Orthosulfamuron

Endpoint summary

Description of key information

IR5878 was suspended in aqueous solution of Methocel 350-.p.a.s (0.5% w/v) and administered to Sprague Dawley Crl: CD (SD) BR rats, by oral gavage at the dose level of 5000 mg/kg bw (5 males and 5 females). The oral LD₅₀of IR5878 in rats was greater than 5000 mg/kg bw.

IR5878 was diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered to three female HanIbm: NMRI (SPF) mice, by oral gavage at the dose level of 5000 mg/kg bw.

The oral LD₅₀of IR5878 in female mice was greater than 5000 mg/kg bw.

IR5878 was diluted in 1% carboxymethylcellulose solution and administered to one female CHS New Zealand albino rabbit, by oral gavage at the dose level of 5000 mg/kg bw. An addition group of two females received IR5878 at the same dose level, as the first animal survived. The oral LD₅₀of IR5878 in female rabbits was greater than 5000 mg/kg bw.

Groups of 5 Sprague Dawley Crl: CD (SD) BR rats per sex were administered a dosage of 5000 mg/kg (limit dose) of IR5878, applied as such uniformly onto a porous gauze moistened with 0.9% NaCl solution (single 24-hour dermal application). The dermal LD₅₀of IR5878 in rats was greater than 5000 mg/kg bw.

IR5878 was administered to 5 male and 5 female HanIbm: WIST (SPF) rats by nose-only, flow-past inhalation exposure for a single continuous 4-hour period, followed by an observation period of 14 days.

The acute inhalation LC₅₀of IR5878 in rats was estimated to be greater than the highest technically achievable aerosol concentration of 2.190 mg/L air (gravimetrically determined mean aerosol concentration).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 23 to July 17, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 17, 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Specific details on test material used for the study:

IR5878
Batch number: G 009/02
Purity: 98.56 ± 0.19 %

Species:

mouse

Strain:

other: HanIbm: NMRI (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

Test animals:
Species and Strain: Female HanIbm: NMRI (SPF) mice
Age: 8 weeks
Body weight: 23.5 ÷ 27.6 g
Housing: 1 to 2 animals per Makrolon type-3 cage with wire mesh tops and standard softwood bedding.
Feed: pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet ad libitum. Community tap water from Füllinsdorf ad libitum.

Environmental conditions:
Temperature and humidity measured during the study were 22 ± 3°C and 30 ÷ 70%, respectively.
Light: 12 hours fluorescent light and 12 hours dark (music during the light period).

Route of administration:

oral: gavage

Vehicle:

other: PEG

Details on oral exposure:

IR5878 was diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered to three female HanIbm: NMRI (SPF) mice, by oral gavage at the dose level of 5000 mg/kg bw.

Doses:

concentration of 0.5 g/mL
dose volume of 10 mL/kg

No. of animals per sex per dose:

3 females

Control animals:

not specified

Details on study design:

The test material was diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered to three female HanIbm: NMRI (SPF) mice fasted for 3 to 4 hours, by oral gavage at the dose level of 5000 mg/kg bw; the test substance preparation was applied at a dose volume of 10 mL/kg.
The animals were examined for mortality, clinical signs and body weight from day 1 to day 14. On day 15 mice were killed by i.p. overdosage of pentobarbitone and examined macroscopically.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities were observed in this test.

Clinical signs:

No clinical signs were observed during the course of the study.

Body weight:

One animal showed body weight loss (3.6%) from day 8 to the end of the observation period. Body weight of the other animals was not affected.

Gross pathology:

At gross necroscopy no macroscopic findings were recorded.

Conclusions:

The oral LD50 of IR5878 in female mice was greater than 5000 mg/kg bw.

Executive summary:

IR5878 was diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered to three female HanIbm: NMRI (SPF) mice, by oral gavage at the dose level of 5000 mg/kg bw.

