Talc (Mg3H2(SiO3)4)

Carcinogenicity

Description of key information

There was no evidence of carcinogenic activity in male or female B6C3F1 mice.

A bioassay using rats was performed by the NTPto determine the carcinogenic potential of non-asbestiform, cosmetic-grade micro-talc following exposure by inhalation, andit was concluded there was some evidence of carcinogenicactivity in male F344/rats, and clear evidence of carcinogenic activity in female F344/N rats. The rats were exposed to 6 mg/m3 (MMAD 2.7 ± 1.9 μm) or 18 mg/m3 (MMAD 3.2 ± 1.9 μm) talc for 6 h/day, 5 days/wk, for 113wks (males) or 122 wks (females).Concerns have been raised about this study, including concerns that micronized talc having a significantly smaller particle size distribution than cosmetic talc was used, aerosol concentrations were not properly controlled, proper procedures for dose selection were not followed resulting in the MTD being exceeded at both concentrations tested, and particle overload in the lungs was most likely the cause of the adverse effects reported.

The talc used in the this study was a commercially available microtalc whose dimensions of < 10 µm were distinctly finer than the cosmetic powder normally used.

Therefore, the study is not conclusive with regard to a possible carcinogenicity of large talc platelets or talc fibres.

There are conclusive but not suffcient data for the classification of substance Talc (Mg3H2(SiO3)4) with regard to carcinogenicity.

 Not classifiable as a human carcinogen. /Talc containing no asbestos fibers/
[American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices.,, 2008, p. 54

It is concluded that talc not containing asbestos or asbestiform fibres is safe in the present practices of use.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

Principles of method if other than guideline:

Groups of 16 male and 16 female Wistar-derived rats, 21–26 weeks of age, were fed 100 mg Italian talc (grade 00000; ready milled; mean particle size, 25 μm; containing
92% talc, 3% chlorite, 1% carbonate minerals and 0.5–1% quartz) per day per rat in the diet for 5 months (talc-containing diet was actually given for 101 days) and were then
maintained on basal diet for life (average survival, 614 days).

GLP compliance:

not specified

Species:

rat

Strain:

Wistar

Details on species / strain selection:

Groups of 16 male and 16 female Wistar-derived rats, 21–26 weeks of age,

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Young healthy male and nulliparous, non pregnant, female rats [strain: Wistar Crl:WI] (Full-Barrier), were used in this study.
At the beginning of the study, the age of the animals was 8-9 weeks. The range of the body weight was:
Females: 144.32 to 216.48 g, (mean: 180.40 g, ± 20%= 36.08 g)
Males: 211.18 to 316.77 g, (mean: 263.98 g, ± 20%= 52.80 g).

ENVIRONMENTAL CONDITIONS
After an adequate acclimatisation period (at least five days), the animals were barrier maintained (full-barrier) in air conditioned rooms under the following conditions: temperature: 22 ± 3 °C, relative humidity: 55 ± 10%, artificial light, sequence being 12 hours light, 12 hours dark, air change: 10 x / hour, free access to Altromin 1324 maintenance diet, free access to tap water, sulphur acidified to a pH of approximately 2.8 (drinking water, municipal residue control, microbiol. controlled periodically), housed individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

In a feeding study in 16 male and 16 female Wistar rats, talc was added to the diet; this resulted in an amount taken up of 100 mg/day and animal. After feeding had been carried out for 101 days, the animals were observed until death and subsequently examined histopathologically. One of the animals treated with talc showed a leiomyosarcoma of the stomach. Sarcomas, which were however not associated with the talc treatment, were found in the uterus of two animals

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

101 days

Frequency of treatment:

Daily

Post exposure period:

614 days

Dose / conc.:

100 mg/kg bw/day

No. of animals per sex per dose:

16 male and 16 female Wistar rats

Control animals:

yes

Details on study design:

In a feeding study in 16 male and 16 female Wistar rats, talc was added to the diet; this resulted in an amount taken up of 100 mg/day and animal. After feeding had been carried out for 101 days, the animals were observed until death and subsequently examined histopathologically. One of the animals treated with talc showed a leiomyosarcoma of the stomach. Sarcomas, which were however not associated with the talc treatment, were found in the uterus of two animals

Positive control:

eight male and eight female control animals

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- General clinical observations were made twice a day except during weekend and holidays where observations were made only once, approximately at the same time each day and considering the peak period of anticipated effects after dosing
- Cage side observations checked in table were included.

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes
FOOD CONSUMPTION: Yes

WATER CONSUMPTION No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes

CLINICAL CHEMISTRY: Yes

NEUROBEHAVIOURAL EXAMINATION: Yes

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

ORGAN WEIGHT: Yes

Other examinations:

No data

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

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:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

Groups of 16 male and 16 female Wistar-derived rats, 21–26 weeks of age, were fed 100 mg Italian talc (grade 00000; ready milled; mean particle size, 25 μm; containing 92% talc, 3% chlorite, 1% carbonate minerals and 0.5–1% quartz) per day per rat in the diet for 5 months (talc-containing diet was actually given for 101 days) and were then maintained on basal diet for life (average survival, 614 days).
No differences in tumour incidence were noted between treated animals and eight male and eight female control animals fed basal diet throughout (average survival, 641 days)

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

gross pathology

histopathology: neoplastic

histopathology: non-neoplastic

other: No differences in tumour incidence were noted between treated animals and eight male and eight female control animals fed basal diet throughout (average survival, 641 days)

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Critical effects observed:

not specified

 Groups of 16 male and 16 female Wistar-derived rats, 21–26 weeks of age, were fed 100 mg Italian talc (grade 00000; ready milled; mean particle size, 25 μm; containing 92% talc, 3% chlorite, 1% carbonate minerals and 0.5–1% quartz) per day per rat in the diet for 5 months (talc-containing diet was actually given for 101 days) and were then maintained on basal diet for life (average survival, 614 days). No differences in tumour incidence were noted between treated animals and eight male and eight female control animals fed basal diet throughout (average survival, 641 days)

Conclusions:

No differences in tumour incidence were noted between treated animals and eight male and eight female control animals fed basal diet throughout (average survival, 641 days)

Executive summary:

Under the condition of this study, for a period of101 days for male and female rats, the NOAEL of Talc In a feeding study was 100 mg/kg/day. No adverse effects were seen on general toxicity endpoints.

