N-butylbenzenesulphonamide

Endpoint summary

Description of key information

LD50 values for acute toxicity is higher than 2000 mg/kg bw in both the oral and dermal study and higher than 4066 mg/m³ air in the inhalation 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:

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

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

fixed dose procedure

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

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.

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.

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:/

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 070 mg/kg bw

Quality of whole database:

Reliable

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Kres Paderborn
- Age at study initiation: 2 to 3 months
- Weight at study initiation: 180 - 210g
- Fasting period before study:
- Housing:Makrolon-cages type III, 5 animals by cage.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-2°c
- Humidity (%): +- 50%
- Air changes (per hr): +- 10 changes per hour
- Photoperiod 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 23-11-1990 To: 07-12-1990

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: breathing room from the firma Rhema Labortechnik
- Exposure chamber volume: Ø: 30cm, h: 28cm, (volume: +- 20l)
- Method of holding animals in test chamber:
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols:
- Method of particle size determination:
- Treatment of exhaust air: aerosolfilter
- Temperature, humidity, pressure in air chamber: with rats: temperature: 25°c, humidity: 34%
without rats: temperatures: 24°c, humidity: 14%


TEST ATMOSPHERE
- Brief description of analytical method used: GC FID
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable):/
- Concentration of test material in vehicle (if applicable):/
- Justification of choice of vehicle: /
- Lot/batch no. (if required): /
- Purity: /


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: With an aerodynamic particle sizer with laser-velocimeter (TSI-APS 3300)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

BBSA 99.8% - concentration at saturation (in air) : 0.06 µg/l at 20°c

No. of animals per sex per dose:

air controle: 5 males/5 females
3431 mg/m³: 5 males/5 females
3439 mg/m³: 5 males/5 females
4066 mg/m³: 5 males/5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing:twice a day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other:

Preliminary study:

standard acute method

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 066 mg/m³ air

Exp. duration:

4 h

Mortality:

no mortality

Clinical signs:

other:

Body weight:

no changes in body weight

Gross pathology:

no changes

Other findings:

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

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50-inhalation (aerosol) is > 4066 mg/m³ (4h). The NOEL is 3431 mg/m³. At the lowest applied dose (3431 mg/m³) the rats tolerated the test substance without symptoms. At higher doses (3439 mg/m³and
4066 mg/m³) piloerection was observed. After one day no clinical symptoms were observed.

Executive summary:

An acute inhalation study in male and female Wistar rats was conducted according to nose/head only procedure at concentrations of 3431 and 3439 mg/m³.The LC50-inhalation (aerosol) is > 4066 mg/m³ (4h) and the NOEC is 3431 mg/m³. At the lowest applied dose (3431 mg/m³) the rats tolerated the test substance without symptoms. At higher doses (3439 mg/m³and

4066 mg/m³) piloerection was observed. After one day no clinical symptoms were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 066 mg/m³ air

Quality of whole database:

Reliable

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2/08 - 16-08 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

no information provided on control animals

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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: 7 - 10 weeks
- Weight at study initiation: 220 to 250g
- Fasting period before study: no
- Housing: the rats were allocated without conscious bias to cages within the treatment group. They were housed individually in metal cages with wire mesh floors in building R14 room 6.
- Diet (e.g. ad libitum): standard laboratory rodent diet (SDS LAD 1) were 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: 2/08 - 16-08-1995 To: 16-08 1995

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: the dorso-lumbar region
- % coverage: 10%
- Type of wrap if used: covered with gauze which was held in place with a non-irritative dressing encircled firmly around the trunk.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated area of skin was washed with warm (30-40°c) water and blotted dry with absorbent paper.
- Time after start of exposure: 24h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1,8 ml/kg bodyweight
- Concentration (if solution): /
- Constant volume or concentration used: yes/no
- For solids, paste formed: yes/no


VEHICLE
- Amount(s) applied (volume or weight with unit): /
- Concentration (if solution): /
- Lot/batch no. (if required): /
- Purity: /

Duration of exposure:

24h during 15 days.

Doses:

1,8 ml/kg bodyweight

No. of animals per sex per dose:

a group of 10 rats (5 males and 5 females) was treated at 2,0 g/kg bodyweight

Control animals:

not required

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 period of approximately five hours). On subsequent days animals 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 and Sundays. The nature and severity of the clinical signs and time were recorded at each observation.
Individual body weight were recorded on Days 1, 8 and 15. Individual weekly bodyweight changes and group mean bodyweight data were calculated.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: mortality, dermal respons, macroscopic examintion

Statistics:

NO DATA

Preliminary study:

standard acute method

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

2 000 mg/kg bw

Mortality:

There were no deaths following a single dermal application of BBSA at a dosage of 2,0 g/kg bw.

Clinical signs:

other: There were no signs of systemic reaction to treatment.

Gross pathology:

No macroscopic abnormalities were observed for animals killed on day 15.

Other findings:

- Organ weights: /
- Histopathology: /
- Potential target organs: /
- Other observations: dermal responses: Sites of application of BBSA showed no irritation or other dermal changes (scores of zero for erythema and oedema were recorded for all animals).

Dermal response

Local dermal irritation at the treatment site was assessed daily using the following numerical system:

 

Erythema and eschar formation:

No erythema:  0

Slight erythema:  1

Well-defined erythema:  2

Moderate erythema:  3

Severe erythema (beet redness) to slight eschar formation (injuries in depth):  4

Oedema formation:   

No oedema:  0

Slight oedema:  1

Well-defined oedema (edges of area well-defined by definite rising):  2

Moderate oedema (raised approximately 1 mm):  3

Severe oedema (raised more than 1 mm and extending beyond the area of exposure):  4

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal dermal dose to rats of BBSA was found to be greater than 2,0 g/kg bodyweight.

Executive summary:

Acute dermal toxicity was tested in Spraque-Dawley rats at 2.0 g/kg under occlusive dressing. The acute lethal dermal dose to rats of BBSA was found to be greater than 2,0 g/kg bodyweight. No macroscopic abnormalities were observed for animals killed on day 15.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Following acute toxicity studies were conducted with N-n-butylbenzenesulphonamide:

A key 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 (HLS, 1995). 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.

A key acute inhalation study in male and female Wistar rats was conducted according to nose/head only procedure at concentrations of 3431 and 3439 mg/m³ (Bayer, 1991). The LC50-inhalation (aerosol) is > 4066 mg/m³ (4h) and the NOEC is 3431 mg/m³. Pilo-erection was observed at 4066 mg/m³:

A key acute dermal toxicity was conducted in Sprague-Dawley rats at 2.0 g/kg under occlusive dressing (HRC, 1995). The acute lethal dermal dose to rats of BBSA was found to be greater than 2,0 g/kg bodyweight. No macroscopic abnormalities were observed for animals killed on day 15.

Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – inhalation endpoint
Key study

Justification for classification or non-classification

Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC) and CLP regulation (EC No. 1272/2008 of 16 December 2008), N-butylbenzenesulphonamide does not have to be classified and has no obligatory labelling requirement for acute toxicity.