Talc (Mg3H2(SiO3)4)

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study.

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

Specific details on test material used for the study:

“Italian talc” (about92% talc, 3% chlorite, 1% carbonate minerals and 0.5–1% quartz)
Italian talc (grade 00000; ready milled; mean particle size, 25 μm;

Test animals

Species:

rat

Strain:

Wistar

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

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral 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

Duration of treatment / exposure:

101 days

Frequency of treatment:

7 days per week

Doses / concentrations

Dose / conc.:

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

No. of animals per sex per dose:

16 male and 16 female Wistar rats

Control animals:

yes, plain diet

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:

no

Examinations

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

HISTOPATHOLOGY: Yes

Other examinations:

No

Results and discussion

Results of examinations

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):

no effects observed

Food efficiency:

not specified

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

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

Effect levels

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: 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

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

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.

100 mg/day and animal: tumours in the stomach (1/16 animals with leiomyosarcoma) and in the uterus (2/16 animals with sarcomas, which were not attributed to treatment)

Applicant's summary and conclusion

Conclusions:

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.

Executive summary:

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)