https://ntp.niehs.nih.gov/go/tox091abs

Abstract for TOX-91

Toxicity Studies of Abrasive Blasting Agents Administered by Inhalation to F344/NTac Rats and Sprague Dawley (HSD:Sprague Dawley SD) Rats

Substances:

  • Blasting sand (CASRN BLASTINGSAND)
  • Coal slag (CASRN COALSLAG)
  • Crushed glass (CASRN CRUSHEDGLASS)
  • Garnet (CASRN GARNET)
  • Specular hematite (CASRN HEMATITESPEC)

Report Date: July 2020

Full Report PDF

Abstract

Erratum: [September 1, 2022] Errors were identified in the NTP Toxicity Report on Abrasive Blasting Agents (TOX 91). Incorrect supplier information was reported for the five test materials, and detailed information about trade names and bulk material preparation was inadvertently omitted. These errors have been corrected.

Abrasive blasting, commonly known as sandblasting, involves forcibly projecting a stream of abrasive particles through compressed air or steam against a surface to change its quality or to remove contaminants. Silica blasting sand contains high levels of crystalline silica—which can cause pulmonary fibrosis (silicosis) after exposure through inhalation and is considered a lung carcinogen—and constitutes approximately 63% of all abrasives used in abrasive blasting. Other abrasives, including specular hematite, are recommended as alternative blasting agents. Due to the health risks associated with using blasting sand in the abrasive blasting process and the lack of toxicity data on alternatives to blasting sand, the National Institute for Occupational Safety and Health (NIOSH) proposed testing blasting sand and alternative abrasives to characterize their associated toxicity.

Using inhalation (whole-body) exposure, male F344/NTac rats were first exposed to blasting sand, coal slag, crushed glass, garnet, or specular hematite in 2-week studies. In subsequent studies, male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats were exposed to blasting sand or specular hematite for up to 27 weeks (females) or 39 weeks (males). In the 2‑week studies, groups of five male F344/NTac rats were exposed by whole-body inhalation to blasting sand, coal slag, crushed glass, or garnet aerosol at concentrations of 0, 3, 15, or 30 mg/m3 or specular hematite aerosol at concentrations of 0, 3, 15, 30, or 60 mg/m3 for 6 hours plus T90 (theoretical value for the time to achieve 90% of the target concentration after the beginning of aerosol generation; 12 minutes) per day, 5 days per week for 2 weeks, plus 2 days for 12 exposures (day 16). Additional groups of 35 male F344/NTac rats were exposed to the same concentrations of blasting sand, coal slag, crushed glass, garnet, or specular hematite for tissue burden analysis through day 16.

In the 2-week studies of blasting sand, coal slag, crushed glass, garnet, and specular hematite, all core study rats survived to the end of the study; there were no significant differences between exposed groups and the chamber control group in mean body weights for core rats. Except for one coal slag-exposed rat in the 30 mg/m3 group that had an ocular discharge on days 5 and 8, no clinical observations were associated with exposure to blasting sand, coal slag, crushed glass, garnet, or specular hematite. The absolute lung weights of core study rats exposed to 15 or 30 mg/m3 crushed glass in the 2-week study were significantly increased compared to the chamber control group. Lung burdens continued to increase through the last exposure day (day 16) for all five test articles indicating that steady-state lung burdens were not achieved during the 2-week studies. Crushed glass exhibited the shortest clearance half-life.

The incidence of minimal histiocytic cellular infiltration was significantly increased in the lungs of 15 and 30 mg/m3 coal slag-exposed rats compared to the chamber control group in the 2-week study. The incidence of minimal to mild histiocytic cellular infiltration was significantly increased in the lungs of 30 and 60 mg/m3 specular hematite-exposed rats compared to the chamber control group.

The incidence of minimal goblet cell hypertrophy in the nasopharyngeal duct of the nose was significantly increased in 60 mg/m3 specular hematite-exposed rats compared to the chamber control group in the 2-week study.

All crushed glass-exposed rats, except for one in the 3 mg/m3 group, exhibited minimal to mild goblet cell hypertrophy of the respiratory epithelium in the nose, a significant increase compared to the chamber control groups. The severity of goblet cell hypertrophy increased with increasing crushed glass exposure concentration.

In the larynx, the incidences of minimal to mild hyperplasia, squamous hyperplasia, and inflammation of the epiglottis were significantly increased in the 15 and 30 mg/m3 crushed glass-exposed groups in the 2-week study compared to the chamber control groups.

In the lungs of garnet-exposed rats, the incidence of minimal to mild chronic active inflammation was significantly increased in the 15 and 30 mg/m3 groups compared to the chamber control group in the 2-week study.

