Pentyl 2-cyano-(3-(6-methoxybenzothiazol-2-ylimino)-2,3-dihydro-1H-isoindol-1-ylidene)acetate

Endpoint summary

Description of key information

The available data for test substance indicates a low potential for acute oral (LD50 >2000 mg/kg bw) and dermal toxicity (LD50 >2000 mg/kg bw).

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:

From Aug. 22, 2000 to Nov. 24, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HARLAN WINKELMANN, Gartenstr. 27, 33178 Borchen, SPF breeding colony
- Age at study initiation: 6-10 wk
- Weight at study initiation: 233± 8.5 g (males); 194± 4.2 g (females)
- Fasting period before study: Yes, 16 h
- Housing: MacroIon cages (type 4) on soft wood granulate in groups of 5 animals
- Diet (e.g. ad libitum): ssnif R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): Tap water in plastic bottles, ad libitum
- Acclimation period: At least 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 °C
- Humidity (%): 50±20 °C
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

IN-LIFE DATES: From: Aug. 22, 2000 To: Sep. 05, 2000

Route of administration:

oral: gavage

Vehicle:

other: Tylose H 4000 G4 PHA (0.5 % in deionized water)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 % suspension

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): Test substance was suspended in the Tylose H 4000 G4 PHA (0.5 % in deionized water) and distributed homogeneously by means of a magnetic stirrer.
The stability and the homogeneity of the test substance in the vehicle was determined by analytical methods.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends
and public holidays only once. The animals were weighed weekly.
- Necropsy of survivors performed: yes; animals were killed by carbon dioxide
asphyxiation, dissected and examined for macroscopically visible changes.
- Other examinations performed: clinical signs, body weight- Yes

Statistics:

not applicable

Preliminary study:

No

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortalities occurred during the whole study.

Clinical signs:

other: With exception of discolored orange faeces, between 4 h and Day1 after administration, no clinical signs were observed until the end of the study.

Gross pathology:

No gross pathology changes observed

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the acute oral LD50 of the test substance was found to be >2000 mg/kg in Sprague-Dawley CD rats.

Executive summary:

A study was conducted to assess the acute oral toxicity of test substance in Sprague-Dawley CD rats according EU Method B.1. and OECD guideline 401 in compliance with GLP.

Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a 20 % suspension in Tylose H 4000 G4 PHA (0.5 % in deionized water), at a dose level of 2000 mg/kg. The animals were observed for 14 d after the day of dosing and were then killed and subjected to gross pathological examination. There were no mortalities in the study. With exception of discolored orange feces, between 4 h and Day 1 after administration, no clinical signs were observed until the end of the study. Development of body weight was not impaired, except one female, which suffered a loss of weight between Day 8 and Day 15. No abnormalities were noted at necropsy.

 

Under the test conditions, the acute oral LD50 of the test substance was found to be >2000 mg/kg in Sprague-Dawley CD rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

From Aug. 23, 2000 to Nov. 27, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HARLAN WINKELMANN, Gartenstr. 27, 33178 Borchen, SPF breeding colony
- Age at study initiation: 6-10 wk
- Weight at study initiation: 288± 11 g (males); 212± 12 g (females)
- Fasting period before study: Yes, 16 h
- Housing: MacroIon cages (type 4) on soft wood granulate, one animal/cage
- Diet (e.g. ad libitum): ssnif R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): Tap water in plastic bottles, ad libitum
- Acclimation period: At least 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 °C
- Humidity (%): 50±20 °C
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

IN-LIFE DATES: From: Aug. 23, 2000 To: Sep. 06, 2000

Type of coverage:

semiocclusive

Vehicle:

other: Tylose H 4000 G4 PHA (0.5 % in deionized water)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal skin of the area (30 cm2)
- Type of wrap if used: Elastic plaster bandage fixed around the animal's body (Fixomull and Elastoplast, 8 cm in width)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 0.5 g of test substance was moistened with 0.5 mL Tylose H 4000 G4 PHA (0.5 % in deionized water).
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL Tylose H 4000 G4 PHA (0.5 % in deionized water).

