Toluene-2-sulphonamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07/01/1998 - 29/01/1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Toluene-2-sulphonamide

EC Number:

201-808-8

EC Name:

Toluene-2-sulphonamide

Cas Number:

88-19-7

Molecular formula:

C7H9NO2S

IUPAC Name:

2-methylbenzene-1-sulfonamide

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

(Crj: CD, SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Japan Charles River Co. Atsugi rearing center
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 5-week old
- Weight at study initiation: on administration date, males average was 129.7 g (124.2-135.7 g) and females average was 108.3 g (100.9-113.7 g)
- Fasting period before study: yes, about 18h prior to administration. Feeding resumed at 4 hours after dosing.
- Housing: metal mesh floor cage (220WX270DX190H, (m))
- Diet: solid feed (CE-2, CLEA Japan), ad libitum.
- Water: tap water (Kanno City Waterworks Bureau water supply, ad libitum.
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24.0 - 25.0°C
- Humidity (%): 54 - 64%
- Air changes (per hr): 15 times / hour
- Photoperiod (hrs dark / hrs light): 12 hours (7: 00-19: 00) light / 12 hours dark

IN-LIFE DATES: Arrival date of animals: January 7, 1998. Date of administration: January 15, 1998

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% w/v aqueous solution

Details on oral exposure:

VEHICLE
- Lot/batch no. (if required): Japanese Pharmacopoeia CMC sodium, lot number: 6Z09, Maruishi Pharmaceutical Co., Ltd., and water for injection of Japanese Pharmacopoeia, lot number: 9707SA, manufactured by HIKARI PHARMACEUTICAL CO., LTD.
- Purity: 0.5% w/v solution

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

700, 1000, 1400 and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights 1, 2, 4, 8, 11 and 15 days after administration; clinical findings and mortality hourly until 6h after administration and daily afterwards.
- Necropsy of survivors performed: yes

Statistics:

Mean values and standard deviations were determined for body weight measurements. From the mortality rate of this study, it was not possible to calculate the LD50 value and the 95% confidence limit by the probit method.

Results and discussion

Preliminary study:

In a preliminary study (A-97-028), 3 male and 3 female rats were administered the test item at 2000 mg/kg bw. Deaths were observed in both groups. Therefore, an additional preliminary study (A-97-039) was conducted by administering the test item at 1000 mg/kg bw. Symptoms such as hypothermia and respiratory depression were recognized, but no deaths were observed.

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

In males, no deaths were observed in any of the treatment groups. In females, one animal died on the day of administration in the 1400 mg/kg dose group, and two died on the second day of observation, and in the 2000 mg/kg dose group two animals died on the day of administration.

Clinical signs:

other: Both males and females showed strong toxicity symptoms such as sedation, weakness, laterality, non-responsiveness to stimuli, respiratory distress, decreased respiratory rate, hypothermia, catalepsy, etc. immediately after administration.

Gross pathology:

The lungs of the females in the 1400 mg/kg dose group who died were colored red, and the gastric mucosa was cloudy. In addition, black spots were found in the glandular gastric mucosa in one case. In the 2000 mg / kg group, microscopic cysts were observed in the subcapsular cortex of the left and right kidneys, and the gastric mucosa was cloudy, and red spots were scattered in the glandular gastric mucosa. In one case, the lungs were partially reddish, cysts were scattered in the subcapsular cortex of the left and right kidneys, and white turbidity in the gastric mucosa and retention of samples in the stomach were observed. Therefore, it was presumed that the main cause of death was a strong central depressant action.
No abnormal findings were observed at necropsy of the surviving animals.

Any other information on results incl. tables

Table 2. Mortality of rats after single oral administration of o-toluenesulfonamide         

Sex	Dose	No. of animals	Mortality											Total	LD50 value (mg/kg)
	(mg/kg)		0-1 h	1-2h	2-3h	3-4h	4-5h	5-6h	2d	3d	4d	5-9d	10-14d
Male	700	5	0	0	0	0	0	0	0	0	0	0	0	0	>2000
	1000	5	0	0	0	0	0	0	0	0	0	0	0	0
	1400	5	0	0	0	0	0	0	0	0	0	0	0	0
	2000	5	0	0	0	0	0	0	0	0	0	0	0	0
Female	700	5	0	0	0	0	0	0	0	0	0	0	0	0	1000-2000
	1000	5	0	0	0	0	0	0	0	0	0	0	0	0
	1400	5	0	0	0	0	1	2	0	0	0	0	0	3
	2000	5	0	0	0	1	1	0	0	0	0	0	0	2

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

EU criteria

Conclusions:

Based on the study results, the LD50 value of the test item was between 1000 and 2000 mg/kg for females and more than 2000 mg/kg for males.

Executive summary:

An Acute Oral Toxicity test was performed according to OECD 401, under GLP conditions. A total of 40 Sprague-Dawley (Crj: CD) male and female (20M/20F) rats were divided in 4 groups consisting of 5 animals per group and received a single oral administration of 700, 1000, 1400 and 2000 mg/kg of the test item. All animals were subject to daily observations and weekly determinations of body weight. Necropsy was performed on the day of their death or after sacrifice, at the end of the observation period. No deaths were observed in males at any dose tested, but 3 females in the 1400 mg/kg group and 2 females in the 2000 mg/kg group died. Both males and females showed severe toxic symptoms such as sedation, weakness, laterality, non-responsiveness to stimuli, respiratory distress, decreased respiratory rate, decreased body temperature, catalepsy, etc. immediately after administration. Some suppression of body weight gain was observed in most groups the second day after administration, but it normalized thereafter. In the necropsy findings of the death cases, it was presumed that the main cause of death was a strong central depressant action, because there were no organic changes caused by the test substance leading to the death. From these facts, it was estimated that the LD50 value of o-toluenesulfonamide under this test condition was between 1000 and 2000 mg/kg for females and more than 2000 mg/kg for males.