Talc (Mg3H2(SiO3)4)

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

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

To determine the deposition, distribution, and clearance of talc, 44 female Syrian golden hamsters received a single 2-h nose-only exposure to a neutron-activated talc aerosol and sub-groups of 4 animals were then killed at 11 different intervals from 15 min to 132 days after exposure.
The talc tested was a commercial baby powder. Nine unexposed control animals were used; four were killed on the day the test animals were exposed and five were killed on the final day of the study. The aerosol exposure system had 7 tiers of exposure ports, and the talc aerosol was passed through a cyclone elutriator to remove particles that were larger than ~10 μm in diameter; the activity median aerodynamic diameter was 6.4-6.9 μm. The mean aerosol concentration was 40 and 75 μg/l at the 15-30 and 60-90 min sampling periods, respectively. In the presentation of the results, the γ-ray counts from the controls were expressed as μg talc equivalent, and the γ-ray counts of the exposed animals were not corrected for control values.

GLP compliance:

no

Radiolabelling:

yes

Species:

hamster, Syrian

Strain:

other: female Syrian golden hamsters

Details on species / strain selection:

44 female Syrian golden hamsters

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- 44 female Syrian golden hamsters
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Photoperiod: 12 hours dark/light cycle

Route of administration:

inhalation: aerosol

Vehicle:

other: neutron-activated talc aerosol

Duration and frequency of treatment / exposure:

a single 2-h nose-only exposure to a neutron-activated talc aerosol

Dose / conc.:

40 mg/m³ air

Dose / conc.:

75 mg/m³ air

No. of animals per sex per dose / concentration:

44 female Syrian golden hamsters

Control animals:

yes

no

Positive control reference chemical:

no data

Details on study design:

The talc tested was a commercial baby powder. Nine unexposed control animals were used; four were killed on the day the test animals were exposed and five were killed on the final day of the study. The aerosol exposure system had 7 tiers of exposure ports, and the talc aerosol was passed through a cyclone elutriator to remove particles that were larger than ~10 μm in diameter; the activity median aerodynamic diameter was 6.4-6.9 μm. The mean aerosol concentration was 40 and 75 μg/l at the 15-30 and 60-90 min sampling periods, respectively. In the presentation of the results, the γ-ray counts from the controls were expressed as μg talc equivalent, and the γ-ray counts of the exposed animals were not corrected for control values.

Variations among animals killed at the same time were attributed to variations in aerosol concentration at different tiers. The mean pulmonary talc content in the lungs of test animals at various time intervals was 33.08 (15 min after exposure), 24.08 (100 min), 42.70 (4 h), 18.75 (21 h), 21.30 (2 days), 21.03 (after 4 days), 13.85 (after 8 days), and 8.95μg (after 18 days); the mean for the day 0 control animals was 1.78 μg. The biological half-life of the talc deposited in the lungs was 7-10 days. At the time of termination of the final group, i.e. 132 days, there was no statistically significant difference in the talc burden of the lungs of test (3.70 μg) and control (2.30 μg) animals. The amount of talc in the liver, kidneys, and lungs was also determined; the only statistically significant differences compared to controls in any of these organs were found in the liver; there was a decrease at 4 h compared to day 0 controls, an increase at day 36 compared to both day 0 and day 132 controls, and an increase on day 68 compared to day 132 controls.

Details on dosing and sampling:

The mean pulmonary talc content in the lungs of test animals at various time intervals was 33.08 (15 min after exposure), 24.08 (100 min), 42.70 (4 h), 18.75 (21 h), 21.30 (2 days), 21.03 (after 4 days), 13.85 (after 8 days), and 8.95μg (after 18 days); the mean for the day 0 control animals was 1.78 μg. The biological half-life of the talc deposited in the lungs was 7-10 days. At the time of termination of the final group, i.e. 132 days, there was no statistically significant difference in the talc burden of the lungs of test (3.70 μg) and control (2.30 μg) animals. The amount of talc in the liver, kidneys, and lungs was also determined; the only statistically significant differences compared to controls in any of these organs were found in the liver; there was a decrease at 4 h compared to day 0 controls, an increase at day 36 compared to both day 0 and day 132 controls, and an increase on day 68 compared to day 132 controls.

Statistics:

Analysis of the data using the Kruskal-Wallis test

Details on absorption:

In an inhalation study with hamsters, neutron-activated cosmetic talc was administered in concentrations of 40 to 75 mg/m3 for 2 hours. The purity was 95 mass percent. 20 to 80 µg corresponding to 6% to 8% of the amount inhaled were deposited in the alveolar region per animal. Clearance was absolutely complete after only 4 months. No transition to other organs, such as the liver, kidneys or ovaries, was observed

Details on distribution in tissues:

Analysis of the data using the Kruskal-Wallis test showed that there were no significant differences among the mean talc burden values for the liver, kidneys, and ovaries, including the control values, and that there was no significant trend, indicating there was no translocation of talc to these tissues.

Details on excretion:

no translocation from the respiratory tract to other tissues was found in this study, and the clearance of talc from the lungs was complete within 4 months after exposure.

Metabolites identified:

not specified

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
In an inhalation study with hamsters, neutron-activated cosmetic talc was administered in concentrations of 40 to 75 mg/m3 for 2 hours. The purity was 95 mass percent. 20 to 80 µg corresponding to 6% to 8% of the amount inhaled were deposited in the alveolar region per animal. Clearance was absolutely complete after only 4 months. No transition to other organs, such as the liver, kidneys or ovaries, was observed

Executive summary:

To determine the deposition, distribution, and clearance of talc, 44 female Syrian golden hamsters received a single 2-h nose-only exposure to a neutron-activated talc aerosol and sub-groups of 4 animals were then killed at 11 different intervals from 15 min to 132 days after exposure.

The talc tested was a commercial baby powder. Nine unexposed control animals were used; four were killed on the day the test animals were exposed and five were killed on the final day of the study. The aerosol exposure system had 7 tiers of exposure ports, and the talc aerosol was passed through a cyclone elutriator to remove particles that were larger than ~10μm in diameter; the activity median aerodynamic diameter was 6.4-6.9μm. The mean aerosol concentration was 40 and 75μg/l at the 15-30 and 60-90 min sampling periods, respectively. In the presentation of the results, theγ-ray counts from the controls were expressed asμg talc equivalent, and theγ-ray counts of the exposed animals were not corrected for control values.

Variations among animals killed at the same time were attributed to variations in aerosol concentration at different tiers. The mean pulmonary talc content in the lungs of test animals at various time intervals was 33.08 (15 min after exposure), 24.08 (100 min), 42.70 (4 h), 18.75 (21 h), 21.30 (2 days), 21.03 (after 4 days), 13.85 (after 8 days), and 8.95μg (after 18 days); the mean for the day 0 control animals was 1.78μg. The biological half-life of the talc deposited in the lungs was 7-10 days. At the time of termination of the final group, i.e. 132 days, there was no statistically significant difference in the talc burden of the lungs of test (3.70μg) and control (2.30μg) animals. The amount of talc in the liver, kidneys, and lungs was also determined; the only statistically significant differences compared to controls in any of these organs were found in the liver; there was a decrease at 4 h compared to day 0 controls, an increase at day 36 compared to both day 0 and day 132 controls, and an increase on day 68 compared to day 132 controls.

Analysis of the data using the Kruskal-Wallis test showed that there were no significant differences among the mean talc burden values for the liver, kidneys, and ovaries, including the control values, and that there was no significant trend, indicating there was no translocation of talc to these tissues.

As noted, no translocation from the respiratory tract to other tissues was found in this study, and the clearance of talc from the lungs was complete within 4 months after exposure.

Reference 2

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

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

Six female Syrian golden hamsters (outbred Ela:ENG strain) were dosed by gavage with 1 ml neutron-activated talc suspended in physiological saline containing 0.6% (w/w) 1% methyl cellulose, and the animals were killed 24 h after dosing. The talc used was a commercial baby powder.

GLP compliance:

no

Radiolabelling:

yes

Species:

hamster, Syrian

Strain:

other: outbred Ela:ENG strain

Details on species / strain selection:

Six female Syrian golden hamsters (outbred Ela:ENG strain)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Six female Syrian golden hamsters (outbred Ela:ENG strain)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Photoperiod: 12 hours dark/light cycle

Route of administration:

oral: gavage

Vehicle:

physiological saline

Duration and frequency of treatment / exposure:

single administration

Dose / conc.:

2.94 mg/kg bw/day (actual dose received)

Remarks:

Six female Syrian golden hamsters (outbred Ela:ENG strain) were dosed by gavage with 1 ml neutron-activated talc suspended in physiological saline containing 0.6% (w/w) 1% methyl cellulose.The γ-ray counts of the tissue and excreta of the dose animals were equivalent to a total of 2.94 mg talc.

No. of animals per sex per dose / concentration:

6 female Syrian golden hamsters

Control animals:

yes

Positive control reference chemical:

Four hamsters were dosed similarly with a non-irradiated talc solution. The neutron-activated talc was exposed to an integrated neutron flux of 7 x 1016 n/cm2 30 days prior to dosing.

