Dermatotoxicological aspects of metallic chromium

ARTICLE

Chromium (Fig. 1) may occur in several valence states; of these, only valence states 0, 3+ and 6+ are stable, and only the trivalent and hexavalent salts are able to act as haptens, i.e. to form covalent bonds with proteins [1, 2], and cause allergy. This protein-binding capacity is the general precondition for the immunogenic activity of a hapten, as demonstrated 60 years ago [3]. It is generally accepted that the chromium metal itself does not act as a hapten, and is, accordingly non-sensitising [1, 2]. It is important to emphasise this difference compared to certain other metals, e.g. nickel.

Theoretically e.g. sweat or plasma can transform metallic chromium into allergenic chromate salts. Saliva could have a similar action on intraoral devices containing chromium. The chromium released from household utensils may also transform into chromates. Accordingly, oral ingestion of chromate may induce systemic contact dermatitis [4].

The leaching of toxic elements from cooking utensils is a long-recognised problem, and covers a wide range of different elements, the old examples including e.g. lead (mainly from earthenware), and copper (typically from coffee pots with defective tin-plating). More recently, nickel and aluminium from kitchenware have raised concerns. In this article, the literature on hazards caused by chromium leaching from kitchen utensils and other consumer items is discussed from a dermatotoxicologic point of view.

Importance of chromium

Studies of patients on total parenteral nutrition have indicated that lack of chromium may lead to disturbances in glucose metabolism [5]. Also, the glucose balance of diabetic patients with low chromium intake has been reported to be improved by addition of 200 µg chromium per day to the diet [6]. Thus, although no improvement in glucose tolerance was observed among non-selected diabetics on a normal diet [7], chromium is at present, generally considered an essential element to humans [8-10]. The US National Research Council has published a recommended daily chromium intake of 50-200 µg/day.

Toxicity of chromium

The toxicity of chromium depends on the valence state: hexavalent chromium compounds are considered to be more toxic than trivalent chromium compounds. Specifically, occupational exposure to hexavalent chromium compounds by inhalation has been shown to result in an elevated incidence of cancer in the respiratory system (nose and lung) and several studies have demonstrated that hexavalent chromium compounds induce cancer in experimental animals. Available data show no such association between exposure to trivalent or metallic chromium and cancer induction [11]. A recent study also reported that stainless steel, implanted intramuscularly into rats, failed to induce local tumours (whereas high-nickel (96.2%) alloy was clearly carcinogenic in similar circumstances) [12]. Only very limited studies are available on the carcinogenicity of chromium after oral administration; no carcinogenic response has been described after oral exposure to chromium (III) compounds, the only valence state studied [11]. Hexavalent chromium compounds are mutagenic in a large variety of different test systems, whilst again, trivalent compounds are generally not [11]. Some chromium compounds are also allergenic and induce mainly allergic contact dermatitis. Hexavalent chromium salts, and especially chromic acid, are corrosive and may induce corrosive skin damage, the best known of these is the perforation of the nasal septum.

Allergenicity of chromate salts

The bivalent salts are unstable and therefore are not used commercially [12]. The trivalent compounds include chromic acid, chromic sulphate and chromium trichloride, all of which are putative sensitizers [1, 2]. Trivalent chromium penetrates the skin poorly, so it is not used for patch testing [13], although patch testing with trivalent chromate does give allergic reactions (Fig. 1). The hexavalent chromium compounds, or dichromates, are widely used in industry and are the most sensitising of the chromium compounds [1, 2]. Allergic contact dermatitis caused by chromate, known since 1925 [14], is common [1, 2].

A maximisation test was used by Kligman [15] to assess the sensitising potential of trivalent and hexavalent chromium compounds. About half of a group of 23 human subjects were sensitised with trivalent chromate salts, and all of the 23 subjects were sensitised to potassium dichromate. On a 1 to 5 scale in which grade 5 is the most potent allergen, trivalent chromium was graded as 3 and hexavalent chromium as 5, i.e. an extreme sensitizer. In a guinea pig maximisation test, potassium chromate was graded as 4 on the same scale [16].