The oral LD₅₀of IR5878 in female mice was greater than 5000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 27 to September 18, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 17, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Specific details on test material used for the study:

IR5878
Batch number: G 009/02
Purity: 98.56 ± 0.19 %

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Details on test animals or test system and environmental conditions:

Test animals:
Species and Strain: CHS New Zealand Albino female rabbits
Age: 8-12 weeks
Body weight: 1.8 ÷ 2.4 kg
Housing: animals were housed in cages of standard dimensions with sawdust bedding.
Feed: SDS/DIETEX STANRAB (P) SQC ad libitum. Potable water was available ad libitum.

Environmental conditions:
Temperature and humidity measured during the study were 19 ÷ 23°C and 45 ÷ 65%, respectively.
Light: 12 hours light and 12 hours darkness.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The test material was diluted in 1% carboxymethylcellulose solution, and administered to one female CHS New Zealand albino rabbit, by oral gavage at the dose level of 5000 mg/kg bw; the test substance preparation was applied at a dose volume of 10 mL/kg.

Doses:

dose level of 5000 mg/kg bw
dose volume of 10 mL/kg

No. of animals per sex per dose:

3 females

Control animals:

not specified

Details on study design:

The test material was diluted in 1% carboxymethylcellulose solution, and administered to one female CHS New Zealand albino rabbit, by oral gavage at the dose level of 5000 mg/kg bw; the test substance preparation was applied at a dose volume of 10 mL/kg. An addition group of two females received the test substance at the same dose level, as the first animal survived. Animals were fasted overnight before treatment.
The animals were examined for mortality, clinical signs and body weight from day 1 to day 14. On day 15 the rabbits were killed by subtotal exsanguination after i.p. anaesthesia with sodium pentobarbital and examined macroscopically.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occurred during the study.

Clinical signs:

No clinical signs were observed during the course of the study.

Body weight:

Mean weight gain in treated animals was normal when compared with strain data.

Gross pathology:

A red coloration on the glandular zone of the stomach was noted at necropsy of all animals

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of IR5878 in female rabbits was greater than 5000 mg/kg bw.

Executive summary:

IR5878 was diluted in 1% carboxymethylcellulose solution and administered to one female CHS New Zealand albino rabbit, by oral gavage at the dose level of 5000 mg/kg bw. An addition group of two females received IR5878 at the same dose level, as the first animal survived.

The oral LD₅₀of IR5878 in female rabbits was greater than 5000 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 23 to July 14, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981 and subsequent revisions

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

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:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

Test animals:
Species and Strain: Male and Female Sprague Dawley Crl: CD (SD) BR rats
Age: no more than three months
Body weight: 280 ÷ 350 g (males); 200 ÷ 252 g (females)
Housing: 5 animals/cage for each sex in air-conditioned room.
Feed: GLP 4RF21 top certificate pelleted diet 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 22 ± 2°C and 55 ± 10%, respectively.
Light was 12 hour cycle (07:00 – 19:00 h).

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The test article was adminstered as a suspension in deionized water at the dosage of 5000mgkg. The volume of administration was 20ml/kg, separated in two adminstrations (10ml/kg/time) with an interval of about 2 hours.

Doses:

dose level of 5000 mg/kg bw
dose volume of 20 mL/kg (10 mL/kg/time with an interval of about 2 hours)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

The test article was adminstered as a suspension in deionized water at the dosage of 5000mgkg. The volume of administration was 20ml/kg, separated in two adminstrations (10ml/kg/time) with an interval of about 2 hours. All rats were treated after a 16-hour fasting period.
The animals were weighed twice before treatment and on day 3, 8 and 14 and they were clinically observed following the treatment. On day 15 the rats were killed by excision of the femoral arteries after i.p. overdosage anaesthesia with 5% sodium pentobarbital and were subjected through autopsy.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities were observed in this test.

Clinical signs:

No clinical signs were observed in both sexes

Body weight:

Body weight was unaffected by treatment.