Details on study design:

Six female Syrian golden hamsters (outbred Ela:ENG strain) were dosed by gavage with 1 ml neutron-activated talc suspended in physiological saline containing 0.6% (w/w) 1% methyl cellulose, and the animals were killed 24 h after dosing. The talc used was a commercial baby powder.
Four hamsters were dosed similarly with a non-irradiated talc solution. The neutron-activated talc was exposed to an integrated neutron flux of 7 x 1016 n/cm2 30 days prior to dosing. The skinned carcass, gastrointestinal (GI) tract, lungs, liver, kidneys, and excreta were analyzed for 60Co and 46Sc by γ-ray spectrometry, and the γ-ray counts were compared with those of four hamsters that were not dosed with talc.

Details on dosing and sampling:

Dosed by gavage with 1 ml neutron-activated talc suspended in physiological saline containing 0.6% (w/w) 1% methyl cellulose, and the animals were killed 24 h after dosing. The talc used was a commercial baby powder.
Four hamsters were dosed similarly with a non-irradiated talc solution. The neutron-activated talc was exposed to an integrated neutron flux of 7 x 1016 n/cm2 30 days prior to dosing. The skinned carcass, gastrointestinal (GI) tract, lungs, liver, kidneys, and excreta were analyzed for 60Co and 46Sc by γ-ray spectrometry, and the γ-ray counts were compared with those of four hamsters that were not dosed with talc.

Statistics:

The skinned carcass, gastrointestinal (GI) tract, lungs, liver, kidneys, and excreta were analyzed for 60Co and 46Sc by γ-ray spectrometry, and the γ-ray counts were compared with those of four hamsters that were not dosed with talc.

Details on absorption:

The γ-ray counts of the tissue and excreta of the dose animals were equivalent to a total of 2.94 mg talc. Based on γ-ray counts, 74.5% of the neutron-activated talc was recovered in the feces and 23.5% was recovered in the GI tract, while 1.91% was recovered in the skinned carcass, 0.09% in the urine, 0.04% in the kidneys, and 0.02% in the liver. The amount found in the urine of the hamsters given irradiated talc was statistically significantly increased compared to the controls. No talc was recovered in the lungs.

Details on distribution in tissues:

Based on γ-ray counts, 74.5% of the neutron-activated talc was recovered in the feces and 23.5% was recovered in the GI tract, while 1.91% was recovered in the skinned carcass, 0.09% in the urine, 0.04% in the kidneys, and 0.02% in the liver. The amount found in the urine of the hamsters given irradiated talc was statistically significantly increased compared to the controls

Details on excretion:

Based on γ-ray counts, 74.5% of the neutron-activated talc was recovered in the feces and 23.5% was recovered in the GI tract, while 1.91% was recovered in the skinned carcass, 0.09% in the urine, 0.04% in the kidneys, and 0.02% in the liver. The amount found in the urine of the hamsters given irradiated talc was statistically significantly increased compared to the controls

Metabolites identified:

not specified

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
The distribution of talc taken up orally was examined in Syrian golden hamsters. After a single administration of talc the elimination of radioactivity was determined in the urine and faeces.

Executive summary:

Six female Syrian golden hamsters (outbred Ela:ENG strain) were dosed by gavage with 1 ml neutron-activated talc suspended in physiological saline containing 0.6% (w/w) 1% methyl cellulose, and the animals were killed 24 h after dosing. The talc used was a commercial baby powder.

 Four hamsters were dosed similarly with a non-irradiated talc solution. The neutron-activated talc was exposed to an integrated neutron flux of 7 x 1016 n/cm2 30 days prior to dosing. The skinned carcass, gastrointestinal (GI) tract, lungs, liver, kidneys, and excreta were analyzed for 60Co and 46Sc byγ-ray spectrometry, and theγ-ray counts were compared with those of four hamsters that were not dosed with talc.

 

Theγ-ray counts of the tissue and excreta of the dose animals were equivalent to a total of 2.94 mg talc. Based onγ-ray counts, 74.5% of the neutron-activated talc was recovered in the feces and 23.5% was recovered in the GI tract, while 1.91% was recovered in the skinned carcass, 0.09% in the urine, 0.04% in the kidneys, and 0.02% in the liver. The amount found in the urine of the hamsters given irradiated talc was statistically significantly increased compared to the controls. No talc was recovered in the lungs.

 

Reference 3

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

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

The absorption, distribution, and excretion of orally administered talc was determined in mice, rats, and guinea pigs.With all species, [3H]talc was administered as a suspension in aqueous (aq.) glycerol jelly solution (10 mg/ml; 1 μCi/ml).

