2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

1970

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: early study, limited design and reporting, no Guideline or GLP; poor documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1970

Report date:

1970

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

reduced dose groups, reduced parameters

GLP compliance:

no

Remarks:

pre-dates GLP regulation

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione

EC Number:

248-702-8

EC Name:

2-octadecyl-1H-thioxantheno[2,1,9-def]isoquinoline-1,3(2H)-dione

Cas Number:

27870-92-4

Molecular formula:

C36H45NO2S

IUPAC Name:

14-octadecyl-8-thia-14-azapentacyclo[10.6.2.0²,⁷.0⁹,¹⁹.0¹⁶,²⁰]icosa-1(19),2,4,6,9,11,16(20),17-octaene-13,15-dione

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation:m: 112 -167g; f: 104-134 g

- Housing: groups of 5 per sex
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 25
- Humidity (%): 35 - 60

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency):once
- Mixing appropriate amounts with (Type of food): Altromin R powder
- Storage temperature of food: no data

VEHICLE
-none

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

30days

Frequency of treatment:

via feed

Doses / concentrations

Remarks:

Doses / Concentrations:
0 - 1 - 5 %
Basis:
nominal in diet

No. of animals per sex per dose:

10

Control animals:

yes, plain diet

Positive control:

none

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: once per week


HAEMATOLOGY: Yes
- Time schedule for collection of blood: before and at the end of treatment
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all
- Parameters: Hb, Number of red cells, white cells, differential cell count, Heinzbodies

URINALYSIS: Yes
- Time schedule for collection of urine: before and at the end of treatment
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters examined: Color, protein, glucose, bilirubin, specific gravity, sediment

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

yellow discoloration of fatty tissue and liver

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

LOAEL

Effect level:

>= 50 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects, no analytic confirmation of concentrations

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Repeated oral administration of the test item to rats over 30 days via food at a maximal concentration of 50000 ppm, did not produce any adverse effects.

Executive summary:

The test item was administered to wistr rats for 30 days via food at concentrations of 0, 1, or 5 % (w/w).

All animals behaved completely normal throughout the treatment. Clinical symptom were not detected. Food consumption was not affected. Body weight gain of treated rats was comparable to that of control animals. Hematology as well as urinalysis did not reveal pathologic differences. No adverse effect were detected during necropsy and histopathology.

The NOAEL was greater than 5% of the test item in diet.