2-[[(4-methoxyphenyl)methylhydrazono]methyl]-1,3,3-trimethyl-3H-indolium methyl sulphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-08-15 to 1989-11-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

; adopted 1987-02-24

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-[[(4-methoxyphenyl)methylhydrazono]methyl]-1,3,3-trimethyl-3H-indolium methyl sulphate

EC Number:

258-946-7

EC Name:

2-[[(4-methoxyphenyl)methylhydrazono]methyl]-1,3,3-trimethyl-3H-indolium methyl sulphate

Cas Number:

54060-92-3

Molecular formula:

C20H24N3O.CH3O4S C21H27N3O5S

IUPAC Name:

2‐{[2‐(4‐methoxyphenyl)‐2‐methylhydrazin‐1‐ylidene]methyl}‐1,3,3‐trimethyl‐3H‐indol‐1‐ium methyl sulfate

Details on test material:

- Name of test material (as cited in study report): ASTRAZON Goldgelb GLN trocken

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adults
- Weight at study initiation: males: 198 g; females: 176 g (females)
- Fasting period before study: 16 hours before and 4 hours after application
- Housing: 5 animals per macrolon cage type III
- Diet (e.g. ad libitum): pellets of Altromin R 1234, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

RATIONALE FOR SELECTION OF DOSES:
The doses chosen in this experiment were based on preliminary data.

Doses:

100, 200, 300 and 400 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observations: at least twice a day (weekends once a day)
- Frequency of weighing: before application, after one week and after 14 days.
- Necropsy of survivors performed: yes, all animals

Statistics:

If a calculation of the mean (median) LD50 was possible, the calcuation was conducted after the method of "moving averages" by Spärman and Kärber.

Results and discussion

Preliminary study:

N.A.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

>= 300 - <= 400 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 200 - <= 300 mg/kg bw

Based on:

test mat.

Mortality:

All animals in the 400 mg/kg bw dose groups died within 2-4 hours after treatment. Four females and one male died in the 300 mg/kg bw dose group within 24 hours. For further details please see Table 1 in section "any other information on results incl. tables"

Clinical signs:

other: In the dose groups 200 to 400 mg/kg bw the following signs of toxicity were observed: poor general condition and prone position. Piloerection was noted in the dose groups 200 and 300 mg/kg bw for both sexes. Males of the dose group 200 mg/kg bw showed an

Gross pathology:

The intestines of animals died (dose groups 200-400 mg/kg bw) during the study were bloated. The liver of these animals were coloured black and the lungs were reddened. All animals of the dose groups 100-300 mg/kg bw examined at the end of the study were macroscopically unobtrusive.

Other findings:

N.A.

Any other information on results incl. tables

Table 1: Mortality
Dosis         (mg/kg bw)	Animals died	time of death	mortality (%)
males
100	0/5	-	0
200	0/5	-	0
300	1/5	4h	20
400	5/5	2-4h	100
females
100	0/5	-	0
200	1/5	4h	20
300	4/5	2h -1d	80
400	5/5	2h	100

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, in an acute oral toxicity study, the LD50 was determined to be 300-400 mg/kg bw for male and 200-300 mg/kg bw for female Wistar rats.

Executive summary:

In an acute oral toxicity study (OECD 401), groups of young adult Wistar rats (5/sex) were given a single oral dose of the test item in water at doses of 100, 200, 300 and 400 mg/kg bw and were observed for14 days. The oral LD50 (males) was determined to be between 300-400 mg/kg bw and the LD50 (females) was determined to be between 200 -300 mg/kg bw.