GLP compliance:

no

Radiolabelling:

yes

Species:

mouse

Strain:

other: LACA mice

Details on species / strain selection:

Four LACA female mice were given a single oral dose of 40 mg/kg [3H]talc.

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Four LACA female mice
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Photoperiod: 12 hours dark/light cycle

Route of administration:

oral: gavage

Vehicle:

other: suspension in aqueous (aq.) glycerol jelly solution (10 mg/ml; 1 μCi/ml).

Duration and frequency of treatment / exposure:

single administration

Dose / conc.:

40 mg/kg bw/day

No. of animals per sex per dose / concentration:

Four LACA female mice

Control animals:

yes

Details on study design:

[3H]talc was administered as a suspension in aqueous (aq.) glycerol jelly solution (10 mg/ml; 1 μCi/ml).
Four LACA female mice were given a single oral dose of 40 mg/kg [3H]talc. Two mice were killed at 6 h and two at 24 h after dosing.

Details on dosing and sampling:

Four LACA female mice were given a single oral dose of 40 mg/kg [3H]talc

Details on absorption:

In the mice killed 6 h after dosing, 95 and 96% of the radioactivity was recovered in the large intestines and feces, 9 and 7% was recovered in the small intestines and stomach, and 0.7 and 0% in the urine of each mouse. In the two mice killed 24 h after dosing, 99 and 101% of the radioactivity was recovered in the large intestines and feces, 4 and 6% was recovered in the small intestines and stomach, and 1.3 and 1.5% in the urine of each mouse. Less than 0.005% of the radioactivity was found in the carcass of any of the mice.

Details on distribution in tissues:

In the mice killed 6 h after dosing, 95 and 96% of the radioactivity was recovered in the large intestines and feces, 9 and 7% was recovered in the small intestines and stomach, and 0.7 and 0% in the urine of each mouse. In the two mice killed 24 h after dosing, 99 and 101% of the radioactivity was recovered in the large intestines and feces, 4 and 6% was recovered in the small intestines and stomach, and 1.3 and 1.5% in the urine of each mouse. Less than 0.005% of the radioactivity was found in the carcass of any of the mice.

Details on excretion:

In the mice killed 6 h after dosing, 95 and 96% of the radioactivity was recovered in the large intestines and feces, 9 and 7% was recovered in the small intestines and stomach, and 0.7 and 0% in the urine of each mouse. In the two mice killed 24 h after dosing, 99 and 101% of the radioactivity was recovered in the large intestines and feces, 4 and 6% was recovered in the small intestines and stomach, and 1.3 and 1.5% in the urine of each mouse. Less than 0.005% of the radioactivity was found in the carcass of any of the mice.

Metabolites identified:

not specified

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
The distribution of talc taken up orally was examined in LACA female mice . After a single administration of talc the elimination of radioactivity was determined in the urine and faeces.

Executive summary:

Four LACA female mice were given a single oral dose of 40 mg/kg [3H]talc. Two mice were killed at 6 h and two at 24 h after dosing. In the mice killed 6 h after dosing, 95 and 96% of the radioactivity was recovered in the large intestines and feces, 9 and 7% was recovered in the small intestines and stomach, and 0.7 and 0% in the urine of each mouse. In the two mice killed 24 h after dosing, 99 and 101% of the radioactivity was recovered in the large intestines and feces, 4 and 6% was recovered in the small intestines and stomach, and 1.3 and 1.5% in the urine of each mouse. Less than 0.005% of the radioactivity was found in the carcass of any of the mice.

 

Reference 4

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

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

The absorption, distribution, and excretion of orally administered talc was determined in mice, rats, and guinea pigs.With all species, [3H]talc was administered as a suspension in aqueous (aq.) glycerol jelly solution (10 mg/ml; 1 μCi/ml).

GLP compliance:

no

Radiolabelling:

yes

Species:

rat

Strain:

Wistar

Details on species / strain selection:

Three male Wistar albino rats

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Three male Wistar albino rats
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Photoperiod: 12 hours dark/light cycle

Route of administration:

oral: gavage

Vehicle:

other: suspension in aqueous (aq.) glycerol jelly solution (10 mg/ml; 1 μCi/ml).

Duration and frequency of treatment / exposure:

six daily oral doses by gavage of 50 mg/kg body wt [3H]talc.

Dose / conc.:

50 mg/kg bw/day

No. of animals per sex per dose / concentration:

Three male Wistar albino rats

Control animals:

yes

Details on study design:

Three male Wistar albino rats were given a single oral dose and three rats were given six daily oral doses by gavage of 50 mg/kg body wt [3H]talc. After the last dose, urine and feces were collected every 24 h for 4 days and on day 10; the rats were then killed.

