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Diss Factsheets

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

Constituent 1
Chemical structure
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.