IngredientsCr2O3 is an inorganic compound that goes by the chemical name chromic oxide. Alternative names include dichromium trioxide, chromium sesquioxide, chromium(III) oxide, chrome green, and chromia. Its CAS registry number is 1308-38-9. Because of its considerable stability, chromia has long been used as a pigment and was originally called viridian.
Chromium(III) oxide occurs naturally as the rare mineral eskolaite and is typically produced synthetically as a fine, light to dark green crystalline powder that is odorless and insoluble in water but amphoteric, dissolving in strong acids and concentrated alkalies (albeit slowly). This compound exhibits a corundum-type trigonal crystal structure (space group R-3c), consisting of CrO6 octahedra where each oxygen atom is bonded to four chromium atoms, contributing to its high thermal stability with a melting point of 2435 °C and a density of approximately 5.21 g/cm³.
The monoisotopic mass of chromic oxide (Cr2O3) is 151.866 Da and the molar mass is 151.9904 g/mol. The chemical composition consists of 68.46% chromium and 31.58% oxygen by mass. In this compound the metal chromium is in a +3 oxidation state. Chemically amphoteric, it serves as a stable trivalent chromium source, resisting corrosion and oxidation at elevated temperatures. It is odourless and insoluble in water, acids, and alkalis. Its green colour is very stable and does not fade with exposure to light or heat.
Chromic oxide occurs naturally in a mineral named eskolaite, a rare mineral with a trigonal crystal structure similar to corundum. The rare natural mineral form of Cr2O3 is eskolaite, named after Finnish geologist Pentti Eskola. It naturally occurs in chromium-rich skarns, tremolite, chlorite veins, and meta quartzites. Eskolaite is also a rare component of chondrite meteorites.
Chromium is widely distributed in soil and rock and makes up 0.037% of the Earth's crust. The major chromium mineral is chromite (FeCr2O4). Under intermediate and reducing conditions, chromium appears at a valence of +3 and mostly in the form of chromium oxide (Cr2O3). Industrially, chromic oxide is manufactured from the mineral chromite mined in southern Africa, Asia, Turkey, and Cuba.
Chromium oxide is an inorganic compound that occurs naturally in eskolaite; owing to its scarcity in nature, it is typically derived from the reduction-oxidation (redox) reaction of sodium dichromate with sulfur at elevated temperatures. The oxide is also formed by the decomposition of chromium salts such as chromium nitrate, or by the exothermic decomposition of ammonium dichromate.
Chromic oxide is used as a polishing compound (also called stropping) for the edges of knives, razors, and surfaces of optical devices on a piece of leather, balsa, cloth or other material; it is available in powder or wax form and in this context is known as "green compound." In nutritional and biological research contexts, it is employed exclusively as a fine powder, incorporated directly into experimental animal diets or pelleted delivery systems. Cr2O3 can be added to experimental diets at rates between 0.01% and 3%. It is not available in established pharmaceutical dosage forms for human therapeutic use.
The element chromium was found in lead chromate in 1797 by Louis-Nicolas Vauquelin, and the element was named chromium because so many colored compounds can be produced from it. As early as 1809, chromium oxide was used as an enamel in porcelain factories. The Parisians Pannetier and Binet first prepared the transparent hydrated form of Cr2O3 in 1838 via a secret process, sold as a pigment. Several sources indicate chromium oxide was not used as a painting pigment until 1862, but there is evidence that it was used earlier — this pigment has been confirmed on a painting by J.M.W. Turner dating to 1812, and George Field mentioned a self-made example of this pigment in his diary in 1815.
A process for synthetically producing anhydrous, opaque chrome oxide green was developed in 1809 by Vauquelin, and the colorant was listed as an artist's pigment in the 1840 Winsor and Newton catalog. Chromic oxide has limited use in paints because of its dull color; however, it has been popular for deck paints and camouflage coatings for military purposes because it absorbs infrared radiation well.
The predominant inert marker in fish nutrition studies is chromic oxide (Cr2O3), which was first used to estimate digestibility in livestock at the beginning of the 20th century (Edin, 1918). This represents the most substantial documented history of chromic oxide as a feed/nutritional additive. For over a century, agricultural scientists have administered Cr2O3 as an indigestible reference compound to quantify how efficiently animals digest their feed.
