Ferrocene

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

absorption

distribution

Principles of method if other than guideline:

In a peer reviewed study groups of male and female Fischer 344 rats were exposed (nose-only) to ferrocene vapour labelled with 59Fe and tritium.
The exposure duration was 17 minutes and the average ferrocene concentration was 88 mg/m3

GLP compliance:

not specified

Radiolabelling:

yes

Remarks:

59Fe and tritium

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

23 male and 22 female rats

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

17 minutes

Dose / conc.:

88 mg/m³ air (nominal)

Control animals:

yes

Details on absorption:

Internal deposition was 61.4 ± 3.7 μg per rat, corresponding to 36.6 ± 2.2% of the total inhaled vapour. Estimated ingestion was 5-25 micrograms. The fate of ingested ferrocene is that it sequests in the liver after passage throught the mucosal barrier of the gastrointestinal tract

Details on distribution in tissues:

At the earliest sacrifice time (0hr), 55% of the internally deposited ferrocene was in the nasopharyngeal region, and 30% was in the bronchopulmonary region. The remaining 15% was associated with the gastrointestinal tract or other organs.

Over 75% of the tritium label was excreted within the first day but the 59Fe label largely remained in the bronchopulmonary and nasopharyngeal regions over the duration of the experiment. The remaining 10% of the iron was primarily associated with the liver.

There was a protracted clearance of ferrocene-introduced iron (FII) from the respiratory tract, particulary in the lungs. For the FII remaining after 14 days, half times for clearance of 200 and 70 days can be estimated for the bronohopulmonary and nasopharyngeal regions respectively.

8% of the initially deposited FII was swallowed during or quickly after exposure (fur licking may have contributed to the GI tract FII. Estimated ingestion was 5-25 micrograms. The fate of ingested ferrocene is that it sequests in the liver after passage throught the mucosal barrier of the gastrointestinal tract.

Details on excretion:

Of the total initial tritium burden, 75% was excreted in the urine, about 9% was excreted in volatile components and 2% faeces all within 24 hours.

Only 7% of the Fe59 burden was excreted in the urine within the first 48hr. Overall only 15% of Fe59 was excreted by all routes in this period

Metabolites identified:

not measured

Details on metabolites:

The chemical form of the retained iron was not determined. It was not Ferrocene however as 75% of the tritium label (and correspondingly Cyclopentadiene) was rapidly separated from the ferrocene (24hours)

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results For the FII remaining after 14days, half times for clearance of 200 and 70 days can be estimated for the bronohopulmonary and nasopharyngeal regions respectively.

Internal deposition was 61.4 ± 3.7 μg per rat, corresponding to 36.6 ± 2.2% of the total inhaled vapour. Estimated ingestion was 5-25micrograms. The fate of ingested ferrocene is that it sequests in the liver after passage throught the mucosal barrier of the gastrointestinal tract.

At the earliest sacrifice time (0hr), 55% of the internally deposited ferrocene was in the nasopharyngeal region, and 30% was in the bronchopulmonary region. The remaining 15% was associated with the gastrointestinal tract or other organs.

Over 75% of the tritium label was excreted within the first day but the 59Fe label largely remained in the bronchopulmonary and nasopharyngeal regions over the duration of the experiment. The remaining 10% of the iron was primarily associated with the liver.

There was a protracted clearance of ferrocene-introduced iron (FII) from the respiratory tract, particulary in the lungs. For the FII remaining after 14days, half times for clearance of 200 and 70 days can be estimated for the bronohopulmonary and nasopharyngeal regions respectively.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1964

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

absorption

bioaccessibility (or bioavailability)

distribution

excretion

toxicokinetics

Principles of method if other than guideline:

Report is a peer reviewed study performed on the absorption, distribution and utilization of iron, in fat-soluble form (ferrocene)

GLP compliance:

not specified

Species:

other: 3 species; mice, rats and guinea pigs

Route of administration:

oral: unspecified

Vehicle:

not specified

Duration and frequency of treatment / exposure:

single dose of 59Fe-ferrocene

Details on absorption:

After a single oral dose of 59Fe-ferrocene, the compound was well absorbed via the gastrointestinal tract by mice, rats, and guinea pigs

Details on distribution in tissues:

Six hours after the administration, 13% of the label was found in the liver and 6% in the large intestine of rats. Only 40% of the dose was accounted for.
One day after the administration, 21% of the label was found in the rat liver, 5 to 9% in the guinea pig liver, and 40% in the mouse liver
For stomach and intestines together, these numbers were 10% (rat), 1.6% (guinea pig), and 5.2% (mouse), respectively

Details on excretion:

Faecal excretion amounted to 10% (rats), 2.0% (guinea pigs), and 7.7% (mice) after 3 days.
Urinary excretion amounted to 11% (rats), 36% (guinea pigs), 1.9% (mice) of the 59Fe-label in the first day.
The percentage label excreted after 3 days was 17% (rats), 38% (guinea pigs), 5.7% (mice).

Metabolites identified:

no

Bioaccessibility (or Bioavailability) testing results:

When rats, guinea pigs and rabbits were given diets containing ferrocene for up to 24 weeks, the liver iron content rose progressively.

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results . The percentage label excreted after 3 days was 17% (rats), 38% (guinea pigs), 5.7% (mice).

After a single oral dose of 59Fe-ferrocene, the compound was well absorbed via the gastrointestinal tract by mice, rats, and guinea pigs. Six hours after the administration, 13% of the label was found in the liver and 6% in the large intestine of rats. 40% of the dose was accounted for. One day after the administration, 21% of the label was found in the rat liver, 5 to 9% in the guinea pig liver, and 40% in the mouse liver. For stomach and intestines together, these numbers were 10% (rat), 1.6% (guinea pig), and 5.2% (mouse), respectively. Faecal excretion amounted to 10% (rats), 2.0% (guinea pigs), and 7.7% (mice) after 3 days. Urinary excretion amounted to 11% (rats), 36% (guinea pigs), 1.9% (mice) of the 59Fe-label in the first day. The percentage label excreted after 3 days was 17% (rats), 38% (guinea pigs), 5.7% (mice). When rats, guinea pigs and rabbits were given diets containing ferrocene for up to 24 weeks, the liver iron content rose progressively

Executive summary:

After a single oral dose of 59Fe-ferrocene, the compound was well absorbed via the gastrointestinal tract by mice, rats, and guinea pigs. Six hours after the administration, 13% of the label was found in the liver and 6% in the large intestine of rats. 40% of the dose was accounted for. One day after the administration, 21% of the label was found in the rat liver, 5 to 9% in the guinea pig liver, and 40% in the mouse liver. For stomach and intestines together, these numbers were 10% (rat), 1.6% (guinea pig), and 5.2% (mouse), respectively. Faecal excretion amounted to 10% (rats), 2.0% (guinea pigs), and 7.7% (mice) after 3 days. Urinary excretion amounted to 11% (rats), 36% (guinea pigs), 1.9% (mice) of the 59Fe-label in the first day. The percentage label excreted after 3 days was 17% (rats), 38% (guinea pigs), 5.7% (mice). When rats, guinea pigs and rabbits were given diets containing ferrocene for up to 24 weeks, the liver iron content rose progressively

Description of key information

In a peer reviewed study on oral absorption, distribution and utilisation, Ferrocene was absorbed at 40% (Golberg, Martin, 1964)

In a peer reviewed study on inhalation absorption and distribution, Ferrocene was absorbed at 37% (Dahl, Briner, 1980)

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

40

Absorption rate - inhalation (%):

36.6

Additional information

2 peer reviewed studies and a supporting study provide information on the basic toxiokinetics, metabolism and adsorption of Ferrocene.

In a peer reviewed study on inhalation absorption and distribution (Dahl, Briner, 1980), internal deposition was 61.4 ± 3.7 μg per rat, corresponding to 36.6 ± 2.2% of the total inhaled vapour. The fate of ingested ferrocene is that it sequests in the liver after passage throught the mucosal barrier of the gastrointestinal tract. At the earliest sacrifice time (0hr), 55% of the internally deposited ferrocene was in the nasopharyngeal region, and 30% was in the bronchopulmonary region. The remaining 15% was associated with the gastrointestinal tract or other organs. Over 75% of the tritium label was excreted within the first day but the 59Fe label largely remained in the bronchopulmonary and nasopharyngeal regions over the duration of the experiment. The remaining 10% of the iron was primarily associated with the liver. There was a protracted clearance of ferrocene-introduced iron (FII) from the respiratory tract, particulary in the lungs. For the FII remaining after 14 days, half times for clearance of 200 and 70 days can be estimated for the bronohopulmonary and nasopharyngeal regions respectively. A human breathing ferrocene at the TLV concentration of 10 mg/m3 would acquire 1.7 g of ferrocene-derived iron in the pulmonary region at steady state.

In a peer reviewed study on oral absorption, distribution and utilisation (Golberg, Martin, 1964), after a single oral dose of 59Fe-ferrocene, the compound was well absorbed via the gastrointestinal tract by mice, rats, and guinea pigs. Absorption was ca. 40%.

Another supporting study shows that once Ferrocene is ingested orally it is metabolised into a bioavailable form of iron (Madinaveitia, 1964)