Talc (Mg3H2(SiO3)4)

Basic toxicokinetics

Administrative data

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

Data source

Reference

Reference Type:

publication

Title:

Pulmonary deposition, translocation and clearance of inhaled neutron-activated talc in hamsters.

Author:

Wehner AP, Wilderson CL, Cannon WC, Buschbom RL, and Tanner TM.

Year:

1977

Bibliographic source:

Fd Cosmet Toxicol. 1977;15:213-224.

Materials and methods

Objective of study:

absorption

distribution

excretion

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Talc (Mg3H2(SiO3)4)

EC Number:

238-877-9

EC Name:

Talc (Mg3H2(SiO3)4)

Cas Number:

14807-96-6

Molecular formula:

H2Mg3O12Si4

IUPAC Name:

Talc (Mg3H2(SiO3)4)

Test material form:

solid

Radiolabelling:

yes

Test animals

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

Administration / exposure

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

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

40 mg/m³ air

Doses / concentrations 2

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

Results and discussion

Toxicokinetic / pharmacokinetic studies

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.

Metabolite characterisation studies

Metabolites identified:

not specified

Applicant's summary and conclusion

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.