Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary literature

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
14-Day subchronic oral toxicity study in the rat.
Author:
Trimmer, G.W., Phillips, R.D. & Damico, J.S.
Year:
1992
Bibliographic source:
East Millstone, N.J. Unpublished report to the Flavor and Extract Manufacturers Association. Submitted to WHO by the Flavor and Extract Manufacturers Association of the United States, Washington DC, USA. Cited in WHO (2004) WHO Food Additives Series 52.
Reference Type:
review article or handbook
Title:
WHO FOOD ADDITIVES SERIES: 52 - ALIPHATIC AND AROMATIC ETHERS
Author:
WHO JECFA
Year:
2004

Materials and methods

Principles of method if other than guideline:
The study method appears to be based on OECD test guideline 407: Repeated dose 28-day oral toxicity study in rodents, which allows for administration over 14 days under some circumstances. Justification for using a 14-day exposure period should be given, but was not in this short summary from a secondary source.
The principle of the test is to administer the test substance orally on a daily basis in graduated doses to several groups of animals. Animals are then observed and necropsied to determine any possible dose-related toxicity. However, only one tested group was used in this study (10 mg/kg bw/d), so limiting the overall value of the study.
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
None

Test animals

Species:
rat
Strain:
other: Charles River
Sex:
male/female
Details on test animals and environmental conditions:
No data.

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION – No data.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 days.
Frequency of treatment:
Daily (no further information).
Doses / concentrations
Remarks:
Doses / Concentrations:
10 mg/kg bw/d (nominal)
Basis:
no data
No. of animals per sex per dose:
10 (5 male and 5 female).
Control animals:
yes, plain diet
Details on study design:
No data
Positive control:
No positive control.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data.

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule for examinations of morbidity and mortality: no data

BODY WEIGHT: Yes
- Time schedule for examinations: no data

FOOD CONSUMPTION AND COMPOUND INTAKE: - yes, but no further details given.

FOOD EFFICIENCY: - No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: No data

HISTOPATHOLOGY: Yes, liver and kidney only.
Other examinations:
The summary states that body and organ weights were recorded, but there is no information on which organs were examined. Necropsies and histopathological examinations of the kidneys and livers were performed on all animals. Details on lungs and dermal abnormalities were reported, indicating that these organs were also examined.
Statistics:
No data.

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 specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Details on results:
Dermal abnormalities (scabs and sores) observed in control and treated animals were not considered to be treatment-related.
Discolouration of the lungs was noted in two animals from each group (0 and 10mg/kg bw/day), and was attributed to the method of asphyxiation used in the study.

Effect levels

Dose descriptor:
NOEL
Effect level:
10 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: No treatment-related effects on survival, body weight, food consumption, organ weights and histopathology were reported.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No treatment-related effects on survival, body weight, food consumption, organ weights and histopathology were reported. The NOEL is 10 mg/kg bw/day.
Executive summary:

Male and female rats (5/sex) were dosed with veratrole at 10 mg/kg bw/d for 14 days through the feed. No treatment-related effects on survival, body weight, food consumption, organ weights and histopathology were reported. The NOEL is 10 mg/kg bw/day.