 One of the animals treated with talc showed a leiomyosarcoma of the stomach. Sarcomas, which were however not associated with the talc treatment, were found in the uterus of two animals.

 No chronic pathological effect was associated with oral administration of Italian talc (92% pure; 100 mg per day on 101 days over 5 months) to rats.

No differences in tumour incidence were noted between treated animals and eight male and eight female control animals fed basal diet throughout (average survival, 641 days)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Oral effects:
Under the condition of this study, for a period of101 days for male and female rats, the NOAEL of Talc In a feeding study was 100 mg/kg/day. No adverse effects were seen on general toxicity endpoints.
One of the animals treated with talc showed a leiomyosarcoma of the stomach. Sarcomas, which were however not associated with the talc treatment, were found in the uterus of two animals.
No chronic pathological effect was associated with oral administration of Italian talc (92% pure; 100 mg per day on 101 days over 5 months) to rats.
No differences in tumour incidence were noted between treated animals and eight male and eight female control animals fed basal diet throughout (average survival, 641 days)

Carcinogenicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

carcinogenicity: 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

Qualifier:

no guideline followed

Principles of method if other than guideline:

In a lifetime experiment, three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age, were exposed by inhalation to an aerosol of talc baby powder that was prepared from Vermont talc by flotation (95% w/w platy talc with trace quantities of magnesite, dolomite, chlorite and rutile) for 3, 30 or 150 minute per day on 5 days a week for 30 days. The mean aerosol concentration was 37.1 mg/m3, with a measurable respiratory fraction of 9.8 mg/m3 and a MMAD of 4.9 μm. A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days. The mean aerosol concentration was 27.4 mg/m3, with a measurable respiratory fraction of 8.1 mg/m3 and a MMAD of 6.0 μm. Another sham-exposed group comprised 25 males and 25 females. The survivors of the last two talc-exposed groups were killed at the age of 20 months.

GLP compliance:

not specified

Species:

hamster

Strain:

other: Syrian golden hamsters

Details on species / strain selection:

three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: The mean aerosol concentration was 37.1 mg/m3, with a measurable respiratory fraction of 9.8 mg/m3 and a MMAD of 4.9 μm.
A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days. The mean aerosol concentration was 27.4 mg/m3, with a measurable respiratory fraction of 8.1 mg/m3 and a MMAD of 6.0 μm. Another sham-exposed group comprised 25 males and 25 females.

Details on exposure:

Groups of 50 male and 50 female Syrian golden hamsters were exposed to talc aerosol for 3, 30 or 150min/day, 5 days/wk for 30 days, or for 30 or 150min/day either until they died naturally or for a maximum of 300 days. The mean concentration of the ‘respirable’ aerosol fraction was approximately 8 μg/litre and the mass mean aerodynamic diameter was 6 μm. Following the exposures, the animals were observed for the remainder of their lifespan. At death, lungs trachea, larynx, liver, one kidney, stomach, uterus, one ovary, or one testis, and all tissues showing gross lesions were collected for histopathological examination. Deposition of talc particles in the lungs of the exposed animals was demonstrated by X-ray fluorescence and by X-ray diffraction.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

30 days

Frequency of treatment:

3, 30 or 150min/day, 5 days/wk for 30 days, or for 30 or 150min/day

Post exposure period:

300 days

Dose / conc.:

37.1 mg/m³ air

Dose / conc.:

27.4 mg/m³ air

Dose / conc.:

9.8 mg/m³ air

Dose / conc.:

8.1 mg/m³ air

No. of animals per sex per dose:

three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age,

Control animals:

yes

Details on study design:

In a lifetime experiment, three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age, were exposed by inhalation to an aerosol of talc baby powder that was prepared from Vermont talc by flotation (95% w/w platy talc with trace quantities of magnesite, dolomite, chlorite and rutile) for 3, 30 or 150 minute per day on 5 days a week for 30 days. The mean aerosol concentration was 37.1 mg/m3, with a measurable respiratory fraction of 9.8 mg/m3 and a MMAD of 4.9 μm. A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days. The mean aerosol concentration was 27.4 mg/m3, with a measurable respiratory fraction of 8.1 mg/m3 and a MMAD of 6.0 μm. Another sham-exposed group comprised 25 males and 25 females. The survivors of the last two talc-exposed groups were killed at the age of 20 months.

Positive control:

A group of 25 male and 25 female guinea pigs served as the control group. A single tier exposure was used.A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days.

Observations and examinations performed and frequency:

Following the exposures, the animals were observed for the remainder of their lifespan. At death, lungs trachea, larynx, liver, one kidney, stomach, uterus, one ovary, or one testis, and all tissues showing gross lesions were collected for histopathological examination. Deposition of talc particles in the lungs of the exposed animals was demonstrated by X-ray fluorescence and by X-ray diffraction.

Sacrifice and pathology:

Syrian golden hamsters exposed to 8.1-mg/m3 aerosols of cosmetic-grade talc for up to 150 minutes per day on 5 days a week for 30 days showed no histopathological change in the lungs, heart, liver, renal tissues, stomach or uterus.

Other examinations:

no

Statistics:

no data

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

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:

not specified

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

Exposure of hamsters to talc via inhalation did not produce carcinogenic effects. Groups of 50 male and 50 female Syrian golden hamsters were exposed for 30 or 150 min/day, 5 days/wk, to 27.4 ± 3.4 μg/l mean total aerosol concentration commercial baby powder (95% w/w platy talc with trace quantities of carbonates and platy chlorite and rutile) until natural death, or, for a maximum of 300 days. A group of 25 male and 25 female guinea pigs served as the control group. A single tier exposure was used. There was no statistically significant difference in survival time among groups, but there was a significant difference between males and females within all groups. No clinical signs of toxicity to talc were observed. The type, incidence, and severity of lesions indicated no trend toward a dose-response and no statistically significant differences between exposed and control groups. The incidence of focal alveolar cell hyperplasia (25% in treated groups; 10% in controls) appeared to be affected by treatment, but a two-way weighted analysis showed no significant association.

Relevance of carcinogenic effects / potential:

In a lifetime inhalation study, a carcinogenic effect was not observed upon exposure of hamsters to a commercial baby powder containing 95% platy talc for 30 or 150 min/day, 5 days/wk.

