Registration Dossier

Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
review article or handbook
Title:
Chronic toxicity/carcionogenicity study of trans-anethole in rats
Author:
R. Truhaut, B. Le Bourhis, M. Attia, R. Glomot, J. Newman and J. Caldwell
Year:
1989
Bibliographic source:
Fd Chem. Toxic. Vol. 27, No. 1, pp. 11-20, 1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, F-76410 St Aubin-les-Elbeuf France
- Age at study initiation: 28 day-old
- Weight at study initiation: 50-80 g
- Housing: The animals were randomly assigned in pairs of the same sex to plastic cages with sawdust bedding.
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2ºC
- Humidity (%): 60 +/- 20%
- Air changes (per hr): 10-16 changes/hr
- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
no data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
117-121 weeks
Post exposure period:
4 wk
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0%
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0.25%
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0.5%
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
1%
Basis:
nominal conc.
No. of animals per sex per dose:
Six dose groups: 0% (52 male, 52 female, control 1), 0% (52 male, 52 female, control 2), 0.25% (78 male, 78 female), 0.5% (52 male, 52 female) and 1.0% (52 male, 52 female)
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: The dose were selected on the basis of previous data, which demostrate that, in rats, the 2% level in the diet induces a reduction in bodey weight in males and females and that the 1% level induces this effect only in males.
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
BODY WEIGHT: Yes
- Time schedule for examinations: weekly for the first 26 wk and monthly thereafter.

FOOD/WATER CONSUMPTION AND COMPOUND INTAKE:
Food and water consumption was recorded daily for the first 32 wk and then 1 day/month for wk 34-117. The trans-anethole intake of the rats (mg/kg body weight/day) was calculated monthly from their food consumption and mean body weight.
Sacrifice and pathology:
Rats showing signs of severe debility were isolated and killed if moribund. Rats that died during the study were necropsied and tissues from all organs were preserved for histological examination. At wk 117, only 20% of the animals in the 1% female group remained and it was decided to terminate the study. Final examination took 4 wk and the animals received their assigned food until they were killed. The rats were deprived of food (but not water) overnight and killed by decapitation. They were exsanguinated and the blood was examined (erythrocyte count, haemoglobin concentration, mean corpuscular volume, haematocrit value, mean corpuscular haemoglobin concentration, leucocyte count, differential blood count).

Gross findings were recorded and the following organs of each surviving animal were weighed: brain, caecum, heart, kidneys, liver, ovaries, spleen and testes. Samples of these organs and of the adrenals, abdominal aorta, aortic arch, bone marrow, bone sternum, bone femur, colon, costochondral junction, duodenum, eyes, ileum, jejunum, larynx, lungs with bronchia, lymph nodes, lymph cervical, lymph mes- enteric, mammary gland, pituitary, prostate, rectum, salivary glands, sciatic nerve, seminal vesicles, skele- tal muscle, skin, spinal cord, stomach (glandular and non-glandular), thymus, thyroids (with para- thyroids), trachea, urinary bladder, uterus, vagina and all macroscopic abnormal tissues detected post rnortem were examined. All organs and tissues were placed in fixative, prepared in paraffin wax blocks, sectioned (5u) and stained with Masson's trichrome.
Other examinations:
no data
Statistics:
Using Student's t-test the treated groups and the second control group were compared with the first control group in terms of body weight, food consumption, haematological parameters and organ weights.
Differences in the mortality rate between groups were examined using the log rank test of Kalbfleisch & Prentice (1980) at a confidence level of 5%.
For statistical analysis of the incidence of lesions, the two control groups were considered as one group. Inter-group differences were examined with a chi-square test, and for trends with dose and comparisons with the control groups, one-tailed chi- squared test was used where relevant.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
transient retardation of body-weight gain
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
No apparent reactions to treatment were noted. Only the animals that died or were killed when moribund showed clinical signs, such as decreased body weight, anorexia and lethargy.
Relevance of carcinogenic effects / potential:
None

Applicant's summary and conclusion

Conclusions:
Transient retardation of body-weight gain