Talc (Mg3H2(SiO3)4)

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

other: Human observational study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented publication.

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 oxide also should be taken into account

Data source

Reference

Reference Type:

publication

Title:

Human pulmonary responses to experimental inhalation of high concentration fine and ultrafine magnesium oxide particles

Author:

Kuschner, W.G.; et al.

Year:

1997

Bibliographic source:

Environ. Health Perspectives, Vol. 105, No. 11, 1234-1237

Materials and methods

Type of sensitisation studied:

respiratory

Study type:

study with volunteers

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Characterisation of human pulmonary responses to controlled experimental high-dose exposure to fine and ultrafine magnesium oxide particles.
The autors exposed six normal volunteer subjects to inhaled purified magnesium oxide particles. The autors produced metal oxide fume with a furnace system under controlled conditions and quantified cumulative magnesium oxide dose for each exposure. The autors assessed partide size and particle shape by cascade impactor analysis and scanning electron microscopy. The autors analyzed pulmonary inflammatory cell and cytokine responses 20 hr postexposure by analysis of bronchoalveolar lavage (BAL) fluid and we compared these findings with paired control BAL samples in the same six subjects obtained without prior magnesium oxide exposure. They also compared peripheral blood neutrophil and pulmonary function 18 hr postexposure with baseline values. The investigation was approved by the University of California, San Francisco, Committee on Human Research.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium oxide

EC Number:

215-171-9

EC Name:

Magnesium oxide

Cas Number:

1309-48-4

Molecular formula:

MgO

IUPAC Name:

Magnesium oxide

Test material form:

solid

Method

Type of population:

general

Ethical approval:

confirmed, but no further information available

Subjects:

Subjects: 6 healthy volunteers, 4 male and 2 female subjects, 3 smokers and 3 non-smokers, aged between 21 and 43.
Treatment: Inhalation of fine and ultrafine magnesium oxide particles produced from a furnace system model. Individual exposure concentrations were (duration in parentheses) 5.8 (45 min), 230 (15 min), 210 (20 min), 123 (45 min), 110 (45 min), and 143 (45 min) mg/m³, given as MgO. By weight, 28 % of the fume particles were ultrafine (<0.1 µm in diameter) and over 98 % of fume particles were fine (<2.5 µm in diameter).
Subjects inhaled magnesium oxide fume with medical-grade air through a mouth-breathing face mask.
Observations: 18 to 20 hours after inhalation, bronchoalveolar lavage (BAL) cell and cytokine concentrations, pulmonary function and peripheral blood neutrophil concentrations were quantified. Post-exposure studies were compared with control studies from the same 6 subjects.

Route of administration:

inhalation

Details on study design:

The autors produced controlled quantities of freshly generated purified magnesium oxide fume utilizing a furnace system design originally developed by McCarthy and colleagues, which the autors later used in human zinc oxide studies. The autors assessed fume partide size by cascade impactor analysis. The autors used a micro-orifice uniform deposit impactor (MOUDI), model no. 110, with an operation flow rate of 30 I/min (MSP Corporation, Minneapolis, MN).
The MOUDI cut points were inlet cut point, 18 pm; stages 1-10 (in pm), 10, 5.6, 3.2, 1.8, 1.0, 0.56, 0.32, 0.18, 0.1, 0.056. By weight, over 98% of fume particles were fine or ultrafine and 98.6% were less than 1.8 pm in diameter. The greatest percentage (42.0%) of particles by weight were between 0.1 and 0.18 pm in diameter; 28.6% of partides were ultrafine (<0.1 pm in diameter). The total concentration during partide size sampling was 90.6 mg/m3. For comparison, is the partide size distribution for zinc oxide particles generated by the same furnace system and used in a previously published experimental inhalation investigation .
The autors quantified magnesium concentration for each experimental exposure by sampling a known volume filtered through a cellulose acetate membrane (0.22 pm pore), which was analyzed for metallic magnesium by inductively coupled plasma atomic emission (D & M Laboratories, Petaluma, CA, and Data Chem Laboratories, Cincinnati, OH).
The autors carried out exposures over a range of magnesium oxide concentrations. The median magnesium concentration (range) was 133.0 mg/m3 (5.8-230.0 mg/m3). The autors varied exposure time in order to produce a range of cumulative exposures; exposure duration was determined prior to exposure. They calculated cumulative exposure levels as the cross-product of the concentration of magnesium oxide, measured as metallic magnesium in milligrams per cubic meter, times the duration of the inhalation exposure expressed in minutes (min x mg/m3). Cumulative magnesium exposure ranged from 261 to 6,435 min x mg/mi3.
Subjects inhaled magnesium oxide fume with medical-grade air through a mouth-breathing face mask. All subjects completed an exposure in full without discomfort or difficulty. Subjects were asked to record their body temperature during the evening following the afternoon exposure and to document any symptoms including flulike symptoms of myalgias, fatigue, and rigors.

