Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: other route
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The vehicle tested was toxic, and Ethyl vanillin was not tested in an other non-toxic vehicle.

Data source

Reference
Reference Type:
publication
Title:
Test for carcinogenicity of food additives and chemotherapeutic agents by the pulmonary tumor response in strain A mice.
Author:
Stoner GD, Shimkin MB, Kniazeff AJ, Weisburger JH, Weisburger EK and Go GB
Year:
1973
Bibliographic source:
Cancer Research, 33(12), 3069-3085

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
repeated chronic study by i.p. route in mice.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
lot/batch No: Lot QM-16
Supplier: Mosanto, St Louis, Mo.

Test animals

Species:
mouse
Strain:
other: A/He
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Institute for Cancer Research, Philadelphia or National Cancer Institute
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: 18 to 20 g
- Fasting period before study: no data
- Housing: 5 per plastic boxes
- Diet (e.g. ad libitum): Purina laboratory chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: impure tricaprylin
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: with sterile technique, Ethyl vanillin was injected by i.p.route as 0.1 ml/dose of solutions in tricaprylin that was purchased from Eastman.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
8 weeks
Frequency of treatment:
3 times weekly
Doses / concentrations
Remarks:
Doses / Concentrations:
350 and 1800 mg/kg
No. of animals per sex per dose:
20 females
Control animals:
other: 1 control with no treatment, and 1 control with vehicle
Details on study design:
Post-exposure period: 24 weeks after first injection
Dose selection rationale: for each chemical under test, a MTD was determined. Serial 2-fold dilutions of the chemical were injected into groups of 5
mice. The MTD for that chemical was the maximum single dose that all 5 mice tolerated after receiving 6 i.p. injections over a 2-week period. For
evidence of delayed toxicity, particularly as occured with the chemotherapeutic compounds, animals receiving 6 doses of the MTD were held for 1 to 2 months before experimental groups were initiated.

Examinations

Observations and examinations performed and frequency:
no data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
no data
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
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:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
At 1800 mg/kgthere were 10/20 survivors. 1 mouse had lung tumor.
At 350 mg/kg, there were 12/20 survivors, and no mice had lung tumor.
It was described that the vehicle tricaprylin batch 2097 was toxic, so we can suppose that the mortality is due to this vehicle.

Effect levels

Dose descriptor:
NOAEL
Sex:
female
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion