Chromium VI

Human Health

Chromium, a metallic element, is naturally occurring in rocks and minerals, most usually in its trivalent state, chromium III. Chromium III is an essential nutrient, albeit in trace quantities. The element has a role in the metabolism of glucose, fat and protein, by making the action of the hormone, insulin, more effective. Chromium also exists in valence states other than chromium III, and one of these forms, chromium VI, has been released to the environment as a result of industrial processes. Chromium VI is also known as hexavalent chromium, and the name may be abbreviated to Cr+6. There is wide industrial use of chromium VI compounds, and a few examples of the industries that utilize them include wood preservation; hard and soft chrome plating; pigment manufacture, the aerospace industry; leather tanning, and the textile industry. Chromium VI was formerly in wide use as a corrosion inhibitor in wastewater systems and to prevent degradation of iron and steel pipe. Although decades have passed since its use as a corrosion inhibitor, it may still be found plated to treated pipes.

Occupational exposure to chromium VI generally occurs by inhalation and by skin (dermal) contact. However, when a substance is inhaled, a small amount is inevitably ingested. Workers may be exposed by inhalation to fumes and mists containing chromium VI when hot-cutting or welding stainless steel, or other chromium-containing metal alloys. Portland cement contains chromium VI as an impurity, and workers may be exposed by inhaling cement dust. Workers in the electroplating industry can be exposed to chromium VI by inhaling mists of electroplating solutions and by dermal contact with them. The production of chromium VI pigments, and their use in sprayed-on coatings by the aerospace industry, has exposed workers by skin contact and inhalation.

The general public may be exposed to chromium VI by drinking from contaminated groundwater wells, inhaling mists from cooling towers where water flows over treated timber, inhaling fugitive dusts from cement and chromate producing plants, and inhaling emissions from motor vehicles' catalytic converters.

Particulate chromium VI may be inhaled, and deposited in the lungs, but the pattern of deposition in the lungs is dependent on airflow patterns in the lungs. Some sites in the lung may preferentially build up chromium VI to create areas of high concentration. Chromium VI is absorbed into the cells of the lung by facilitated diffusion through non-specific ion channels and is thence rapidly absorbed into the bloodstream. The readily soluble chromates reach the bloodstream more rapidly than less soluble compounds, but even chromium VI encapsulated in paint may be absorbed from the lung. Some inhaled chromium VI is removed from the lungs by mucociliary clearance. Mucociliary clearance and swallowing can move inhaled substances to the digestive tract. Ingested chromium VI is largely reduced to insoluble chromium III in the gastrointestinal tract. However, animal studies show that a proportion of ingested chromium VI is absorbed. Chromium VI is absorbed through intact skin, easily crossing the epidermis to the underlying layer, the dermis, and from the dermis into deeper tissues. Once absorbed, chromium VI is distributed through the body via the bloodstream. Tissues retrieved from autopsies of chromate workers indicate high chromium VI concentrations in the lungs, and higher than background concentrations in liver, bladder, and bone. Chromium VI is excreted in urine as low molecular weight chromium III complexes, and to a lesser extent by biliary excretion into feces.

The toxicity of chromium VI has been investigated in laboratory animal studies, and results have been reported from both short and long-term investigations. A recent National Toxicology Program (NTP) study, reported January 2007, examined the mid-term toxicity of chromium VI to rats and mice. The test animals were administered sodium dichromate in their drinking water for 3 months, and this exposure resulted in focal ulceration, metaplasia, and hyperplasia of the glandular stomach on both rats and mice. Evidence of histiocytic infiltration of the liver, duodenum, and pancreatic lymph nodes was also observed. Microcytic, hypochromic anemia was noted in rats, and, to a lesser extent, in mice. The development of anemia was considered a toxic response to the oral ingestion of chromium VI. Other studies have demonstrated that rats exposed to chromium VI by inhalation for a period of 3 months show an increase in lung and spleen weight and in macrophage activity.

