A high number of studies regarding hexavalent chromium and leather have been carried out during the past ten years. Most of the studies have been focused on the analytical method to determine hexavalent chromium in leather and especially the extraction process and the specificity of the method has been discussed. The question which has been raised is whether the results from the analytical methods can, in fact, actually determine the content of hexavalent chromium in the leather. These reports and studies will not be discussed in this paper.
Furthermore, some research work has been carried out to determine which factors can provoke the formation of hexavalent chromium in leather and ways to prevent it. Here, the conclusions have been similar in most of the reports and several guidelines on how to avoid the formation of hexavalent chromium in leather have been published.
The results from these studies have been valuable for the leather industry but it seems that we now have to go one step further in order to achieve greater progress. It is important to go back to the reason for analysing the eventual amount of hexavalent chromium in leather.
The main reason for carrying out the analyses is that a limited number of people may develop chromium allergy from leather products. For example, it can be mentioned that there are around 200-300 new cases of chromium allergy in Denmark every year due to footwear.
Although the number of new cases of chromium allergy is low, it is in the interest of the leather industry to reduce this number. The allergy is a big problem for the individual suffering from the allergy but, taking into consideration the number of cases of chromium allergy, we should not overestimate the problem.
In 2002, Leather International presented the results from a study made by the author (Investigation of the content of Cr (VI) and Cr (III) in Leather Products on the Danish market). The Danish study was financed by the Danish EPA and showed that around 35% of the leather products on the Danish market contained hexavalent chromium.
The Danish EPA decided to carry out additional studies in Denmark in order to find a correlation between the content of hexavalent chromium in leather and allergy. These studies were carried out by the National Allergy Research Centre for Chemical Substances in Consumer Products at Gentofte Hospital in Denmark.
The research centre at Gentofte Hospital has a very high scientific reputation and is an institution of excellence. Data from the centre has been used regularly by the European Commission’s advisory services to provide recommendations for protecting the consumer.
The studies were mentioned in Leather International (p44, September 2002) and these have recently been finished. The results will mainly be published in scientific journals for dermatology and, hence, the results will mainly be spread to researchers in this field. The results are highly interesting and relevant for the leather sector and the main results from the study will be presented in this paper.
Before going into the details of the study, some basic facts about allergy and chromium allergy in particular will be presented.
Allergic contact dermatitis
Allergic contact dermatitis (ACD) is an inflammatory skin condition caused by skin contact with sensitising molecules in the environment. ACD occurs when the immune system reacts to a substance (allergen). Examples of chemicals which can give allergic contact dermatitis are metals, biocides/preservatives, fragrance chemicals and dyes.
The mechanism of ACD can be separated into two distinct phases: the sensitisation phase and the elicitation phase. The sensitisation phase includes the events following the first contact with the hapten (allergen) and is complete when the individual is sensitised and capable of giving an ACD reaction.
The elicitation phase is initiated upon re-exposure of the same hapten to the skin and results in the clinical manifestations of ACD. The dose and time is much higher for the sensitisation phase compared with the elicitation phase (when the patient already has developed sensibility for the allergen).
Today the sensitisation potential of a substance is investigated in animal models only, while the elicitation is normally determined by dose response studies using patch testing. Hence, the standard procedure for diagnosing allergic contact dermatitis (ACD) is patch testing.
Patch testing is a way of identifying whether a substance that comes in contact with the skin causes inflammation of the skin. The test involves the application of various test substances to the skin under adhesive tape that is then left in place for 48 hours. The skin is then examined two, three and seven days later for any response.
The trivalent and hexavalent oxidation state of chromium are sufficiently stable to act as haptens. The hexavalent chromium penetrates the skin to a larger extent than trivalent chromium since the latter binds to skin proteins, thereby becoming captured in the stratum corneum and epidermis.
Furthermore, some studies in the past have shown that there is a greater skin barrier rejection of Cr (III) and that this may explain the difference in allergic potency between Cr (III) and Cr (VI). Haptens (allergens) must bind to proteins in order to obtain an allergic reaction. It is, therefore, believed that Cr (VI) becomes reduced to Cr (III) within the skin.