Mineral values have been commonly measured as differences between intake and faecal excretion in balance or digestibility trials; by adding inert, unabsorbable markers such as chromic and titanium oxides to poultry diets, disappearance of mineral from the gut can be measured before digesta reach the cloaca. This technique has been widely applied in ruminants, swine, poultry, equines, dogs, and aquaculture species.
Chromic oxide as a specific compound has not been used in traditional human dietary supplementation. The broader use of trivalent chromium-containing compounds in human nutrition arose from mid-20th century laboratory research rather than traditional medicinal practice. The essential role of chromium in nutrition was first recognized by Schwarz and Mertz in 1959; these researchers observed that rats fed torula yeast developed glucose intolerance, but rats fed brewer's yeast did not. A substance present in brewer's yeast but not torula yeast was termed glucose tolerance factor (GTF), and it was later demonstrated that the active ingredient in GTF is chromium(III).
Schwarz and Mertz in the 1950s published a series of experiments providing evidence that chromium is an essential nutrient forming the active component of what was called the "glucose tolerance factor." From this research, interest in chromium supplementation — primarily via more bioavailable forms such as chromium picolinate, chromium chloride, and chromium polynicotinate — developed. Chromic oxide itself has been studied specifically as a supplement source for poultry, swine, and livestock, where its low bioavailability and inert behavior in the gut make it suitable for digestibility marker studies but less appropriate as a nutritional supplement for humans.
Chromic oxide is a single, well-defined inorganic compound. It contains no organic constituents, secondary metabolites, or traditional botanical components. The chemical composition of chromic oxide has 68.46% chromium and 31.58% oxygen by mass. Its entire biological relevance — whether as a nutritional marker or potential chromium source — derives from its content of trivalent chromium (Cr³⁺).
Chromium exists in several valence states including metallic chromium (valence zero, Cr-0), which is inert; chromium III (Cr-III), which is stable and the biologically active form; and chromium VI (Cr-VI), which when bound to oxygen is a strong oxidizing agent that is readily reduced to Cr-III in an acidic environment such as the stomach.
Trivalent chromium is an essential element that potentiates insulin action in peripheral tissue and is essential for lipid, protein, and fat metabolism in animals and human beings. Chromium deficiency causes changes in the metabolism of glucose and lipids and may be associated with maturity-onset diabetes, cardiovascular diseases, and nervous system disorders.
Cr(III) is generally considered benign due to poor membrane permeability, and Cr(III) compounds are even recognized as essential micronutrients involved in important physiological functions, such as the biological activity of insulin.
Chromium has been recognized for decades as a nutritional factor that improves glucose tolerance by enhancing in vivo insulin action, but the molecular mechanism is unknown. Several hypotheses have been proposed:
Despite decades of research, chromium remains the only essential transition metal whose mechanism of action is not known.
At low levels of dietary intake (10 µg), about 2% of trivalent chromium is absorbed. When intake increases to more than 40 µg, the absorption efficiency drops to approximately 0.5%. The bioavailability of chromium is highly dependent on the specific chemical form. Chromic oxide (Cr2O3) is notably poorly soluble and poorly absorbed compared to organic chromium complexes. Chromic oxide (Cr2O3) is characterized as a nondigestible, nonabsorbable marker when included in animal diets. Chromium(III) present in soil (and by extension as insoluble Cr2O3) is generally not very soluble or mobile under most environmental conditions and is not readily bioavailable.
The most extensively documented nutritional application of chromic oxide is its use as an indigestible reference marker in animal digestibility trials. Several assumptions are made when the inert marker method is used: (a) the marker is physiologically inert, (b) the ratio of nutrient to marker in the material ingested is the same as in the feed, (c) the marker is not absorbed from the digestive tract of the test animal or lost from the feces, and (d) the marker and feed material pass through the digestive system at the same rate.
Ruminants and Sheep: Recovery of Cr2O3 in the faeces of sheep ranged from 91 to 101%, and predicted dry-matter digestibilities were similar to those obtained by total collection. There was no diurnal variation, but there was marked random variation in the concentration of Cr2O3 in spot samples of faeces. Cr2O3 was shown to behave independently of the particulate matter in digesta. Cr2O3 thus overestimated digestion in the stomach and underestimated digestion in the intestines, and it was concluded that Cr2O3 was not a satisfactory marker for studies of the flow of digesta when digesta samples are taken from a simple cannula. This represents an important limitation identified in the peer-reviewed literature.
