Benzo[b]thiophene, 7-chloro-3-methyl-

Endpoint summary

Description of key information

Key study: Test method according to OECD Guideline 420. GLP study. The substance was classified as category 4 according to CLP Regulation (EC) no. 1272/2008 since the dose of 2000 mg/kg bw caused death in the sighting study. No effects were observed at 300 mg/kg bw (main study).

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:

29 October 2014 - 21 November 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test method according to OECD Guideline 420. GLP study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Experimental Medicine Centre at the Medical University in Białystok
- Age at study initiation: 10-week-old
- Weight at study initiation: 189.0 g (average body weight).
- Fasting period before study: about 18 hours before the administration of the test item. Food was given back 3 hours after the administration of the test item.
- Housing: plastic cages covered with wire bar lids (dimensions: 58 x 37 x 21 cm). UV-sterilized wood shavings were used as bedding.
- Diet (e.g. ad libitum): “Murigran” standard granulated laboratory fodder, ad libitum.
- Water (e.g. ad libitum): tap water, ad libitum.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 23°C
- Humidity (%): 40 – 75%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 60 mg/mL
- Amount of vehicle (if gavage): 1 mL

MAXIMUM DOSE VOLUME APPLIED: 0.5 mL/100 g b.w.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose for the sighting study was selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg b.w. as a dose expected to produce evident toxicity. Since no data were available, the sighting study commenced with the administration of the test item at a dose of 300 mg/kg b.w. to one female rat. Since no evident toxicity was produced, the test item at a single dose of 2000 mg/kg b.w. was administered to the second animal. On the grounds of the sighting study results (the animal given 2000 mg/kg b.w. died on day 2), the dose of 300 mg/kg b.w. was selected to be used in the main study.

Doses:

Sighting study: 300 and 2000 mg/kg.
Main study: 300 mg/kg.

No. of animals per sex per dose:

Sighting study: 2 animals.
Main study: 4 animals.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: on days 0 (directly before the administration of the test item), 7, and 14 (before euthanasia).
- Necropsy of survivors performed: yes/no
- Other examinations performed:
General condition: observation of all animals for morbidity and mortality: twice a day or once a day (on days off).
Detailed clinical observations: on the day of the test item administration (day 0), i.e. 10, 30, and 60 minutes after the administration and then at hourly intervals up to the 5th hour after the administration. From the 1st to the 14th day of the experiment, the detailed clinical observations were performed once a day.
Gross examinations: After the 14-day observation period, all animals were euthanized by intraperitoneal administration of morbital at a dose of 200 mg/kg b.w. and subjected to gross examinations. The detailed gross examinations involved the observation of the external body surface, all natural apertures, and the cranial, thoracic, and abdominal cavities with their contents

clinical signs, body weight,organ weights, histopathology, other:

Preliminary study:

Clinical signs: following single administration of the test item at a dose of 300 mg/kg b.w. no signs of toxicity were observed. The animal survived the experiment. Following single administration of the test item at a dose of 2000 mg/kg b.w. to the second animal, signs of toxicity were observed on days 0 and 1. The first signs occurred 30 minutes post-administration. These were: wavering gait, a slight decrease in locomotor activity, and dejection. They were observed till the 5th hour post-administration. The decrease in locomotor became more distinct 3 hours after the administration. Additionally, the animal was easy to catch from the 3rd to the 5th hour post-administration. On day 1 lying on the abdomen, lying inertly, no movement, and no reactions to sound stimuli were observed. The animal was also easy to catch. It died on the second day of the observation period.
Body weight: body weight of the surviving animal increased (dose of 300 mg/kg b.w.).
Gross examinations: the gross examinations of the accidently dead and the euthanized females did not reveal any lesions.

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (evident toxicity)

Mortality:

All animals survived the experiment.

Clinical signs:

other: No signs of toxicity were observed.

Gross pathology:

No pathological changes were observed.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The substance was classified as category 4 according to CLP Regulation (EC) no. 1272/2008 since the dose of 2000 mg/kg bw caused death in the sighting study. No effects were observed at 300 mg/kg bw (main study).

Executive summary:

The acute oral toxicity study based on a fixed dose method was performed according to OECD Guideline 420, following the Principles of GLP. The experiment commenced with a sighting study in which the test item at a single dose of 300 mg/kg b.w. was administered to one animal. As the dose of 300 mg/kg b.w. did not produce evident toxicity, the dose of 2000 mg/kg b.w. was given to the next animal. On the grounds of the sighting study results (the animal given 2000 mg/kg b.w. died) four animals used in the main study were given the test item at a dose of 300 mg/kg b.w. After the administration of the test item, the animals were observed for 14 days. General and detailed clinical observations were conducted daily during the entire experiment. Body weights of the animals were determined. After the 14-day observation period, the animals were euthanized and subjected to a detailed gross examination. Following single administration of the test item at a dose of 300 mg/kg b.w. to four animals used in the main study, no signs of toxicity were observed. All animals survived the experiment. During the experiment, body weights of all surviving animals increased. Gross examinations did not reveal any pathological changes. The substance was classified as category 4 according to CLP Regulation (EC) no. 1272/2008 since the dose of 2000 mg/kg bw caused death in the sighting study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

300 mg/kg bw

Quality of whole database:

Klimisch score = 1. GLP study.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Key study: The acute oral toxicity study based on a fixed dose method was performed according to OECD Guideline 420, following the Principles of GLP. The experiment commenced with a sighting study in which the test item at a single dose of 300 mg/kg b.w. was administered to one animal. As the dose of 300 mg/kg b.w. did not produce evident toxicity, the dose of 2000 mg/kg b.w. was given to the next animal. On the grounds of the sighting study results (the animal given 2000 mg/kg b.w. died) four animals used in the main study were given the test item at a dose of 300 mg/kg b.w. After the administration of the test item, the animals were observed for 14 days. General and detailed clinical observations were conducted daily during the entire experiment. Body weights of the animals were determined. After the 14-day observation period, the animals were euthanized and subjected to a detailed gross examination. Following single administration of the test item at a dose of 300 mg/kg b.w. to four animals used in the main study, no signs of toxicity were observed. All animals survived the experiment. During the experiment, body weights of all surviving animals increased. Gross examinations did not reveal any pathological changes. The substance was classified as category 4 according to CLP Regulation (EC) no. 1272/2008 since the dose of 2000 mg/kg bw caused death in the sighting study.

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for classification or non-classification

Based on the available results, the substance is classified for Acute Toxicity Category 4 according to CLP Regulation (EC) no. 1272/2008.