Specular hematite and crushed glass appeared to be the least toxic of the four alternative abrasives tested in the 2‑week studies on the basis of lung histopathology, but specular hematite was selected for further testing because crushed glass exhibited a relatively short clearance half‑life.

In the 39-week studies, groups of 62 male Sprague Dawley rats were exposed by whole-body inhalation to blasting sand or specular hematite aerosol at concentrations of 0, 15, 30, or 60 mg/m3 for 6 hours plus T90 (12 minutes) per day, 5 days per week for up to 39 weeks. Groups of 32 female Sprague Dawley rats were exposed to the same concentrations of blasting sand or specular hematite for up to 27 weeks for immunotoxicity studies.

In the 39-week study of blasting sand, all male rats survived to interim sacrifice or to the end of the study; mean body weights of all exposed groups were similar to the chamber control group. There were no clinical observations associated with exposure to blasting sand. The absolute and relative lung weights in the 30 and 60 mg/m3 groups were significantly increased compared to the chamber control group beginning at week 16 or 8, respectively. The absolute and relative bronchial lymph node weights in the 60 mg/m3 group at all time points and in the 30 mg/m3 group at week 26 were significantly increased compared to the chamber control group. The absolute mediastinal lymph node weights were significantly increased at weeks 16, 26, and 39 in the 60 mg/m3 group, and the relative mediastinal lymph node weights were increased in this group at weeks 16 and 39. Absolute numbers of macrophages, neutrophils, and lymphocytes, and lactate dehydrogenase activity and MCP-1 levels in bronchoalveolar lavage fluid generally increased in magnitude with increasing exposure concentration and time, with the 60 mg/m3 groups often most severely affected. Blasting sand lung burdens continued to increase through the last exposure week indicating that steady-state lung burdens were not achieved during the study. By the end of the study, lung overload conditions were achieved at all exposure concentrations. Time of onset of lung overload was calculated to be 137, 55, and 30 days for 15, 30, and 60 mg/m3 blasting sand groups, respectively. Treatment-related nonneoplastic lesions occurred in the nose, lung (including chronic inflammation, alveolar proteinosis, and interstitial fibrosis), and bronchial and mediastinal lymph nodes. The incidences of these lesions generally increased with increasing exposure concentration and time.

In the 39-week study of specular hematite, two male rats, one chamber control and one exposed to 60 mg/m3, were removed during week 37 for reasons unrelated to exposure to the test article; mean body weights of all exposed groups were similar to those of the chamber control group. There were no clinical observations associated with exposure to specular hematite. Compared to those in the chamber control group, the absolute and relative lung weights were significantly increased in the 30 and 60 mg/m3 groups at weeks 16, 26, and 39. Absolute and relative bronchial lymph node weights were significantly increased at weeks 16, 26, and 39 in the 60 mg/m3 group and at week 26 in the 30 mg/m3 group. The absolute and relative mediastinal lymph node weights were significantly increased at weeks 16 and 26 in the 60 mg/m3 group but not at week 39. Absolute numbers of neutrophils and lymphocytes, and lactate dehydrogenase activity and MCP-1 levels in bronchoalveolar lavage fluid generally increased in magnitude with increasing exposure concentration and time, with the 60 mg/m3 groups often severely affected. Specular hematite lung burdens continued to increase through the last exposure week indicating that steady-state lung burdens were not achieved during the study. By the end of the study, lung overload conditions were achieved in the 30 and 60 mg/m3 groups; the specular hematite volume was at 90% of the overload threshold in the 15 mg/m3 group. Time of onset of lung overload was calculated to be 344 (i.e., after 39 weeks), 118, and 55 days for 15, 30, and 60 mg/m3 specular hematite, respectively. Treatment-related nonneoplastic lesions occurred in the nose, lung (including chronic inflammation, alveolar epithelial hyperplasia, and interstitial fibrosis), larynx (squamous metaplasia of epiglottis), and bronchial and mediastinal lymph nodes. The incidences of these lesions generally increased with increasing exposure concentration and time.

