Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 30 January 1992 and 18 February 1992.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Test material: NSABZ (2-(Naphthalene-2'-sulphonylamino)-benzoic acid)
Date of receipt: 20 December 1991.
Description: Very light brown powder.
Storage: In original container at room temperature.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Data relating to the identity, purity and stability of the test material are the responsibility of the sponsor.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test material was freshly prepared, as required, as a suspension at the appropriate concentration in arachis oil B.P.
- Homogeneity was assured by the use of a Si Iverson homogeniser. The concentration, homogeneity and stability of the test material preparations were not
determined.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, U.K.
- Age at study initiation: approximately five to eight weeks old
- Weight at study initiation: the males weighed 129 - 147g, and the females 125 - 136g
- Fasting period before study: an overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: in groups of five by sex in solid-floor polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): free access throughout the study (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.)
- Water (e.g. ad libitum): free access throughout the study
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22°C
- Humidity (%): 52 - 63%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Justification for choice of vehicle: not specified

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
Range-finding study: 1 male, 1 female
Main study: 5 males, 5 females
Control animals:
no
Details on study design:
DOSING:
- All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

RANGE-FINDING STUDY:
- Duration of observation period following administration: Deaths and overt signs of toxicity were recorded 30 min, 1, 2 and 4 hours after dosing and subsequently once daily for 5 days.
- Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.

MAIN STUDY:
- Duration of observation period following administration: Deaths and overt signs of toxicity were recorded 30 min, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Frequency of observations and weighing: Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes, at the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The appearance of any macroscopic abnormalities was recorded.
Statistics:
Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.
The results were interpreted according to the Commission Directive 83/467/EEC which adapts Council Directive 67/548/EEC on the regulations relating to the classification, packaging and labelling of dangerous substances.

Results and discussion

Preliminary study:
The results of the range-finding study indicated that the acute oral median lethal dose of the test material was greater than 2000 mg/kg bodyweight.
Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study
Body weight:
All animals showed expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of 2-(Naphthalene-2'-sulphonylamino)-benzoic acid in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

 A study was performed to assess the acute oral toxicity of 2-(Naphthalene-2'-sulphonylamino)-benzoic acid in the Sprague-Dawley strain rat, following OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity". Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of 2-(Naphthalene-2'-sulphonylamino)-benzoic acid as a suspension in arachis oil B.P., at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination.  There were no deaths, no signs of systemic toxicity noted during the study nor any abnormalities noted at necropsy. The acute oral median lethal dose (LD50) of 2-(Naphthalene-2'-sulphonylamino)-benzoic acid in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.