Toluenesulphonamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 April 1986 - 06 May 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed under GLP and according to internationally accepted guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

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:

Toluenesulphonamide

EC Number:

215-578-1

EC Name:

Toluenesulphonamide

Cas Number:

1333-07-9

Molecular formula:

C7H9NO2S

IUPAC Name:

methylbenzenesulfonamide

Constituent 2

Reference substance name:

Toluenesulphonamide (o/p-TSA)

IUPAC Name:

Toluenesulphonamide (o/p-TSA)

Test material form:

solid: flakes

Details on test material:

- Trade name/code: Ketjenflex-9
- Batch no.: PA 20/1/86
- Appearance: Fl akes
- Purity: Mixture of toluene sulfonamides (o/m/p= 41/8/51); water content 0.35%, sulphate content= 135 ppm
- Solubility: Insoluble in water
- Stability: Stable
- Storage: At ambient temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Credo, Brussels, Belgium
- Age at study initiation: no data, young.
- Weight at study initiation: The body weights of the males on day 0 ranged from 354 to 435 those of the females from 225 to 273 g.
- Fasting period before study: Feed was withheld overnight before dosing till approximately 4 hours after administration of the test substance.
- Housing: Four days prior to dosing the animals were individually housed in polycarbonate cages.
- Diet (e.g. ad libitum): ad libitum, standard laboratory animal diet (RMH-By pellet diameter 10 mm), which was obtained from Hope Farms, Woerden, The Netherlands.
- Water (e.g. ad libitum): ad libitum, tap-water
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 40-80
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: 14 April 1986 - 06 May 1986

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: details not provided
- Amount of vehicle (if gavage): Fixed volume for all concentrations in ml/kg; does not exceed 10 ml/kg
- Justification for choice of vehicle: details not provided
- Lot/batch no. (if required): details not provided
- Purity: details not provided

MAXIMUM DOSE VOLUME APPLIED: does not exceed 10 ml/kg

DOSAGE PREPARATION (if unusual): no data

Doses:

1800, 2100, 2400 mg/kg bw day

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals are observed for a period of 14 days, i .e. every two hours on the day of administration of the test substance and once every day thereafter. Individual body weights of the animals are determined on the day of dosing, weekly thereafter and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: none

Statistics:

The LD50 value, where possible a seperate value for males and females, is calculated from the observed mortality data, using any established statistical procedure, e.g. that of Litchfield and Wilcoxon (l949), Weil (1952) or Finney (1971).

Results and discussion

Preliminary study:

Based on literature data on the LD50 values of the separate components of the test substance and the LD50 value of a related substance as provided
by the sponsor, three dose levels were selected: 1800, 2400 and 3200 mg/kg body weight. However, the highest dose presented a too viscose suspension that could not be adequately administered as one single dose. It was therefore decided to select one dose level in between 1800 and 2400 mg/kg, namely 2100 mg/kg.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 400 mg/kg bw

Mortality:

Only in the high dose group 5 out of 10 animals died. There was no evident sex related effect. One female animal of the mid dose group had received only approximately 25% of its dose due to clogging of the test material in the dosing cannula. However this is not considered to have affected the outcome of this study, since no mortality was found in this treatment group. All deaths occurred within 3 days of dosing.

Clinical signs:

other: Major signs of toxicity were lethargy, unbalanced gait, dyspnea for the mid and low dose groups, and for the high dose group in addition to the afore mentioned symptoms, coma, bloody eye encrustation, absent or bloody stool and slimy salivation. All anima

Gross pathology:

Macroscopic examination of animals found dead generally revealed test substance related petechiae and/or haemorrhages of the stomach frequently combined with bloody intestinal content and marked haematuria. One male of the high dose group revealed an atrofic testis, which was not considered to be test substance related. Macroscopic examination of surviving animals at the end of the study showed no test substance related gross abnormalities.

Any other information on results incl. tables

Mortality:

Sex	Dose (mg/kg)	# deaths	Total # animals	Day 1	Day 2	Day 3	Day 4-15
	1800	0	5	0	0	0	0
M	2100	0	5	0	0	0	0
	2400	2	5	0	1	1	0
	1800	0	5	0	0	0	0
F	2100	0	5	0	0	0	0
	2400	3	5	2	1	0	0

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The LD50 value for the sexes combined was estimated to be approximately 2400 mg/kg body weight.

Executive summary:

According to OECD401 and under GLP an acute oral toxicty study was performed with o/p-TSA. Three groups of Wistar rats, each comprising 5 males and 5 females, received a single oral dose of o/p-TSA at 1800, 2100 and 2400 mg/kg body weight, respectively. Only in the high dose group 5 out of 10 animals died. There was no evident sex related effect. All deaths occurred within 3 days of dosing. Major signs of toxicity were lethargy, ataxia and dyspnea for surviving animals, whereas for dead animals also coma was observed. For surviving animals these signs were reversible since as of day 4 no more abnormalities were observed during the 14-day observation period. Macroscopic examination of animal s found dead generally revealed test substance related petechiae and/or haemorrhages of the stomach frequently accompanied by bloody intestinal content and marked haematuria. Macroscopic examination of surviving animals at autopsy revealed no treatment related gross abnormalities. The LD50 value for the sexes combined was estimated to be approximately 2400 mg/kg body weight.