1,2-Benzisothiazole, 3-methyl-, 1,1-dioxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-10-25 to 2016-11-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-1λ⁶,2-benzothiazole-1,1-dione

EC Number:

812-907-6

Cas Number:

34989-82-7

Molecular formula:

C8H7NO2S

IUPAC Name:

3-methyl-1λ⁶,2-benzothiazole-1,1-dione

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Lot: 216-106
- Expiry date: 2018-06-16
- Storage conditions: Keep at room temperature

Test animals

Species:

rat

Strain:

other: Crl:WI

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 11 weeks
- Weight at study initiation: 227-234 g (first group), 214-220 g (second group)
- Fasting period before study: on day before treatment
- Housing: 3 animals/sex/cage
- Diet: ad libitum, ssniff® SM R/M-Z+H complete diet
- Water: ad libitum, tap water
- Acclimation period: 26 days in first group and 27 days in second group

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): above 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
Formulations were prepared just before the administration and stirred continuously during the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose:
The starting dose was selected on the basis of the available information about the test item. A limit test was performed.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (3 in first and 3 in second group)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually after dosing once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, after the treatment and once per day for 14 days thereafter. The body weight were recorded on day 0 (shortly before the treatment), on day 7 and on day 15 on all animals.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item did not induce mortality following a single oral administration to female rats at a dose of 2000 mg/kg bw. All rats isurvived until the end of the 14-day observation period.

Clinical signs:

other: Animals showed following clinical signs: decreased activity, tremor, abnormal gait, limb position, incoordination, bedding chewing, closed eyes, piloerection and clonic convulsion. These symptoms were observed between 30 minutes and Day 2 after the treatm

Gross pathology:

No pathological changes were found related to the test item during the macroscopic examination of animals.

Other findings:

- Other observations: No.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute oral toxicity study with rats a LD50 > 2000 mg/kg bw was determined.

Executive summary:

An acute oral toxicity study was carried out using the acute toxic class method according to OECD guideline 423. The method was conducted using a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so three further female rats were treated with the same dose. No animal died in the second step, therefore no further testing was required. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day after the treatment. No lethality was noted following oral administration of a single dose of 2000 mg/kg bw. In the first step at a dose level of 2000 mg/kg bw, CNS - and emotion symptoms (decreased activity, tremor, bedding chewing, closed eyes, clonic convulsion), disturbances of the coordination (abnormal gait, limb position, incoordination) and disturbance of the autonomic functions (piloerection) were observed in animals on the treatment day between 30 minutes and 4 hours after the treatment. In the second step at a dose level of 2000 mg/kg bw, similar CNS - and emotion were observed in animals between 30 minutes and Day 2 after the treatment. Those temporary effects were considered to be test item related. Body weight gain backwardness was observed in one female in the second week. It was evaluated as an individual variation without toxicological meaning of the test item. All animals survived until the scheduled autopsy on Day 15. All organs of all animals proved to be free of gross pathological changes. For this acute oral toxicity study with the test item in rats the determined LD50 is above 2000 mg/kg bw. Therefore the test substance is not classified for acute oral toxicity according to CLP (EU-GHS).