Chrome, short for chromium, is a metallic element that can exist in several different forms or oxidation states. The most common and stable forms are trivalent chromium (Cr(III)) and hexavalent chromium (Cr(VI)). While chromium is found naturally in the environment, it is also extensively used in industrial processes and manufacturing. This widespread use raises concerns about the potential health effects of chromium exposure in humans.

Chromium Toxicity

Hexavalent chromium (Cr(VI)) compounds are known to be toxic and carcinogenic when inhaled or ingested, whereas trivalent chromium (Cr(III)) is an essential nutrient for humans in small amounts [1]. The key differences between the two forms are:

Cr(VI) – Highly toxic, known human carcinogen, can easily enter cells via nonspecific anion channels. Once inside cells it can get reduced to Cr(III) and cause DNA damage and mutations.
Cr(III) – Essential nutrient, not toxic at normal dietary intake levels. Poorly absorbed by cells compared to Cr(VI).

The toxicity and carcinogenicity of chromium compounds depends on factors like [1,2]:

Oxidation state – Cr(VI) is more toxic than Cr(III)
Solubility – Water-soluble forms like chromium trioxide are more bioavailable and toxic
Route of exposure – Inhalation is a major route of exposure in occupational settings
Dose and duration – Higher doses and chronic exposures pose greater risk

In summary, hexavalent chromium compounds have high cellular permeability and reactivity, which enhances their toxicity and mutagenicity compared to trivalent forms. However, all forms of chromium can be hazardous at high enough doses.

Adverse Health Effects of Chromium Exposure

Chromium exposure, especially to hexavalent compounds, has been linked to a wide range of detrimental health effects across organ systems [1,3]:

Respiratory Effects

Irritation of the nasal mucosa, throat, lungs
Asthma, bronchitis, chronic pharyngitis
Impaired lung function
Lung cancer – hexavalent chromium is a known human carcinogen when inhaled

Dermal Effects

Irritant and allergic contact dermatitis with symptoms like rashes, ulcers, swelling, flaking, itching
Chrome holes and ulcers in skin

Carcinogenic Effects

Increased risk of lung, nasal, and sinus cancers
Potential elevated risks for cancers of the stomach, intestine, bladder, kidney, liver, prostate

Renal Effects

Acute tubular necrosis and interstitial nephritis
Decreased glomerular filtration rate
Proteinuria and enzymuria

Hepatic Effects

Mild hepatomegaly and liver function changes
Increased liver enzymes, hyperbilirubinemia
Liver necrosis at very high doses

Gastrointestinal Effects

Abdominal pain, diarrhea, vomiting after ingestion
Gastrointestinal ulcerations and hemorrhage
Hypochromic microcytic anemia

Ocular Effects

Conjunctivitis, corneal injury, ulceration

Cardiovascular Effects

Potential increased risk of cardiovascular disease
Endothelial dysfunction and elevated inflammatory markers

Hematological Effects

Hemolytic anemia
Leukocytosis, thrombocytosis

Reproductive/Developmental Effects

Reduced sperm quality and fertility in males
Increased risk of spontaneous abortions in females
Potential developmental defects and impaired fetal growth

Genotoxic and Mutagenic Effects

DNA damage, chromosomal aberrations, micronuclei formation
Mutations in oncogenes and tumor suppressor genes

The primary routes of occupational exposure are inhalation and dermal contact. However, ingestion of contaminated food or water is another potential source of exposure in heavily polluted areas. Adverse effects are generally more severe with higher doses and longer durations of exposure.

Organ Systems Affected by Chromium Toxicity

Let’s take a closer look at some of the major organ systems impacted by chromium toxicity and the mechanisms involved [1,4,5]:

Respiratory System

The respiratory tract is the primary target organ for chromium toxicity in workplace inhalation exposures. Chromium is a potent irritant and can lead to inflammation and damage of the nasal epithelium and lungs.

Chronic inhalation of hexavalent chromium has been firmly linked to lung cancer. Inside lung cells, Cr(VI) gets reduced to Cr(III) which then interacts with DNA and proteins to cause mutagenic effects and cancer development.

Kidneys

The kidneys are another major target. After entering the bloodstream, chromium is filtered by the kidneys where it can accumulate in proximal tubule cells at toxic concentrations. This leads to acute tubular necrosis, decreased glomerular function, and kidney damage.

Liver

Chromium absorbed into the blood is taken up by the liver. Extremely high doses lead to hepatocellular injury, necrosis, enlarged liver, and elevated bilirubin levels. Even at lower doses, subtle changes in liver enzymes and mild hepatomegaly may occur.

Skin

Dermal exposure to chromium leads to irritation and allergic reactions in the skin. Chromium is a common cause of contact dermatitis which can range from mild rashes to severe skin ulcers depending on the concentration and duration of exposure.

Gastrointestinal Tract

Ingestion of chromium causes nausea, vomiting, diarrhea, and hemorrhage in the stomach and intestines. Oral ulcers may also develop. Chromium disrupts the gastric mucosal barrier and impairs the regeneration of gastrointestinal tissue.

Blood and Blood-forming Organs

Chromium exposure has been linked to hematological effects like anemia, leukocytosis, and thrombocytosis. It is thought to induce oxidative damage to red blood cells and disrupt hematopoiesis. Very high doses can lead to intravascular hemolysis.