Details on dosing and sampling:

rats were given six daily oral doses by gavage of 50 mg/kg body wt [3H]talc

Details on absorption:

Within 24 h after administration of the single dose, approximately 75% of the radioactivity was recovered in the feces and only 1% was recovered in the urine. After 96 h, a total of 95.8% of the dose was excreted in the feces and 1.7% in the urine, with a total excretion of 97.5% of the dose. No radioactivity was recovered in the liver or kidneys 10 days after a single dose of talc. On day 10 in the rats given six daily doses of [3H]talc, there was no radioactivity found in the feces or livers, and there was a trace of radioactivity (<0.02%) in the kidneys of these rats.

Details on distribution in tissues:

Within 24 h after administration of the single dose, approximately 75% of the radioactivity was recovered in the feces and only 1% was recovered in the urine. After 96 h, a total of 95.8% of the dose was excreted in the feces and 1.7% in the urine, with a total excretion of 97.5% of the dose. No radioactivity was recovered in the liver or kidneys 10 days after a single dose of talc. On day 10 in the rats given six daily doses of [3H]talc, there was no radioactivity found in the feces or livers, and there was a trace of radioactivity (<0.02%) in the kidneys of these rats.s found in the carcass of any of the mice.

Details on excretion:

After 96 h, a total of 95.8% of the dose was excreted in the feces and 1.7% in the urine, with a total excretion of 97.5% of the dose.

Metabolites identified:

not specified

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
The distribution of talc taken up orally was examined in Wistar albino rats . After a 6 day administration of talc the elimination of radioactivity was determined in the urine and faeces.

Executive summary:

Three male Wistar albino rats were given a single oral dose and three rats were given six daily oral doses by gavage of 50 mg/kg body wt [3H]talc. After the last dose, urine and feces were collected every 24 h for 4 days and on day 10; the rats were then killed. Within 24 h after administration of the single dose, approximately 75% of the radioactivity was recovered in the feces and only 1% was recovered in the urine. After 96 h, a total of 95.8% of the dose was excreted in the feces and 1.7% in the urine, with a total excretion of 97.5% of the dose. No radioactivity was recovered in the liver or kidneys 10 days after a single dose of talc. On day 10 in the rats given six daily doses of [3H]talc, there was no radioactivity found in the feces or livers, and there was a trace of radioactivity (<0.02%) in the kidneys of these rats.

 

Reference 5

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

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

The absorption, distribution, and excretion of orally administered talc was determined in mice, rats, and guinea pigs.With all species, [3H]talc was administered as a suspension in aqueous (aq.) glycerol jelly solution (10 mg/ml; 1 μCi/ml).

GLP compliance:

no

Radiolabelling:

yes

Species:

guinea pig

Strain:

Dunkin-Hartley

Details on species / strain selection:

Three male Wistar albino rats

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Three female Dunkin Hartley guinea pigs
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Photoperiod: 12 hours dark/light cycle

Route of administration:

oral: gavage

Vehicle:

other: suspension in aqueous (aq.) glycerol jelly solution (10 mg/ml; 1 μCi/ml).

Duration and frequency of treatment / exposure:

a single oral dose of 25 mg/kg [3H]talc,

Dose / conc.:

25 mg/kg bw/day

No. of animals per sex per dose / concentration:

Three female Dunkin Hartley guinea pigs

Control animals:

yes

Details on study design:

Three female Dunkin Hartley guinea pigs were administered a single oral dose of 25 mg/kg [3H]talc, and urine and feces were collected; all animals were killed on day 10.

Details on dosing and sampling:

a single oral dose of 25 mg/kg [3H]talc

Details on absorption:

Within 24 h after dosing, 31% of the radioactivity was recovered in the feces, and 0.2% was recovered in the urine.
At 24-48 h and 48-72 h after dosing, 39% and 19% of the radioactivity, respectively, was recovered in the feces, with <0.01% of the dose being recovered in the urine at each of these time periods. Within 96 h of dosing, a total of 94.4% of the radioactivity was recovered in the feces and 0.2% was recovered in the urine, with a total of 94.6% of the dose being excreted over 96 h.

Details on distribution in tissues:

Within 24 h after dosing, 31% of the radioactivity was recovered in the feces, and 0.2% was recovered in the urine.
At 24-48 h and 48-72 h after dosing, 39% and 19% of the radioactivity, respectively, was recovered in the feces, with <0.01% of the dose being recovered in the urine at each of these time periods. Within 96 h of dosing, a total of 94.4% of the radioactivity was recovered in the feces and 0.2% was recovered in the urine, with a total of 94.6% of the dose being excreted over 96 h.

