Hazardous substance assessment – Quartz silica

WHMIS classification

Health hazards:

• Carcinogenicity – Category 1A
• Specific Target Organ Toxicity – Repeated Exposure – Category 1

Physical hazards:

Quartz silica does not meet the criteria for classification.

Health hazards

Acute Toxicity (Oral):

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category of Acute Toxicity (Oral).

Acute Toxicity (Dermal):

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category of Acute Toxicity (Dermal).

Acute Toxicity (Inhalation – Gases):

Not applicable

Quartz silica is not a gas. The classification criteria for Acute Toxicity (Inhalation – Gases) do not apply to this substance.

Acute Toxicity (Inhalation – Vapours):

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category of Acute Toxicity (Inhalation - Vapours).

Acute Toxicity (Inhalation – Dusts and Mists):

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category of Acute Toxicity (Inhalation – Dusts and Mists).

Skin Corrosion / Irritation:

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category or subcategory of Skin Corrosion / Irritation.

Serious Eye Damage / Eye Irritation:

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category or subcategory of Serious Eye Damage / Eye Irritation.

Respiratory Sensitization:

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category or subcategory of Respiratory Sensitization.

Skin Sensitization:

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category or subcategory of Skin Sensitization.

Germ Cell Mutagenicity:

Does not meet criteria

In vivo:

Blood samples (lymphocytes) were collected from workers from diverse occupational settings with confirmed exposures to quartz silica dust. Sister chromatid exchange, deoxyribonucleic acid (DNA) damage and micronucleus assays all reported positive results in exposed workers compared to controls^{Note de bas de page 1}. A study measuring oxidative DNA damage was conducted in 10 female rats exposed once to an amount of 0, 0.3, 1.5 or 7.5 milligrams (mg) of DQ-12, a standard experimental grade of quartz dust, and that were observed for 90 days. Inflammation markers and 8-oxoGua (a DNA lesion from reactive oxygen species) were examined. Positive oxidative DNA damage was found in bronchoalveolar lavage fluid (BALF) and a clear DNA damage dose-response relationship was observed^{Note de bas de page 2} . In another study, that did not follow good laboratory practices (non-GLP) and that measured DNA damage (comet assay), 5 female rats were administered a dose of 8 to 10 milligrams of quartz silica per kilogram of body weight (mg/kg-bw). DNA damage in lung epithelial cells was determined using DNA strand break analysis. DNA strand breakage was significantly increased in epithelial cells of rats that were exposed to DQ-12 quartz silica^{Note de bas de page 2} .

In vitro:

Rat alveolar epithelial cells were incubated with BALF from rats exposed to quartz silica in an Hprt mutation assay. Both macrophage- and neutrophil-enriched lavage cells induced mutation in the exposed alveolar epithelial cells^{Note de bas de page 1}. In a non-GLP DNA damage assay in A549 human lung cells, DNA damage was determined by immuno-cytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) and the alkaline comet-assay following exposure to different quartz silica particle preparations for 4 hours at a concentration of 40 micrograms per centimetre squared (µg/cm²). The study results were positive for DNA damage (8-OHdG) and DNA strand breaks at concentrations ≥ 40 µg/cm^{2Note de bas de page 2}.

The available studies only describe DNA damage and it is not possible to determine whether this will lead to mutagenicity.

The available data do not meet the classification criteria for a category or subcategory of Germ Cell Mutagenicity.

Carcinogenicity:

Category 1A

Quartz silica has been classified by the International Agency for Research on Cancer as a Group 1 carcinogen, namely that it is carcinogenic to humans^{Note de bas de page 3} and by the American Conference of Governmental Industrial Hygienists as A2, a suspected human carcinogen ^{Note de bas de page 4}. Respirable crystalline silica, primarily quartz dusts occurring in industrial and occupational settings, is known to be a human carcinogen according to the National Toxicology Program^{Note de bas de page 5}.

Data collected from a multi-cancer occupational exposure case-referent study indicated that silica exposure increases the risk of lung cancer in humans^{Note de bas de page 6} . Lung cancer rates in silicotic workers who had no exposure to other known occupational carcinogens were 1.5 times higher than those of a referent group of coal miners with coal-worker’s pneumoconiosis and 2.4 times higher than those of a referent group of non-silicotic metal miners. Age- and smoking-adjusted lung cancer rates in silicotics were 3.9 times higher compared to those of a group of metal miners^{Note de bas de page 7} . Lung cancer rates are higher in workers confirmed to have silicosis than in similarly exposed workers who do not have silicosis. Cancer risk is often more significant in workers exposed to crystalline silica over a 20-year period or to higher cumulative exposure levels^{Note de bas de page 1} .

