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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

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1987
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment

Data source

Reference
Reference Type:
publication
Title:
INDUCTION OF FORESTOMACH LESIONSIN RATS BY ORAL ADMINISTRATIONS OFNATURALLY OCCURRING ANTIOXIDANTSFOR 4 WEEKS
Author:
Hirose M.
Year:
1987
Bibliographic source:
Japanese Journal of Cancer Research 78, 317- 321.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The effects of naturally occurring antioxidants including ferulic acid on rat forestomach epithelium were compared with those of synthetic antioxidants, butylatedhydroxyanisole (BHA) and butylated hydroxytoluene (BHT), of which the former is a known forestomach carcinogen. Groups of five F344 male rats were given diet containing BHA, BHT, gallic acid, syringic acid, sesamol, caffeic acid, chlorogenic acid, ferulic acid, eugenol or esculin for 4 weeks at a level of 0.7% for BHT or 2% for other compounds.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-hydroxy-3-methoxycinnamic acid
EC Number:
214-490-0
EC Name:
4-hydroxy-3-methoxycinnamic acid
Cas Number:
1135-24-6
Molecular formula:
C10H10O4
IUPAC Name:
4-hydroxy-3-methoxycinnamic acid
Test material form:
solid

Test animals

Species:
rat
Strain:
Fischer 344
Details on species / strain selection:
male F344 rats
Sex:
male
Details on test animals or test system and environmental conditions:
6-week-old male F344 rats.

Administration / exposure

Route of administration:
oral: feed
Details on route of administration:
Oriental M powdered basal diet
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The rats had free access to food and water. They were kept in an air-conditionedroom at 22-24°C with a 12 hr-12 hr light-dark cycle.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Each day over a 4 week period.
Frequency of treatment:
The rats had free access to food (2% in diet)
Doses / concentrations
Dose / conc.:
2 000 mg/kg bw/day (nominal)
Remarks:
corresponding to 2% in the diet
No. of animals per sex per dose:
For ferulic acid one Group of five male.
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
The rats were weighed weekly.
The liver was weighed, and buffered formalin solution was injected into the stomach. Then the anterior and posterior walls of the forestomach were each cut into 6 to 7 strips for histological examination.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
The body weights of rats given 2% of ferulic acid were not modified.
Food consumption and compound intake (if feeding study):
not examined
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:
no effects observed
Description (incidence and severity):
no effect on the liver weight.
Gross pathological findings:
no effects observed
Description (incidence and severity):
Ferulic acid did not induce any abnormal lesion of the stomach.
Histological examinations of the forestomach showed no lesions in rats.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Organ observed: forestomach
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
Organ observed: forestomach
Other effects:
not examined

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
2 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: induction of forestomach lesions

Target system / organ toxicity

Critical effects observed:
no

Any other information on results incl. tables

Ferulic acid did not induce any abnormal lesion of the stomach.

Histological examinations of the forestomach showed no lesions in rats treated with 2% ferulic acid.

Applicant's summary and conclusion

Conclusions:
In this study, the induction of forestomach lesions in rats for four weeks by the Ferulic acid was evaluated. The limit dose tested 2000 mg/kg bw/day of Ferulic acid produced no adverse effects.
The NOAEL is therefore determined to be 2000 mg/kg bw/day or higher.
Executive summary:

The effects of naturally occurring antioxidants including ferulic acid on rat forestomach epithelium were compared with those of synthetic antioxidants, butylatedhydroxyanisole (BHA) and butylated hydroxytoluene (BHT), of which the former is a known forestomach carcinogen. Groups of five F344 male rats were given diet containing BHA, BHT, gallic acid, syringic acid, sesamol, caffeic acid, chlorogenic acid, ferulic acid, eugenol or esculin for 4weeks at a level of 0.7% for BHT or 2% for other compounds.

In this study, no effect was observed following an exposure of 4 week of 2% ferulic acid in diet. The NOAEL is therefore determined to be 2000 mg/kg bw/day (corresponding to the2% ferulic acid in diet).