Details on excretion:

total of 94.6% of the dose being excreted over 96 h.

Metabolites identified:

not specified

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
The distribution of talc taken up orally was examined in Three female Dunkin Hartley guinea pigs . After a single oral dose administration of talc the elimination of radioactivity was determined in the urine and faeces.

Executive summary:

Three female Dunkin Hartley guinea pigs were administered a single oral dose of 25 mg/kg [3H]talc, and urine and feces were collected; all animals were killed on day 10. Talc was excreted more slowly in the guinea pig than in the rat.

 

Within 24 h after dosing, 31% of the radioactivity was recovered in the feces, and 0.2% was recovered in the urine.

At 24-48 h and 48-72 h after dosing, 39% and 19% of the radioactivity, respectively, was recovered in the feces, with <0.01% of the dose being recovered in the urine at each of these time periods. Within 96 h of dosing, a total of 94.4% of the radioactivity was recovered in the feces and 0.2% was recovered in the urine, with a total of 94.6% of the dose being excreted over 96 h.

 

 

Reference 6

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:

distribution

Qualifier:

no guideline followed

Principles of method if other than guideline:

Wistar rats were used to determine the systemic distribution of talc following intrapleural administration. Groups of 20 rats were administered 10 or 20 mg talc in 1 ml of saline as a slurry into the pleural cavity. Ten animals of each group were killed 24 h after instillation, and the remaining 10 animals were killed 48 h after instillation. The lungs, chest wall, liver, kidneys, spleen, heart, and brain of each animal were removed for examination.

GLP compliance:

no

Radiolabelling:

yes

Species:

rat

Strain:

Wistar

Details on species / strain selection:

Three male Wistar albino rats

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-20 Wistar rats
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Photoperiod: 12 hours dark/light cycle

Route of administration:

other: intrapleural

Vehicle:

other: 1 ml of saline as a slurry into the pleural cavity.

Duration and frequency of treatment / exposure:

10 or 20 mg talc in 1 ml of saline as a slurry into the pleural cavity.

Dose / conc.:

10 mg/kg bw/day

Remarks:

10 mg talc in 1 ml of saline as a slurry into the pleural cavity.

Dose / conc.:

20 mg/kg bw/day

Remarks:

20 mg talc in 1 ml of saline as a slurry into the pleural cavity.

No. of animals per sex per dose / concentration:

20 Wistar rats

Control animals:

yes

Details on study design:

Wistar rats were used to determine the systemic distribution of talc following intrapleural administration. Groups of 20 rats were administered 10 or 20 mg talc in 1 ml of saline as a slurry into the pleural cavity. Ten animals of each group were killed 24 h after instillation, and the remaining 10 animals were killed 48 h after instillation. The lungs, chest wall, liver, kidneys, spleen, heart, and brain of each animal were removed for examination.

Details on dosing and sampling:

10 or 20 mg talc in 1 ml of saline as a slurry into the pleural cavity.

Details on absorption:

Talc was absorbed rapidly through the pleura, reaching the systemic circulation with deposition in other organs within 24 h after administration, and that the distribution was not dose-related.

Details on distribution in tissues:

There were no gross lesions in the examined tissues. Microscopic examination revealed that the chest wall had the most common lesions, and these lesions were represented by an early pneumoconiosis characterized by stellate interstitial collections of dust-laden macrophages containing pale yellow particles associated with inflammatory infiltrate of lymphocytes with mild fibroblastic proliferation. Polarized light used to locate birefringent particles revealed “large numbers of irregular, strongly birefringence platy, acicular, and “Maltese Cross” crystals that varied in length from 5.7 – 70 μm” in the chest wall. The deposition index of talc crystals was greater in the chest wall and the lungs after administration of 10 mg (3.90 in the chest and 3.18 in the lungs) than 20 mg talc (3.58 in the chest and 2.50 in the lungs); this difference was statistically significant.

Details on excretion:

Pneumoconiosis reactions were not observed in the other organs; however talc crystals were present inside of the microvessels.

Metabolites identified:

not specified

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
Talc administered into the pleural space of rats is distributed systemically throughout the body.

Executive summary:

Wistar rats were used to determine the systemic distribution of talc following intrapleural administration. Groups of 20 rats were administered 10 or 20 mg talc in 1 ml of saline as a slurry into the pleural cavity. Ten animals of each group were killed 24 h after instillation, and the remaining 10 animals were killed 48 h after instillation. The lungs, chest wall, liver, kidneys, spleen, heart, and brain of each animal were removed for examination.

