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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

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

Data source

Reference
Reference Type:
publication
Title:
Tellurium-Induced Neuropathy: metabolic alternations associated with demyelination and remyelination in rat sciatic nerve
Author:
Harry G.J., CoodrumJ.J, Bouldin T.W., Wagner-Recio M., Toews A.D.,and Morell P.
Year:
1989
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:
no
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

Species:
rat
Strain:
Long-Evans
Sex:
male
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
Remarks:
+ 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

Conclusions:
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.