lithium hydrogen 7-{(E)-[2-amino-4-(2-naphthyl)-1,3-thiazol-5-yl]diazenyl}naphthalene-1,3,5-trisulfonate (2:1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-02-25 to 2014-03-20

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:

2014

Report date:

2014

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 (Acute Toxicity (Oral))

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:

lithium hydrogen 7-{(E)-[2-amino-4-(2-naphthyl)-1,3-thiazol-5-yl]diazenyl}naphthalene-1,3,5-trisulfonate (2:1:1)

EC Number:

940-433-0

Molecular formula:

C23H14Li2N4O9S4

IUPAC Name:

lithium hydrogen 7-{(E)-[2-amino-4-(2-naphthyl)-1,3-thiazol-5-yl]diazenyl}naphthalene-1,3,5-trisulfonate (2:1:1)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

other: Wistar (RccHan:WIST)

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 females were nulliparous and non-pregnant. After an acclimatization 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 body weight variation did not exceed ±20% of the body weight of the initially dosed animal.

The animals were housed in groups of up to 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 analyzed 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. 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

Details on oral exposure:

For the purpose of the study the test item was freshly prepared, as required, as a solution in distilled water.

The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP.

Using available information on the toxicity of the test item, 2000 mg/kg 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
2000 / 200 / 10 / 3
2000 / 200 / 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 body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.

Doses:

2000 mg/kg

No. of animals per sex per dose:

2 groups of 3 rats

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 body weights 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:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths

Clinical signs:

Red/brown staining around the mouth was noted in one animal thirty minutes and one hour after dosing.

No signs of systemic toxicity were noted in five animals during the observation period.

Red colored staining on the tail was commonly noted in one animal.

Red colored staining of the bedding and environmental enrichment items was noted in the cage of all group 2 animals two and three days after dosing.

Body weight:

All animals showed expected gains in body weight over the observation period.

Gross pathology:

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 item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

This study was designed to be compatible with the procedures indicated by the following internationally accepted guidelines and recommendations:

·     OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001)

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

Results & Conclusions

There were no deaths during the study. Red/brown staining around the mouth was noted in one animal thirty minutes and one hour after dosing.  No signs of systemic toxicity were noted in five animals during the observation period. Red colored staining on the tail was commonly noted in one animal.Red colored staining of the bedding and environmental enrichment items was noted in the cage of all group 2 animals two and three days after dosing.

All animals showed expected gains in body weight over the observation period.

 

No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD₅₀) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

 

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.