Dose descriptor:

NOAEC

Effect level:

8.1 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

histopathology: neoplastic

histopathology: non-neoplastic

other: In a lifetime inhalation study, a carcinogenic effect was not observed upon exposure of hamsters to a commercial baby powder containing 95% platy talc for 30 or 150 min/day, 5 days/wk.

Remarks on result:

other:

Remarks:

Syrian golden hamsters exposed to 8.1-mg/m3 aerosols of cosmetic-grade talc for up to 150 minutes per day on 5 days a week for 30 days showed no histopathological change in the lungs, heart, liver, renal tissues, stomach or uterus.

Critical effects observed:

not specified

Exposure of hamsters to talc via inhalation did not produce carcinogenic effects. Groups of 50 male and 50 female Syriangolden hamsters were exposed for 30 or 150 min/day, 5 days/wk, to 27.4 ± 3.4 μg/l mean total aerosol concentration commercialbaby powder (95% w/w platy talc with trace quantities of carbonates and platy chlorite and rutile) until natural death,or, for a maximum of 300 days. A group of 25 male and 25 female guinea pigs served as the control group. A single tier exposurewas used. There was no statistically significant difference in survival time among groups, but there was a significantdifference between males and females within all groups. No clinical signs of toxicity to talc were observed. The type, incidence,and severity of lesions indicated no trend toward a dose-response and no statistically significant differences betweenexposed and control groups. The incidence of focal alveolar cell hyperplasia (25% in treated groups; 10% in controls) appearedto be affected by treatment, but a two-way weighted analysis showed no significant association.

Conclusions:

In a lifetime inhalation study, a carcinogenic effect was not observed upon exposure of hamsters to a commercial baby powder containing 95% platy talc for 30 or 150 min/day, 5 days/wk.

Executive summary:

Exposure of hamsters to talc via inhalation did not produce carcinogenic effects.

In a lifetime experiment, three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age, were exposed by inhalation to an aerosol of talc baby powder that was prepared from Vermont talc by flotation (95% w/w platy talc with trace quantities of magnesite, dolomite, chlorite and rutile) for 3, 30 or 150 minute per day on 5 days a week for 30 days. The mean aerosol concentration was 37.1 mg/m3, with a measurable respiratory fraction of 9.8 mg/m3 and a MMAD of 4.9 μm. A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days. The mean aerosol concentration was 27.4 mg/m3, with a measurable respiratory fraction of 8.1 mg/m3 and a MMAD of 6.0 μm. Another sham-exposed group comprised 25 males and 25 females. The survivors of the last two talc-exposed groups were killed at the age of 20 months.

Reference 2

Endpoint:

carcinogenicity: 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

Principles of method if other than guideline:

A 2-yr study was performed in mice; groups of 50 male and 50 female B6C3F1 mice (7 wks old) were exposed to target concentrations of 0, 6, or 18 mg/m3 talc for 6 h/day, 5 days/wk, for 103-104 wks. The concentrations were selected based on the results of a 4-wk inhalation study in B6C3F1 mice; These exposure concentrations provided a dose equivalent of 0, 2, or 6 mg/kg/day for male mice, respectively, and 0, 1.3, or 3.9 mg/kg/day for female mice, respectively.
The MMAD was 3.3 ± 1.9 μm in the 6 mg/m3 chamber and 3.6 ± 2.0 μm in the 18 mg/m3 chamber. Groups of 40 male and 40 female mice were similarly exposed and killed at 6, 12, and 18 mos for interim microscopic evaluations. Some problems were experienced in maintaining control of the chamber concentrations, and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations.

GLP compliance:

not specified

Species:

mouse

Strain:

B6C3F1

Details on species / strain selection:

groups of 50 male and 50 female B6C3F1 mice (7 wks old)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
groups of 50 male and 50 female B6C3F1 mice (7 wks old)

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

whole body

Vehicle:

air

Remarks on MMAD:

The MMAD was 3.3 ± 1.9 μm in the 6 mg/m3 chamber and 3.6 ± 2.0 μm in the 18 mg/m3 chamber. Groups of 40 male and 40 female mice were similarly exposed and killed at 6, 12, and 18 mos for interim microscopic evaluations. Some problems were experienced in maintaining control of the chamber concentrations, and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations.

Details on exposure:

Groups of 50 male and 50 female B6C3F1 mice, 7 weeks of age, that were fed an NIH-07 diet, were exposed by inhalation to aerosols containing 0, 6 or 18 mg/m3 MP 10–52 grade talc for 6 hours per day on 5 days per week for up to 104 weeks (dose equivalent, 0, 2 or 6 mg/kg bw per day for male mice and 0, 1.3 or 3.9 mg/kg bw per day for female mice). MP 10–52 grade is a high-purity microtalc (from a strip mine located in Missouri State, USA) that has a maximal particle size of 10 μm and is reported to contain no tremolite or any asbestiform minerals. After analysis, the talc was found to be free of asbestos and almost free of silica.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

104 weeks

Frequency of treatment:

6 hours per day on 5 days per week

Dose / conc.:

0 mg/m³ air

Dose / conc.:

6 mg/m³ air

Dose / conc.:

18 mg/m³ air

No. of animals per sex per dose:

groups of 50 male and 50 female B6C3F1 mice (7 wks old)

Control animals:

yes

Details on study design:

A 2-yr study was performed in mice; groups of 50 male and 50 female B6C3F1 mice (7 wks old) were exposed to target concentrations of 0, 6, or 18 mg/m3 talc for 6 h/day, 5 days/wk, for 103-104 wks. The concentrations were selected based on the results of a 4-wk inhalation study in B6C3F1 mice; These exposure concentrations provided a dose equivalent of 0, 2, or 6 mg/kg/day for male mice, respectively, and 0, 1.3, or 3.9 mg/kg/day for female mice, respectively.
The MMAD was 3.3 ± 1.9 μm in the 6 mg/m3 chamber and 3.6 ± 2.0 μm in the 18 mg/m3 chamber. Groups of 40 male and 40 female mice were similarly exposed and killed at 6, 12, and 18 mos for interim microscopic evaluations. Some problems were experienced in maintaining control of the chamber concentrations, and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations.