There were no gross lesions in the examined tissues. Microscopic examination revealed that the chest wall had the most common lesions, and these lesions were represented by an early pneumoconiosis characterized by stellate interstitial collections of dust-laden macrophages containing pale yellow particles associated with inflammatory infiltrate of lymphocytes with mild fibroblastic proliferation. Polarized light used to locate birefringent particles revealed“large numbers of irregular, strongly birefringence platy, acicular, and“Maltese Cross”crystals that varied in length from 5.7–70μm”in the chest wall. The deposition index of talc crystals was greater in the chest wall and the lungs after administration of 10 mg (3.90 in the chest and 3.18 in the lungs) than 20 mg talc (3.58 in the chest and 2.50 in the lungs); this difference was statistically significant.

 

Pneumoconiosis reactions were not observed in the other organs; however talc crystals were present inside of the microvessels. Talc was absorbed rapidly through the pleura, reaching the systemic circulation with deposition in other organs within 24 h after administration, and that the distribution was not dose-related.

 

Reference 7

Endpoint:

dermal absorption

Data waiving:

other justification

Justification for data waiving:

other:

Reference 8

Endpoint:

dermal absorption, other

Remarks:

(Q)SAR calculated endpoint

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction:US EPA accepted QSAR method for chemicals properties assessment.

Qualifier:

no guideline required

Principles of method if other than guideline:

Using the DERMWIN v2.01 QSAR model

GLP compliance:

no

Remarks:

not applicable to QSAR models

Radiolabelling:

no

Species:

other: QSAR model,

Strain:

other: QSAR model,

Sex:

not specified

Type of coverage:

other: QSAR model

Vehicle:

other: QSAR model

Duration of exposure:

not applicable to QSAR models

Doses:

not applicable to QSAR models

No. of animals per group:

not applicable to QSAR models

Control animals:

no

Details on study design:

not applicable to QSAR models

Details on in vitro test system (if applicable):

not applicable to QSAR models

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

A QSAR model predicts that the permeability of Talc (Mg3H2(SiO3)4) to human skin is quite low. The permeability coefficient was determined to be 5.24e-008 mg/cm2, which is around 0.1% of the skin penetration rate.
Predicted dermally absorbed coefficient was determined to be Kp (est)= 6.58e-012 cm/hr.

A QSAR model predicts that the permeability of Talc (Mg3H2(SiO3)4) to human skin is quite low. The permeability coefficient was determined to be 5.24e-008 mg/cm2, which is around 0.1% of the skin penetration rate. Predicted dermally absorbed coefficient was determined to be Kp (est)= 6.58e-012 cm/hr.

Conclusions:

A QSAR model predicts that the permeability of Talc (Mg3H2(SiO3)4) to human skin is quite low. The permeability coefficient was determined to be 5.24e-008 mg/cm2, which is around 0.1% of the skin penetration rate.
Predicted dermally absorbed coefficient was determined to be Kp (est)= 6.58e-012 cm/hr.

Executive summary:

A QSAR model predicts that the permeability of Talc (Mg3H2(SiO3)4) to human skin is quite low. The permeability coefficient was determined to be 5.24e-008 mg/cm2, which is around 0.1% of the skin penetration rate.

Predicted dermally absorbed coefficient was determined to be Kp (est)= 6.58e-012 cm/hr.

Description of key information

In studies in rats, mice, guinea-pigs and hamsters that used radioactive tracer techniques, no intestinal absorption or translocation of ingested talc to the liver or kidneys was detected .

No translocation of talc into the ovaries was detected after single or multiple intravaginal applications of talc to rabbits or monkeys.

There are no indications that orally or inhalation administered talc is absorbed by rats, mice, hamsters or guinea pigs 

Talc administered into the pleural space of rats is distributed systemically throughout the body.

Talc elimination of radioactivity was determined in the urine and faeces and thereforeTalc (Mg3H2(SiO3)4) has not bioaccumulation potential

A QSAR model predicts that the permeability of Talc (Mg3H2(SiO3)4) to human skin is quite low. The permeability coefficient was determined to be 5.24e-008 mg/cm2, which is around 0.1% of the skin penetration rate.

Predicted dermally absorbed coefficient was determined to be Kp (est)= 6.58e-012 cm/hr.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

0.1

Additional information

Absorption/Distribution/ Excretion

 

There are no indications that inhalation of talc is absorbed by rats, mice, hamsters or guinea pigs .

In an inhalation study with hamsters, neutron-activated cosmetic talc was administered in concentrations of 40 to 75 mg/m³ for 2 hours. The purity was 95 mass percent. 20 to 80 µg corresponding to 6% to 8% of the amount inhaled were deposited in the alveolar region per animal. Clearance was absolutely complete after only 4 months.

