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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Peer reviewed data

Data source

Reference
Reference Type:
review article or handbook
Title:
Food Flavouring amd Compounds of Related Structure II. Subacute and Chronic toxicity
Author:
E.C. Hagan. W.H. Hansen, O.G. Fitzhugh, P.M. Jenner, W.I. Jones, Jean M. Taylor, Eleanor L. Long, A.A. Nelson and J.B. Brouwer
Year:
1967
Bibliographic source:
Fd Cosmet. Toxicol. Vol. 5, pp. 141-157. Pergamon Press 1967

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 452 (Chronic Toxicity Studies)
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
16 weeks
Frequency of treatment:
animals had unlimited access to food
Doses / concentrations
Remarks:
Doses / Concentrations:
10000 ppm
Basis:
actual ingested
No. of animals per sex per dose:
10
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes. food at all times

FOOD EFFICIENCY: no data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes, water at all times

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes, white cell counts, red cell counts, haemoglobins and haemotocrits were measured at the end of the experiment

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data

ORGAN WEIGHTS: yes: lives, kidneys, spleen heart, and testes

GROSS PATHOLOGY: no data

HISTOPATHOLOGY: non-neoplastic: Liver

HISTOPATHOLOGY: neoplastic: no effects

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Liver: microscopic- slight hydropic changes of hepatic cells in males only
Mortality:
mortality observed, treatment-related
Description (incidence):
Liver: microscopic- slight hydropic changes of hepatic cells in males only
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
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:
effects observed, treatment-related
Description (incidence and severity):
Liver: microscopic- slight hydropic changes of hepatic cells in males only
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 10 000 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: Liver: microscopic- slight hydropic changes of hepatic cells in males only

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Slight hydropic changes of hepatic cells in males only