It should be noted that trivalent chromium which is bound into the leather does not have any role in contact allergy. Only soluble chromium which can penetrate into the skin may play a role in chromium allergy. There is hence no relevance to analyse (or regulate) the total amount of chromium in leather in relation to avoidance of leather-induced chromium dermatitis.
Finally, it should be noted that the investigations, which have been made in Denmark and will be described, have been carried out on patients who are chromium allergics.
Studies at the National Allergy Research Centre, Denmark
In the first study made by the National Allergy Research Centre, response studies (patch test with different concentrations of potential allergens) were performed in order to determine the minimum eliciting threshold (MET) concentration for Cr (III) and Cr (VI) in Cr (VI)-sensitive patients. A total of 18 chromium-allergic patients were patch-tested on the back with a dilution series of potassium chromate (Cr (VI) and chromium trichloride (Cr (III)).
The study concluded that although Cr (VI) was confirmed as being the most potent hapten, Cr (III) also demonstrated a significant capacity to elicit allergic reactions. Most studies in the past have shown a significant difference between hexavalent chromium and trivalent chromium in relation to allergy. It should be once again noted that the investigations are made on patients who were existing chromium allergics.
In the second study, the relationship between the content of Cr (VI) and soluble Cr (III) in leather and the ability of the leather to elicit eczema in chromium-allergic patients were investigated. This study is of high relevance for tanneries since it is the first study actually looking at the correlation between hexavalent chromium in leather and allergy.
A group of 15 chromium-allergic patients with a history of foot dermatitis and leather exposure was exposed to a selection of 14 chromium and one vegetable-tanned (control) leather samples on the upper back. The leather was applied as small squares (4cm2) on the upper back using Scanpore tape. The content of hexavalent chromium in the leather samples was determined according to DIN 53314 and the soluble Cr (III) was determined by atomic absorption spectrometry in the DIN 53314 buffer. Five of the 14 chromium-tanned leather samples elicited an allergic reaction in at least one patient and four patients reacted to at least one leather sample. The results are shown in Table 1.
As can be seen from Table 1, the leather sample eliciting a reaction in the highest number of patients was the one with the lowest content of Cr (VI) and soluble Cr (III). The leather samples with the highest concentration of Cr (VI) which were 16.9ppm and 15.5ppm did not cause any reaction.
The conclusion from the clinical studies is: No relation was observed between the measured content of Cr (VI) and soluble Cr (III) in the leather and the elicitation of eczema (at the concentrations used in the studies).
Discussion of results
Using the DIN 53314 method, no relation was observed between the amount of Cr (VI) and soluble Cr (III) in leather and the elicitation of eczema. However, the study does not reject a connection between the content of Cr (VI) and soluble Cr (III) and the development of eczema. It simply demonstrates that the DIN 53314 method lacks the capacity to determine the relevant bioavailable pools of Cr (VI) and soluble Cr (III) in leather and, therefore, cannot be used for analysing the Cr (VI) content in relation to avoidance of leather-induced chromium dermatitis.
Furthermore, it must be underlined that there is no direct evidence that the ‘chemical agent’ eliciting eczema is chromium. Leather contains many chemicals and, in theory, other chemical components may cause the observed dermatitis.
It should also be mentioned that the relation between Cr (III) and other shoe-related allergens is unknown. There may be synergetic effects which are unknown so far. It is possible that the presence of other shoe allergies would increase the risk of developing chromium sensitivity. Thus the increased risk for foot dermatitis in the patients sensitive to chromium may be caused by shoe allergens and not by chromium.
Shoe allergens (eg rubber chemicals or adhesive chemicals) may have affected the skin barrier and thereby promoted the development of chromium allergy. It is possible that the leather manufacturer and the use of chromium has been unjustifiably blamed for shoe allergy and instead other allergic components present in shoes may play a bigger role.
Based on the results from the study, it must be concluded that the DIN 53314 method (and other available analytical methods on the market) lacks the capacity to determine the bioavailable pools of Cr (VI) and soluble Cr (III) in leather and cannot be used for analysing the Cr (VI) content in relation to avoidance of leather-induced chromium allergy. New methods have to be developed to take into consideration the true exposure situation.
The final recommendation to the leather industry is to continue to avoid the formation of hexavalent chromium in leather and furthermore to ensure that the trivalent chromium is properly fixed so there is no free chromium in the leather.