Results and discussion

Results of examinations:

Symptoms, pulmonary function, and peripheral blood polymorphonuclear leukocyte concentrations.
None of the subjects documented a fever or reported symptoms postexposure consistent with classic metal fume fever (myalgia, malaise, headache, or respiratory complaints). There was no overall postexposure fall in pulmonary function; slight increases in TLC (mean increase of 100 cc) and DLCO (mean increase of 0.9 ml/min/mm Hg) were not statistically significant. There was a mean decrease of peripheral blood polymorphonuclear leukocyte concentrations postexposure of 1.1 x 10-3 ± 1.0 x 10-3 (SE)/mm3 compared with baseline, which was also not statistically significant (p>0.3).

Bronchoalveolar lavage cells and cytokines.
There were no significant differences in BAL inflammatory cell concentrations, BAL interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor, pulmonary function, or peripheral blood neutrophil concentrations postexposure compared with control. Our findings suggest that high-dose fine and ultrafine magnesium oxide particle exposure does not produce a measurable pulmonary inflammatory response. These findings are in marked contrast with the well-described pulmonary inflammatory response following zinc oxide particle inhalation. They conclude that fine and ultrafine particle inhalation does not result in toxicity in a generic manner independent of particle composition

Applicant's summary and conclusion

Conclusions:

Inhalation of fine and ultrafine particulate magnesium oxide did not result in a symptomatic response or in any meaningful changes in lung function or in BAL concentrations of proinflammatory cells or cytokines at 20-hr follow-up.

Executive summary:

Exposure to air polluted with particles less than 2.5 micron in size is associated epidemiologically with adverse cardiopulmonary health consequences in humans. The goal of this study was to characterize human pulmonary responses to controlled experimental high-dose exposure to fine and ultrafine magnesium oxide particles.The autorsquantified bronchoalveolar lavage (BAL) cell and cytokine concentrations, pulmonary function, and peripheral blood neutrophil concentrations in six healthy volunteers 18 to 20 hr after inhalation of fine and ultrafine magnesium oxide particles produced from a furnace system model.The autorscompared postexposure studies with control studies from the same six subjects. Mean +/- standard deviation (SD) cumulative magnesium dose was 4,138 +/- 2,163 min x mg/m3. By weight, 28% of fume particles were ultrafine (<0.1 micron in diameter) and over 98% of fume particles were fine (<2.5 micron in diameter).

There were no significant differences in BAL inflammatory cell concentrations, BAL interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor, pulmonary function, or peripheral blood neutrophil concentrations postexposure compared with control. Our findings suggest that high-dose fine and ultrafine magnesium oxide particle exposure does not produce a measurable pulmonary inflammatory response. These findings are in marked contrast with the well-described pulmonary inflammatory response following zinc oxide particle inhalation.Theyconclude that fine and ultrafine particle inhalation does not result in toxicity in a generic manner independent of particle composition. Our findings support the concept that particle chemical composition, in addition to particle size, is an important determinant of respiratory effects.