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Acute Toxicity: oral

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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

Constituent 1
Chemical structure
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-[[(4-methoxyphenyl)methylhydrazono]methyl]-1,3,3-trimethyl-3H-indolium methyl sulphate
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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
>= 300 - <= 400 mg/kg bw
Based on:
test mat.
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:
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 increased diuresis. After the first day the animals recovered and showed no adverse signs of toxicity anymore. Animals from the low dose showed no signs of toxicity.
Body weight:
No effects on the body weight were noted.
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. 

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