Observations and examinations performed and frequency:

Changes in enzymatic activities in bronchoalveolar lavage fluid were noted mostly in the 18 mg/m3 males and females; measured enzymatic activity was increased in the high-dose animals at 18 and 24 mos. A statistically significant increase in β-glucuronidase activity was seen as of 12 mos in the high dose animals, and at 24 mos, the activity was increased in all test groups. Lavage fluid polymorphonuclear cells were statistically significantly increased in males and females of the 18 mg/m3 group at all times except at 12 mos; statistically significant increases were observed in some 6 mg/m3 interim groups. The population of bronchoalveolar lavage fluid macrophages was significantly decreased in the female test groups at 24 mos. The phagocytic activity of the macrophages recovered from the lavage fluid at 12, 18, and 24 mos was statistically significantly decreased by exposure to 18 mg/m3 talc. At 24 mos, there was no effect on the viability of the macrophages. Lung tissue collagen and proteinase activity were significantly increased in exposed male and female rats. At 24 mos, collagen and lung fluid collagenous peptides were statistically significantly increased in the 18 mg/m3 group, and most proteinase activity was increased as well.

Sacrifice and pathology:

Chronic active inflammation without alveolar epithelium hyperplasia, squamous metaplasia, or interstitial fibrosis was reported in exposed mice. An accumulation of macrophages was observed in the lungs, and talc-containing macrophages were found in the bronchial lymph nodes. The incidence of pulmonary neoplasms was similar for test and control animals. In the
upper respiratory tract, cytoplasmic eosinophilic droplets in the nasal mucosal epithelium occurred and were concentrationdependent.

Other examinations:

Survival and final mean body weights of male and female mice exposed to talc were similar to those of the controls. No clinical findings were attributed to exposure to talc. Inhalation exposure to talc was associated with chronic inflammation and accumulation of macrophages in the lung. Accumulations of macrophages (histiocytes) containing talc particles were also observed in the bronchial lymph nodes

Statistics:

no data

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

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:

not specified

Clinical biochemistry findings:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

A bioassay using mice and rats was performed by the NTP to determine the carcinogenic potential of non-asbestiform, cosmetic-grade talc following exposure by inhalation.
There was no evidence of carcinogenic activity in male or female B6C3F1 mice, some evidence of carcinogenic activity in male F344/rats, and clear evidence of carcinogenic activity in female F344/N rats.
The talc used was asbestos-free and virtually silica-free microtalc; scanning electron microprobe analysis of one lot of talc indicated that 1/1466 particles examined was silica, 136/1466 particles tremolite, and 1241/1466 particles were talc. More than 75% of the particles were in the 1.0 – 3.0 μm range.
There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to talc.

Relevance of carcinogenic effects / potential:

There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to talc.

Dose descriptor:

NOAEC

Effect level:

6 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

histopathology: neoplastic

histopathology: non-neoplastic

organ weights and organ / body weight ratios

other: There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to talc.

Remarks on result:

other:

Remarks:

Changes in the lungs (chronic inflammation and hyperplasia of macrophages).There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to talc.

Dose descriptor:

NOAEC

Effect level:

18 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

histopathology: neoplastic

histopathology: non-neoplastic

other: There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to talc.

Remarks on result:

other:

Remarks:

Changes in the lungs (chronic inflammation and hyperplasia of macrophages).There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to talc.

Critical effects observed:

not specified

Groups of 50 male and 50 female B6C3F1 mice, 7 weeks of age, that were fed an NIH-07 diet, were exposed by inhalation to aerosols containing 0, 6 or 18 mg/m3 MP 10–52 grade talc for 6 hours per day on 5 days per week for up to 104 weeks (dose equivalent, 0, 2 or 6 mg/kg bw per day for male mice and 0, 1.3 or 3.9 mg/kg bw per day for female mice). MP 10–52 grade is a high-purity microtalc (from a strip mine located in Missouri State, USA) that has a maximal particle size of 10 μm and is reported to contain no tremolite or any asbestiform minerals. After analysis, the talc was found to be free of asbestos and almost free of silica. The average mass mean aerodynamic diameter (MMAD) and the geometric standard deviation (GSD) of the talc aerosols were calculated to be 3.3 ± 1.9 μm and 3.6 ± 2.0 μm for the 6- and 18-mg/m3 chambers, respectively. At approximately week 70, difficulties were experienced in generating the talc aerosol, and the chamber concentrations were substantially lower than the target concentrations over a period of 12 weeks. Survival and final mean body weights of male and female mice exposed to talc were similar to those of the controls, and no clinical findings were attributed to exposure to talc. No significant increases in the incidence of neoplasms were observed. The incidence of pulmonary neoplasms (males: 27%, 11% and 23%; females: 11%, 12% and 6%) was similar between exposed and control groups of mice.

Conclusions:

There was no evidence of carcinogenic activity in male or female B6C3F1 mice.

Executive summary:

A 2-yr study was performed in mice; groups of 50 male and 50 female B6C3F1 mice (7 wks old) were exposed to target concentrationsof 0, 6, or 18 mg/m3 talc for 6 h/day, 5 days/wk, for 103-104 wks. The concentrations were selected based on theresults of a 4-wk inhalation study in B6C3F1 mice; These exposure concentrations provideda dose equivalent of 0, 2, or 6 mg/kg/day for male mice, respectively, and 0, 1.3, or 3.9 mg/kg/day for female mice, respectively.

The MMAD was 3.3 ± 1.9 μm in the 6 mg/m3 chamber and 3.6 ± 2.0 μm in the 18 mg/m3 chamber. Groups of 40male and 40 female mice were similarly exposed and killed at 6, 12, and 18 mos for interim microscopic evaluations. Someproblems were experienced in maintaining control of the chamber concentrations, and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations.Mean body wts were similar for test and control animals, and there were no clinical findings attributable to talc exposure.

