5-amino-6-methyl-1,3-dihydrobenzoimidazol-2-one

Endpoint summary

Description of key information

The acute oral LD50 for the test substance is above 200 (0/3 animals died) and lower than or equal as 2000 mg/kg bw  (all animals died) for both male and female rats. The dermal LD50 value exceeds 2000 mg/kg bw for male and female rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-03-25 - 1998-05-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted March 22, 1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 1996

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 7 - 9 weeks
- Weight at study initiation:
- Fasting period before study:
- Housing: 3 animals per sex and cage (polycarbonate cages)
- Diet: standard pelleted laboratory diet, ad libitum (Carfil Quality BVBA, Oud-Turnhout, Belgium)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL

Doses:

200, 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability: twice daily; Body weights: on Days 1, 8, 15; Clinical signs: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic findings

Statistics:

Not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The incidence of mortality for males was 3/3 (2000 mg/kg), 0/3 (200 mg/kg) and for females 1/3 (2000 mg/kg), 0/3 (200 mg/kg).

Clinical signs:

other: 2000 mg/kg: - Lethargy, hunched posture, uncoordinated movements, piloerection, red staining of the nose, laboured respiration and emaciation was noted among the animals that died. - Lethargy, hunched posture, uncoordinated movements among the surviving

Gross pathology:

Beginning of autolysis, enlarged kidneys and reduction in size of spleen, thymus and seminal vesicles was found among the animals that died during the study. No abnormalities were found at macroscopic post mortem examination of the surviving animals.

Other findings:

none

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

200 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

1998-03-25 - 1998-04-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

adopted 1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks
- Weight at study initiation: males (mean): 332 g; females (mean): 227 g
- Housing: individually
- Diet: standard pelleted laboratory diet, ad libitum (Carfil Quality BVBA, Oud-Turnhout, Belgium)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: back of the animals
- % coverage: 10 %
- Type of wrap if used: coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with tap water
- Time after start of exposure: 24 hours after application

TEST MATERIAL
- Concentration (if solution): 200 mg/mL
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality: twice daily; Body weight: Day 1, 8, 15; Clinical signs: daily
- Necropsy of survivors performed: yes

Statistics:

Not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Red staining of the neck was noted in two females between days 7 and 12. Brown staining of the treated skin-area was seen among the animals during the observation period and erythema was seen in the treated skin-area of one male on day 2.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

None

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

Additional information

Acute oral toxicity

The study was performed according to OECD guideline 423 (adopted 22.03.1996) and EU method B.1 tris. Initially, the test substance was administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight. In a stepwise procedure additional groups of animals were dosed at 2000 (males), 200 (females) and 200 (males) mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (day 15).

The incidence of mortality for males was 3/3 (2000 mg/kg), 0/3 (200 mg/kg) and for females 1/3 (2000 mg/kg), 0/3 (200 mg/kg). The decedents were found dead between days 5 and 8.

Clinical signs observed during the study period were as follows:

2000 mg/kg:

- Lethargy, hunched posture, uncoordinated movements, piloerection, red staining of the nose, laboured respiration and emaciation was noted among the animals that died.

- Lethargy, hunched posture, uncoordinated movements among the surviving animals on day 1 only. Hunched posture recurred in one animal between days 5 and 10.

200 mg/kg :

- Uncoordinated movements in all animals on day 1

The body weight gain shown by the surviving animals over the study period was considered to be normal.

Beginning of autolysis, enlarged kidneys and reduction in size of spleen, thymus and seminal vesicles was found among the animals that died during the study. No abnormalities were found at macroscopic post mortem examination of the surviving animals.

The oral LD50 value in Wistar rats was established to be within the range of 200-2000 mg/kg bw. (NOTOX B.V., 1998).

Further information is available from the 5 -day dose-range-finding study for the repeated-dose study. In this study, the dose level of 200 mg/kg bw caused mortality in one of three animals after 4 days whereas the dose-level of 1000 mg/kg bw caused mortality in all three animals within three days. In the full 28 -day study, the highest dose level of 75 mg/kg bw was tolerated without adverse effects. Overall, it is concluded, that the LD50 should be higher than 300 mg/kg bw.

Acute dermal toxicity

The study was performed according to OECD guideline 402. The test substance was administered to five rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Red staining of the neck was noted in two females between days 7 and 12. Brown staining of the treated skin-area was seen among the animals during the observation period and erythema was seen in the treated skin-area of one male on day 2. Body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found in the animals at macroscopic post mortem examination.

The dermal LD50 value of the test substance in rats was established as exceeding 2000 mg/kg body weight. (NOTOX B.V., 1998)

Justification for selection of acute toxicity – oral endpoint
only study available

Justification for selection of acute toxicity – dermal endpoint
only study available

Justification for classification or non-classification

Based on the available acute oral toxicity data, the test item has to be classified and labelled as category 4 (H302: harmful if swallowed) according to Regulation (EC) No 1272/2008 (CLP) and as Xn, R22 (Harmful if swallowed) according to Directive 67/548/EEC (DSD). The LD50 is expected to be higher than 300 mg/kg bw.

Based on the available acute dermal toxicity data, the test substance dose not need to be classified and labelled according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).