Swine: Two experiments were conducted to determine apparent ileal dry matter and crude protein digestibilities in rations fed to pigs, and an evaluation was made of Cr2O3 and HCl-insoluble ash as digestive markers. The effects of body weight on apparent ileal DM and CP digestibilities were also studied. The postprandial patterns of nitrogen and chromium passage were more similar than those of nitrogen and HCl-insoluble ash, indicating Cr2O3 is more suitable as a marker than HCl-insoluble ash in this context.
Dogs: In cannulated dogs, ileal recovery of Cr2O3 was almost complete (94%) and was greater than fecal recovery (87%). Recovery was not different among diet groups. Chromic oxide concentration in chyme varied widely during each collection but increased at the start and declined towards the end; spot sampling may therefore result in inaccurate estimates of nutrient digestibility.
Equines: In equines, Cr2O3 is widely accepted as an indigestible marker, but there are health concerns regarding the carcinogenic properties of Cr2O3. Recently, TiO2 has been suggested as an alternative digestibility marker in equines.
Aquaculture: While chromic oxide is the most commonly reported marker in aquaculture, some questions have been raised about the validity of its use. One researcher considered it not valid to use chromic oxide as it had differential passage, relative to organic matter, in the gut of the American lobster. In fish, chromic oxide does not appear to satisfy the criteria for an ideal inert marker. Most importantly, dietary chromic oxide is not always totally recovered in the faeces, and it must therefore be included at relatively high concentrations (5–10 g/kg feed) in order to obtain homogeneous analytical results. High dietary levels of chromic oxide may disturb the absorption and metabolism of nutrients in fish. In studies with Arctic char, dietary Cr2O3 at 10 g/kg feed reduced the concentration of fat in the faeces and altered the aerobic bacterial flora in the intestine. Studies with hybrid tilapia also indicated that dietary chromic oxide at 5–20 g/kg feed affected the digestibility of carbohydrate, growth, and body composition.
Evidence strength: The body of literature on chromic oxide as a digestibility marker is large, spanning multiple decades and species. The weight of evidence from peer-reviewed animal science journals identifies Cr2O3 as a useful but imperfect marker with species-specific limitations, particularly in fish. No human clinical trials of Cr2O3 as a digestibility marker exist.
The following evidence applies to trivalent chromium supplementation broadly; it is important to note that most human clinical trials used chromium picolinate, chromium chloride, or chromium enriched yeast — not chromic oxide (Cr2O3) itself. Because of Cr2O3's extremely low bioavailability, it is not the source used in human supplementation studies.
Data from chromium supplementation studies provide some evidence for short-term and long-term efficacy, as evidenced by reductions in fasting and 2-hour glucose and insulin values, and long-term reductions in hemoglobin A1c concentrations utilizing varying doses of chromium (200, 500, or 1000 µg).
Over time, the essentiality of chromium has been increasingly challenged. A 1997 review by Anderson concluded that chromium is an essential nutrient for sugar and fat metabolism, yet the dietary intake in the United States and most other developed countries is suboptimal, leading to widespread symptoms similar to those of diabetes and/or cardiovascular diseases.
For an element to be essential, three things must be true: (1) it has a defined biochemical function; (2) its lack causes death or reproduction failure; and (3) the addition of it to the diet can prevent such effects.
The essentiality of Cr(III) for humans has been questioned based on the criteria required for inorganic elements. It was noted that attempts to create chromium deficiency in animal models have not produced consistent results, and that there is no evidence of essentiality of Cr(III) in animal nutrition.
Evaluating the possibility of Cr(III) as an essential element for humans, the evidence from reported improvements associated with chromium supplementation in patients on total parenteral nutrition was considered the most convincing, but overall data do not provide sufficient information on the reversibility of the possible deficiencies and the nature of any dose–response curve in order to identify a dietary requirement for humans. The EFSA Panel concludes that no Average Requirement and no Population Reference Intake for chromium can be defined.
Several studies assessed the effect of chromium supplementation on glucose and/or lipid metabolism. In the only study for which information on total chromium intake was available, there was no difference in parameters of glucose metabolism of normoglycaemic subjects between the placebo and chromium-supplemented periods. The EFSA Panel considered that there is no evidence of beneficial effects associated with chromium intake in healthy subjects, and concluded that the setting of an Adequate Intake for chromium is also not appropriate.