In industrialised countries, chromate has been one of the most common sensitizers [1, 2]. Chromate is a more common sensitiser in men than in women [1, 2], although the ratio of women to men has been increasing [17]. The difference probably depends on the pattern of employment. The causes of allergy to chromate vary from country to country depending on local industry and the chemical environment. Cement is usually the most common cause [1, 2, 17]. The greatest hazard from cement occurs on building and construction sites, but men are also at risk in the manufacture of cement, including cement used at home for do-it-yourself jobs [1, 2, 17]. Eczema is most commonly localised to the hands [1, 2, 17]. A diagnosis of cement dermatitis (allergic or irritant) must be considered in all patients working with cement or plaster. Cement eczema has a poor prognosis [1, 2, 17, 18].

Humans often have multiple sensitivity to metals. As regards simultaneous reactivity to chromate and cobalt, a recent guinea pig maximization test showed that chromate and cobalt do not cross-react [19]. In 1982, Nethercott reviewed the world literature on routine patch testing for chromate (17,021 cases), and found an incidence of 7.9% positivity to potassium dichromate [20]. The incidence of chromium dermatitis has decreased during the 1980s and 1990s [21].

Sources of dietary chromium

The concentration of chromium in different dietary items is generally low: dairy products are especially low in chromium (< 0.5 µg/serving), while meat, poultry, grain products, fruits and vegetables generally provide 1-10 µg chromium per serving [22]. The peeling of apples decreases their chromium content to one third; this would indicate that part of their chromium content is derived from surface contamination. The chromium content of separate samples of several food items varys markedly, e.g. 100-fold for different samples of beer or breakfast cereals [22-24]. The concentration of chromium is higher in bread and fu (wheat gluten product) and natto (fermented soybean product) than in wheat flour and soybean, respectively [25]. Chromium is reported to leach into wine from bottles (coloured with chromium-containing pigments) and also during storage in stainless steel tanks [26, 27]. Another study reported lower chromium levels in wine stored in stainless steel vessels than in wine stored in redwood caskets [28]. Kumpulainen and co-workers reported that the mixing of meat in the presence of orange juice in a standard kitchen mixer with stainless steel blades almost doubled its chromium content in three minutes [29].

It thus appears that a large proportion, in some cases most, of the chromium found in food does not originate from the raw materials but is rather added during food processing. There is no reason to believe that this exogenous chromium behaves differently from endogenous, inorganic chromium.

The daily human chromium intake varies between different geographic areas, and is usually between 20 and 85 µg/day, although values of up to 130 µg/day have been reported [30-32]. It would seem that at present, the levels at the low end of the scale are found mainly in countries in the West.

Stainless steel

Allergic contact dermatitis caused by stainless steel is generally considered to be due to nickel [33-40]. Stainless steel became popular more than 80 years ago when Brearley discovered that a ferrous mixture containing at least 12% chromium is resistant to corrosion and oxidation [39]. Stainless steel often contains nickel. In addition to chromium and nickel, stainless steel may contain carbon, nitrogen, manganese, magnesium, phosphorus, sulphur, cobalt, copper, silicon and molybdenum [36, 39, 40]. Accordingly, there are many types of stainless steel. The austenitic stainless steels (containing 8 to 34% nickel) are the most widely used [39]. The commonly used, 18/8 stainless steel contains 18% chromium and 8% nickel. High-quality stainless steel is not regarded by dermatologists to be a health hazard [40], but some types of stainless steel release enough nickel to provoke dermatitis in nickel-sensitive patients [33-40]. Recently, Haudrechy et al. [36] showed that 14% of nickel allergic patients reacted on patch testing to high-sulphur stainless steel (AISI 303 grade), whereas low-sulphur stainless steel (AISI 304, 316L and 430) did not elicit allergic reactions. Although most stainless steels do not release nickel easily, significant amounts may be leached by sweat or household detergents [33]. This release is accentuated by an acid pH, and thus nickel may be released in the handling and cooking of acid fruit and vegetables [34].

