Talc (Mg3H2(SiO3)4)

Endpoint summary

Description of key information

Skin sensitisation

Studies in Animals - No experimental data are available on the Talc (Mg3H2(SiO3)4) powder and silicates. Studies in Humans - There is long experience in humans. Data collected from industrial hygiene surveillance over the last 50 years do not indicate any potential for skin sensitisation. Despite the widespread cosmetic use of talc and special studies in volunteers (BIBRA (The British Industrial Biological Research Association) (1991) BIBRA Toxicity Profile – Talc. BIBRA, Carshalton, GB) , there are no indications of any allergenic effect. Latex allergy caused by rubber gloves also seems to occur more often after powdering with starch than after powdering with talc. It was demonstrated that latex allergens are bound far better by talc than by starch powder (Lundberg et al. 1997). Hypersensitivity of the skin was observed to starch powder, but not to talc (Grant et al. 1976). Given the inherent physico-chemical properties and ubiquitous nature of this material, there is no structural alert to indicate a sensitising potential. On these ground, this end point has been waived.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 also should be taken into account

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

see "rationale for reliability"

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

yes

Remarks:

see "rationale for reliability"

Principles of method if other than guideline:

The test animals are initially exposed to the test substance by intradermal injection (day 0) and topical induction (day 7). Following a rest period of 14 days (inductionperiod), during which an immune response may develop, the animals are exposed to a challenge dose. The extent and degree of skin reaction to the challenge exposure (patch removal after 24h) in the test animals is compared with that demonstrated by control animals which undergo sham treatment during induction and receive the challenge exposure (48h after beginning of the challenge).

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The test animals are initially exposed to the test substance by intradermal injection (day 0) and topical induction (day 7). Following a rest period of 14 days (inductionperiod), during which an immune response may develop, the animals are exposed to a challenge dose. The extent and degree of skin reaction to the challenge exposure (patch removal after 24h) in the test animals is compared with that demonstrated by control animals which undergo sham treatment during induction and receive the challenge exposure (48h after beginning of the challenge).

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Weight at study initiation: 400-550g
- Housing: in pairs in clean plastic cages (55 x 32.8 x 19 cm^3) on standard bedding
- Diet: ad libitum, standard pellets
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3°C
- Humidity: humidity of 30-70%
- Photoperiod: 2 hours dark/light cycle
No further details are given.

Route:

intradermal and epicutaneous

Vehicle:

other: see "concentration"

Concentration / amount:

100%
All test items were tested both in a dissolved and in a solid state parallel to positive and negative control substances. Therefore, the magnesium alloys were dissolved by boiling in 2 mol/L HCl solution and buffered with 1 mol/L NaOH solution at pH 5.5. The supernatants were microfiltrated and the ion metal content was confirmed by ICP-AES.

Route:

epicutaneous, semiocclusive

Vehicle:

other: see "concentration"

Concentration / amount:

100%
All test items were tested both in a dissolved and in a solid state parallel to positive and negative control substances. Therefore, the magnesium alloys were dissolved by boiling in 2 mol/L HCl solution and buffered with 1 mol/L NaOH solution at pH 5.5. The supernatants were microfiltrated and the ion metal content was confirmed by ICP-AES.

No. of animals per dose:

20 animals for each test substance; 10 with the solid material and 10 with the dissolved material. 15 animals in the negative control group and 15 animals in the positive control group.

Details on study design:

An intradermal test and an epicutaneous patch test were performed. The skin reaction was interpreted by a qualitative grading of three independent observers immediately and 24 hours after patch removal. For grading of the skin reaction, the erythema classification according to Magnusson-Klingman test was used. A skin reaction graded greater than zero was defined as erythema.

The test site was clipped for intradermal injection. For topical application, the hair was clipped and closely shaved. Cellulose filters (2 x 4cm^2 and 2 x 2cm^2) were used as patches. Applied test patches were covered with overlapping pieces of impermeable plastic tape and fixed with 25cm long strips of elastic tape bandage which was secured by twp pieces of tape.

Cutaneous biopsies were harvested 24 hours after patch removal and analysed for histomorphological criteria. Epidermis and dermis were included in cell counting and histomorphological analysis.

