Registration Dossier

Toxicological information

Toxicity to reproduction: other studies

Currently viewing:

Administrative data

toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
other information
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference Type:
Tellurium-Induced Neuropathy: metabolic alternations associated with demyelination and remyelination in rat sciatic nerve
Harry G.J., CoodrumJ.J, Bouldin T.W., Wagner-Recio M., Toews A.D.,and Morell P.
Bibliographic source:
Journal of Neurochemistry 52(3): 938-945

Materials and methods

Principles of method if other than guideline:
- Principle of test: animal model to study myelination/ demyelination of schwann cells
- Short description of test conditions: animals were fed for 7 days with Tellurium containing chow and effects were analyses at different times ranging from 1 to 30 days following initiation of the treatment.
- Parameters analysed / observed:
morphological analysis: ultrastructural alterations of the sciatic nerves
in vitro studies/ biochemical analysis: capacity of the sciatic nerve segments to synthesie lipids (incorporation of radioactive acetate / glycerol ).
GLP compliance:
Type of method:
in vivo

Test material

Specific details on test material used for the study:
Elemental Tellurium powder (60 mesh, 99% pure (alfa Products, Danvers, MA,USA)

Test animals

Details on test animals and environmental conditions:
pre-pubertal animals (17 days) , maintained at constant room temperature of 21 +/-2°C , relative humidity 50 +/- 10% , 12h light/dark

Administration / exposure

Route of administration:
oral: feed
Details on exposure:
start treatment at 20 days of age
Duration of treatment / exposure:
7 consecutive days
Frequency of treatment:
continues free access to supplemented chow
Duration of test:
1 to 30 days
Doses / concentrations
Dose / conc.:
12 500 mg/kg diet
+ minimal amount of corn oil to prevent separation
No. of animals per sex per dose:
male rats from 6 litters (random distribution over treatment / control group)
Control animals:
yes, concurrent vehicle

Results and discussion

Observed effects

Ultrastructural changes were present in myelinating Schwann cells within 1 day of placing rats on the tellurium diet, and demye- hated fibers were numerous by day 5.
Observed metabolic alterations:
- a rapid and massive accumulation of ['4C]acetate-derived radioactivity in squalene (23% of total lipid radioactivity after 1 day of tellurium treat- ment, compared to ~0.5% in controls).
- the marked decrease in overall incorporation of radioactive acetate into lipids during the demyelinating phase of tellurium neuropathy.
- There was a preferential decrease in the incorporation of label into cerebrosides and ethanolamine plas- malogens, lipids which are enriched in myelin.
- a (twofold) increase in reesterification of fatty acids into glycerolipids

Within 30 days of beginning a 7-day exposure to tellurium, remyelination was complete and our assay system no longer detected metabolic alterations in lipid synthesis in nerve.

Applicant's summary and conclusion

From this paper only the relevant information and results, that could have an impact on the reproductive function are included in this summary.
Executive summary:

The tellurium induced observed effect, points to the inhibition of squalene epioxidase activity, an enzyme in the cholesterol synthesis pathway. Cholesterol is a precursor in the steroidogenesis pathway, but is not a rate limiting factor.