Sodium bis[4-hydroxy-3-[(2-hydroxy-1-naphthyl)azo]-N-(3-methoxypropyl)benzenesulphonamidato(2-)]cobaltate(1-)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well performed OECD study with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The initial testing was undertaken to the wrong method and a single animal was dosed at 2000 mg/kg . Two further animals were treated at 2000 mg/kg to complete the ‘group’ of three animals required under the Acute Toxic Class Method.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The initial testing was undertaken to the wrong method and a single animal was dosed at 2000 mg/kg . Two further animals were treated at 2000 mg/kg to complete the ‘group’ of three animals required under the Acute Toxic Class Method.

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:

Sodium bis[4-hydroxy-3-[(2-hydroxy-1-naphthyl)azo]-N-(3-methoxypropyl)benzenesulphonamidato(2-)]cobaltate(1-)

EC Number:

275-959-3

EC Name:

Sodium bis[4-hydroxy-3-[(2-hydroxy-1-naphthyl)azo]-N-(3-methoxypropyl)benzenesulphonamidato(2-)]cobaltate(1-)

Cas Number:

71735-61-0

Molecular formula:

C40H38CoN6O10S2.Na

IUPAC Name:

Cobaltate(1-), bis[4-(hydroxy-kO)-3-[2-[2-(hydroxy-kO)-1-naphthalenyl]diazenyl-kN1]-N-(3-methoxypropyl)benzenesulfonamidato(2-)]-, sodium (1:1)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, 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 5 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 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight of the initially dosed 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 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, 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 12 hours continuous light and 12 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

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females per dose, 2 dose groups

Control animals:

no

Details on study design:

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

Statistics:

None recorded.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% CL not reported

Mortality:

Individual mortality data are given in Table 1.

There were no deaths.

Clinical signs:

other: Individual clinical observations are given in Table 1 Noisy respiration and red/black staining of the snout were noted in one treated animal during the day of dosing and Day 1. There were no signs of systemic toxicity noted in any other treated animal.

Gross pathology:

Individual necropsy findings are given in Table 3.

No abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

Evaluation of Data

Data evaluations included the relationship, if any, between the exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioral and clinical observations, gross lesions, body weight 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 item was made.

Table1     Individual Clinical Observations and Mortality Data

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Female	0	0	0	0	0	0	0F	0F	0F	0	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	0	0	0	0	0F	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	RnSs	RnSs	RnSs	RnSs	RnSsF	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	0	0	0	0	0F	0	0	0	0	0	0	0	0	0	0	0	0	0

 

0=   No signs of systemic toxicity

Rn = Noisy respiration

Ss = Red/black staining of the snout

F =   Red/black staining of feces

Table 2     Individual Body Weights and Body Weight Changes

  

Dose Level mg/kg	Animal Number and Sex	Body Weight (g) at Day			Body Weight Gain (g) During Week
		0	7	14	1	2
2000	1-0 Female	177	184	201	7	17
	2-0 Female	179	202	215	23	13
	2-1 Female	171	185	193	14	8
	3-0 Female	168	179	198	11	19
	3-1 Female	165	187	191	22	4
	3-2 Female	169	183	187	14	4

Table 3     Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	1-0 Female	Killed Day 14	No abnormalities detected
	2-0 Female	Killed Day 14	No abnormalities detected
	2-1 Female	Killed Day 14	No abnormalities detected
	3-0 Female	Killed Day 14	No abnormalities detected
	3-1 Female	Killed Day 14	No abnormalities detected
	3-2 Female	Killed Day 14	No abnormalities detected

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 2500 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

Executive summary:

Introduction

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

  

Methods

A group of three fasted females was treated with the test item at a dose level of 2000 mg/kg body weight. This was followed by a further group of three fasted females at the same dose level. Dosing was performed sequentially.

 

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

  

Results

Mortality. There were no deaths.

 

Clinical Observations. Noisy respiration and red/black staining of the snout were noted in one treated animal during the day of dosing and Day 1. There were no signs of systemic toxicity noted in any other treated animal. Red/black staining of feces was also noted during the observation period.

 

Body Weight. All animals showed expected gains in body weight.

 

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 2500 mg/kg body weight (Globally Harmonized Classification System - Unclassified).