye of each animal for an exposure period of 24 hours.IR5878 when administrated to rabbits by dermal route is to be considered as NON IRRITANT to the rabbit 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:

July 6 to July 9, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

IR5878
ISO common name: Orthosulfamuron
Batch number: FCF/T/159-99 (ex 20274/71)
Purity: 93.72 ± 1.05 %

Details on animal used as source of test system:

Species and Strain: Male and Female New Zealand White rabbits
Age: 2 months
Body weight: 1.8 ÷ 2.3 kg
Housing: for the entire duration of the study the rabbits were kept in metal cages with stainless feeders.
Feed: diet “2 RB 15 GLP certificate” produced by Charles River Italia’s feed licensee Mucedola Srl, Settimo Milanese. The diet was supplemented by the Producer with vitamins and traces elements. The diet was available ad libitum to the animals. Water was distributed ad libitum to the animals.

Details on test system:

Environmental conditions:
Temperature and humidity measured during the study were 19 ± 2°C and 55 ± 10%, respectively.
Light: artificial lighting with a 12-hour circadian cycle (07:00 – 19:00).

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

4 males and 2 females
Animal room controls were set to mantain temperature and relative humidity at 19C +/- 2 and 55% +/- 10 respectively. There were 15-20 air changes per hour. The room was iluminated by artifical lighting with a 12 hour circadian cycle. For the entire duration of the study the rabbits were kept in metal cages with stainless steel feeders. The cages were hung on multiple metal cage racks. The waste was periodically flushed away by a time-programmed siphon system from above.

Preparation of test site:

clipped

Amount / concentration applied:

0.5g/site

Duration of treatment / exposure:

single application.
Exposure time 3 minutes, 1 hours (first rabbit) and 4 hours (all rabbits)

Observation period:

treatment sites were examined for signs of erythema and edema immediately after the 3 minute and the 1 hour exposure period (first rabbit). These sites were also examined after 72 hours. After removal of the patch applied for 4 hours, animals were examined for erythema and edema and the responses scored at 30 minutes and 60 minutes and at 24, 48 and 72 hours after patch removal. Adjacent areas of untreated skin of each animal served as control for the test.

Number of animals:

4 males and 2 females

Details on study design:

Approximately 24 hours before the test the fur was clipped from the trunk of the animals. Care was taken not to abrade the skin and only animals with intact skin were used.

0.5g of the test article were moistened with about 1mL of water and then applied to a small area (approximately 6cm2) of skin and covered with a gauze patch held in place with non-ittitating tape. The patch was loosely held in contact with the skin by a means of a suitable semocclusive dressing fur the duration of the exposure period. At the end of each exposure period residual test substance was removed with water without altering the existing response or the integrity of the epidermis.

Exposure followed a stepwise procedure: Firstly one rabbit was used and three treatment sites of the skin were prepared. On the first site the patch was applied for an exposure period of 1 hour on the second site. Since no gross reaction was observed the patch was applied for an exposure period of 4 hours on the third skin site. The test was completed using five additional animals each with one patch only, for a 4 hour exposure period.

Adjacent areas of untreated skin of each animal served as control for the test.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 4 hours

Score:

ca. 0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 4 hours

Score:

ca. 0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 3 minutes

Score:

ca. 0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1 hour

Score:

ca. 0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No changes were seen at any of the skin evaluation of the test article application sites.

Other effects:

Neither mortality nor adverse general clinical modifications were seen during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

The test article IR5878 when administrated to rabbits by dermal route is to be considered as NON IRRITANT to the rabbit skin.

Executive summary:

IR5878 was moistened with about 1 mL of water and then applied to a small area (approximately 6 cm²) of skin of New Zealand White rabbits (4 males and 2 females). 0.5 mg of IR5878 were applied to the skin of each animal and covered with a gauze patch, which was loosely held in contact with the skin by means of a suitable semi-occlusive dressing for the duration of the exposure periods: 3 minutes, 1 hour (first animal only) and 4 hours.

IR5878 when administrated to rabbits by dermal route is to be considered as NON IRRITANT to the rabbit skin.