Long-term (chronic) animal studies have primarily focused on the potential of chromium VI to cause cancer. The results of a recent 2 year NTP study on the effects of chromium VI in drinking water in rats and mice found clear evidence of carcinogenicity of sodium dichromate. Carcinogenic effects of oral administration of chromium VI were seen in both rats and mice of both sexes. Squamous cell papillomas, or squamous cell carcinomas were seen in the oral mucosa or tongue of rats. Mice in the same investigation developed neoplasms, and adenomas or carcinomas of the duodenum, jejunum, or ileum. Lung implantation of chromium VI in rats has shown a statistically significant increase in squamous metaplasia, a condition that may progress to carcinoma of the lungs. Some investigations, but not all, have found statistically significant increases in bronchial carcinoma after intrabronchial instillation of chromium VI compounds. Subcutaneous, "site of injection," cancers have been reported for chromium VI.

Two animal studies show chromium VI to be toxic to the developing embryo. Mice and rats exposed to chromium VI in drinking water during gestation exhibited retarded fetal development, and embryo and fetotoxic effects that included reductions in the number of fetuses and fetal weight and a higher incidence of stillbirth and post-implantation loss. Both studies found significantly reduced bone ossification. However, a multigenerational dietary study performed by NTP observed no reproductive changes due to the toxicity of chromium VI. There is no clear evidence that chromium VI is a human reproductive toxicant following occupational exposure. The only studies that address this issue are of poor quality and provide insufficient data to draw any conclusions about the reproductive toxicity of chromium VI in man.

Both soluble and insoluble chromium VI compounds are able to cause structural damage to DNA, leading to genotoxicity. Chromium VI compounds, such as sodium dichromate, are mutagenic in Salmonella typhimurium reverse mutation assays, and in Escherichia coli tests. Studies indicate that chromium VI induced DNA damage may result in clastogenesis, altered gene expression, and the inhibition of DNA replication and transcription. The genotoxic action of chromium VI is probably responsible for the induction of neoplastic change.

There are strong occupational health studies in chromate production workers from the USA, United Kingdom (UK), Germany, Japan, and Italy. Chromate production plants in the USA and UK have been repeatedly studied for extended periods, one in Painsville, Ohio for over 50 years. These studies provide evidence that chromium VI is carcinogenic to workers, as they report an elevated lung cancer mortality that is related to cumulative exposure, and length of employment. Occupational health studies also provide data for the non-cancer effects of chromium VI. Inhalation of chromium VI leads to ulceration of nasal tissues and to nasal septum perforation. Chromium VI is an airway sensitizer and can produce occupational asthma in sensitized individuals, and in addition, can cause allergy contact and irritant contact dermatitis. Skin ulcers, known as "chrome holes," can occur on exposed skin. These ulcers are persistent, painful, and may result in deep penetration of tissues underlying the skin.

A study of villagers in China using chromium VI-contaminated well water (20 milligrams per liter) for domestic purposes reported the following effects of oral exposure: vomiting, oral ulcers, abdominal pain, indigestion, and diarrhea. Hematological effects such as leucocytosis and immature neutrophils were also noted.

Chromium VI has been classified by the US EPA under the 1986 cancer guidelines as Group A-known human carcinogen by the inhalation route of exposure, and as Group D-carcinogenicity cannot be determined by the oral route of exposure. Under the interim 1996 cancer guidelines EPA classifies chromium VI as a "known human carcinogen by the inhalation route of exposure." The Report on Carcinogens (11th Edition) states that, "chromium hexavalent (VI) compounds are known to be human carcinogens."

Ecological Impacts

Chromium is an essential nutrient for human beings and chromium containing low molecular weight peptides (chromodulin) have been identified in many mammalian species. However, it is not known whether chromium is a dietary requirement for other terrestrial vertebrates. Although chromium does bioaccumulate, it is not reported to undergo biomagnification in the food chain. Many biotic and abiotic factors can modify the toxic effects of chromium in the environment. For example, chromium VI is more toxic to freshwater biota in soft, slightly acidic water. Early life stages are generally more sensitive to the effects of chromium VI than adults.

