Alcohols, C12-14

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

other: published data

Adequacy of study:

supporting study

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:

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

Year:

1979

Bibliographic source:

Invest. Urology 17(3):176-180

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Type: other: Effects on the rat prostate

GLP compliance:

not specified

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Docosan-1-ol

EC Number:

211-546-6

EC Name:

Docosan-1-ol

Cas Number:

661-19-8

IUPAC Name:

docosan-1-ol

Details on test material:

EC# : 211-546-6 CAS# : 661-19-8 Substance Name : docosan-1-ol Molecular Formula : C22H46O

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Duration of test:

Duration of test: 28 days

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 10, 100 mg/kg
Basis:

Control animals:

yes, concurrent vehicle

Details on study design:

Duration of test: 28 days

Results and discussion

Effect levels

Dose descriptor:

NOAEC

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: 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.

Remarks on result:

not determinable

Remarks:

no NOAEC identified

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.
Docosanol is closely related to the registered substance, Alcohols, C16-18, and it is considered that read-across is valid.