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:

July 15 to July 18, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

Commission Directive 92/69/EEC, (B.5)
US EPA OPPTS 870.2400
MAFF 59 Nohsan No. 4200
Deviations: none

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

IR5878
ISO common name: Orthosulfamuron
Batch number: FCF/T/159-99 (ex 20274/71)
Purity: 93.72 ± 1.05 %

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test animals:
Species and Strain: Male and Female New Zealand White rabbits
Age: 2 months
Body weight: 1.8 ÷ 2.3 kg
Housing: for the entire duration of the study the rabbits were kept in metal cages with stainless feeders.
Feed: diet “2 RB 15 GLP certificate” produced by Charles River Italia’s feed licensee Mucedola Srl, Settimo Milanese. The diet was supplemented by the Producer with vitamins and traces elements. The diet was available ad libitum to the animals. Water was distributed ad libitum to the animals
Environmental conditions:
Temperature and humidity measured during the study were 19 ± 2°C and 55 ± 10%, respectively.
Light: artificial lighting with a 12-hour circadian cycle (07:00 – 19:00).

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.1g/animal

Observation period (in vivo):

The eyes were examined at 1,24,48 and 72 hours after the test article application. After the 24 hour reading the cornea was examined after instillation of one drop of 1% sodium fluorescein and successive washing out with sterile saline solution.

Number of animals or in vitro replicates:

4 males and 2 females

Details on study design:

Both eyes of each experimental animal provisionally selected for the study were examined within 24 hours of testing. All these rabbits were free of eye irritation ocular defects or pre-existing corneal injury. 0.1g of the test article was placed in the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball . The lids were then gently held together for about one second in order to rpevent loss of the material. The other eye (the left eye) served as a control. At 24 hours a washout was performed following the application of one drop of sodium fluorescein.

Irritation parameter:

other: Conjunctivae Redness

Run / experiment:

Animal #9M

Value:

ca. 1

Irritation parameter:

other: Conjunctivae Redness

Run / experiment:

Animal #15M

Value:

ca. 2

Irritation parameter:

other: Conjunctivae Redness

Run / experiment:

Animal #20M

Value:

ca. 1

Irritation parameter:

other: Conjunctivae Redness

Run / experiment:

Animal #41F

Value:

ca. 1

Irritation parameter:

other: Conjunctivae Redness

Run / experiment:

Animal #43F

Value:

ca. 2

Irritation parameter:

other: Conjunctivae Chemosis

Run / experiment:

Animal #9M

Value:

ca. 1

Irritation parameter:

other: Conjunctivae Chemosis

Run / experiment:

Animal #15M

Value:

ca. 1

Irritation parameter:

other: Conjunctivae Chemosis

Run / experiment:

Animal #20M

Value:

ca. 1

Irritation parameter:

other: Conjunctivae Chemosis

Run / experiment:

Animal #21M

Value:

ca. 2

Irritation parameter:

other: Conjunctivae Chemosis

Run / experiment:

Animal #41F

Value:

ca. 1

Irritation parameter:

other: Conjunctivae Chemosis

Run / experiment:

Animal #43F

Value:

ca. 2

Other effects / acceptance of results:

Redness score (refers to palpebral and bulbar conjunctive, excluding cornea and iris) = 0 (normal), 1 (some blood vessels hyperemic), 2 (Diffuse, crimson colour, individual blood vessels not easily discernible), 3 (Diffuse beefy red)
Chemosis score (lids and or nictitating membranes) = 0 (no swelling), 1 (any swelling above normal), 2 (obvious swelling with partial eversion of lids), 3 (swelling with lids about half closed), 4 (swelling with lids more than half closed)

	Conjunctivae												Cornea						Iris
	Redness						Chemosis						Opacity						Iritis
Rabbit No.	9M	15M	20M	21M	41F	43F	9M	15M	20M	21M	41F	43F	9M	15M	20M	21M	41F	43F	9M	15M	20M	21M	41F	43F
Time
1 h	1	2*	1	2*	1	2*	1	1	1	2*	2*	2*	0	0	0	0	0	0	0	0	0	0	0	0
24 h	1	1	1	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
48 h	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
72 h	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The test article IR5878 when administrated to rabbits by dermal route is to be considered as NON IRRITANT to the rabbit eyes.

Executive summary:

IR5878 as such was placed into the conjunctival sac of the right eye of New Zealand White rabbits (4 males and 2 females). 0.1 mg of IR5878 was applied to the eye of each animal for an exposure period of 24 hours.

IR5878 when administrated to rabbits by dermal route is to be considered as NON IRRITANT to the rabbit eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available