Several studies have investigated the leaching of chromium from stainless steel utensils under various conditions. Cold, 5% acetic acid (acidity chosen to simulate that of vinegar) did not cause chromium to leach from 6 different saucepans. When the acid was boiled for 5 min in the saucepans, the concentration of chromium observed did not differ from the analytical background (0.035 mg/l) in 3 of these, it was 2-fold higher in 2 pans, and 8-fold higher (0.3 mg/l) in the sixth. Since the last pot also corroded visibly during the study, the authors considered it likely that its chromium content was probably less than 11% [41]. All the pans tested were more than 1-year-old; the authors also tested one new saucepan and reported (no figures given) that to begin with it leached more metals, and only after 2 months was it similar to the others.

Three out of four stainless steel pots tested released small amounts (< 0.2 mg/l) of chromium in 4% acetic acid in three, consecutive, half-hour extractions at 100° C. The fourth pot released 20 times this amount at the first extraction, but very little thereafter [42].

No leaching of chromium into tea, coffee, milk, or fruit juice could be detected from either old or new stainless steel bowls or tumblers (chromium content 9.74-20.80%), while the leaching was 0.04 to 0.4 µg/g into curd or lemon pickle from new utensils, and 0.03 to 0.3 µg/g from old utensils. When new utensils were used, leaching into 5% sodium carbonate and 5% acetic acid decreased with successive experiments [43].

The chromium content of crayfish hepatopancreas cooked in a stainless steel pan increased from approximately 0.05 to 0.15 mg/kg fresh weight. When crayfish abdominal muscle was similarly cooked, the levels compared with the raw crayfish remained very similar [44].

The cooking of peeled potatoes in new steel pots increased their chromium content by 60%, while a decrease was observed after cooking in old steel kettles. In both new and old kettles, a minor decrease in the chromium content was observed in potatoes boiled in their jackets [45].

The preparation of meals from food items increased their chromium contents so that, of the total 82.6 µg chromium present in three typical German daily meals (breakfast, lunch, dinner), 45.3 µg were added during the food preparation process [46].

The leaching of chromium into 4% acetic acid from 18-8 steel kitchenware (spoons, ladles, knives) was less than 60 ng (0.5 ng/cm²) while it was ten times higher from several steel items of unknown composition. More chromium was dissolved from new than from used pudding cups [47].

Between 30-50 µg/l of chromium were released into HCl-acidified water (pH 2.5), canned tomato juice, bottled pineapple juice and lemon juice upon 1 h of boiling in a stainless steel pot; no chromium leaching was observed into non-acidified water [48].

Chromium is thus leached into food items, especially into those with marked acidity, from stainless steel kitchen utensils. Leaching is more pronounced at elevated temperatures, such as boiling water and is more extensive from steels containing lower proportions of chromium. When the utensils have been in use, the amount of chromium leached decreases. It is very unlikely that the total amount of chromium leached from stainless steel utensils, even into acidic foods, exceeds 50 µg/day, i.e., an amount considered to be beneficial to health.

There is still very little information on the valence state of chromium in different dietary items and especially on chromium leaching from kitchen utensils and on the changes of valence states during food storage.

Chromium speciation

Nearly all hexavalent chromium in the natural state is anthropogenic [49]. Scanty information is available on the valence state of chromium released from stainless steel surfaces. Recently it was reported that the erythrocyte/plasma chromium concentration ratio was elevated in patients with joint arthroplasty and having cobalt-chromium orthopedic implants. Although no quantitative interpretation is possible, this finding was interpreted as meaning a release of at least some hexavalent chromium from the implants upon corrosion [50]. However, it would seem that as far as the chromium released from stainless steel during cooking is concerned, this is unlikely to occur to a significant extent in the hexavalent state. Acidic food items leach more chromium from stainless steel than do neutral or basic food items. Hexavalent chromium is unstable in acid solution, and tends to be rapidly reduced to the trivalent state. Furthermore, upon ingestion, the dietary chromium ends up in the stomach, the contents of which are clearly acidic, as low as pH 1. This acidity would further enhance the rate of the reduction of chromium (VI). It is thus likely that most chromium leached in the gastrointestinal tract from kitchen utensils is in the form of chromium (III). This is not discrepant with more pronounced toxicity and faster absorption of ingested chromium (VI) compounds in comparison to chromium (III) compounds: in experiments with high doses, some chromium (VI) will be absorbed before it has time to be reduced, whilst at low doses reduction is likely to occur in the gastrointestinal tract.