 No transition to other organs, such as the liver, kidneys or ovaries, was observed (Wehner et al. 1977)

 

There are no indications that orally administered talc is absorbed by rats, mice, hamsters or guinea pigs 

Six female Syrian golden hamsters (outbred Ela:ENG strain) were dosed by gavage with 1 ml neutron-activated talc suspended in physiological saline containing 0.6% (w/w) 1% methyl cellulose, and the animals were killed 24 h after dosing.(Wehner et al. 1977).The talc used was a commercial baby powder. The distribution of talc taken up orally was examined in Syrian golden hamsters. After a single administration of talc the elimination of radioactivity was determined in the urine and faeces.

 

Four LACA female mice were given a single oral dose of 40 mg/kg [3H]talc.(Phillips et al. 1978, Two mice were killed at 6 h and two at 24 h after dosing. In the mice killed 6 h after dosing, 95 and 96% of the radioactivity was recovered in the large intestines and feces, 9 and 7% was recovered in the small intestines and stomach, and 0.7 and 0% in the urine of each mouse. In the two mice killed 24 h after dosing, 99 and 101% of the radioactivity was recovered in the large intestines and feces, 4 and 6% was recovered in the small intestines and stomach, and 1.3 and 1.5% in the urine of each mouse. Less than 0.005% of the radioactivity was found in the carcass of any of the mice.

 

The distribution of talc taken up orally was examined in LACA female mice . After a single administration of talc the elimination of radioactivity was determined in the urine and faeces.

 

Three male Wistar albino rats were given a single oral dose and three rats were given six daily oral doses by gavage of 50 mg/kg body wt [3H]talc.(Phillips et al. 1978, After the last dose, urine and feces were collected every 24 h for 4 days and on day 10; the rats were then killed. Within 24 h after administration of the single dose, approximately 75% of the radioactivity was recovered in the feces and only 1% was recovered in the urine. After 96 h, a total of 95.8% of the dose was excreted in the feces and 1.7% in the urine, with a total excretion of 97.5% of the dose. No radioactivity was recovered in the liver or kidneys 10 days after a single dose of talc. On day 10 in the rats given six daily doses of [3H]talc, there was no radioactivity found in the feces or livers, and there was a trace of radioactivity (<0.02%) in the kidneys of these rats.

The distribution of talc taken up orally was examined in Wistar albino rats . After a 6 day administration of talc the elimination of radioactivity was determined in the urine and faeces.

 

Wistar rats were used to determine the systemic distribution of talc following intrapleural administration. Groups of 20 rats were administered 10 or 20 mg talc in 1 ml of saline as a slurry into the pleural cavity. Ten animals of each group were killed 24 h after instillation, and the remaining 10 animals were killed 48 h after instillation. The lungs, chest wall, liver, kidneys, spleen, heart, and brain of each animal were removed for examination.

There were no gross lesions in the examined tissues. Microscopic examination revealed that the chest wall had the most common lesions, and these lesions were represented by an early pneumoconiosis characterized by stellate interstitial collections of dust-laden macrophages containing pale yellow particles associated with inflammatory infiltrate of lymphocytes with mild fibroblastic proliferation. Polarized light used to locate birefringent particles revealed“large numbers of irregular, strongly birefringence platy, acicular, and“Maltese Cross”crystals that varied in length from 5.7–70μm”in the chest wall. The deposition index of talc crystals was greater in the chest wall and the lungs after administration of 10 mg (3.90 in the chest and 3.18 in the lungs) than 20 mg talc (3.58 in the chest and 2.50 in the lungs); this difference was statistically significant.

 

Pneumoconiosis reactions were not observed in the other organs; however talc crystals were present inside of the microvessels. Talc was absorbed rapidly through the pleura, reaching the systemic circulation with deposition in other organs within 24 h after administration, and that the distribution was not dose-related.

 

Talc administered into the pleural space of rats is distributed systemically throughout the body.

 

 

Conclusion

In studies in rats, mice, guinea-pigs and hamsters that used radioactive tracer techniques, no intestinal absorption or translocation of ingested talc to the liver or kidneys was detected (Wehner et al., 1977; Phillips et al., 1978).

No translocation of talc into the ovaries was detected after single or multiple intravaginal applications of talc to rabbits (Phillips et al., 1978) or monkeys (Wehner et al., 1985, 1986).

There are no indications that orally or inhalation administered talc is absorbed by rats, mice, hamsters or guinea pigs 

Talc administered into the pleural space of rats is distributed systemically throughout the body.

Talc elimination of radioactivity was determined in the urine and faeces and thereforeTalc (Mg3H2(SiO3)4) has not bioaccumulation potential