The U.S. Food and Nutrition Board/Institute of Medicine estimated Adequate Intakes for adults at approximately 35 µg/day for men and 25 µg/day for women in the 19–50 year age range. Chromium had no recommendation in the Nordic Nutrition Recommendations 2012 and EFSA did not set reference values either. Methods for evaluating chromium status are lacking, and there is still uncertainty about how chromium deficiency in humans manifests itself. The essentiality of chromium is also disputed.
Chromium was first proposed as an essential element for normal glucose metabolism in 1959, but its biological function has not been identified. Cases of deficiency were described in people who received all of their nutrition intravenously for long periods of time. The essentiality of chromium has been challenged.
Evidence strength: The evidence that chromium is a conventional essential trace element is currently considered insufficient by major European regulatory bodies (EFSA, 2014). The U.S. IOM has set Adequate Intake values, but these were based on estimated dietary intakes rather than dose–response studies demonstrating deficiency reversal. No clinical trial has specifically used Cr2O3 as the chromium source in human supplementation.
Trivalent chromium is considered an essential micronutrient needed for optimum carbohydrate, protein, and fat metabolism along with glucose-insulin sensitivity. The exact mechanism by which trivalent chromium plays a role is not clear, but multiple in vitro and in vivo studies indicate that Cr(III) has a crucial role in normal glucose and lipid homeostasis. As noted above, most of this evidence relates to more bioavailable chromium salts rather than to Cr2O3 itself.
Cr(III) is generally benign due to poor membrane permeability and is recognized as an essential micronutrient involved in important physiological functions, such as the biological activity of insulin.
Trivalent chromium is considered essential for lipid and fat metabolism in animals and human beings, and chromium deficiency may be associated with cardiovascular diseases. These associations have been explored mainly in studies using organic chromium complexes, not Cr2O3.
Chromic oxide does not exert physiological activity in the gastrointestinal tract under normal conditions of use as a marker. Assumptions for use as an inert marker include that it is physiologically inert and not absorbed from the digestive tract. This is the basis of its principal nutritional science application.
Cr2O3 can be added to experimental diets at rates between 0.01% and 3%. In fish studies, it must be included at relatively high concentrations of 5–10 g/kg feed in order to obtain homogeneous analytical results. In a study of Welsh pony geldings, diets were supplemented with 3.2 g Cr/day as Cr2O3.
Groups of 60 male and female rats were fed chromic oxide (Cr2O3) baked in bread at dietary levels of 0%, 1%, 2%, or 5%, 5 days/week for 600 feedings (840 total days). The average total amounts of ingested Cr2O3 were given as 360, 720, and 1,800 g/kg body weight for the 1%, 2%, and 5% treatment groups, respectively.
Studies with varying doses of chromium (200, 500, or 1000 µg) provided some evidence for short-term and long-term efficacy on glucose and HbA1c in type 2 diabetic populations. The National Research Council identified an estimated safe and adequate daily dietary intake (ESADDI) for chromium of 50–200 µg/day, corresponding to 0.71–2.9 µg/kg/day for a 70 kg adult. These dosages apply to trivalent chromium generally from various sources, not to chromic oxide specifically.
Once in the trivalent state, chromium is poorly absorbed by cells and thus poses little or no carcinogenic risk to humans. When ingested, hexavalent chromium can be reduced to trivalent chromium by reducing agents within the gastrointestinal (GI) tract, but the reverse of this process — oxidation of trivalent to hexavalent chromium — will not occur in the human body.
The International Agency for Research on Cancer (IARC) catalogues Cr(VI) in Group 1 of toxic substances as "carcinogenic to humans." According to U.S. EPA-IRIS data, although the possibilities of interconversion between Cr(III) and Cr(VI) call for caution, no risks of Cr(III) causing cancer have been demonstrated, not even via inhalation.
In contrast, Cr(VI) compounds can actively penetrate cell membranes through channels for isoelectric and isostructural anions, such as SO42− and HPO42− channels. Cr(VI) compounds can enter the cell via the sulfate-anion channel and be subjected to reduction by cellular reductants such as glutathione and ascorbate, with formation of highly reactive Cr(V/IV) intermediates and finally Cr(III) products. The resultant intermediates further react with H2O2 to generate a spectrum of reactive oxygen species, and excessive ROS interaction with these intermediates may give rise to oxidative stress and DNA damage.