Under the conditions of these 39-week inhalation studies, the lung was the major target tissue in male Sprague Dawley rats exposed to blasting sand or specular hematite. The incidences of chronic active inflammation and interstitial fibrosis were significantly lower in rats exposed to specular hematite (compared to blasting sand) at some time points under some exposure conditions. After 39 weeks of exposure to specular hematite, the lowest-observed-effect level was 15 mg/m3 for chronic active inflammation and interstitial fibrosis within the lung. Alveolar proteinosis was present at week 39 in the lungs of rats exposed to the highest concentration (60 mg/m3) of blasting sand but was notably absent in the lungs of rats exposed to specular hematite. Alveolar epithelial hyperplasia was present at week 16 in the lungs of rats exposed to the two highest concentrations (30 or 60 mg/m3) of specular hematite but not blasting sand. Specular hematite exhibited potential to be an inhalation toxicant in exposed workers who perform abrasive blasting operations but to a lesser degree than blasting sand because the lungs of rats exposed to specular hematite showed a lower incidence of interstitial fibrosis and an absence of alveolar proteinosis.

National Toxicology Program (NTP). 2020. NTP technical report on the toxicity studies of abrasive blasting agents administered by inhalation to F344/NTac rats and Sprague Dawley (HSD:Sprague Dawley SD) rats. Research Triangle Park, NC: National Toxicology Program. Toxicity Report 91. https://doi.org/10.22427/NTP-TOX-91

Studies

Summary of Key Findings Considered Toxicologically Relevant in Male Sprague Dawley Rats Exposed to Abrasive Blasting Agents by Inhalation for Thirty-nine weeks
  Blasting Sand Study Specular Hematite Study
Concentrations in air 0, 15, 30, or 60 mg/m3 0, 15, 30, or 60 mg/m3
Body weights Exposed groups similar to the chamber control group Exposed groups similar to the chamber control group
Survival rates 13/13, 13/13, 13/13, 13/13 12/13, 13/13, 13/13, 12/13
Clinical observations None None
Organ weights ↑ Absolute and relative lung weights;
↑ Absolute and relative bronchial lymph node weights;
↑ Absolute and relative mediastinal lymph node weights
↑ Absolute and relative lung weights;
↑ Absolute and relative bronchial lymph node weights;
↑ Absolute and relative mediastinal lymph node weights
Tissue burden ↑ Lung overload time of onset at 137, 55, and 30 days and extent exceeding overload at end of study 1.6, 3.8, 8.4-fold (15, 30, and 60 mg/m3, respectively) ↑ Lung overload time of onset at 334, 118, and 55 days and extent exceeding overload at end of study 0.9, 2.3, 5.5-fold (15, 30, and 60 mg/m3, respectively)
Select nonneoplastic effects Lung: chronic active inflammation (week 4: 0/8, 2/8, 2/8, 3/8; week 16: 1/8, 3/8, 3/8, 8/8; week 26: 2/8, 7/8, 7/8, 8/8; week 39: 2/8, 8/8, 8/8, 8/8); interstitium, fibrosis (week 26: 0/8, 8/8, 7/8, 8/8; week 39: 0/8, 8/8, 8/8, 8/8); proteinosis (week 26: 0/8, 0/8, 0/8, 1/8; week 39: 0/8, 0/8, 0/8, 6/8); alveolar epithelium, hyperplasia (week 26: 0/8, 8/8, 8/8, 8/8; week 39: 0/8, 8/8, 8/8, 8/8)

Larynx: epiglottis, metaplasia, squamous (week 39: 0/8, 1/8, 1/8, 1/8)

Nose: respiratory epithelium, accumulation, hyaline droplet (week 16:0/8, 8/8, 8/8, 7/8)
Lung: chronic active inflammation (week 16: 1/8, 0/8, 0/8, 3/8; week 26: 0/8, 2/8, 0/8, 4/8; week 39: 0/9, 3/8, 2/8, 7/9); interstitium, fibrosis (week 26: 0/8, 0/8, 0/8, 3/8; week 39: 1/9, 2/8, 8/8, 9/9); alveolar epithelium, hyperplasia (week 16: 0/8, 3/8, 8/8, 8/8; week 26: 0/8, 8/8, 8/8, 8/8; week 39: 2/9, 8/8, 8/8, 9/9)

Larynx: epiglottis, metaplasia, squamous (week 4: 0/8, 1/8, 4/8, 5/8; week 16: 0/8, 3/8, 3/8, 4/8; week 26: 0/8, 5/8, 5/8, 7/8; week 39: 0/9, 5/8, 7/8, 7/9)

Nose: respiratory epithelium, accumulation, hyaline droplet (week 16:1/8, 4/8, 5/8, 2/8)
Bronchoalveolar lavage ↑ Total cells counted
↑ Absolute macrophages
↑ Absolute lymphocytes
↑ Absolute neutrophils
↑ Lactose dehydrogenase
↑ MCP-1
↑ Total cells counted
↑ Absolute macrophages
↑ Absolute lymphocytes
↑ Absolute neutrophils
↑ Lactose dehydrogenase
↑ MCP-1