Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
No information
Author:
HSDB
Year:
2004
Bibliographic source:
HSDB Hazardous Substances Data Bank, 2004 on line
Reference Type:
review article or handbook
Title:
Direct and indirect effects of docosanol (IK.2), the active principle in Tadenan, on the rat prostate
Author:
Muentzing J et al.
Bibliographic source:
Invest. Urology 17(3):176-180

Materials and methods

Principles of method if other than guideline:
Type: other: Effects on the rat prostate
Method: other
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
28 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
1, 10, 100 mg/kg
Basis:

Control animals:
yes, concurrent vehicle
Details on study design:
Duration of test: 29 days

Results and discussion

Any other information on results incl. tables

Docosanol administered by gavage to rats aged 6-7 months for 28 days did  not affect bodyweight or the weights of any of the organs weighed other  than a statistically significant increase in weight of the seminal  vesicles at the lower dose levels (1 and 10 mg/kg/day). There were no  histological differences in the accessory sexual organs.

The concentration of radioactive zinc was decreased at 1 and 10 mg/kg in  the dorsolateral prostate and increased in muscle at 10 and 100 mg/kg. At  100 mg/kg RNA concentration of the ventral prostate was increased but RNA  content remained unchanged.  The DNA content and concentration was also  unchanged, the quotient between the conentrations of RNA and DNA was  increased at 100 mg/kg. Protein concentration was unchanged. Plasma LH  was increased at 100 mg/kg while FSH and prolactin were unaffected.

In the older rats the weight of the dorsal prostate was decreased to 85%  of the weight of controls by 1 mg/kg and the weight of the seminal  vesicles increase to 125%  at 10 mg/kg. Spleen weight was decreased to  80% by 1 and 100 mg/kg docosanol.  The quotient between RNA and DNA  concentration was increased (130%) in the ventral prostate at 100 mg/kg.  There were no histopathological changes in the organs examined. Plasma  testosterone was reduced at 100 mg/kg and prolactin cncentration at 1 or  10 mg/kg.

Orchidectomy resulted in a significant increase in weight of prostate,  seminal vesicles and adrenals at 100 mg/kg docosanol but not at lower  dose levels. The concentration of radioactive zinc was reduced in the  dorsolateral prostate at 10 or 100 mg/kg.

Docosanol did not increase the prostrate weight in rats which had been  both orchidectomised and adrenalectomised suggesting a role for the  adrenals in stimulating the prostrate.

Studies in young rats suggested a thymolytic effec as 100 mg/kg docosanol  reduced the weith of both thymus and splenn in intact animals.

Applicant's summary and conclusion

Conclusions:
Docosanol had no effect on the weight or histology of the prostate in intact rats but increased the RNA/DNA quotient in the ventral prostate. Plasma LH and testosterone were reduced. In orchidectomised rats docosanol increased the prostate and adrenal weight but there was no increase in orchidectomised adn adrenalectomised rats, a weight reduction being observed. Also docosanol had a thymolytic effect in intact rats but not in adrenalectomised rats where the thymus weight was increased. These results suggest a stimulation of adrenal steroid secretion but this may not be the only effect of docosanol.

This study was reported in the Hazardous Substances Data Bank, 2004