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends
and public holidays only once. The animals were weighed weekly
- Necropsy of survivors performed: yes; animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.
- Other examinations performed: Clinical signs and body weight

Statistics:

No data

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortalities occurred during the whole study.

Clinical signs:

other: No symptoms were observed after administration of 2000 mg/kg body weight. The skin of the animals showed no signs of irritation.

Gross pathology:

No gross pathological changes were observed

Other findings:

No data

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the acute dermal LD50 of the test substance was found to be >2000 mg/kg in Sprague-Dawley CD rats

Executive summary:

A study was conducted to assess the acute dermal toxicity of test substance in Sprague-Dawley CD rats according EU Method B.3. and OECD guideline 402 in compliance with GLP.

Following a range-finding study, a group of 10 rats (five males and five females) were applied 0.5 g of test substance moistened with 0.5 mL Tylose H 4000 G4 PHA (0.5 % deionised water), at a dose level of 2000 mg/kg. Following the 24 h exposure period, animals were observed for mortality, skin response and general behavior for 14 d and were then killed and subjected to gross pathological examination.

 

No mortality was observed in the study. All animals appeared normal throughout the 24 h exposure period and the 14 d post-exposure observation period. The skin of the animals showed no signs of irritation.

Three female animals showed disturbance of body weight gain during the first week of the study. Up to the end of the study (Day 15) the body weight gain returned to normal. One male animal suffered a loss of weight between Day 8 and Day 15, the body weight of all animals increased during the observation period.

 

Under the test conditions, the acute dermal LD50 of the test substance was found to be >2000 mg/kg in Sprague-Dawley CD rats

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

2 000 mg/kg bw

Additional information

Oral

A study was conducted to assess the acute oral toxicity of test substance in Sprague-Dawley CD rats according EU Method B.1. and OECD guideline 401.

Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a 20 % suspension in Tylose H 4000 G4 PHA (0.5 % in deionized water), at a dose level of 2000 mg/kg. The animals were observed for 14 d after the day of dosing and were then killed and subjected to gross pathological examination. There were no mortalities in the study. With exception of discolored orange feces, between 4 h and Day 1 after administration, no clinical signs were observed until the end of the study. Development of body weight was not impaired, except one female, which suffered a loss of weight between Day 8 and Day 15. No abnormalities were noted at necropsy. The acute oral LD50 of the test substance was found to be >2000 mg/kg in Sprague-Dawley CD rats (Dr. Th. Roth, 2000).

 

Dermal

A study was conducted to assess the acute dermal toxicity of test substance in Sprague-Dawley CD rats according EU Method B.3. and OECD guideline 402.

Following a range-finding study, a group of 10 rats (five males and five females) were applied 0.5 g of test substance moistened with 0.5 mL Tylose H 4000 G4 PHA (0.5 % deionised water), at a dose level of 2000 mg/kg. Following the 24 h exposure period, animals were observed for mortality, skin response and general behavior for 14 d and were then killed and subjected to gross pathological examination. No mortality was observed in the study. All animals appeared normal throughout the 24 h exposure period and the 14 d post-exposure observation period. The skin of the animals showed no signs of irritation. Three female animals showed disturbance of body weight gain during the first week of the study. Up to the end of the study (Day 15) the body weight gain returned to normal. One male animal suffered a loss of weight between Day 8 and Day 15, the body weight of all animals increased during the observation period. The acute dermal LD50 of the test substance was found to be >2000 mg/kg in Sprague-Dawley CD rats (Dr. Th. Roth, 2000).

Justification for classification or non-classification

The available data for test substance indicates a low potential for acute oral (LD50 >2000 mg/kg bw) and dermal toxicity (LD50 >2000 mg/kg bw) and does not meet the requirement for classification according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).