N-butylbenzenesulphonamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 July and 30 August 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

no information on control animals provided

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

N-butylbenzenesulphonamide

EC Number:

222-823-6

EC Name:

N-butylbenzenesulphonamide

Cas Number:

3622-84-2

Molecular formula:

C10H15NO2S

IUPAC Name:

N-butylbenzenesulfonamide

Details on test material:

- Name of test material (as cited in study report): N-n-butyl benzenesulphonamide (BBSA)
- Substance type: mono constituent substance-organic
- Physical state: clear, colourless liquid
- Analytical purity: 99.91%
- Impurities (identity and concentrations): ≤ 0.01% butylamine / ≤ 0.2% benzeendibutylsulphonamine / ≤ 0.1% dibutylbenzeensulphonamine / ≤ 0.1% butylparachlorobenzeensulfonamine / ≤ 0.1% diphenyl sulphone
- Composition of test material, percentage of components: 99.91% N-n-butyl benzenesulphonamide
- Isomers composition:
- Purity test date: 11/09/1994
- Lot/batch No.: 0/941109
- Expiration date of the lot/batch: ≥ July 1996
- Stability under test conditions: stable
- Storage condition of test material: room temperature in dark
- Other:

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Ltd. Bicester, Oxon, England
- Age at study initiation: 4 to 7 weeks
- Weight at study initiation: 87 to 108 g
- Fasting period before study: acces to food was prevented overnight prior to and approximately 4 hours after dosing
- Housing: The rats were allocated without consious bias to cages within the treatment groups. They were housed in groups of up to five rats of the same sex in metal cages with wire mesh floors in building R14 Room 6.
- Diet (e.g. ad libitum): A standard laboratory rodent diet (SDS LAD 1) was provided ad libitum, each batch of diet used for the study was analysed for certain nutrients, possible contaminants and micro-organismes.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days prior to the start of the study.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-3°c
- Humidity (%): 30-70% RH
- Air changes (per hr): 10 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light in each 24-hour period.


IN-LIFE DATES: From: 17-08-1995 To: 30-08-1995

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: /
- Amount of vehicle (if gavage): The appropiate dose volume of the test substance was administered to each rat using a syringe and plastic catheter (8 choke).
- Justification for choice of vehicle:/
- Lot/batch no. (if required): /
- Purity: /


MAXIMUM DOSE VOLUME APPLIED: 1,8 ml/kg bodyweight
preliminary study: 2.8 ml/kg bodyweight


DOSAGE PREPARATION (if unusual):/


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The initial dose level was selected on the basis of the preliminary study. Further groups of male rats were dosed, after review of the results, to permit estimation of a median lethal dose.

Doses:

2,0 g/kg bodyweight. The initial dose level was selected on the basis of the preliminary study. Further groups of male rats were dosed, after review of the result, to permit estimation of a median lethal dose.

dates dosed 27/07/95 16/08/95 01/08/95 16/08/95
dose (g/kg) 1,26 1,26 2,0 3,2
dose volume (ml/kg) 1,1 1,1 1,8 2,8
No. of rats:
F 2 - 5 -
M 2 5 5 5

No. of animals per sex per dose:

A group of ten rats (5 males and 5 females) was treated at 2,0 g/kg bodyweight.
9 rats (7males and 2 females): 1.1 ml/kg
5 male rats: 2.8 ml/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?) 14 days after dosing.
- Frequency of observations and weighing:Animals were observed soon after dosing and at frequent intervals for the remainder of day 1 (a minimum period of four hours). On subsequent days the animals surviving were observed once in the morning and again at the end of the experimental day. This latter observations was at approximately 16.30 hours on week days or 11.30 hours on Saturdays, Sundays and public holidays. The nature and severity of the clinical signs and time were recorded at each observation.
Individual bodyweights were recorded on Days 1, 8 and 15 or at death. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: macroscopic examination, mortality

Statistics:

The acute median lethal oral dose (LD50) to male rats was calculated using the method of Finney.

Results and discussion

Preliminary study:

The results of the preliminary study indicated that the acute lethal oral dose to male and female rats of BBSA was greater than 1,26 g/kg bodyweight.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 070 mg/kg bw

95% CL:

95

Mortality:

2 males and 1 female at 2,0 g/kg and all rats at 3,2 g/kg died during the study. All deaths occured between 26 and 45 hours of dosing. A slight bodyweight loss was recorded for all decedents.
macroscopic examination of these animals revealed:
males&females-2,0 g/kg: congestion (characterised by gaseous distension) and yellow staining in the stomach of the female decedent.
males-3,2g/kg: Congestion (characterised by darkened tissue) in the heart, lungs, liver and kidneys, with splenic atrophy and congestion and pale subcutaneous tissue. Congestion (identified by gaseous distension, food/yellow fluid contents and thickening/bleaching) was seen in the stomach and along the alimentary tract, with the stomachs of 3 animals also having a shrunken appearance. Congestion, red fluid contents and prominent blood vessels were seen in the brain. In addition, green/black fluid contents were observed in the urinary bladder of one animal.

Clinical signs:

other: Piloerection was observed in all rats within 7 minutes of dosing and throughout the remainder of day1. This sign persisted and was accompanied on day 1 and/or later intervals by: Hunched posture in all rats at all dosages; Waddling in all males at 1,26 an

Gross pathology:

Macroscopic examination of animals killed on day 15 revealed changes characterised by shrunken appearance and inflammation in the stomachs of all animals dosed at 1,26 g/kg bodyweight.

Other findings:

- Organ weights: /
- Histopathology: /
- Potential target organs: /
- Other observations:/

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal oral dose (LD50) and its 95% confidence limits to male rats of BBSA was estimated to be 2,07 (1,74 to 2,46) g/kg bodyweight.

Executive summary:

An acute oral toxicity study was conducted in Sprague-Dawley rats according to fixed dose procedure at doses/volumes of 1.26, 2.0 and 3.2 g/kg bodyweight. The acute median lethal oral dose (LD50) and its 95% confidence limits to male rats of BBSA was estimated to be 2,07 (1,74 to 2,46) g/kg bodyweight. Macroscopic examination of animals killed on day 15 revealed changes characterised by shrunken appearance and inflammation in the stomachs of all animals dosed at 1,26 g/kg bodyweight. Piloerection was observed in all rats within 7 minutes of dosing and throughout the remainder of day1; this sign persisted and was accompanied on day 1 and/or later intervals by hunched posture in all rats at all dosages and waddling in all males at 1,26 and 3,2 g/kg.