Challenge controls:

Negative control: sodium-lauryl-sulfate
Preliminary test performed with all test items with one animal each; non irritant concentration were determined

Positive control substance(s):

yes

Remarks:

hydroxy-cinnamon-aldehyde

Positive control results:

All guinea pigs exposed to the standard allergen showed persisting erythema for more than 24 hours after patch removal. One animal died during the challenge phase for reasons not related to the test and one skin biopsy was lost because of technical problems. The histological analysis showed in 12 (92.3%) of the remaining 13 biopsies all four criteria of allergy such as spongiosis, oedema, and diffuse as well as perivascular mononuclear infiltrates. The positive control biopsies contained a mean of 52.7 basophile cells/400 leukocyte cells. Furthermore, in biopsies of the positive control group, a significant higher number of basophile cells was found compared to the negative control group and all tested substances (p=0.001, ANOVA)

Reading:

1st reading

Hours after challenge:

48

Group:

other: AZ91

Dose level:

dissolved test substance

No. with + reactions:

3

Total no. in group:

10

Clinical observations:

mild skin reactions

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: AZ91. Dose level: dissolved test substance. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: mild skin reactions.

Reading:

1st reading

Hours after challenge:

0

Group:

other: AZ31

Dose level:

dissolved test substance

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

mild clinical skin response; 24h after the patch was removed, all erythema had faded.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 0.0. Group: other: AZ31. Dose level: dissolved test substance. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: mild clinical skin response; 24h after the patch was removed, all erythema had faded..

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

No. with + reactions:

15

Total no. in group:

15

Clinical observations:

persisting erythema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. No with. + reactions: 15.0. Total no. in groups: 15.0. Clinical observations: persisting erythema.

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

No. with + reactions:

0

Total no. in group:

15

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 15.0.

Reading:

1st reading

Hours after challenge:

48

Group:

other: WE43 and LAE442

Dose level:

dissolved test substance

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

remarks: 10 per test substance (in total 20 animals)

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 48.0. Group: other: WE43 and LAE442. Dose level: dissolved test substance. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: remarks: 10 per test substance (in total 20 animals).

Test results for all substances used as received.

Between 90% (AZ31) and 100% (AZ91) of the tested skin areas displayed erythema immediately after patch removal. However, after 24 hours the erythema remained in 20% of the AZ91 group and 11% of the LAE442. To identify allergic erythema after 24 hours, dermal biopsies were taken. All biopsies exhibited significantly (p=0.001) less histomorphological criteria of allergenicity compared to the positive control group. In all biopsies no significant differences were found for basophile cells compared to the negative control. In the LAE442 group of the solid test substances, one animal died unrelated to the study conditions. Animals treated with AZ91and LAE442 which still had an erythema 24 hours after patch removal, showed no criteria of allergenicity in histomorphological analysis. No correlation was found between the cell count of eosinophiles and the concentration of aluminium in the test solutions (p>0.05).

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The tested magnesium alloys (with a total magnesium content between 89.2 – 96.8%) provide no sensitising potential compared to the control groups.

Reference 2

Endpoint:

skin sensitisation: in chemico

Remarks:

Data waiving based on inherent physico-chemical substance properties and ubiquitous nature of this compound.

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation

Studies in Animals - No experimental data are available on the Talc (Mg3H2(SiO3)4) powder and silicates. Studies in Humans - There is long experience in humans. Data collected from industrial hygiene surveillance over the last 50 years do not indicate any potential for skin sensitisation. Despite the widespread cosmetic use of talc and special studies in volunteers (BIBRA (The British Industrial Biological Research Association) (1991) BIBRA Toxicity Profile – Talc. BIBRA, Carshalton, GB) , there are no indications of any allergenic effect. Latex allergy caused by rubber gloves also seems to occur more often after powdering with starch than after powdering with talc. It was demonstrated that latex allergens are bound far better by talc than by starch powder (Lundberg et al. 1997). Hypersensitivity of the skin was observed to starch powder, but not to talc (Grant et al. 1976). Given the inherent physico-chemical properties and ubiquitous nature of this material, there is no structural alert to indicate a sensitising potential. On these ground, this end point has been waived.