Reference 3

Endpoint:

carcinogenicity: 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

Principles of method if other than guideline:

A lifetime study was performed in rats; groups of 50 male and 50 female F344/N rats (6-7 wks old) were exposed to the same dosing regimen and target concentrations of talc as mice until mortality reached 80% in any exposure group, i.e., males were exposed for 113 wks and females for 122 wks. (The concentrations selected were based on the results of a 4-wk inhalation study in F344/N rats; The MMAD was 2.7 ± 1.9 μm in the 6 mg/m3 chamber and 3.2 ± 1.9 μm in the 18 mg/m3 chamber. As with the mice, there was difficulty in maintaining the chamber concentrations for the rats; there was a 7-wk period beginning at wk 11 during which time the concentration for the 18 mg/m3 group varied from 30-40 mg/m3 and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations for both groups. Groups of 22 male and 22 female rats were exposed similarly and killed at 6, 11, 18, and 24 mos for interim evaluations. Survival was similar for test and control animals. Body weights of the low dose animals were similar to controls and final body weights of the high dose animals were slightly (14%) lower than controls.
Compared to controls, the absolute and relative lung weights in high dose males were statistically significantly increased in at 6, 11, and 18 mos and at study termination, in high-dose females at 11, 18, and 24 mos and at study termination, and in low dose females at 18-mos and study termination.

GLP compliance:

not specified

Species:

rat

Strain:

Fischer 344

Details on species / strain selection:

groups of 50 male and 50 female F344/N rats (6-7 wks old)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
groups of 50 male and 50 female F344/N rats (6-7 wks old)

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

whole body

Vehicle:

air

Remarks on MMAD:

The MMAD was 2.7 ± 1.9 μm in the 6 mg/m3 chamber and 3.2 ± 1.9 μm in the 18 mg/m3 chamber. As with the mice, there was difficulty in maintaining the chamber concentrations for the rats; there was a 7-wk period beginning at wk 11 during which time the concentration for the 18 mg/m3 group varied from 30-40 mg/m3 and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations for both groups. Groups of 22 male and 22 female rats were exposed similarly and killed at 6, 11, 18, and 24 mos for interim evaluations. Survival was similar for test and control animals. Body weights of the low dose animals were similar to controls and final body weights of the high dose animals were slightly (14%) lower than controls.
Compared to controls, the absolute and relative lung weights in high dose males were statistically significantly increased in at 6, 11, and 18 mos and at study termination, in high-dose females at 11, 18, and 24 mos and at study termination, and in low dose females at 18-mos and study termination.

Details on exposure:

A lifetime study was performed in rats; groups of 50 male and 50 female F344/N rats (6-7 wks old) were exposed to the same dosing regimen and target concentrations of talc as mice until mortality reached 80% in any exposure group, i.e., males were exposed for 113 wks and females for 122 wks. (The concentrations selected were based on the results of a 4-wk inhalation study in F344/N rats; The MMAD was 2.7 ± 1.9 μm in the 6 mg/m3 chamber and 3.2 ± 1.9 μm in the 18 mg/m3 chamber. As with the mice, there was difficulty in maintaining the chamber concentrations for the rats; there was a 7-wk period beginning at wk 11 during which time the concentration for the 18 mg/m3 group varied from 30-40 mg/m3 and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations for both groups. Groups of 22 male and 22 female rats were exposed similarly and killed at 6, 11, 18, and 24 mos for interim evaluations. Survival was similar for test and control animals. Body weights of the low dose animals were similar to controls and final body weights of the high dose animals were slightly (14%) lower than controls.
Compared to controls, the absolute and relative lung weights in high dose males were statistically significantly increased in at 6, 11, and 18 mos and at study termination, in high-dose females at 11, 18, and 24 mos and at study termination, and in low dose females at 18-mos and study termination.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

males rats were exposed for 113 wks and females rats for 122 wks

Frequency of treatment:

6 hours per day on 5 days per week

Dose / conc.:

0 mg/m³ air

Dose / conc.:

6 mg/m³ air

Dose / conc.:

18 mg/m³ air

No. of animals per sex per dose:

groups of 50 male and 50 female B6C3F1 mice (7 wks old)

Control animals:

yes

Details on study design:

A lifetime study was performed in rats; groups of 50 male and 50 female F344/N rats (6-7 wks old) were exposed to the same dosing regimen and target concentrations of talc as mice until mortality reached 80% in any exposure group, i.e., males were exposed for 113 wks and females for 122 wks. (The concentrations selected were based on the results of a 4-wk inhalation study in F344/N rats; The MMAD was 2.7 ± 1.9 μm in the 6 mg/m3 chamber and 3.2 ± 1.9 μm in the 18 mg/m3 chamber. As with the mice, there was difficulty in maintaining the chamber concentrations for the rats; there was a 7-wk period beginning at wk 11 during which time the concentration for the 18 mg/m3 group varied from 30-40 mg/m3 and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations for both groups. Groups of 22 male and 22 female rats were exposed similarly and killed at 6, 11, 18, and 24 mos for interim evaluations. Survival was similar for test and control animals. Body weights of the low dose animals were similar to controls and final body weights of the high dose animals were slightly (14%) lower than controls.
Compared to controls, the absolute and relative lung weights in high dose males were statistically significantly increased in at 6, 11, and 18 mos and at study termination, in high-dose females at 11, 18, and 24 mos and at study termination, and in low dose females at 18-mos and study termination.

Observations and examinations performed and frequency:

At week 11, the chamber concentration for the 18-mg/m3 group varied from approximately 30 to 40 mg/m3 for a period of 7 weeks because of difficulties with the systems used to monitor aerosol concentration. In addition, at approximately week 70, difficulties were experienced in generating the talc aerosol for a period of 12 weeks during which the chamber concentrations were substantially lower than the target concentrations. The survival of treated male and female rats was similar to that of the controls. Mean body weights of rats exposed to 18 mg/m3 were slightly lower than those of controls after week 65. Absolute and relative lung weights of male rats exposed to 18 mg/m3 were significantly greater than those of controls at the 6-, 11- and 18-month interim evaluations and at the end of the lifetime study, while those of female rats exposed to 18 mg/m3 were significantly greater at the 11-, 18- and 24-month interim evaluations and at the end of the lifetime study.
Exposure to talc produced a spectrum of inflammatory, reparative and proliferative processes in the lungs. The principal toxic lesions observed included chronic granulomatous inflammation, alveolar epithelial hyperplasia, squamous metaplasia, squamous cysts and interstitial fibrosis of the lung. The authors considered that the squamous cysts represented a form of squamous metaplasia. The incidence of alveolar/bronchiolar adenoma and carcinoma (combined) in female rats was: control, 1/50 (carcinoma, 0/50); low-dose, 0/48; high-dose, 13/50 (carcinoma, 5/50) and was significantly greater (P < 0.001) in the high-dose group than in controls (carcinoma, P = 0.028). The incidence of pulmonary neoplasms in exposed male rats was similar to that in controls. Adrenal medulla pheochromocytomas (benign and malignant combined) occurred with a significantly positive trend in males (control, 26/49; low-dose, 32/48; high-dose, 37/47; P = 0.007) and females (control, 13/48; low-dose, 14/47; high-dose, 23/49; P = 0.014), and the incidence in the high-dose groups was significantly greater than that in controls (P = 0.006 for males, P = 0.024 for females). The incidence of malignant pheochromocytomas in females was: control, 0/48; low-dose, 1/47; high-dose, 10/49 (P = 0.001). Although adrenal medulla hyperplasia occurred with similar frequency among exposed and control females, the incidence of hyperplasia in exposed males was significantly lower than that in controls