Gross pathology:

At gross necroscopy no macroscopic changes were detected in any animal.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of IR5878 in rats was greater than 5000 mg/kg bw.

Executive summary:

The test article IR5878 when administered to rats at a dose of 5000mg/kg by oral route did not induce any appreciable changes in the treated rats.

The oral LD₅₀of IR5878 in rats was greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Deviations: some minor deviations from the study plan were present but considered not to affect the validity of the study results.

GLP compliance:

yes

Test type:

acute toxic class method

Specific details on test material used for the study:

Test material:
IR5878
Batch number: FCF/T/168-00 (ex 20525/03/9)
Purity: 98.54 ± 0.51 %

Species:

rat

Strain:

other: Male and Female HanIbm: WIST (SPF) rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
Species and Strain: Male and Female HanIbm: WIST (SPF) rats
Age: 6 weeks (males); 9 weeks (females)
Body weight: 180.4 ÷ 194.7 g (males); 183.3 ÷ 189.0 g (females)
Housing: 5 animals per Makrolon type-4 cage with wire mesh tops and standard softwood bedding.
Feed: pelleted standard Kliba 3433, rat maintenance diet ad libitum (except during the exposure period, when they were restrained in exposure tubes). Community tap water from Füllinsdorf ad libitum (except during the exposure period, when they were restrained in exposure tubes).

Environmental conditions:
Temperature and humidity measured during the study were 22 ± 3°C and 30 ÷ 70%, respectively.
Light: 12 hours fluorescent light and 12 hours dark (music during the light period).

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Mass median aerodynamic diameter (MMAD):

ca. 3.02 µm

Geometric standard deviation (GSD):

ca. 2.94

Details on inhalation exposure:

IR5878 was administered to 5 male and 5 female HanIbm: WIST (SPF) rats by nose-only, flow-past inhalation exposure for a single continuous 4-hour period, followed by an observation period of 14 days.
IR5878 aerosol was generated using a CR 3020 powder generator feeding a micronising Jet-Mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutraliser with a target Mass Median Aerodynamic Diameter (MMAQD) of 1 to 4 μm. Based on preliminary technical trials which showed that the exposure system blocked after about 1 hour at concentration of about 3 mg/L air, two exposure systems were prepared to generate an aerosol concentration of about 2 mg/L. The second aerosol generator/Jet-Mill replaced the first one after 2 hour and 10 minutes of exposure - remaining the animals in the same tower. The changeover took one minute to complete and this time was added to the end of exposure.
The exposure conditions (range of temperature, humidity and oxygen content) measured during the exposure were acceptable. The mean gravimetric concentration was the highest technically achievable concentration.
The animals were examined for mortality, clinical signs and body weight for 14 days. On day 15 the rats were killed by i.p. overdosage of pentobarbitone and examined macroscopically.

Duration of exposure:

ca. 4 h

Concentrations:

Based on preliminary technical trials which showed that the exposure system blocked after about 1 hour at concentration of about 3 mg/L air, two exposure systems were prepared to generate an aerosol concentration of about 2 mg/L. The second aerosol generator/Jet-Mill replaced the first one after 2 hour and 10 minutes of exposure - remaining the animals in the same tower. The changeover took one minute to complete and this time was added to the end of exposure.

No. of animals per sex per dose:

IR5878 was administered to 5 male and 5 female HanIbm: WIST (SPF) rats by nose-only, flow-past inhalation exposure for a single continuous 4-hour period, followed by an observation period of 14 days.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.19 mg/L air

Based on:

act. ingr.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortalities were observed in this test.

Clinical signs:

other: No clinical signs were observed in both sexes

Body weight:

Body weight was unaffected by treatment.

Gross pathology:

At gross necroscopy no macroscopic changes were observed in any animal.

In Table 5.2-1 and 5.2-2 are summarised the technical conditions measured during the exposure and the atmosphere analysis.