Respiratory sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

respiratory sensitisation: in vivo

Type of information:

other: Published data

Adequacy of study:

weight of evidence

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 should be taken into account

Qualifier:

no guideline followed

Principles of method if other than guideline:

In experimental exposure chambers, aerosols were prepared using particulates that were collected from electrostatic filters in a Slovak magnesite
work, consisting of 88.5% MgO, 7.6% Fe2O3, 2.7% CaO, 0.5% Al2O3, SiO2, and traces of other elements and having a mean dust particle diameter of 1.8 μm. Wistar rats and C57 BL mice were exposed to concentrations ranging from 10- 1000 mg/m3, 3-5 hours/day, 5 days/week, for 3-9 months

GLP compliance:

not specified

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

A total of 15 male Wistar rats, housed at a biomonitoring station, were exposed to the emissions from a magnesite facility

Route of induction exposure:

inhalation

Route of challenge exposure:

inhalation

Vehicle:

unchanged (no vehicle)

Concentration:

concentrations ranging from 10- 1000 mg/m3, 3-5 hours/day, 5 days/week, for 3-9 months

Results:

The findings showed that magnesite dust was eliminated by both blood and lymph.
After a single exposure, 41% of magnesite dust was eliminated with an intermediate fibrogenic effect.
Following long-term exposure, the ability to eliminate dust diminished. Serum magnesium increased moderately during exposure and returned to the initial level 25 days after the end of the exposure. There was a significant increase in magnesium excretion with urine. The findings showed that inhaled dust was gradually dissolved in the body. The magnesium content was evaluated in the reticuloendothelial organs (liver and spleen) 25 days after the last exposure and was found to increase by 20.1% in the spleen and by 15.6% in the liver.
A concomitant histological exam of internal organs confirmed that the dust was retained in the lungs (without fibrotic changes), that particles were present in the spleen (sinusoid macrophages) and that the red pulp was hemorrhagic.
No signs of pulmonary fibrosis were found even after 6 months after the last exposure. Dust particles were found in thickened interalveolar septa and macrophages.
Proliferative histiocytic elements with particles present were found in the subcapsular sinuses and medulla of hilus lymphatic nodes.

Interpretation of results:

other: not sensitising

Conclusions:

No signs of pulmonary fibrosis were found even after 6 months after the last exposure..The findings showed that magnesite dust was eliminated by both blood and lymph.

Executive summary:

After a single exposure, 41% of magnesite dust was eliminated with an intermediate fibrogenic effect.

Following long-term exposure, the ability to eliminate dust diminished. Serum magnesium increased moderately during exposure and returned to the initial level 25 days after the end of the exposure. There was a significant increase in magnesium excretion with urine. The findings showed that inhaled dust was gradually dissolved in the body. The magnesium content was evaluated in the reticuloendothelial organs (liver and spleen) 25 days after the last exposure and was found to increase by 20.1% in the spleen and by 15.6% in the liver.

A concomitant histological exam of internal organs confirmed that the dust was retained in the lungs (without fibrotic changes), that particles were present in the spleen (sinusoid macrophages) and that the red pulp was hemorrhagic.

No signs of pulmonary fibrosis were found even after 6 months after the last exposure. Dust particles were found in thickened interalveolar septa and macrophages.

Proliferative histiocytic elements with particles present were found in the subcapsular sinuses and medulla of hilus lymphatic nodes.

 

Reference 2

Endpoint:

respiratory sensitisation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Due to the absence of chemical groups or other structural alerts this substance is not considered to exhibit an high hazard potential. Talc (Mg3H2(SiO3)4) is of low priority for further work based on a low hazard potential. Therefore testing for Respiratory sensitisation does not need to be performed.

Justification for classification or non-classification

Based on the hazard assessment ofTalc (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

Respiratory Sensitisation Xn R42 May cause sensitization by inhalation Respiratory Irritation Xi R37 irritating to respiratory system

 

CLP	Respiratory Sensitisation H334 Resp. Sens. 1 May cause allergy or asthma symptoms or breath-ing difficulties if inhaled Respiratory Irritation H335 STOT SE 3 May cause respiratory irritation

  

It is concluded that the substance Talc (Mg3H2(SiO3)4), does not meet the criteria to be classified for human health hazards for Inhalation-local effect:respiratory irritation/corrosion and/or respiratory sensitisation.