Several studies in rats have shown increases in lung tumours after chronic inhalation exposure to quartz silica at concentrations ranging from 1 to 50 milligrams per cubic metre (mg/m³) (1, 6 and 30 mg/m³ of DQ-12 quartz silica; 12 and 50 mg/m³ of Min-U-Sil 5 quartz silica) and over exposure durations ranging from 29 days to 2 years^{Note de bas de page 1} .

The available data for quartz silica in a respirable form meet the classification criteria for Carcinogenicity – Category 1A [HPR 8.6.1].

Reproductive Toxicity:

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category or subcategory of Reproductive Toxicity.

Specific Target Organ Toxicity – Single Exposure:

Does not meet criteria

Oral Route of Exposure: No data available

Dermal Route of Exposure: No data available

Inhalation Route of Exposure: In Fischer 344 rats, a single 4-hour exposure via inhalation to respirable quartz silica dust at a concentration of 100 mg/m³ produced persistent pulmonary inflammation, as evidenced by increased numbers of polymorphonuclear leukocytes (PMN) recovered from bronchopulmonary lavage fluid samples taken up to 3 months post-exposure. The quartz silica exposure also resulted in morphological changes of lung cells recovered up to 3 months post-exposure, namely the presence of hypersegmented PMN and binucleated alveolar macrophages, and increased activation of the alveolar macrophages recovered up to 3 months post-exposure, namely increased phagocytic indices and capacities and increased mycocidal activity. No functional tests were performed on the rat lungs to determine if the quartz silica exposure and the resulting inflammation caused alterations in lung function and capacity. Silica particles were eventually cleared from the lungs^{Note de bas de page 8}.

Groups of male Crl:CD BR rats were exposed to aerosols of α-quartz for a single exposure of 6 hours at a target concentration of 10, 50 or 100 mg/m³. Enzyme and protein indicators of pulmonary cytotoxicity in BALF were elevated post-exposure, as early as immediately following exposure. Some indicators remained elevated at the end of the 3-month post-exposure monitoring period. In vitro phagocytic capacity of lavage-recovered pulmonary macrophages was depressed in rats at the mid- and high-concentration exposures and their chemotactic responses to zymosan-activated rat serum were impaired in a concentration-dependent manner. Pulmonary lesions were observed but were less severe than those observed in a separate group of animals that had been exposed to α-quartz for 6 hours per day for 3 days. No functional tests were performed on the rat lungs to determine if the inhalation of quartz silica and the resulting pulmonary cytotoxicity and lesions caused alterations in lung function and capacity^{Note de bas de page 9}.

Male Sprague-Dawley rats (4 per dose) were exposed to a single intratracheal instillation of 5, 15 or 45 mg of respirable α-quartz suspended in 0.1 mL of physiological saline. Rats were observed on a daily basis for 90 days following exposure. At 90 days, rats were sacrificed and subject to post-mortem examination. There was no mortality throughout the observation period in any exposure group. The only clinical signs of morbidity were traces of bloody nasal discharge in 2 of the 4 high-dose rats at the end of the observation period. There were significant decreases in body weight gain and significant increases in total lung volume at the mid and high doses, with the latter ascribed to a proliferation of fibrotic tissue in the lungs. Lesions were noted in all lung lobes of the treated groups. Dense fibrosis of the lung was identified in all exposure groups, increasing in severity in a dose-dependent manner. Granulomas in the lung were identified in the mid- and high-dose groups. Particle-laden pulmonary alveolar macrophages and alveolar neutrophils were identified in all exposure groups^{Note de bas de page 10} . The method of administration used in this study does not allow for comparison of the doses tested with the inhalation guidance values of this hazard class.

The available data do not meet the classification criteria for a category of Specific Target Organ Toxicity – Single Exposure.

Specific Target Organ Toxicity – Repeated Exposure:

Category 1

Oral Route of Exposure: No data available

Dermal Route of Exposure: No data available

Inhalation Route of Exposure:

Human Evidence: An abundance of evidence from human epidemiological and case studies has shown that inhalation of quartz/silica results in silicosis and severe lung effects, including accelerated silicosis leading to death^{Note de bas de page 3Note de bas de page 11Note de bas de page 12Note de bas de page 13Note de bas de page 14Note de bas de page 15Note de bas de page 16Note de bas de page 17Note de bas de page 18}. An historical mortality study, conducted in Italy among 520 silicotic subjects, confirmed the existence of a causal association between silicosis and increased mortality from both malignant and non-malignant respiratory tract diseases^{Note de bas de page 19} .