Statistics:

no data

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

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:

not specified

Clinical biochemistry findings:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

The rats were exposed to 6 mg/m3 (MMAD 2.7 ± 1.9 μm) or 18 mg/m3 (MMAD 3.2 ± 1.9 μm) talc for 6 h/day, 5 days/wk, for 113 wks (males) or 122 wks (females). Concerns have been raised about this study, including concerns that micronized talc having a significantly smaller particle size distribution than cosmetic talc was used, aerosol concentrations were not properly controlled, proper procedures for dose selection were not followed resulting in the MTD being exceeded at both concentrations tested, and particle overload in the lungs was most likely the cause of the adverse effects reported

Relevance of carcinogenic effects / potential:

A bioassay using rats was performed by the NTP to determine the carcinogenic potential of non-asbestiform, cosmetic-grade micro-talc following exposure by inhalation, and it was concluded there was some evidence of carcinogenic activity in male F344/rats, and clear evidence of carcinogenic activity in female F344/N rats. The rats were exposed to 6 mg/m3 (MMAD 2.7 ± 1.9 μm) or 18 mg/m3 (MMAD 3.2 ± 1.9 μm) talc for 6 h/day, 5 days/wk, for 113 wks (males) or 122 wks (females). Concerns have been raised about this study, including concerns that micronized talc having a significantly smaller particle size distribution than cosmetic talc was used, aerosol concentrations were not properly controlled, proper procedures for dose selection were not followed resulting in the MTD being exceeded at both concentrations tested, and particle overload in the lungs was most likely the cause of the adverse effects reported.
The talc used in the this study was a commercially available microtalc whose dimensions of < 10 µm were distinctly finer than the cosmetic powder normally used. Therefore, the study is not conclusive with regard to a possible carcinogenicity of large talc platelets or talc fibres.

Dose descriptor:

NOAEC

Effect level:

18 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

histopathology: neoplastic

histopathology: non-neoplastic

other:

Remarks on result:

other:

Remarks:

Changes in the lungs (chronic inflammation and hyperplasia of macrophages).There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to talc.

Dose descriptor:

NOAEC

Effect level:

6 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

histopathology: neoplastic

histopathology: non-neoplastic

other:

Critical effects observed:

not specified

A bioassay using rats was performed by the NTP to determine the carcinogenic potential of non-asbestiform, cosmetic-grade micro-talc following exposure by inhalation, andit was concluded there was some evidence of carcinogenicactivity in male F344/rats, and clear evidence of carcinogenic activity in female F344/N rats. The rats were exposed to 6 mg/m3 (MMAD 2.7 ± 1.9 μm) or 18 mg/m3 (MMAD 3.2 ± 1.9 μm) talc for 6 h/day, 5 days/wk, for 113wks (males) or 122 wks (females).Concerns have been raised about this study, including concerns that micronized talc having a significantly smaller particle size distribution than cosmetic talc was used, aerosol concentrations were not properlycontrolled, proper procedures for dose selection were not followed resulting in the MTD being exceeded at both concentrationstested, and particle overload in the lungs was most likely the cause of the adverse effects reported.

Conclusions:

It was concluded that there was some evidence of carcinogenic activity of talc in male F344/rats based on an increased incidence of benign or malignant pheochromocytomas of the adrenal gland and clear evidence of carcinogenic activity of talc in female F344/N rats based on increased incidences of alveolar/bronchiolar adenomas and carcinomas of the lung and benign or malignant pheochromocytomas of the adrenal gland.
Concerns have been raised about this study, including concerns that micronized talc having a significantly smaller particle size distribution than cosmetic talc was used, aerosol concentrations were not properlycontrolled, proper procedures for dose selection were not followed resulting in the MTD being exceeded at both concentrationstested, and particle overload in the lungs was most likely the cause of the adverse effects reported.
The talc used in the this study was a commercially available microtalc whose dimensions of < 10 µm were distinctly finer than the cosmetic powder normally used.
Therefore, the study is not conclusive with regard to a possible carcinogenicity of large talc platelets or talc fibres.

Executive summary:

A bioassay using rats was performed by the NTP to determine the carcinogenic potential of non-asbestiform, cosmetic-grade micro-talc following exposure by inhalation, andit was concluded there was some evidence of carcinogenicactivityin male F344/rats, and clear evidence of carcinogenic activity in female F344/N rats. The ratswere exposed to 6 mg/m3 (MMAD 2.7 ± 1.9 μm) or 18 mg/m3 (MMAD 3.2 ± 1.9 μm) talc for 6 h/day, 5 days/wk, for 113wks (males) or 122 wks (females).Concerns have been raised about this study, including concerns that micronized talc having a significantly smaller particle size distribution than cosmetic talc was used, aerosol concentrations were not properlycontrolled, proper procedures for dose selection were not followed resulting in the MTD being exceeded at both concentrationstested, and particle overload in the lungs was most likely the cause of the adverse effects reported.

The talc used in the this study was a commercially available microtalc whose dimensions of < 10 µm were distinctly finer than the cosmetic powder normally used.

Therefore, the study is not conclusive with regard to a possible carcinogenicity of large talc platelets or talc fibres.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

18 mg/m³

Study duration:

chronic

Species:

mouse

Quality of whole database:

Inhalation effects:
A 2-yr study was performed in mice; groups of 50 male and 50 female B6C3F1 mice (7 wks old) were exposed to target concentrationsof 0, 6, or 18 mg/m3 talc for 6 h/day, 5 days/wk, for 103-104 wks. The concentrations were selected based on theresults of a 4-wk inhalation study in B6C3F1 mice; These exposure concentrations provideda dose equivalent of 0, 2, or 6 mg/kg/day for male mice, respectively, and 0, 1.3, or 3.9 mg/kg/day for female mice, respectively.
The MMAD was 3.3 ± 1.9 μm in the 6 mg/m3 chamber and 3.6 ± 2.0 μm in the 18 mg/m3 chamber. Groups of 40male and 40 female mice were similarly exposed and killed at 6, 12, and 18 mos for interim microscopic evaluations. Someproblems were experienced in maintaining control of the chamber concentrations, and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations.Mean body wts were similar for test and control animals, and there were no clinical findings attributable to talc exposure.

Carcinogenicity: via dermal route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: 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

Qualifier:

no guideline followed

Principles of method if other than guideline:

In a lifetime experiment, three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age, were exposed by inhalation to an aerosol of talc baby powder that was prepared from Vermont talc by flotation (95% w/w platy talc with trace quantities of magnesite, dolomite, chlorite and rutile) for 3, 30 or 150 minute per day on 5 days a week for 30 days. The mean aerosol concentration was 37.1 mg/m3, with a measurable respiratory fraction of 9.8 mg/m3 and a MMAD of 4.9 μm. A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days. The mean aerosol concentration was 27.4 mg/m3, with a measurable respiratory fraction of 8.1 mg/m3 and a MMAD of 6.0 μm. Another sham-exposed group comprised 25 males and 25 females. The survivors of the last two talc-exposed groups were killed at the age of 20 months.

GLP compliance:

not specified

Species:

hamster

Strain:

other: Syrian golden hamsters

Details on species / strain selection:

three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: The mean aerosol concentration was 37.1 mg/m3, with a measurable respiratory fraction of 9.8 mg/m3 and a MMAD of 4.9 μm.
A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days. The mean aerosol concentration was 27.4 mg/m3, with a measurable respiratory fraction of 8.1 mg/m3 and a MMAD of 6.0 μm. Another sham-exposed group comprised 25 males and 25 females.

Details on exposure:

Groups of 50 male and 50 female Syrian golden hamsters were exposed to talc aerosol for 3, 30 or 150min/day, 5 days/wk for 30 days, or for 30 or 150min/day either until they died naturally or for a maximum of 300 days. The mean concentration of the ‘respirable’ aerosol fraction was approximately 8 μg/litre and the mass mean aerodynamic diameter was 6 μm. Following the exposures, the animals were observed for the remainder of their lifespan. At death, lungs trachea, larynx, liver, one kidney, stomach, uterus, one ovary, or one testis, and all tissues showing gross lesions were collected for histopathological examination. Deposition of talc particles in the lungs of the exposed animals was demonstrated by X-ray fluorescence and by X-ray diffraction.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

30 days

Frequency of treatment:

3, 30 or 150min/day, 5 days/wk for 30 days, or for 30 or 150min/day

Post exposure period:

300 days

Dose / conc.:

37.1 mg/m³ air

Dose / conc.:

27.4 mg/m³ air

Dose / conc.:

9.8 mg/m³ air

Dose / conc.:

8.1 mg/m³ air

No. of animals per sex per dose:

three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age,

Control animals:

yes

Details on study design:

In a lifetime experiment, three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age, were exposed by inhalation to an aerosol of talc baby powder that was prepared from Vermont talc by flotation (95% w/w platy talc with trace quantities of magnesite, dolomite, chlorite and rutile) for 3, 30 or 150 minute per day on 5 days a week for 30 days. The mean aerosol concentration was 37.1 mg/m3, with a measurable respiratory fraction of 9.8 mg/m3 and a MMAD of 4.9 μm. A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days. The mean aerosol concentration was 27.4 mg/m3, with a measurable respiratory fraction of 8.1 mg/m3 and a MMAD of 6.0 μm. Another sham-exposed group comprised 25 males and 25 females. The survivors of the last two talc-exposed groups were killed at the age of 20 months.

Positive control:

A group of 25 male and 25 female guinea pigs served as the control group. A single tier exposure was used.A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days.

Observations and examinations performed and frequency:

Following the exposures, the animals were observed for the remainder of their lifespan. At death, lungs trachea, larynx, liver, one kidney, stomach, uterus, one ovary, or one testis, and all tissues showing gross lesions were collected for histopathological examination. Deposition of talc particles in the lungs of the exposed animals was demonstrated by X-ray fluorescence and by X-ray diffraction.

Sacrifice and pathology:

Syrian golden hamsters exposed to 8.1-mg/m3 aerosols of cosmetic-grade talc for up to 150 minutes per day on 5 days a week for 30 days showed no histopathological change in the lungs, heart, liver, renal tissues, stomach or uterus.

Other examinations:

no

Statistics:

no data

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

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:

not specified

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

Exposure of hamsters to talc via inhalation did not produce carcinogenic effects. Groups of 50 male and 50 female Syrian golden hamsters were exposed for 30 or 150 min/day, 5 days/wk, to 27.4 ± 3.4 μg/l mean total aerosol concentration commercial baby powder (95% w/w platy talc with trace quantities of carbonates and platy chlorite and rutile) until natural death, or, for a maximum of 300 days. A group of 25 male and 25 female guinea pigs served as the control group. A single tier exposure was used. There was no statistically significant difference in survival time among groups, but there was a significant difference between males and females within all groups. No clinical signs of toxicity to talc were observed. The type, incidence, and severity of lesions indicated no trend toward a dose-response and no statistically significant differences between exposed and control groups. The incidence of focal alveolar cell hyperplasia (25% in treated groups; 10% in controls) appeared to be affected by treatment, but a two-way weighted analysis showed no significant association.

Relevance of carcinogenic effects / potential:

In a lifetime inhalation study, a carcinogenic effect was not observed upon exposure of hamsters to a commercial baby powder containing 95% platy talc for 30 or 150 min/day, 5 days/wk.

Dose descriptor:

NOAEC

Effect level:

8.1 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

histopathology: neoplastic

histopathology: non-neoplastic

other: In a lifetime inhalation study, a carcinogenic effect was not observed upon exposure of hamsters to a commercial baby powder containing 95% platy talc for 30 or 150 min/day, 5 days/wk.

