Sodium p-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzenesulphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 06 December 2012 and 03 January 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

No analysis was carried out to determine the homogeneity, concentration or stability of the test item formulation. This exception is considered not to affect the purpose or integrity of the study.

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium p-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzenesulphonate

EC Number:

223-989-2

EC Name:

Sodium p-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzenesulphonate

Cas Number:

4156-21-2

Molecular formula:

C9H6Cl2N4O3S.Na

IUPAC Name:

sodium 4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzenesulfonate

Test material form:

semi-solid (amorphous): gel

Remarks:

migrated information: paste

Details on test material:

Sponsor's identification: Sodium p-[(4,6-dichloro- 1,3,5-triazin-2-yl)amino]benzenesulphonate
Description : white paste
Batch number : ITA0056831
Purity : 49%
Date received : 11 April 2012
Expiry date : 21 July 2013
Storage conditions: approximately 4C in the dark
The integrity of supplied data relating to the identity, purity and stability of the test item is the responsibility of the Sponsor.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The animals were nulliparous and non pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group.
The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe.

Doses:

613 mg/kg (equivalent to 300 mg active ingredient/kg bodyweight)
4082 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight)

No. of animals per sex per dose:

3 females @ 613 mg/kg
6 females @ 4082 mg/kg

Control animals:

no

Details on study design:

In the absence of data regarding the toxicity of the test item, 613 mg/kg (equivalent to 300 mg active ingredient/kg bodyweight) was chosen as the starting dose.
Groups of fasted animals were treated as follows:
Dose Level(mg/kg) Concentration(mg/ml) Dose Volume(ml/kg) Number of Rats (Female)
613* 61.3 10 3
4082^ 408.2 10 3
4082^ 408.2 10 3
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 the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals.
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

* = Equivalent to 300 mg active ingredient/kg bodyweight
^ = Equivalent to 2000 mg active ingredient/kg bodyweight

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: 95% CL not reported

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 4082 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight) (Globally Harmonised Classification System - Unclassified).

Executive summary:

Introduction.The study was performed to assess the acute oral toxicity of the test item following a single oral administration in the Wistar strain rat. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No. 423 "Acute Oral Toxicity - ACute Toxic Class Mthod" (adopted 17 December 2001)

Method B1 tris Acute Toxicity (Oral) of Commision Regulation (EC) No. 440/2008

Method. A group of three fasted females was treated with the test item at a dose level of613 mg/kg bodyweight (equivalent to 300 mg active ingredient/kg bodyweight). Based on the results from this dose level further groups of fasted females were treated at a dos level of4082 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight). Dosing was performed sequentially.

The test item was administered orally as asuspensionindistilled water. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Bodyweight. All animals showed expected gains in bodyweight over the study period.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute oral median lethal dose (LD₅₀) of the test item in the female Wistar strain rat was estimated to be greater than 4082 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight) (Globally Harmonised Classification System ‑ Unclassified).