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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
6-(cyclohexylamino)-3-methyl-3H-dibenz[f,ij]isoquinoline-2,7-dione
EC Number:
244-320-0
EC Name:
6-(cyclohexylamino)-3-methyl-3H-dibenz[f,ij]isoquinoline-2,7-dione
Cas Number:
21295-57-8
Molecular formula:
C23H22N2O2
IUPAC Name:
6-(cyclohexylamino)-3-methyl-3H-dibenz[f,ij]isoquinoline-2,7-dione
Test material form:
solid
Details on test material:
Purity: 94.2%

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier Labs SAS, Le Genest St. Isle, 53941 Saint Berthevin Cedex, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 11 weeks
- Weight at study initiation: 230 - 245 g
- Fasting period before study: overnight
- Housing: groups of one to five rats
- Historical data: available
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days prior to start of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 45-65%
- Air changes (per hr): at least 8 per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2020-02-10 To: 2020-02-26

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: stability in vehicle given

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: a severe toxicity which may necessitate humane euthanasia was not expected at 2000 mg/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
1 female for the pre-test
4 females for the main study
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and inspections for morbidity / mortality were performed at least three times within the first six hours after application (i.e., 30 minutes and 1 hour, 2 hours and 4 hours after dosing), thereafter at least once daily for 14 days. Body weights were recorded on Day 0 (prior to dosing), Day 7, and 14.
- Necropsy of survivors performed: yes
Statistics:
not needed

Results and discussion

Preliminary study:
In the sighting test with one female and a single dose of 2000 mg/kg bw
Effect levels
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Hunched posture, stained faeces (dark red), decreased activity, fur stained by test item, piloerection, partially closed eyes, abdominal tension, secretion of Haderian glands, and nervousness were noted in all treated females, starting at about 4 hour after dosing. Until day 2 after dosing the clinical signs dissappeared.
Body weight:
All animals showed expected gains in body weight.
Gross pathology:
Macroscopic examination at study termination on Day 14 revealed red to pink fur, congestion of the genitalia, enlarged heart, slightly blue coloured pharynx, slightly blue coloured front teeth of the lower jaw.
Other findings:
Stained fur was observed throughout the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Executive summary:

The registered substance was tested in a single dose of 2000 mg/kg bw in an acute oral toxicity study in female Wistar rats following OECD TG 420. There were no deaths during the study. As clinical signs hunched posture, stained faeces (dark red), decreased activity, fur stained by test item, piloerection, partially closed eyes, abdominal tension, secretion of Haderian glands, and nervousness were noted in the first two days after dosing. The animal showed expected gains in body weight over the observation period. The acute median lethal oral dose (LD50) to rats of Macrolex Fluoreszenzrot 4B was demonstrated in this study to be greater than 2000 mg/kg body weight.

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