Chromium VI, at a concentration of 10 parts per billion (ppb) reduced fecundity and survival of the invertebrate Daphnia magna when the organisms were exposed to the metal for 32 days, but is also associated with adverse impact to other invertebrates from widely differing taxa. Chromium VI is reported to be slightly to moderately toxic to aquatic polychaete and oligochaete worms in median lethal concentration (LC₅₀) studies.

Some fish species are sensitive to chromium VI, and relatively low concentrations (16 21 ppb) reduced the growth of young rainbow trout and chinook salmon during a 14 16-week exposure period.

LC₅₀ studies have determined that chromium VI is not acutely toxic, to slightly toxic to amphibians (Indian toad and skipping frog subjects under test).

Very little information is available for the effects of chromium VI on terrestrial mammals and birds. Laboratory animal studies have provided mammalian toxicity data. An egg injection study of the effects of chromium IV on the developing domestic fowl resulted in deformities that included twisted limbs, exencephaly, everted viscera, deformed beaks, and growth stunting. However, no effects were seen in adult chickens fed chromium VI at 100 ppm in their diet for 32 days.

Plants can be adversely affected by chromium VI. Chromium VI reduces the growth and chlorophylls a and b content of the small, floating aquatic fern Azolla caroliniana at concentrations of 1-2 ppm. Reduced germination, a decrease in root length and dry weight, reductions in plant height, number of flowers, leaf number, leaf area and biomass, and an up to 50% reduction in grain weight, with increased seed deformity have all been reported in response to chromium VI.

For Further Information

Abstract: Evaluation of Aquatic Toxicities of Chromium and Chromium-Containing Effluents in Reference to Chromium Electroplating Industries
A. Baral, R. Engelken, W. Stephens, J. Farris and R. Hannigan
Archives of Environmental Contamination and Toxicology Volume 50, Number 4 / May, 2006

Abstract: Carcinogenic Cr(VI) and the Nutritional Supplement Cr(III) Induce DNA Deletions in Yeast and Mice
Z. Kirpnick-Sobol, R. Reliene, and R. H. Schiestl

Methods to Develop Inhalation Cancer Risk Estimates for Chromium and Nickel Compounds
U.S. EPA, Office of Air Quality Planning and Standards.
EPA 452-R-11-012, 19 pp, 2011

This paper discusses the methods used to develop inhalation cancer risk estimates associated with emissions of chromium and nickel compounds from coal- and oil-fired electric utility steam generating units. The derivation of cancer risk estimates is based on the speciation data available from the source type and on the available unit risk estimates reflecting the dose that corresponds to a specific level of cancer risk. See Section 2 for the discussion of chromium.

Public Health Goals for Chemicals in Drinking Water: Hexavalent Chromium (Cr VI)
Sedman, R., J. Beaumont, J. Budroe, and C. Vidair.
California Environmental Protection Agency, Office of Environmental Health Hazard Assessment, 162 pp, 2011

In 2011, CalEPA published the nation's first public health goal of 0.02 ppb for Cr(VI) in drinking water.

Environmental Risk RED Chapter
U.S. EPA, Office of Pesticides

A Probabilistic Risk Assessment for Children Who Contact CCA-Treated Playsets and Decks
Chen, J., N. Mottl, T. Lindheimer, and N. Cook.
U.S. EPA, Office of Pesticide Programs, 266 pp, 2008

See also additional resources

A Review of Human Carcinogens: Chromium (VI) Compounds
A Review of Human Carcinogens. Part C: Arsenic, Metals, Fibres, and Dusts
World Health Organization, International Agency for Research on Cancer (IARC) Monographs, Vol 100C, p 147-167, 2012

Toxicological Reference Values for Wildlife
Oak Ridge National Laboratory, 1996