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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from peer-reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Food Flavourings and Compounds of Related Structure.II. Subacute and Chronic Toxicity
Author:
E. C. HAGAN et al
Year:
1967
Bibliographic source:
Food and cosmetics toxicology

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as below
Principles of method if other than guideline:
Subacute repeated toxicity study of test substance orally in rats
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl formate
EC Number:
203-721-0
EC Name:
Ethyl formate
Cas Number:
109-94-4
Molecular formula:
C3H6O2
IUPAC Name:
ethyl formate

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data available
- Age at study initiation: No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Housed individually in wire cages.
- Diet (e.g. ad libitum): food ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period:No data available

ENVIRONMENTAL CONDITIONS
No data available

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: Diet
Details on oral exposure:
Details on oral exposure
PREPARATION OF DOSING SOLUTIONS: Fresh diets were made by mixing test substance.

DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Rat diet were used
- Concentration in vehicle: 0, 1000, 2500 and 10,000 ppm
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
17 weeks
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 other: mg/kg-bw/day
Remarks:
0 ppm
Dose / conc.:
50 other: mg/kg-bw/day
Remarks:
1000 ppm
Dose / conc.:
125 other: mg/kg-bw/day
Remarks:
2500 ppm
Dose / conc.:
500 other: mg/kg-bw/day
Remarks:
10000 ppm
No. of animals per sex per dose:
Total: 80
0 ppm: 10 male and 10 female
50 ppm: 10 male and 10 female
125 ppm: 10 male and 10 female
500 ppm: 10 male and 10 female
Control animals:
yes, concurrent vehicle
Details on study design:
Details on study design
- Dose selection rationale: No data available
- Rationale for animal assignment (if not random): Animals were randomized by weight (every level having animals of equal weight).
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available

Examinations

Observations and examinations performed and frequency:
Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included: Mortality was observed.

DETAILED CLINICAL OBSERVATIONS: Yes
–Time schedule: Weekly

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available.

FOOD EFFICIENCY:
No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available

OPHTHALMOSCOPIC EXAMINATION: No data available

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At termination.
- Anaesthetic used for blood collection: No data available.
- Animals fasted: No data available.
- How many animals: No data available.
- Parameters checked in table [No.?] were examined: White cell counts, red cell counts, hemoglobin and haematocrits were examined.

CLINICAL CHEMISTRY: No data available

URINALYSIS: No data available

NEUROBEHAVIOURAL EXAMINATION: No data available

OTHER:
Organ weight: Yes

Organs weighted:
Liver, kidneys, spleen, heart and testes were weighed.
Sacrifice and pathology:
Sacrifice and pathology
GROSS PATHOLOGY: Yes, Necropsied with the process of exsanguinean.

Abnormalities, gross changes and the suspected reason for death were noted.

HISTOPATHOLOGY: Yes,
Organs were preserved in 10% buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin.

A detailed microscopic examination in the study was done on 6 or 8 rats, evenly divided by sex, from the high dose group and the control group. If changes attributable to the test compound were found in the high dose group, additional animals on lower dosage levels were examined as indicated. So microscopic examination was not performed for 1000 and 2500 ppm dose level.

Organs examined: Liver, kidneys, spleen, heart, testes, and thoracic viscera, one hind leg, for bone, bone marrow and muscle were examined.
Other examinations:
No data available
Statistics:
No data available

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No effect were observed on growth of treated rat as compared to control.
Mortality:
no mortality observed
Description (incidence):
No effect on survival were observed in treated rat as compared to control.
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
No effect were observed on hematological parameters of treated rat as compared to control.
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No gross pathological abnormalities were observed in treated rat as compared to control.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No microscopic changes in the tissues were observed in treated rat as compared to control.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Pathological changes attributable to disease or age have not been included.

Effect levels

Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical signs
gross pathology
haematology
histopathology: non-neoplastic
mortality
Remarks on result:
other: No effect observed

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 500 mg/kg body weight/day when Osborne-Mendel male and female rats treated with tes substance for 17 week by oral feed.
Executive summary:

In a Chronic repeated dose oral toxicity study, Osborne-Mendel male and female rats treated with test substance in the concentrations of50, 125 and 500mg/kg bw orally in diet. The animals were observed for clinical sign, body weight, food consumption, Hematology, gross and Histopathology. Results show that no effect was observed on survival and growth of all the treated rats. Similarly, no effect was observed on hematological parameters of treated rat as compared to control. In addition, No gross pathological abnormalities and microscopic changes in the tissues were observed in all treated rat as compared to control. Therefore, NOAEL was considered to be 500 mg/kg body weight/day when Osborne-Mendel male and female rats treated with test substance for 17 weeks by oral feed.