 

Table 5.2-1     Exposure conditions measured during the exposure

Temperature (°C)	Relative humidity (%)	O2Concentration (Vol. %)
22.4 ±(n=9)	6.4 ± 1.96 (n=9)	20.7 ±(n=9)

 

Table 5.2-2     Data on the test atmosphere analysis

Group	Test atmosphere concentration (mg/L)		MMAD (µm) and [GSD]
	Nominal	Gravimetric ± SD
1	4.641	2.190 ± 0.047 (n=5)	3.02  [2.94]

MMAD: Mass Median Aerodynamic Diameter

GSD: Geometric Standard Deviation

 

No mortalities were observed in this test.

No clinical signs were observed in both sexes.

Body weight was unaffected by treatment.

At gross necroscopy no macroscopic changes were observed in any animal.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation LC50 of IR5878 in rats was estimated to be greater than the highest technically achievable aerosol concentration of 2.190 mg/L air (gravimetrically determined mean aerosol concentration).

Executive summary:

IR5878 was administered to 5 male and 5 female HanIbm: WIST (SPF) rats by nose-only, flow-past inhalation exposure for a single continuous 4-hour period, followed by an observation period of 14 days.

The acute inhalation LC₅₀of IR5878 in rats was estimated to be greater than the highest technically achievable aerosol concentration of 2.190 mg/L air (gravimetrically determined mean aerosol concentration).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 190 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Test material:
IR5878
Batch number: FCF/T/159-99 (ex 20274/71)
Purity: 93.72 ± 1.05 %

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
Species and Strain: Male and Female Sprague Dawley Crl: CD (SD) BR rats
Age: no more than three months
Body weight: 334 ÷ 350 g (males); 200 ÷ 221 g (females)
Housing: individually during the treatment period and then 5 animals/cage/sex in air-conditioned room.
Feed: GLP 4RF21 top certificate pelleted diet 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 dermal exposure:

Approximately 24 hours before the test fur was clipped from the dorsal and ventral area of the trunk of the test animals. Care was taken to avoid abrading the skin which could alter its permeability. An area of about 6x5 cm of the body dorsal surface was cleared for the application of the test article. This area corresponded to about 10% of the total body surface.
The test artcile was applied uniformly onto a porous gauze which was moistened with 0.9% NaCL solution. Th treated area was covered with the porous gauze dressing fixed to the skin with hypoallergenic non-irritating tape. The test site was further covered in a suitable amnner in order to ensure that the animals could no ingest the test substance. At the end of the exposure period the residual test article was wiped off with water.

Duration of exposure:

Groups of 5 Sprague Dawley Crl: CD (SD) BR rats per sex were administered a dosage of 5000 mg/kg (limit dose) of IR5878, applied as such uniformly onto a porous gauze moistened with 0.9% NaCl solution (single 24-hour dermal application).
The animals were examined for mortality, clinical signs and body weight during the 14 days after the treatment.

Doses:

Groups of 5 Sprague Dawley Crl: CD (SD) BR rats per sex were administered a dosage of 5000 mg/kg (limit dose) of IR5878, applied as such uniformly onto a porous gauze moistened with 0.9% NaCl solution (single 24-hour dermal application).

No. of animals per sex per dose:

Groups of 5 Sprague Dawley Crl: CD (SD) BR rats per sex

Details on study design:

The observation period was 14 days after the 24 hour exposure period.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortalities were observed in this test.

Clinical signs:

No clinical signs were observed in both sexes

Body weight:

Body weight was unaffected by treatment.

Gross pathology:

At gross necroscopy no macroscopic changes were observed in any animal.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of IR5878 in rats was greater than 5000 mg/kg bw.

Executive summary:

Groups of 5 Sprague Dawley Crl: CD (SD) BR rats per sex were administered a dosage of 5000 mg/kg (limit dose) of IR5878, applied as such uniformly onto a porous gauze moistened with 0.9% NaCl solution (single 24-hour dermal application).

The dermal LD₅₀of IR5878 in rats was greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw