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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Chronic toxicity of dicyclopentadienyliron (ferrocene) in dogs
Author:
R.A. Yeary
Year:
1969
Bibliographic source:
Toxicol Appl Pharmacol. Nov;15(3):666-76.

Materials and methods

Principles of method if other than guideline:
No exact method guidelines given in publication, but a chronic oral study on dogs is described.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Ferrocene
EC Number:
203-039-3
EC Name:
Ferrocene
Cas Number:
102-54-5
Molecular formula:
C10H10Fe
IUPAC Name:
iron(2+) dicyclopenta-2,4-dienide

Test animals

Species:
dog
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
oral: capsule
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
dogs were administered ferrocene in gelatin capsules once each day at 30, 100, 300, and 1000 mg/kg. Controls were given empty gelatin capsules
Duration of treatment / exposure:
180 days
Frequency of treatment:
Daily
Control animals:
yes, concurrent no treatment

Examinations

Sacrifice and pathology:
Animals were sacrificed at 12 and 24 weeks or observed for 1 year or 26 months after the 12 week treatment period.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
there were no deaths
Mortality:
no mortality observed
Description (incidence):
there were no deaths

Effect levels

Key result
Dose descriptor:
LOAEL
Effect level:
30 mg/kg bw/day (actual dose received)
Basis for effect level:
other: Hemosiderosis was observed

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Hemosiderosis was observed at 30, 100, and 300 mg/kg ferrocene at 6 months and 1000 mg/kg at 3 months. There was a dose related accumulation of iron.

There was a reversible decrease in hemoglobin, packed cell volume, and erythrocyte counts with greatest change occurring during the first 4 weeks at doses of 300 mg/kg. Cirrhosis was seen with 1000 and 300 mg/kg ferrocene, and testicular hypoplasia occurred with 300 and 100 mg/kg ferrocene.

Dogs observed for 12 to 26 months after the 6 month treatment period showed no latent effects from massive iron overload. The ferrocene induced hepatic iron overload was reduced by repeated venesection and removal of large quantities of iron. This resulted in mobilization of the storage iron for hemoglobin synthesis.

All other parameters were normal

Applicant's summary and conclusion

Executive summary:

Mongrel-dogs were administered ferrocene in gelatin capsules once each day at 30, 100, 300, and 1000 mg/kg. Controls were given empty gelatin capsules.

Animals were sacrificed at 12 and 24 weeks or observed for 1 year or 26 months after the 6 month treatment period.

Liver biopsies were taken from ferrocene treated dogs (10th month) and from dogs used in the ferrous reversibility study. At necropsy, all tissues were examined grossly and later histologically. Blood and urine samples were collected at intervals and measured for hematologic and biochemical parameters including iron absorption and storage. There were no deaths.

Hemosiderosis was observed at 30, 100, and 300 mg/kg ferrocene at 6 months and 1000 mg/kg at 3 months. There was a dose related accumulation of iron. There was a reversible decrease in hemoglobin, packed cell volume, and erythrocyte counts with greatest change occurring during the first 4 weeks at doses of 300 mg/kg. Cirrhosis was seen with 300 and 1000 mg/kg ferrocene, and testicular hypoplasia occurred with 100 and 300 mg/kg ferrocene or 150 and 500 mg/kg ferrous-sulfate at 6 months.

Dogs observed for 12 to 26 months after the 6 month treatment period showed no latent effects from massive iron overload. The ferrocene induced hepatic iron overload was reduced by repeated venesection and removal of large quantities of iron. This resulted in mobilization of the storage iron for hemoglobin synthesis.

All other parameters were normal.