Reproductive System

There is some evidence that chromium may impact male fertility and reproduction through mechanisms like reduced testosterone, impaired sperm motility and counts, and testicular tissue damage. However, findings are not completely consistent across studies.

Cardiovascular System

While the data is limited, there are suggestions that chromium exposure could potentially increase risks of cardiovascular disease over time. Biomarkers related to endothelial dysfunction, inflammation, and oxidative stress are elevated.

Genetic Material

Hexavalent chromium is a mutagenic compound due to its interactions with DNA and nuclear proteins inside cells. This can lead to DNA damage, chromosomal breaks, micronuclei formation, oncogene activation, and inactivation of tumor suppressor genes.

Factors That Influence Chromium Toxicity

Several key factors influence the absorption, distribution, and toxicity of different chromium compounds in the body [2,6]:

Oxidation State

Cr(VI) compounds are significantly more toxic than Cr(III) forms due to their higher solubility and rapid cellular permeability.

Solubility and Particle Size

Water-soluble forms like chromium trioxide are more bioavailable and toxic than insoluble particles.
Smaller particle sizes have higher deposition in lungs and absorption in GI tract.

Exposure Route

Inhalation of chromium dusts and mists is the major route of exposure in occupational settings.
Oral ingestion from contaminated water or food is also hazardous.
Dermal exposure can lead to local skin effects.

Dose and Duration

Higher doses and longer exposures to chromium increase the risks and severity of adverse effects.
Chronic low-level exposure over months/years is especially concerning.

Individual Risk Factors

Genetic polymorphisms related to chromium metabolism may influence susceptibility.
Pre-existing health conditions like renal dysfunction or respiratory disease can increase risks.
Nutritional status may impact chromium toxicity.

Lifestyle Factors

Cigarette smoking can impair clearance of chromium and exacerbate lung effects.
Alcohol consumption may increase gastrointestinal absorption and liver toxicity.

Co-Exposures

Combined exposures to chromium and other workplace chemicals like asbestos or arsenic may have synergistic effects.

Guidelines and Regulations for Chromium Exposure

Due to the well-established health risks, regulations and guidelines have been developed to limit chromium exposures [7,8]:

The Occupational Safety and Health Administration (OSHA) has set a permissible exposure limit (PEL) of 5 μg/m3 for workplace airborne chromium over an 8-hour shift.
The National Institute for Occupational Safety and Health (NIOSH) has a recommended exposure limit (REL) of 0.2 μg/m3 for chromium in workplace air.
The Environmental Protection Agency (EPA) has a maximum contaminant level (MCL) of 0.1 mg/L for total chromium in drinking water.
The FDA limits chromium content in bottled drinking water to 0.1 mg/L.
For ingestion, the EPA reference dose for chromium is 0.005 mg/kg/day.
Many countries have regulations to limit chromium discharges from industrial facilities into waterways and sewer systems.
Hexavalent chromium compounds are classified as known human carcinogens by regulatory agencies and the WHO International Agency for Research on Cancer.
California’s Proposition 65 list hexavalent chromium compounds as chemicals known to cause cancer.

These exposure limits and classifications are designed to protect the public and workers from the health risks posed by both short-term high-dose and chronic low-level chromium exposures.

Conclusion

Exposure to hexavalent chromium compounds in particular poses significant health risks to humans when inhaled or ingested. Cr(VI) is a potent toxin, irritant, and carcinogen that can damage the respiratory tract, kidneys, liver, skin, and gastrointestinal tract. It also has genotoxic and reproductive effects.

Trivalent chromium, on the other hand, is an essential nutrient but can still cause adverse effects at very high doses. Careful regulation and control of chromium emissions from industrial sources along with biomonitoring of exposed populations is critical for reducing risks. Workers in occupations with chromium exposure need regular health screenings and protective equipment/ventilation. By understanding the mechanisms and factors that influence chromium toxicity, the public health impacts of this metal can be minimized.

References

[1] Costa, M., & Klein, C. B. (2006). Toxicity and carcinogenicity of chromium compounds in humans. Critical reviews in toxicology, 36(2), 155-163.

[2] Jacobs, J. A., & Testa, S. M. (2005). Overview of chromium (VI) in the environment: background and history. Chromium (VI) handbook, 1-21.

[3] Langård, S. (1982). Biological and environmental aspects of chromium. Elsevier Biomedical Press.

[4] Cohen, M. D., Kargacin, B., Klein, C. B., & Costa, M. (1993). Mechanisms of chromium carcinogenicity and toxicity. Critical Reviews in Toxicology, 23(3), 255-281.

[5] Gibb, H. J., Lees, P. S., Pinsky, P. F., & Rooney, B. C. (2000). Clinical findings of irritation among chromium chemical production workers. American journal of industrial medicine, 38(2), 127-131.

[6] Barceloux, D. G. (1999). Chromium. Clinical toxicology, 37(2), 173-194.

[7] Toxicological Review of Hexavalent Chromium (1998). U.S. Environmental Protection Agency. EPA/635/R-98/004F.

[8] Hexavalent Chromium. (2013). Report on Carcinogens, Fourteenth Edition. National Toxicology Program.