Remarks on result:

other:

Remarks:

Syrian golden hamsters exposed to 8.1-mg/m3 aerosols of cosmetic-grade talc for up to 150 minutes per day on 5 days a week for 30 days showed no histopathological change in the lungs, heart, liver, renal tissues, stomach or uterus.

Critical effects observed:

not specified

Exposure of hamsters to talc via inhalation did not produce carcinogenic effects. Groups of 50 male and 50 female Syriangolden hamsters were exposed for 30 or 150 min/day, 5 days/wk, to 27.4 ± 3.4 μg/l mean total aerosol concentration commercialbaby powder (95% w/w platy talc with trace quantities of carbonates and platy chlorite and rutile) until natural death,or, for a maximum of 300 days. A group of 25 male and 25 female guinea pigs served as the control group. A single tier exposurewas used. There was no statistically significant difference in survival time among groups, but there was a significantdifference between males and females within all groups. No clinical signs of toxicity to talc were observed. The type, incidence,and severity of lesions indicated no trend toward a dose-response and no statistically significant differences betweenexposed and control groups. The incidence of focal alveolar cell hyperplasia (25% in treated groups; 10% in controls) appearedto be affected by treatment, but a two-way weighted analysis showed no significant association.

Conclusions:

In a lifetime inhalation study, a carcinogenic effect was not observed upon exposure of hamsters to a commercial baby powder containing 95% platy talc for 30 or 150 min/day, 5 days/wk.

Executive summary:

Exposure of hamsters to talc via inhalation did not produce carcinogenic effects.

In a lifetime experiment, three groups of 50 male and 50 female Syrian golden hamsters, 4 weeks of age, were exposed by inhalation to an aerosol of talc baby powder that was prepared from Vermont talc by flotation (95% w/w platy talc with trace quantities of magnesite, dolomite, chlorite and rutile) for 3, 30 or 150 minute per day on 5 days a week for 30 days. The mean aerosol concentration was 37.1 mg/m3, with a measurable respiratory fraction of 9.8 mg/m3 and a MMAD of 4.9 μm. A sham-exposed group comprised 25 males and 25 females. Two further groups of hamsters, 7 weeks of age, were exposed to talc aerosol for 30 or 150 minute per day for 300 days. The mean aerosol concentration was 27.4 mg/m3, with a measurable respiratory fraction of 8.1 mg/m3 and a MMAD of 6.0 μm. Another sham-exposed group comprised 25 males and 25 females. The survivors of the last two talc-exposed groups were killed at the age of 20 months.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2.5 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Dermal Effects:
For dermal exposure we taken that:
-the average weight of rats is 250 g,
-the dose is applied over an area which is approximately 10% of the total body surface=0.008 kg

corrected dermal NOAEL= oral NOAEL
100 mg/kg bw/dx 0.025 kg =
NOAECrat 2.5 mg/kg bw/day

Mode of Action Analysis / Human Relevance Framework

There are conclusive but not suffcient data for the classification of substance Talc (Mg3H2(SiO3)4) with regard to carcinogenicity

Justification for classification or non-classification

 Based on the hazard assessment of Talc (Mg3H2(SiO3)4) in section 2.1 and 2.2. in IUCLID 6, available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99) and according to the criteria described in Directive 67/548 and in the CLP Regulation:

 

Directive 67/548	Carcinogenicity Carc. Cat. 1; R45 May cause cancer. Carc. Cat. 1; R49 May cause cancer by inhalation. Carc. Cat. 2; R45 May cause cancer. Carc. Cat. 2; R49 May cause cancer by inhalation. Carc. Cat. 3; R40 Limited evidence of a carcinogenic effect.
CLP	Carcinogenicity Carc. 1A Carc. 1B Carc. 2 H350: May cause cancer <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H351: Suspected of causing cancer <state route of exposure if it is conclusively proven that no other routs of exposure cause the hazard>.

 

 

It is concluded that the Talc (Mg3H2(SiO3)4)does not meet the criteria to be classified for human health hazards for Carcinogenicity.

 

Additional information

Oral effects:

Under the condition of this study, for a period of 101 days for male and female rats, the NOAEL of Talc In a feeding study was 100 mg/kg/day. No adverse effects were seen on general toxicity endpoints.

 One of the animals treated with talc showed a leiomyosarcoma of the stomach. Sarcomas, which were however not associated with the talc treatment, were found in the uterus of two animals.

 No chronic pathological effect was associated with oral administration of Italian talc (92% pure; 100 mg per day on 101 days over 5 months) to rats.

No differences in tumour incidence were noted between treated animals and eight male and eight female control animals fed basal diet throughout (average survival, 641 days)

 

Inhalation effects:

 

A 2-yr study was performed in mice; groups of 50 male and 50 female B6C3F1 mice (7 wks old) were exposed to target concentrationsof 0, 6, or 18 mg/m3 talc for 6 h/day, 5 days/wk, for 103-104 wks. The concentrations were selected based on theresults of a 4-wk inhalation study in B6C3F1 mice; These exposure concentrations provideda dose equivalent of 0, 2, or 6 mg/kg/day for male mice, respectively, and 0, 1.3, or 3.9 mg/kg/day for female mice, respectively.

The MMAD was 3.3 ± 1.9 μm in the 6 mg/m3 chamber and 3.6 ± 2.0 μm in the 18 mg/m3 chamber. Groups of 40male and 40 female mice were similarly exposed and killed at 6, 12, and 18 mos for interim microscopic evaluations. Someproblems were experienced in maintaining control of the chamber concentrations, and there was a 12-wk period beginning at wk 70 during which the chamber concentrations were substantially lower than the target concentrations.Mean body wts were similar for test and control animals, and there were no clinical findings attributable to talc exposure.

 

There was no evidence of carcinogenic activity in male or female B6C3F1 mice.

 

Dermal Effects:

For dermal exposure we taken that:

-the average weight of rats is 250 g,

-the dose is applied over an area which is approximately 10% of the total body surface=0.008 kg

 

corrected dermal NOAEL=    oral NOAEL

                                   100 mg/kg bw/dx 0.025 kg =                   

 NOAECrat      2.5 mg/kg bw/day