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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
repeated dose toxicity: other route
Remarks:
21 days treatment
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system

Data source

Reference
Reference Type:
publication
Title:
The Effect of Antifungal Agents on Pancreatic and Gastric Secretion in Rats
Author:
Yoon-Kee Park, Sungnack Lee, Won Joon Kim, and Sa Suk Hong
Year:
1979
Bibliographic source:
Archives of dermatological research 266.2 (1979): 103-108.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was undertaken to investigate the effect of 5-FC on pancreatic and gastric secretion in rats during long-term administration. For the experiment of pancreatico-biliary secretion 5-FC 100 mg/kg was given orally in a distilled water suspension i.p. for 3 weeks.
Measurement of Pancreatico-Biliary Enzymes
Mixed bile and pancreatic juice was collected for 2 h. Amylase, Lipase and the levels of cholate and bilirubin were determined.
Measurement of Gastric Secretion and Acidity
After 48 h a pyloric ligature was placed under light ether anesthesia. The animals were killed 5 h after pyloric ligation, and the gastric juice was collected. The volume was measured (mL/h/100 g body wt.) and pH of the juice was determined by Titrator TTT2b (Radiometer, Copenhagen). Free and total acid was determined by Titrator TTTzb connected to Autoburette ABO 11 (Radiometer).
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Flucytosine
EC Number:
217-968-7
EC Name:
Flucytosine
Cas Number:
2022-85-7
Molecular formula:
C4H4FN3O
IUPAC Name:
flucytosine
Test material form:
not specified

Test animals

Species:
rat
Strain:
other: hybrid albino
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 180 g
- Fasting period before study: 24 h

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
water
Details on exposure:
5-FC was given i.p. 100 mg/kg bw daily for 3 weeks
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
21 days
Frequency of treatment:
daily
Doses / concentrations
Dose / conc.:
100 mg/kg bw/day (nominal)
No. of animals per sex per dose:
In 25 animals body weight changes were recorded, in 12 animals pancreaticobiliary secretion was measured, in 11 animals gastric secretion was measured
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
BODY WEIGHT: Yes
- Time schedule for examinations: weekly, for 2 weeks

Sacrifice and pathology:
GROSS PATHOLOGY: No
HISTOPATHOLOGY: No
Other examinations:
Measurement of Pancreatico-Biliary Enzymes
Amylase, Lipase and the levels of cholate and bilirubin from pancreatic juice were determined.
Measurement of Gastric Secretion and Acidity
The volume of gastric juice was measured (mL/h/100 g body wt.) and pH was determined by Titrator TTT2b (Radiometer, Copenhagen).

Results and discussion

Results of examinations

Clinical signs:
not examined
Mortality:
not examined
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
The growth rate of rats treated with 5-FC was markedly retarded. This seems to be caused by indigestion and loss of appetite after 5-FC intake.
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:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed

Effect levels

Key result
Dose descriptor:
dose level: 100 mg/kg bw
Effect level:
> 100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
Remarks on result:
other: There was a significant reduction in body weight gain during the first two weeks of treatment

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
In the present study not conducted according to GLP or OECD guidelines male albino rats were administered 100 mg/kg bw, i.p. daily for 3 weeks. Subsequently, the pancreatic and gastric secretions were determined. The test substance revealed no effects on these parameters. However, the body weight was reduced, this effect was considered to be related to loss of appetite and indigestion. Since no mortalities or other adverse effects occurred a NOAEL value could not be established. Due to methodological deficiencies the study cannot be used for classification and labelling according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).