Nickel, 5-[2-(2-hydroxy-3,7-disulfo-1-naphthalenyl)diazenyl]-1H-1,2,4-triazole-3-carboxylate sodium complexes

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 2002-04-24 and 2002-5-13. Report signed off 2002-12-23.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets the criteria for classification as Reliable without restriction according to Klimisch et al (1997)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

443-510-2

EC Name:

-

Cas Number:

738587-10-5

Molecular formula:

C26H14N10Ni2O18S4 as free acid

IUPAC Name:

dinickel(2+) sodium 3-carboxy-5-[(1E)-2-(7-oxido-2,6-disulfonaphthalen-1-yl)diazen-1-yl]-1H-1,2,4-triazol-1-ide 3-carboxy-5-[(1E)-2-(7-oxido-2-sulfo-6-sulfonatonaphthalen-1-yl)diazen-1-yl]-1H-1,2,4-triazol-1-ide

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Animals and Animal Husbandry

Female Sprague Dawley CD (Crl: CD (SD) IGS BR) strain rats were supplied by a reputable supplier . 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 (Certified Rat and Mouse Diet 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

Remarks:

(Distilled water)

Details on oral exposure:

The test substance was administered orally as a solution in distilled water at a dose level of 2000 mg/kg bodyweight. In the absence of data suggesting the test substance was toxic 2000 mg/kg was chosen at the starting dose. All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calcuated according to the fasted bodyweight at the time of dosing.

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

An initial 3 females at 2000 mg/kg followed by a further group of 3 females at 2000 mg/kg. Sufficient time was allowed between each group being dosed to confirm the survival of the previously dosed animals.

Control animals:

no

Details on study design:

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.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

Female: 2000 mg/kg bw; Number of animals: 6; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: Dark red-coloured staining of the urine was noted in all animals during the study. All animals appeared normal two or four days after dosing.

Gross pathology:

Effects on organs:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight (Global Harmonised Classification System - not classified).

The test substance does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC.

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test substance following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the needs of the following guideline:

OECD Guidelines for the Testing of Chemicals No. 423 'Acute Oral Toxicity - Acute Toxic Class Method' (adapted 17 December 2001).

Method

A group of 3 fasted females were treated with the test substance at a dose level of 2000 mg/kg bodyweight. This was followed by a further group of 3 fasted females at the same dose level. The test item was administered orally as a solution in distilled water. Clinical signs and bodyweight were monitored during the study. All animals were subject to gross necropsy.

Results

Mortality - There were no deaths

Clinical observations - Dark red-coloured staining of the urine was noted in all animals during the study. All animals appeared normal two or four days after dosing.

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

Necropsy - No abnormalities noted.

Conclusion

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight (Global Harmonised Classification System - not classified).

The test substance does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances.