Talc (Mg3H2(SiO3)4)

Endpoint summary

Description of key information

Acute oral toxicity:

The oral LD50 of 18.3% talc in saline was >5000 mg/kg. A single oral dose of 5000 mg/kg of talc prepared as an 18.3% (w/v) suspension in saline was administered to 10 male rats. All animals survived, and there were no signs of toxicity.

 

Acute dermal toxicity:

 

Talc is used as a cosmetic powder and to powder gloves. There are no indications of Acute toxicity dermal. The study is therefore considered scientifically unjustified. Therefore testing for Acute toxicity dermal does not need to be performed.

 

Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium chloride also should be taken into account.

 

Magnesium chloride has of relatively low acute toxicity ( LD50, dermal, rat: >2000 mg/kg bw day;

 

Acute inhalation toxicity:

 

There are no Acute toxicity studies available on the inhalative uptake of talc without asbestos fibres. There are no indications of Acute toxicity inhalation of talc without asbestos fibres. The study is therefore considered scientifically unjustified. Therefore testing for Acute toxicity inhalation does not need to be performed.

 

Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium hydroxide also should be taken into account

 

Magnesium hydroxide has of relatively low acute toxicity (LC50, inhalation, rat: 2100 mg/m3);

 

It is concluded that the substanceTalc (Mg3H2(SiO3)4) does not meet the criteria to be classified for human health hazards for Acute dose toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS (The animals were derived from a controlled full barrier maintained breeding system (SPF). According to Art. 9.2, No.7 of the German Act of Animal Welfare the animals were bred for experimental purposes.)
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: Animals no. 1 - 3, step 1: 151 - 158 g; Animals no. 4 - 6, step 2: 161 -170 g
- Fasting period before study: Prior to administration food was withhel from the test animals for 16 to 19 hours (access to water was permitted). Food was provided again approximately 3 -4 hours post dosing.
- Housing: full-barrier in an air-conditioned room; The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 06.06.09)
- Diet: Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1452)
- Water: Free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, multicipal residue control, microbiological control at regular intervals.)
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Air changes: 10x / hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Route of administration:

oral: gavage

Vehicle:

physiological saline

Details on oral exposure:

A single oral dose of 5000 mg/kg of talc prepared as an 18.3% (w/v) suspension in saline was administered to 10 male rats.
The dose formulations were made shortly before each dosing occasion.
No further information on the oral exposure was stated.

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

10 male rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: All animals were observed for 14 days after dosing for general clinical signs morbidity and mortality.
- Frequency of observations and weighing: Prior to the administration a detailed clinical observation was made of all animals. Following the period of fasting the animals were weighed and the test item was administered.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also, respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: Yes
All animals were subjected to gross necropsy. All gross pathological changes were recorded.
No further information on the study design was stated.

Statistics:

No data

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: No signs of toxicity were observed in any of the animals.

Gross pathology:

No special gross pathological changes were recorded for any animal.

Other findings:

No data

Absolute Body Weights in g and Body Weight Gain in %

Animal no. / sex	g Day 1	g Day 8	g Day 15	% Day 1-15
Step 1 (5000 mg/kg bw)
1 / male	158	182	192	+22
2 / male	155	176	187	+21
3 / male	151	165	171	+13
Step 2 (5000 mg/kg bw)
4 / male	170	203	215	+26
5 / male	161	182	199	+24
6 / male	162	194	204	+26

 

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study, a single oral application of the test item Talc (Mg3H2(SiO3)4) to rats at a dose of 5000 mg/kg body weight was associated with no signs of toxicity or mortality.
A single oral dose of 5000 mg/kg of talc prepared as an 18.3% (w/v) suspension in saline was administered to 10 male rats. All animals survived, and there were no signs of toxicity.
The median lethal dose of Talc (Mg3H2(SiO3)4) after a single oral administration to male rats, observed over a period of 14 days is :LD50 >5000 mg/kg body weight.

Executive summary:

Throughout the 14-day observation period, all animals survived until the end of the study without showing any signs of toxicity.

A single oral dose of 5000 mg/kg of talc prepared as an 18.3% (w/v) suspension in saline was administered to 10 male rats. All animals survived, and there were no signs of toxicity. In conclusion, the median lethal dose of Talc (Mg3H2(SiO3)4) after a single oral administration to male rats, observed over a period of 14 days is :LD50 >5000 mg/kg body weight

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The oral LD50 of 18.3% talc in saline was >5000 mg/kg. A single oral dose of 5000 mg/kg of talc prepared as an 18.3% (w/v) suspension in saline was administered to 10 male rats. All animals survived, and there were no signs of toxicity.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

other: Published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliability score 2 on the basis of the weight of evidence found during review of public documents existing relating to toxicological data

Justification for type of information:

Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium hydroxide also should be taken into account

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species
Rat: Crl:WI(Han) (outbred, SPF-Quality)
Recognised by international guidelines as the recommended test system (e.g. OECD, EC).
Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals
5 males and 5 females (females were nulliparous and non-pregnant) per exposure level.
Age and body weight
Young adult animals were selected (approximately \ weeks old).
Animals used within the study were of approximately the same age and body weight variation did not exceed +/- 20% of the sex mean.
Identification
Earmark
Health inspection
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Test atmosphere generation
Administering the test substance to a stream of dry pressurized air using a combination of a spiral feeder and air mover generated an aerosol. The aerosol was passed through a cyclone, allowing larger particles to settle, before it entered the exposure chamber (Appendix 1, Figure 1). The mean total airflow was 47 L/min. From the exposure chamber the test atmosphere was passed through a filter before it was released to the exhaust of the fume hood.

Nominal concentration
The nominal concentration was calculated by dividing the amount of test substance used by the volume of pressurized air (average air flow times exposure time) entering the exposure chamber used for exposure of the animals.

Actual concentration
The actual concentration was determined twelve times during the exposure period. Samples were drawn from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber. Samples were drawn through a glass fiber filter (type APFC04700, Millipore, Billerica, MA, USA). The collected amount of the test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).

Subsequently the mean concentration with the standard deviation was calculated.

The particle size distribution was characterized twice during the exposure period. The samples were drawn (2 L/min) from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber (Appendix 1, Figures 1 and 2). The samples were collected with an 8 stage Marple personal cascade impactor containing fiber glass filters (SKC 225-713, fiber glass, SKC Omega Specialty Division, Chelmsford, MA, USA) and a fiber glass back-up filter (SEC-290-GFS, Westech, Upper Stondon, Bedfordshire, England). Amounts of test substance collected were measured gravimetrically. Subsequently the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD) were determined.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The collected amount of the test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).

Duration of exposure:

4 h

Concentrations:

The mean actual concentration was 2.1 ± 0.47 mg/L. The nominal concentration was 21.7 mg/L resulting in a generation efficiency (ratio of actual and nominal concentration) of 10%. The concentration measurements distributed over time showed that the substance was sufficiently stable

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Days 1 (pre-administration), 2, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: On Day 1, one and three hours after exposure and once daily thereafter until Day 15.

Statistics:

No statistical analysis was performed.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.1 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 100 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: To convert mg/l into mg/m³ 1 mg/m³ = mg/l x 1000 (2.1 x 1000=2100 mg/m³)

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were noted during exposure. After exposure, ptosis and/or piloerection were noted in two males and one female on Day 1 only.

Body weight:

Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.

To convert mg/l into mg/m³     

1m³=1000L

        

1 mg/m³=mg/l x 1000, 2.1mg/l x1000=2100 mg/m³

 

Interpretation of results:

other: practically nontoxic

Conclusions:

The inhalatory LC50, 4h value of Magnesium hydroxide in Wistar rats was established to exceed 2.1 mg/L.

Executive summary:

Groups of 5 male and female Wistar rats were treated with Magnesium hydroxide as aerosol during 4 hours. No mortality or other relevant adverse effects were observed. An inhalatory LC50 (4h)value for magnesium hydroxide exceeding 2.1 mg/L was determined, being this value the maximum feasible concentration that could be tested.

Reference 2

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 100 mg/m³ air

Quality of whole database:

There are no Acute toxicity studies available on the inhalative uptake of talc without asbestos fibres. There are no indications of Acute toxicity inhalation of talc without asbestos fibres. The study is therefore considered scientifically unjustified. Therefore testing for Acute toxicity inhalation does not need to be performe.
Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium hydroxide also should be taken into account
Magnesium hydroxide has of relatively low acute toxicity (LC50, inhalation, rat: 2100 mg/m3);

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

other: published data

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

Justification for type of information:

Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium chloride also should be taken into account.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

One female animal was slightly below 200 g but this animal was only of 2 g below the accepted range, it was included in the study.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species/strain: Healthy rats, WISTAR Crl: WI(Han) (Full-Barrier)
Source: Charles River, 97633 Sulzfeld, Germany
The female animals were nulliparous and non-pregnant.
Body weight at the beginning of the study: females: 198 - 222 g, males: 241 – 262 g
Age at the beginning of the study: females: 18 - 19 weeks old, males: 8 -9 weeks old
The animals were derived from a controlled full-barrier maintained breeding system (SPF).

Housing and Feeding Conditions: full barrier in an air-conditioned room, 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 for rats and mice, free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological control at regular
intervals), the animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding, adequate acclimatisation period.

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

Aqua ad injectionem

Details on dermal exposure:

Approximately 24 hours before the test, the fur was removed from the dorsal area of the trunk by using an electric clipper. Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used.
No less than 10 % of the body surface was cleared for the application.
The test item was applied at a single dose, uniformly over an area which was approx. 10 % of the total body surface.

Duration of exposure:

The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure period residual test item was not removed.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Prior to the application, a detailed clinical observation was made of all animals.
All animals were observed for 14 days after dosing.
The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Attention was directed to observations of tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.
At the end of the observation period, the animals were sacrificed by an overdosage of pentobarbital injected intraperitoneally. All animals were subjected to gross necropsy. All gross pathological changes were recorded.

Statistics:

Signs of erythema and oedema were assessed using the scoring system laid down in OECD Guideline 404.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No

Clinical signs:

other: The test item showed slight signs of dermal irritation (slight scratches) after a single dose application for one female (n°14) on day 3 and 4. The clinical signs observed were seen only on the day of application and may partly be due to the stress induc

Gross pathology:

At necropsy, female no. 14 showed changes of the tissue on the large intestine, which was filled with liquid. As this finding was seen in only one animal and was not associated with any specific clinical signs, this finding was most probably not test item related.

Other findings:

No

Absolute Body Weights in g and Body Weight Gain in %

Animal No. / Sex	Day 1	Day 8	Day 15	% Day 1 - 15
11 female	222	219	219	-1
12 female	201	208	213	6
13 female	218	216	215	-1
14 female	214	217	215	0.5
15 female	198	195	200	1
21 male	262	288	315	20
22 male	256	275	303	18
23 male	241	268	291	21
24 male	244	264	286	17
25 male	247	273	302	22

Interpretation of results:

other: not classified

Conclusions:

Under the conditions of this study, the dermal LD50 was determined to be > 2000 mg Magnesium chloride hexahydrate/kg body weight.

Executive summary:

Under the conditions of this study, single dermal application of the test item Magnesium chloride hexahydrate to rats at a dose of 2000 mg/kg body weight was associated with no mortality.

The dermal LD50 was determined to be > 2000 mg Magnesium chloride hexahydrate/kg body weight.

Reference 2

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Talc is used as a cosmetic powder and to powder gloves. There are no indications of Acute toxicity dermal. The study is therefore considered scientifically unjustified. Therefore testing for Acute toxicity dermal does not need to be performed.
Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium chloride also should be taken into account.
Magnesium chloride has of relatively low acute toxicity ( LD50, dermal, rat: >2000 mg/kg bw day;

Additional information

Acute oral toxicity:

The oral LD50 of 18.3% talc in saline was >5000 mg/kg. A single oral dose of 5000 mg/kg of talc prepared as an 18.3% (w/v) suspension in saline was administered to 10 male rats. All animals survived, and there were no signs of toxicity.

 

Acute dermal toxicity:

 

Talc is used as a cosmetic powder and to powder gloves. There are no indications of Acute toxicity dermal. The study is therefore considered scientifically unjustified. Therefore testing for Acute toxicity dermal does not need to be performed.

 

Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium chloride also should be taken into account.

 

Magnesium chloride has of relatively low acute toxicity ( LD50, dermal, rat: >2000 mg/kg bw day;

 

Acute inhalation toxicity:

 

There are no Acute toxicity studies available on the inhalative uptake of talc without asbestos fibres. There are no indications of Acute toxicity inhalation of talc without asbestos fibres. The study is therefore considered scientifically unjustified. Therefore testing for Acute toxicity inhalation does not need to be performed.

 

Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium hydroxide also should be taken into account

 

Magnesium hydroxide has of relatively low acute toxicity (LC50, inhalation, rat: 2100 mg/m3);

 

It is concluded that the substanceTalc (Mg3H2(SiO3)4)does not meet the criteria to be classified for human health hazards for Acute dose toxicity.

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

Very Toxic (T+) R28: Very toxic if swallowed R27: Very toxic in contact with skin R26: Very toxic by inhalation R39/26 R39/27 R39/28: Dangerous of very serious irreversible effects Toxic (T):  R25: Toxic if swallowed R24: Toxic in contact with skin R23: Toxic by inhalation R39/23 R39/24 R39/25: Danger of very serious irreversible effects Harmful (Xn): R22: Harmful if swallowed R21: Harmful in contact with skin R20: Harmful by inhalation R65: Harmful may cause lung damage if swallowed R21/22 Harmful; Harmful in contact with skin and if swallowed. R68/20 R68/21 R68/22: Possible risk of irreversible effects Other toxicological properties R67: Vapours may cause drowsiness and dizziness

CLP

H300 Acute Tox. 2 Fatal if swallowed H310 Acute Tox. 1 Fatal in contact with skin H330 Acute Tox. 2 Fatal if inhaled H370 STOT SE 1 H301 Acute Tox. 3 Toxic if swallowed H311 Acute Tox. 3 Toxic in contact with skin H331 Acute Tox. 3 Toxic if inhaled H370 STOT SE 1 H302 Acute Tox. 4 Harmful if swallowed H312 Acute Tox. 4 Harmful in contact with skin H332 Acute Tox. 4 Harmful if inhaled H304 Asp. Tox. 1 H371 STOT SE 2 (May cause damage to organs (or state all organsaffected if known) (state route of exposure if it is conclusively proventhat no other routes of exposure cause the hazard) Other toxicological properties H336 STOT SE 3 May cause drowsiness or dizziness

 

 

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