Dental chromium

It is often not clear whether chromates or other metals and metal salts have caused the allergic reactions elicited by dental metals [40, 51-54]. Hubler and Hubler [51] reported a patient with generalized eczematoid dermatitis which was believed to have been caused by an allergy to chromium liberated from a metal dental plate. In another report, a woman had severe dermatitis and allergic reactions to several metals. She recovered only after removal of a cast chrome-cobalt, partial denture [52]. Foussereau and Laugier cited a case of generalized eczema that occurred after a chromium-nickel denture had been fitted [40]. Skin tests were strongly positive to nickel and chromium, and the dermatitis subsided after the denture was removed [40]. According to Rietschel and Fowler [40], metallic dental chromium is a rare sensitizer. In most instances in which an allergic reaction is attributed to a metallic chrome object, it is nickel that is the actual sensitizer. Nickel readily penetrates the micropores in chrome-plated objects [40].

Chromium in other metals

Allergic reactions from exposure to chromium/chromate has been reported from orthopedic metals [55-57], and acupuncture needles [58]. Burrows [59] proposed that chromate allergy is not a factor in the rejection of hip prostheses (metal head, plastic cup) even in those containing chromium, e.g. stainless steel, and chrome-cobalt (vitallium 26 to 30%) [60-62].

Galvanized sheeting

Iron sheeting is best protected from rusting by galvanizing with zinc applied either by electroplating or by dipping in molten zinc. To prevent the zinc from corroding, oxidizing or whitening with moisture, the metal is coated with chromate. This surface chromate can induce sensitization or exacerbate chromate dermatitis [63-66]. Wass and Wahlberg [67] calculated that the mean release of hexavalent chromate from chromated areas should not exceed 0.3 µg/cm³/20 min in order to prevent elicitation of allergic contact dermatitis.

Electroplating

Electroplating consists of coating one metal with a layer of another metal by means of an electric current. In chromium plating, the bath contains chromic acid and sulphuric acid. Chrome ulcerations of the nose and perforation of the septum have been reported [68]. There is no relationship between chrome ulcers and allergic sensitization [1, 2].

Welding

Chromium may be present in the core and coating of the electrode rods used in electric arc welding. When any of these metals are chromium alloys, such as stainless steel containing 18% chromium and 8% nickel, the amount of hexavalent chromium formed is considerable. During welding the chromium is oxidized to the hexavalent form and is present in the fumes. Airborne exposure to these gases containing chromate may cause an allergic contact dermatitis of the face [69] or the hands [70]. Inhalation of gases during welding may cause asthma and urticaria but the putative allergen has not been identified [71, 72]. Metal fume fever has also been reported [73].

Photosensitivity

Photosensitivity has been said to develop in patients with chromate dermatitis [74, 75] but according to Burrows and Adams [2] it remains to be proved that there is a connection between the two.

Patch testing for chromate sensitivity

Patch testing with 0.5% potassium dichromate in petrolatum is a routine part of the standard patch test series. Accordingly, patients with allergic contact dermatitis to chromate will be diagnosed if patch testing is performed. A dilution series (Fig. 2) may help to distinguish between allergic and irritant reactions, although the reactions in Figure 2 are clearly all allergic.

Prognosis

Allergy to chromate in men has a worse prognosis than does sensitization to other allergens [76-79]. The reason for this is not known. Continued contact with unrecognized chromium in the environment or possibly ingestion of chromate have been considered possible explanations.

CONCLUSION

Small amounts of chromium will leach from stainless steel utensils into food during its processing, storage and during meal preparation. Although it is conceivable that some of this leached chromium may be in the hexavalent state, it is unlikely that this leaching will result in actual absorption of hexavalent chromium by the organism. No toxicity is to be expected from the chromium leached from kitchenware; it may in fact be beneficial to health, since the amounts of chromium present in Western type diets are generally small in comparison to amounts considered to be optimal. Metallic chromium or chromium leached from kitchenware is unlikely to cause skin problems. Solitary cases may nevertheless appear in the literature.

This report is based on 2 recent publications in the Chromium File from the International Chromium Development Association: Aitio A. Stainless steel kitchen utensils as a source of chromium ­ toxicological implications, No 1, September 1996, and Kanerva L. A review of skin sensitisation caused by chromium, No 2, October 1996.

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