Systemic complications linked to silicosis have included rheumatoid arthritis, scleroderma, systemic lupus erythematous, autoimmune effects, kidney effects and vasculitis^{Note de bas de page 17Note de bas de page 20Note de bas de page 21Note de bas de page 22Note de bas de page 23Note de bas de page 24Note de bas de page 25Note de bas de page 26Note de bas de page 27Note de bas de page 28Note de bas de page 29Note de bas de page 30Note de bas de page 31}.

Animal Evidence: Female F344/N rats were exposed for 6 hours per day, 5 days per week for 4 weeks by nose-only inhalation to a concentration of 0, 0.1, 1.0, or 10 mg/m3 of α-quartz aerosol with a mass median aerodynamic diameter (MMAD) of 1.3 to 2.0 μm. Lungs were evaluated by analysis of BALF at 1, 8 or 24 weeks after the end of exposure and by histopathological exam at 24 weeks post-exposure. Quartz silica exposure induced granulomas in the bronchial-associated lymph nodes of the high-exposure group along with pulmonary interstitial granulomas. Rats in the 2 highest exposure groups also had mild to moderate chronic-active pneumonia^{Note de bas de page 32}. The 2 highest concentrations tested caused specific target organ toxicity and meet the guidance value for Category 1 of this hazard class, adjusted for the shorter exposure duration.

Male Crl:CDBR rats were exposed to aerosolized α-quartz silica for 6 hours per day for 3 days at a concentration of 100 mg/m3 and evaluated at 0, 24 and 48 hours, 8 days and 1, 2 and 3 months post-exposure. Enzyme and protein indicators of pulmonary cytotoxicity were elevated in BALF at observation timepoints up to and including 2 months following exposure. In vitro phagocytic capacity of lavage-recovered pulmonary macrophages was depressed in rats in a statistically significant manner immediately after exposure and at 24 hours post-exposure. At 1 month post-exposure, pulmonary lesions were mild in severity and multifocal in distribution. At 2 months post-exposure, the lesions were moderately severe and multifocal in distribution. At 3 months post-exposure, the severity and distribution of the lesions had progressed. The number of foamy macrophages and their presence in alveoli and alveolar ducts increased with increasing post-exposure time. These macrophages were accompanied by neutrophils and fibrin. Type II alveolar hypertrophy and hyperplasia were observed. Thickening of the walls of alveoli and alveolar ducts was observed and was accompanied by interstitial macrophages, lymphocytes and neutrophils^{Note de bas de page 9}. The concentration tested caused specific target organ toxicity and meets the guidance value for Category 1 of this hazard class, adjusted for the shorter exposure duration.

Wistar rats (10 per sex) were exposed head/nose-only to a target concentration of 25 mg/m³ of quartz silica dust for 6 hours per day for 5 days. The mean daily MMAD was 2.08 μm, indicating the particles to be of a respirable size. No changes in body weight gain nor food intake were observed. The only clinical sign was a slightly decreased breathing frequency during the 5-day exposure period. Animals were necropsied the day following the last exposure or 1 or 3 months post-exposure. Increases in neutrophils, total cell number, and protein and enzyme biomarkers of cytotoxicity in BALF were observed at time points up to and including 3 months post-exposure. No significant change in hydroxyproline content, an indicator of lung collagen content, an increase of which is itself a biomarker of fibrosis, was observed in BALF. Only at 3 months post-exposure, slight increases in lung and tracheobronchial lymph node weights were observed. The day following the last exposure, very slight to slight granulocytic cell infiltrate was observed in the lungs; however, at 3 months post-exposure, a pulmonary inflammatory reaction was observed in all exposed animals. This reaction was in the form of alveolar infiltration of inflammatory cells and cellular debris and accumulations of macrophages in the alveoli and in the draining tracheobronchial lymph nodes. In addition, hyperaemia was observed in some exposed animals. Silicon, while not detected in the tracheobronchial lymph nodes at any timepoint, was present at elevated levels in the lung the day following the last exposure and at 1 and 3 months post-exposure^{Note de bas de page 33}. The concentration tested caused specific target organ toxicity and meets the guidance value for Category 1 of this hazard class, adjusted for the shorter exposure duration.

A group of 24 CD rats was exposed 6 hours per day for 3 days to a concentration of 100 mg/m³ of α-quartz aerosol. The MMAD of the α-quartz particles tested was 3.3-3.5 μm, indicating the test material to be respirable. Exposure to α-quartz produced pulmonary inflammatory responses characterized by neutrophil recruitment and consistently elevated biomarkers of cytotoxicity in bronchoalveolar lavage fluids compared to those of a sham control group. These inflammatory responses were persistent at observations made up to 90 days after exposure^{Note de bas de page 34}. The concentration tested caused specific target organ toxicity and meets the guidance value for Category 1 of this hazard class, adjusted for the shorter exposure duration.

