6-(cyclohexylamino)-3-methyl-3H-dibenz[f,ij]isoquinoline-2,7-dione

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

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

Test material information

Constituent 1

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:

10-(cyclohexylamino)-14-methyl-14-azatetracyclo[7.7.1.0²,⁷.0¹³,¹⁷]heptadeca-1(16),2,4,6,9,11,13(17)-heptaene-8,15-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:

other: 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 aft

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.