Talc (Mg3H2(SiO3)4)

Endpoint summary

Description of key information

Oral repeated dose toxicity

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.

Inhalation repeated dose toxicity

F344 rats and B6C3F1 mice were exposed to talc by inhalation for 20 days. The concentrations were 0, 2, 6, and 18 mg/m3. The animals were exposed for 6 hours a day and 5 days per week. Lung burdens in rats increased from 70 µg talc/g lung in the 2 mg/m3 group to 720 µg talc/g lung in the 18 mg/m3 group. The histopathological examinations after 20 days of exposure did not show any exposure-induced lesions in the highest exposure group so that the specimens of the lower exposure groups were not examined.

Dermal repeated dose toxicity

No studies were located regarding long term exposure local effects in animals after dermal exposure to talc

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

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.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 452 (Chronic Toxicity Studies)

GLP compliance:

not specified

Limit test:

no

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;

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

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

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

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

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

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

Critical effects observed:

not specified

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)

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)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

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.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 452 (Chronic Toxicity Studies)

GLP compliance:

not specified

Limit test:

no

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

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.

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

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

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

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

Critical effects observed:

not specified

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

10.8 mg/m³

Study duration:

chronic

Species:

rat

Quality of whole database:

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.

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

sub-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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

20 F344/Crl rats (10 male and 10 female)

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: The mass median aerodynamic diameter (MMAD) of the talc aerosol was 3.0 microns with a geometric standard deviation (sigma g) of 1.9.

Details on inhalation exposure:

F344 rats and B6C3F1 mice were exposed to talc by inhalation for 20 days. The concentrations were 0, 2, 6, and 18 mg/m3. The animals were exposed for 6 hours a day and 5 days per week. Afterwards, the lung burden was investigated in half of the animals exposed. The talc concentration in the lungs was determined via the acid-insoluble fraction of magnesium. The other half of the animals was examined histopathologically.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

20 days

Frequency of treatment:

6 hours a day and 5 days per week

Dose / conc.:

0 mg/m³ air

Dose / conc.:

2 mg/m³ air

Dose / conc.:

6 mg/m³ air

Dose / conc.:

18 mg/m³ air

No. of animals per sex per dose:

10 male and 10 female

Control animals:

not specified

Details on study design:

F344 rats and B6C3F1 mice were exposed to talc by inhalation for 20 days. The concentrations were 0, 2, 6, and 18 mg/m3. The animals were exposed for 6 hours a day and 5 days per week. Afterwards, the lung burden was investigated in half of the animals exposed. The talc concentration in the lungs was determined via the acid-insoluble fraction of magnesium. The other half of the animals was examined histopathologically.

Positive control:

no

Observations and examinations performed and frequency:

- multi-tiered inhalation chambers were used;
animals were killed 24 h after the last exposure;
lung burdens were measured in half of the animals and the other half were used for microscopic examination
- this study was used to determine the exposure concentrations for a 2-yr NTP bioassay

Sacrifice and pathology:

- lung burden averaged 0, 100, 290, and 1020 μg talc/g lung for control, low, mid, and high dose, respectively;
lung burdens normalized for lung wt and exposure conc: n/a, 46, 51, and 50 μg talc/g lung/mg/m3, respectively
- no exposure-related abnormalities were seen at necropsy; microscopically, the only exposure-related lesion was a modest, diffuse increase in free macrophages within the alveolar space; the macrophages, which were focally aggregated, contained talc particles

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:

- lung burden averaged 0, 100, 290, and 1020 μg talc/g lung for control, low, mid, and high dose, respectively;
lung burdens normalized for lung wt and exposure conc: n/a, 46, 51, and 50 μg talc/g lung/mg/m3, respectively
- no exposure-related abnormalities were seen at necropsy; microscopically, the only exposure-related lesion was a modest, diffuse increase in free macrophages within the alveolar space; the macrophages, which were focally aggregated, contained talc particles

Dose descriptor:

NOAEC

Effect level:

2 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: increase of the lung burden, no relevant histopathological findings

Dose descriptor:

NOAEC

Effect level:

18 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: increase of the lung burden, no relevant histopathological findings

Critical effects observed:

not specified

F344 rats and B6C3F1 mice were exposed to talc by inhalation for 20 days. The concentrations were 0, 2, 6, and 18 mg/m3. The animals were exposed for 6 hours a day and 5 days per week. Afterwards, the lung burden was investigated in half of the animals exposed. The talc concentration in the lungs was determined via the acid-insoluble fraction of magnesium. The other half of the animals was examined histopathologically. Lung burdens in rats increased from 70 µg talc/g lung in the 2 mg/m3 group to 720 µg talc/g lung in the 18 mg/m3 group. After normalization for exposure, a statistically significant increase of 30 µg talc/g lung per mg/m3 (2 mg/m3 group) to 42 µg talc/g lung per mg/m3 (18 mg/m3 group) was detected. In mice, the lung burden increased from 100 µg talc/g lung (2 mg/m3 group) to 1020 µg talc/g lung (18 mg/m3 group). Normalization for exposure revealed clearly higher lung burdens for mice than for rats, the normalized lung burdens of 46, 51 and 51 µg talc/g lung per mg/m3 not differing to a relevant extent in the various exposure groups. The histopathological examinations after 20 days of exposure did not show any exposure-induced lesions in the highest exposure group so that the specimens of the lower exposure groups were not examined.

Conclusions:

F344 rats and B6C3F1 mice were exposed to talc by inhalation for 20 days. The concentrations were 0, 2, 6, and 18 mg/m3. The animals were exposed for 6 hours a day and 5 days per week. Afterwards, the lung burden was investigated in half of the animals exposed. The talc concentration in the lungs was determined via the acid-insoluble fraction of magnesium. The other half of the animals was examined histopathologically. Lung burdens in rats increased from 70 µg talc/g lung in the 2 mg/m3 group to 720 µg talc/g lung in the 18 mg/m3 group. After normalization for exposure, a statistically significant increase of 30 µg talc/g lung per mg/m3 (2 mg/m3 group) to 42 µg talc/g lung per mg/m3 (18 mg/m3 group) was detected. In mice, the lung burden increased from 100 µg talc/g lung (2 mg/m3 group) to 1020 µg talc/g lung (18 mg/m3 group). Normalization for exposure revealed clearly higher lung burdens for mice than for rats, the normalized lung burdens of 46, 51 and 51 µg talc/g lung per mg/m3 not differing to a relevant extent in the various exposure groups. The histopathological examinations after 20 days of exposure did not show any exposure-induced lesions in the highest exposure group so that the specimens of the lower exposure groups were not examined

Executive summary:

F344 rats and B6C3F1 mice were exposed to talc by inhalation for 20 days. The concentrations were 0, 2, 6, and 18 mg/m3. The animals were exposed for 6 hours a day and 5 days per week. Afterwards, the lung burden was investigated in half of the animals exposed. The talc concentration in the lungs was determined via the acid-insoluble fraction of magnesium. The other half of the animals was examined histopathologically. Lung burdens in rats increased from 70 µg talc/g lung in the 2 mg/m3 group to 720 µg talc/g lung in the 18 mg/m3 group. After normalization for exposure, a statistically significant increase of 30 µg talc/g lung per mg/m3 (2 mg/m3 group) to 42 µg talc/g lung per mg/m3 (18 mg/m3 group) was detected. In mice, the lung burden increased from 100 µg talc/g lung (2 mg/m3 group) to 1020 µg talc/g lung (18 mg/m3 group). Normalization for exposure revealed clearly higher lung burdens for mice than for rats, the normalized lung burdens of 46, 51 and 51 µg talc/g lung per mg/m3 not differing to a relevant extent in the various exposure groups. The histopathological examinations after 20 days of exposure did not show any exposure-induced lesions in the highest exposure group so that the specimens of the lower exposure groups were not examined

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

18 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

F344 rats and B6C3F1 mice were exposed to talc by inhalation for 20 days. The concentrations were 0, 2, 6, and 18 mg/m3. The animals were exposed for 6 hours a day and 5 days per week. Lung burdens in rats increased from 70 µg talc/g lung in the 2 mg/m3 group to 720 µg talc/g lung in the 18 mg/m3 group. The histopathological examinations after 20 days of exposure did not show any exposure-induced lesions in the highest exposure group so that the specimens of the lower exposure groups were not examined.

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2.5 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
No studies were located regarding long term exposure local effects in animals after dermal exposure to talc


For dermal exposure we taken that:
-the average weight of rats is 250g (200-300g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
corrected dermal NOAEL= oral NOAEL
100 mg/kg bw/dayx0.025 kg =
NOAELrat = 2.5 mg/kg bw/day

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

12.5 mg/cm²

Study duration:

subacute

Species:

rat

Quality of whole database:

Justification for selection of repeated dose toxicity dermal - local effects endpoint:

The dose descriptor for dermal irritation/corrosion come from dermal acute study
In these studies, the dose is reported in the unit mg/kg of body weight/day.
This needs to be modified to enable comparison with the human exposure, generally expressed in mg/cm2/day.
We have taken that:
• the average weight of rats is 230g (210 -251.5g),
• the dose is applied over an area which is approximately 10% of the total body surface, and
• the total body surface of rats is on the average 376 cm2

The generic modification from the dose in mg/kg bw to NOAECmodified(in mg/cm2/day) will be
NOAEC in mg/cm2 =((average animal weight in kg) x (dose in mg/kg bw)) / Treated surface in cm2)
NOAEC in mg/cm2 = (0.23 x 2000)/36.7 =12.5 mg/cm2
-The dose was 2000 mg/kg bw in the acute study
- average animal weight in kg was 0.23 kg
- Treated surface in cm2 was 36.7 cm2
NOAEC in mg/cm2 = (0.23 x 2000)/36.7 =12.5 mg/cm2

Additional information

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint: 

No studies were located regarding long term exposure local effects in animals after dermal exposure to talc

 

 

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

 corrected dermal NOAEL=   oral NOAEL

100 mg/kg bw/dayx0.025 kg =                  

 NOAELrat  = 2.5 mg/kg bw/day

 

 

No studies were located regarding long term exposure systemic effects in animals after dermal exposure to talc

 

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

 corrected dermal NOAEL=   oral NOAEL

100 mg/kg bw/dayx0.025 kg =                  

 NOAELrat  = 2.5 mg/kg bw/day

Justification for selection of repeated dose toxicity dermal - local effects endpoint: 

 

The dose descriptor for dermal irritation/corrosion come from dermal acute study

In these studies, the dose is reported in the unit mg/kg of body weight/day.

This needs to be modified to enable comparison with the human exposure, generally expressed in mg/cm2/day.

We have taken that:

• the average weight of rats is 230g (210 -251.5g),

• the dose is applied over an area which is approximately 10% of the total body surface, and

• the total body surface of rats is on the average 376 cm2 

                                       

The generic modification from the dose in mg/kg bw to NOAECmodified(in mg/cm2/day) will be  

NOAEC in mg/cm2 =((average animal weight in kg) x (dose in mg/kg bw)) / Treated surface in cm2)  

NOAEC in mg/cm2 =      (0.23 x 2000)/36.7 =12.5 mg/cm2  

-The dose was 2000 mg/kg bw in the acute study

- average animal weight in kg was 0.23 kg

 - Treated surface in cm2 was 36.7 cm2

  NOAEC in mg/cm2 =       (0.23 x 2000)/36.7 =12.5 mg/cm2

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

Repeated dose toxicity R33 Danger of cumulative effects. T; R48/23 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation. T; R48/23/24 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin. T; R48/23/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed. T; R48/23/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed. T; R48/24 Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin. T; R48/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed. T; R48/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure if swallowed. Xn; R48/20 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation. Xn; R48/20/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin. Xn; R48/20/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed. Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and if swallowed. Xn; R48/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin. Xn; R48/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed. Xn; R48/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure if swallowed

CLP

Repeated dose toxicity STOT Rep. Exp. 1 STOT Rep. Exp. 2 H372: Causes damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H373: May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

It is concluded that the substance Talc (Mg3H2(SiO3)4) does not meet the criteria to be classified for human health hazards for Repeated dose toxicity