Sodium 3-[[4-amino-9,10-dihydro-3-[2-(2-methoxyethoxy)ethoxy]-9,10-dioxo-1-anthryl]amino]-2,4,6-trimethylbenzenesulphonate

Endpoint summary

Description of key information

Fo1lowing a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material,

as a suspension in distilled water at a dose level of 200 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 were noted during the study. All animals showed expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 200 but less than 2000 mg/kg bodyweight, most probaly >300 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague-Dawley strain rats were supplied by Charles River (UK) Ltd., Manston, Kent, U.K. and Bantin & Kingman Ltd., Grimston, Aldborough, Hull, u.K.
At the start of the main study the males weighed 134 - 185g, and the females 123 - l42g and, were approximately five to eight weeks old. After a minimum acclimatisation period of at least five days the animals were selected at random and given a unique number within the study by indelible ink marking on the tail and a number written on a cage card.
Husbandrv
The animals were housed in groups of five by sex in solid-floor polypropylene cages with sawdust bedding. With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. l, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.
The animal room uJas maintajned at a temperature of 19 - 24"C and relative humidity of 48 - 76%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Route of administration:

oral: gavage

Vehicle:

water

Doses:

10 - 20 - 200 - (2000) mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Deaths and overt signs of toxicity were recorded 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
Individual bodyweights were recorded on the day of treatment (Day 0) and on Days 7 and 14.
At the end of the study the animals were kjlled by cervical dislocation and subjected to gross pathological examination. This consisted of an external examinatjon and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

not required

Preliminary study:

At 2000 mg/kg 1 of 2 animals died
Isotated incidents of systemic toxicity noted were hunched posture and lethargy during the range finding study (2000 mg/kg bw).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured at doses of 10 to 200 mg/kg bw.

Clinical signs:

other: No s'igns of systemic toxicity were noted during the main study (10 - 200 mg/kg bw)

Gross pathology:

no effects

Other findings:

none

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Cat 4 was chosen as there were no effects at all at 200 mg/kg and only at 2000 mg/kg bw 1 of 2 animals died. The LD 50 was esteimated to be > 300 mg/kg bw.

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 200 mg/kg bodyweight but less than 2000 mglkg bodyweight

Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley stra'in rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity" referenced as Method Bl in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67 /548/EEC) .

Fo1lowing a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material, as a suspension in distilled water at a dose level of 200 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 were noted during the study.

All animals showed expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 200 mg/kg bw but less than 2000 mglkg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

reliable with restrictions

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Category 4

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 200 but less than 2000 mg/kg bodyweight, most probaly >300 mg/kg bw.