What health studies have been done on amorphous silica?

The United Nation’s Organization for Economic Co-operation and Development (OECD) has been characterizing the hazardous properties of High Production Volume (HPV) chemicals. The “Screening Information Data Set” (SIDS) for synthetic amorphous silica was released in 2004. The SIDS report concluded that synthetic amorphous silica (SAS) is a low priority for further study. Excerpts from the OECD SIDS Human Health conclusions are included below(1):

Absorption, disposition, elimination: SAS forms [CAS No 7631-86-9] are rapidly eliminated from the lung tissue during and after prolonged inhalation exposure of experimental animals with no disproportionate disposition occurring in the mediastinal lymph nodes, whereas crystalline forms exhibit a marked tendency to accumulate and persist in the lung and lymph nodes. Intestinal absorption of SAS appears to be insignificant in animals and humans. There is evidence of ready renal elimination of bioavailable fractions.

Acute toxicity: Following inhalation exposure of rats to the highest technically feasible concentrations of 140 to ~2000 mg/m3 SAS, no lethal effects were observed. Oral and dermal administration of SAS and amorphous silicates failed to cause mortality at the highest doses tested: LD0 values ranged from 3300 to 20000 mg/kg in rats.

Irritation and sensitization: Synthetic amorphous silica and silicates are not irritating to skin and eyes under experimental conditions, but may produce dryness following prolonged and repeated exposure.

No sensitization experimental data are available on the synthetic amorphous silicas and silicates. However, there is a long work history with these materials at industrial scales. Data collected from industrial hygiene surveillance over the last 50 years do not indicate any potential for skin sensitization. Given the inherent physico-chemical properties and ubiquitous nature of this class of compounds, there is no structural alert to indicate a sensitizing potential.

The US EPA reviewed several toxicity studies for synthetic amorphous silica including four acute toxicity studies (acute oral LD50 in the rat, acute inhalation LC50 in the rat, primary eye irritation in the rabbit, and primary dermal irritation in the rabbit); four mutagenicity studies, and an oral toxicity study. The US EPA summary of these study results was as follows(2):

1. Acute toxicity studies. No mortalities were observed for the oral and inhalation studies. For the primary eye irritation study, there was no corneal opacity or iridial irritation in any of the eyes. For the dermal study, there was no dermal irritation at 72 hours. For the acute toxicity study, the oral LD50 is >5,000 milligrams/kilograms (mg/kg). For the acute inhalation study, the LC50 is >2.08 mg/L. All studies are toxicity category IV.

2. Mutagenic studies. In all four studies there was no indication of any mutagenic activity associated with exposure to silica, amorphous, fumed (crystalline free).

3. Oral toxicity of fumed silica. There were no mortalities or clinical signs. There was no significant difference between the test group and the control group with respect to silica concentration in the carcass.

Based on their analysis of the reviewed studies, the US EPA concluded the following(3):

“Silica, amorphous, fumed (crystalline free) has a demonstrated lack of toxicity. The acute toxicity studies are toxicity category IV. The mutagenicity studies are negative. Silica, amorphous, fumed (crystalline free) is not classifiable, as to its carcinogenicity however, given its amorphous nature, it is not expected to pose a carcinogenic risk. Silicas are considered to be inert when ingested, and due to the high molecular weight it is unlikely to be absorbed through the skin. There should be no concerns for human health, whether the exposure is acute, subchronic, or chronic by any route.”

The health effects of synthetic amorphous silica are significantly different from the health effects of crystalline silica. No evidence of silicosis has been found from epidemiological studies of workers with long-term exposure to intentionally manufactured synthetic amorphous silica(4). From a health standpoint, a significant different between crystalline and amorphous silica could be lung clearance. Studies of various animal species have shown that amorphous silica products can be completely cleared from the lungs(5).

The International Agency for Research on Cancer (IARC) considers synthetic amorphous silica to be not classifiable as to its carcinogenicity to humans (Group 3).

(1) United Nations Environmental Programme (UNEP), Organization for Economic Co-operation and Development (OECD) Screening Information Data Set (SIDS) Initial Assessment Report, Synthetic Amorphous Silica, July 23, 2004.

(2) Federal Register, Vol. 67, No. 94, May 15, 2002, 34616-34620.

(3) Federal Register, Vol. 67, No. 94, May 15, 2002, 34616-34620.

(4) Merget, R et al, “Health hazards due to the inhalation of amorphous silica”, Arch Toxicol (2002) 75: 625-634, November 29, 2001.