The available human and animal data for quartz silica in a respirable form meet the classification criteria for Specific Target Organ Toxicity – Repeated Exposure – Category 1 based on lung effects [HPR 8.9.1].

Aspiration Hazard:

No data available

This substance is not a liquid hydrocarbon and no human data were identified as to its aspiration toxicity.

Biohazardous Infectious Materials:

Not applicable

Quartz silica is not a microorganism, protein or nucleic acid.

Physical hazards

Explosives:

Not evaluated
Explosives are excluded from the HPA and its regulations. Explosives are regulated under the Explosives Act. For more information, visit Natural Resources Canada.

Flammable Gases:

Not applicable

Quartz silica is not a gas. The classification criteria for Flammable Gases do not apply to this substance.

(Flammable) Aerosols:

Not evaluated

Classification of a hazardous product in the Flammable Aerosols or Aerosols hazard class is product dependent.

Oxidizing Gases:

Not applicable

Quartz silica is not a gas. The classification criteria for Oxidizing Gases do not apply to this substance.

Gases Under Pressure:

Not applicable

Quartz silica is not a gas. The classification criteria for Gases Under Pressure do not apply to this substance.

Flammable Liquids:

Not applicable

Quartz silica is not a liquid. The classification criteria for Flammable Liquids do not apply to this substance.

Flammable Solids:

Does not meet criteria

Quartz silica is not combustible ^{Note de bas de page 35} .

The available data do not meet the classification criteria for a category of Flammable Solids.

Self-reactive Substances and Mixtures:

Does not meet criteria

Quartz silica is not combustible^{Note de bas de page 35}.

The available data do not meet the classification criteria for a category of Self-reactive Substances and Mixtures.

Pyrophoric Liquids:

Not applicable

Quartz silica is not a liquid. The classification criteria for Pyrophoric Liquids do not apply to this substance.

Pyrophoric Solids:

Does not meet criteria

Quartz silica is not combustible^{Note de bas de page 35}.

The available data do not meet the classification criteria for a category of Pyrophoric Solids.

Self-heating Substances and Mixtures:

Does not meet criteria

Quartz silica is not combustible^{Note de bas de page 35}.

The available data do not meet the classification criteria for Self-heating Substances and Mixtures.

Substances and Mixtures Which, in Contact with Water, Emit Flammable Gases:

Excluded from classification

Quartz silica is soluble in water to some extent^{Note de bas de page 1} and forms a stable mixture and is, therefore, excluded from classification [HPR 7.12.1(1)(c)].

Oxidizing Liquids:

Not applicable

Quartz silica is not a liquid. The classification criteria for Oxidizing Liquids do not apply to this substance.

Oxidizing Solids:

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category of Oxidizing Solids.

Organic Peroxides:

Not applicable

Quartz silica is not an organic peroxide. The classification criteria for Organic Peroxides do not apply to this substance.

Corrosive to Metals:

No data available

No data are available to determine whether quartz silica meets the classification criteria for a category of Corrosive to Metals.

Combustible Dusts:

Does not meet criteria

Quartz silica is not combustible^{Note de bas de page 35}.

The available data do not meet the classification criteria for a category of Combustible Dusts.

Simple Asphyxiants:

Not applicable

Quartz silica is not a gas. The classification criteria for Simple Asphyxiants do not apply to this substance.

Pyrophoric Gases:

Not applicable

Quartz silica is not a gas. The classification criteria for Pyrophoric Gases do not apply to this substance.

Chemicals Under Pressure:

Not evaluated

Classification of a hazardous product in the Chemicals Under Pressure hazard class is product dependent.

Regulatory and other information

Regulatory information:

Hazardous substance assessments are prepared by Health Canada as educational and information resources. Under the HPA, suppliers of hazardous products must, upon the sale or importation of a hazardous product, provide a safety data sheet and label that meet the requirements set out in the HPR.

Other information:

The information and classifications contained in these hazardous substance assessments are based on publicly available sources, such as peer-reviewed literature or reports by international bodies. New information, including proprietary information, could have an impact on the classification of substances or hazardous products containing them. It is the responsibility of the supplier to ensure the accuracy, sufficiency and reliability of their hazardous product classifications.

Last updated:

2024

Prepared by:

Workplace Hazardous Materials Bureau, Health Canada

References