Talc (Mg3H2(SiO3)4)

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

chronic toxicity: inhalation

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:

Animal experiments with talc.

Author:

Wagner JC, Berry G, Cooke TJ, Hill RJ, Pooley FD, Skidmore JW

Year:

1977

Bibliographic source:

in: Walton WH (Ed.) Inhaled particles IV, Pergamon Press, Oxford, 647–654

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 452 (Chronic Toxicity Studies)

GLP compliance:

not specified

Limit test:

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

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Two groups of 12 male and 12 female Wistar-derived rats, 6–8 weeks

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: mean particle size, 25 μm

Details on inhalation exposure:

Two groups of 12 male and 12 female Wistar-derived rats, 6–8 weeks of age, were exposed by inhalation to a mean respirable dust concentration of 10.8 mg/m3 Italian talc (grade 0000; ready milled; mean particle size, 25 μm in diameter; containing 92% talc, 3% chlorite, 1% carbonate minerals and 0.5–1% quartz) for 7.5 hours per day on 5 days a week for 6 or 12 months (cumulative exposures, 8200 and 16 400 mg/m3 × h, respectively).
Ten days after the end of each exposure period, six rats per group were killed; 12 rats per group died and two rats per group were unaccounted for; the remaining four rats per group were killed 1 year after the end of the exposure period.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

periods of 3, 6 and 12 months.

Frequency of treatment:

Exposure times were 7.5 hours per day and 5 days per week.

Doses / concentrations

Dose / conc.:

10.8 mg/m³ air

No. of animals per sex per dose:

12 male and 12 female Wistar rats

Control animals:

yes

Details on study design:

Two groups of 12 male and 12 female Wistar-derived rats, 6–8 weeks of age, were exposed by inhalation to a mean respirable dust concentration of 10.8 mg/m3 Italian talc (grade 0000; ready milled; mean particle size, 25 μm in diameter; containing 92% talc, 3% chlorite, 1% carbonate minerals and 0.5–1% quartz) for 7.5 hours per day on 5 days a week for 6 or 12 months (cumulative exposures, 8200 and 16 400 mg/m3 × h, respectively).
Ten days after the end of each exposure period, six rats per group were killed; 12 rats per group died and two rats per group were unaccounted for; the remaining four rats per group were killed 1 year after the end of the exposure period.

Positive control:

no

Examinations

Observations and examinations performed and frequency:

animals (6/cage) were exposed to talc dust; SFA chrysotile controls were treated similarly
at each time frame; untreated controls were used; some animals were killed 10 days or 1
yr after final exposure, and the remainder lived until natural death

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

Minimal fibrosis was observed. Talc exposure led to distinct fibrosis that was comparable with that after exposure to chrysotile in the parallel group. A lung adenoma was detected in one of 24 animals treated with talc

Effect levels

Dose descriptor:

NOAEC

Effect level:

10.8 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: increased mortality (50%; 6 and 12 months), fibrosis as the exposure period progressed, 1/24 animals with lung adenoma

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Wistar rats were treated with “Italian talc” (about 92% talc, 0.5–1% quartz, “asbestos-free”) in a respirable dust fraction of 10.8 mg talc/m³ for periods of 3, 6 and 12 months. Exposure times were 7.5 hours per day and 5 days per week. High mortality in the two groups with 6- and 12-month periods of treatment was striking; 50% of the animals died during treatment in both groups. Talc exposure led to distinct fibrosis that was comparable with that after exposure to chrysotile in the parallel group. A lung adenoma was detected in one of 24 animals treated with talc

Applicant's summary and conclusion

Conclusions:

Wistar rats were treated with “Italian talc” (about 92% talc, 0.5–1% quartz, “asbestos-free”) in a respirable dust fraction of 10.8 mg talc/m3 for periods of 3, 6 and 12 months. Exposure times were 7.5 hours per day and 5 days per week. High mortality in the two groups with 6- and 12-month periods of treatment was striking; 50% of the animals died during treatment in both groups. Talc exposure led to distinct fibrosis that was comparable with that after exposure to chrysotile in the parallel group. A lung adenoma was detected in one of 24 animals treated with talc

Executive summary:

In rats exposed by inhalation to 10.8 mg/m³ Italian talc (grade 00000; ready milled; mean particle size, 25 µm) for 3 months, minimal fibrosis was observed, the degree of which did not change during the observation period after exposure. Animals that were exposed for 1 year had minimal to slight fibrosis, the degree of which had increased to moderate within 1 year after cessation of exposure.