The principal toxicological study used to assess chromic oxide was by Ivankovic and Preussmann (1975), titled "Absence of toxic and carcinogenic effects after administration of high doses of chromic oxide pigment in subacute and long-term feeding experiments in rats" (Food Cosmet Toxicol 13:347–351). Groups of 60 male and female rats were fed Cr2O3 baked in bread at dietary levels of 0%, 1%, 2%, or 5%, 5 days/week for 600 feedings. The primary purpose of this study was to assess the carcinogenic potential of Cr2O3. No increase in the incidence of tumors was seen in treated animals with respect to controls.
Regarding toxicity, the safety factor for chromium is greater than that for almost any other nutrient. This characterization applies specifically to trivalent chromium compounds.
Even at small amounts (0.01–3%), chromium oxide may not be totally inert, affecting the assessment of diet digestibility with implications for nutrition and feeding practices. It has been speculated that poorer growth performance of tilapia fed higher levels of chromic oxide may be due to a toxic effect of dietary chromium. Studies with hybrid tilapia also indicated that dietary chromic oxide at 5–20 g/kg feed affected the digestibility of carbohydrate, growth, and body composition.
In 2017, the International Agency for Research on Cancer classified welding fumes as "carcinogenic to humans" (Group 1). Both mild steel welding and stainless steel welding increase lung cancer risk in welders. In experimental studies, Cr(III) oxide [Cr2O3] was compared alongside Cr(VI) calcium chromate [CaCrO4], nickel(II) oxide, iron(III) oxide, and welding fumes for pulmonary toxicity and lung tumor promotion potential. These inhalation-focused concerns are specific to occupational exposure scenarios and are not considered relevant to oral ingestion contexts.
In equines, Cr2O3 is widely accepted as an indigestible marker, but there are health concerns regarding the carcinogenic properties of Cr2O3. Recently, TiO2 has been suggested to be an alternative digestibility marker in equines. This concern has been raised primarily in the context of prolonged or high-level dietary exposure in animal research, not human supplementation.
A study by Anderson et al. (1997) indicated that 15 mg/kg body weight/day chromium (as chromium chloride) was not associated with adverse effects in the rat. Based on this study, and allowing uncertainty factors of 10 for inter-species variation and 10 for inter-individual variation, a total daily intake of about 0.15 mg/kg body weight/day (or 10 mg/person/day) would be expected to be without adverse health effects.
A scoping review for Nordic Nutrition Recommendations 2023 revealed new research activity relating to high-dose chromium supplements and several health outcomes (overweight, obesity, and diabetes). Although these issues are related to health concerns in Nordic/Baltic countries, the relevance for national nutritional recommendations is modest, since such a high intake of chromium cannot be achieved by diet. No strong evidence was identified in the scientific literature that justifies a recommendation for chromium intake.
Studies in gilthead sea bream found that estimates of calcium and phosphorus absorption differed systematically with different concentrations of dietary chromic oxide. This suggests that at sufficiently high doses, Cr2O3 may interfere with mineral absorption. Although Cr(III) is an essential nutrient, exposure to high levels via inhalation, ingestion, or dermal contact may cause adverse health effects.
Chromic oxide (Cr2O3) occupies a unique and somewhat paradoxical position in nutrition science. Its primary documented nutritional role is not as a nutrient source, but as an inert reference standard for measuring feed digestibility in livestock and aquaculture. Decades of animal science research have validated this application while also identifying species-specific limitations. The compound's biological inertness — the basis of its marker utility — also makes it poorly suited as a chromium supplement for humans, where bioavailable organic forms of Cr(III) are standard. In the human clinical literature on chromium supplementation, Cr2O3 has not served as the vehicle of delivery in published trials; those studies relied on chromium picolinate, chromium chloride, or brewer's yeast.
The broader question of chromium's essentiality in humans remains unresolved: the essentiality of Cr(III) for humans has been questioned based on the criteria required for essential inorganic elements. The EFSA Panel concluded that the setting of an Adequate Intake for chromium is not appropriate. The toxicity profile of Cr2O3 at oral doses relevant to its use as a marker is low, but concerns about its inertness and potential biological interactions at high doses have prompted the search for alternative markers in certain species.
Health conditions that Chromic oxide may help support.
Chromic oxide is a form of trivalent chromium used in some nutritional research, though chromium picolinate and nicotinate are more clinically studied forms. The TG evidence relates to the elemental chromium's role in insulin sensitization. Limited specific evidence for chromic oxide form; the TG evidence is extrapolated from chromium supplementation trials.
Body systems that Chromic oxide may help support.
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