New generation fungicide for the leather industry

Over the years there have been a number of changes in the fungicides used to treat leather against fungal attack. If we go back far enough, phenyl mercury compounds like phenyl mercuric acetate (PMA) were in common use. Then we saw the emergence of chlorinated phenols like pentachloro phenol (PCP). By the early 1980s the use of these compounds had fallen out of favour or become restricted, principally due to their high toxicity to humans, their environmental problems and/or their aggressiveness in handling. The fungicide 2-(thiocyanomethylthio) benzothiazole (TCMTB) became the new standard starting in the 1970s and remains in use today. However, with ever increasing demands for safer and environmentally sound fungicides, microbicide manufacturers continue to search for new products that can meet these demands. The limited market size in the leather industry has largely prevented any new fungicides, apart from TCMTB blends, from being introduced until recently. This paper discusses the details concerning the development and introduction of a new non-TCMTB fungicide. Development project Zenith set out to develop a new non-TCMTB fungicide, focusing on identifying existing fungicidal actives that could be utilised to develop new leather fungicides. The broad group of azole antifungals was selected from which to isolate suitable compounds. Azoles comprise the most rapidly expanding group of fungicidal actives in recent years. Major developments in research in the azole class of antifungal agents took place during the 1990s and these have provided expanded options for the treatment in humans of many fungal problems in the form of orally taken drugs as well as topical creams. Besides their application in pharmaceuticals, this group of antifungal actives also has utility in industrial applications. Using proven azole antifungal active technology, Zenith initiated a development programme to create a product specifically for use by the leather industry. Several key technical parameters were established to drive product formulation development. A first objective was to identify suitable actives with a good balance between fungicidal efficacy and a favourable toxicological profile. The second development parameter called for a liquid formulation with such properties that maximum uptake by the leather would be achieved with minimum fungicide residuals remaining in the tanning liquor. This has the dual objective of achieving maximum benefit of the fungicide in the leather and minimising residual fungicide to be treated in the effluent plant. Poor formulation of good fungicidal actives can result in products that remain principally in the tanning liquor and do not get taken up optimally by the leather, resulting in poor product efficiency, higher treatment cost and greater load on the effluent system. A third criterion was that the carrier system would deliver the fungicide to the leather without the use of solvents that are unfriendly to people and the environment. Not only do solvents possess their own inherent toxicity, but they can also contribute to greater absorption of the fungicide product into the human skin, thereby increasing the potential of skin irritation and negatively impacting overall toxicological properties. In addition to the toxicity considerations, solvents also contribute volatile organic components into the atmosphere, which is to be minimised or avoided. A fourth key requirement was to avoid the use of traditional emulsion/suspension in water technology. These types of dispersion do not exhibit long-term stability and are inherently prone to separation and therefore have poor shelf life. Finally, the formulation meeting all these criteria should have a reasonably low cost so that the treatment cost at the tannery level would be no higher than currently used products. New non-TCMTB fungicide  This research initiative led to the development of new non-TCMTB fungicides for tannery application. One candidate in particular met all the project criteria with flying colours and was selected for further commercial development under the designation ‘Zenith 399'. The product is described as an azole-based antimycotic agent in an odourless, low toxicity eco-friendly solvent carrier system, formulated for use in leathermaking systems to achieve maximum uptake by the leather for protection against fungal attack. A summary of the findings for this new fungicide in terms of efficacy, performance and user/eco friendliness is presented below. Comparisons are shown against the reference fungicide, 30% TCMTB in solvent-based formulation sold under various commercial tradenames, and referred to in this paper as TCMTB 30.  Fungicidal efficacy test results Extensive fungicidal efficacy testing against a variety of different fungal species has shown Zenith 399 to possess a broad spectrum of activity. It is very effective against a wide range of fungi even at low dosage levels. For example, it has good effectiveness against Trichoderma, a fungal species against which TCMTB fungicides are less effective. Following the initial battery of laboratory tests to determine efficacy against different species of fungi, further evaluations were carried out under full-scale tannery production conditions. Leather was made in tannery trial batches with Zenith 399 and compared with leathers produced with TCMTB 30 and other reference fungicides under identical conditions. The leathers produced in tanneries were evaluated for mould resistance using the ‘tropical chamber' fungal resistance test. This is a 4-week accelerated test based on ASTM testing standards (American Society for Testing and Materials). These chambers are programmed to cycle through ideal conditions of moisture, humidity, temperature and recirculating air containing a variety of different fungal spores, to generate the most favourable conditions to promote rapid mould growth on leather. Replicate samples of each leather are tested and the average ratings are reported on a weekly basis. Mould growth ratings are based on the percentage of the leather surface covered with mould growth. The scale is from 0 to 100. 0 means 0% of the leather sample is covered with mould growth and 100 means 100% of the surface is covered. Interpretation of the tropical chamber mould growth ratings are as follows:

• Long-term mould resistance: a rating of 0 to 20 in week 4
• Medium-term mould resistance: a rating of 0 to 20 in week 3
• Short-term mould resistance: a rating of 0 to 20 in week 2
• Limited mould resistance: a rating of 0 to 20 in week 1
• No mould resistance: a rating greater than 20 in week 1

Zenith's tropical chambers have been inoculated with a variety of fungal species that grow on leather, including Penicillium sp, Aspergillus niger, A. flavus, A. japonicus, A. nidulans, Mucor sp. and Paecilomyces sp.  In wet-blue leather, at a dosage level of 0.1%, Zenith 399 and TCMTB 30 performed equally with no mould growth after four weeks of exposure in the tropical chamber. Figure 2 shows wet-blue buffalo leather cuttings containing 0.1% of the fungicides and a negative control containing no fungicide after completion of the 4-week tropical chamber test. As can been seen from the results, both fungicides performed very well keeping the leathers completely mould-free throughout the duration of the test and they are therefore considered to possess long term mould resistance. The negative control without any fungicide is completely covered with mould growth. Dosages lower than 0.1% were also tested on wet-blue leather, where differences in performance between the two fungicides became noticeable. Figure 3 shows the mould resistance ratings of European wet-blue cow hide leathers containing 0.05% of fungicide. As can be seen from the results, after one week, both fungicides still perform the same with 0 mould growth. However, after two weeks, the leather treated with Zenith 399 has less mould growth than the leather with TCMTB 30. After three and four weeks, the difference in performance is even more significant. In crust leathers, at a dosage of 0.1%, the difference in performance between Zenith 399 and TCMTB 30 was very apparent. This is due to the fact that these leathers are more susceptible to mould growth since they contain more organic nutrients than wet-blue stock, such as fatliquors. Consequently, higher levels than 0.1% are typically required to provide protection. Figure 4 shows the mould resistance ratings of dyed buffalo crust leather containing 0.1% fungicide. After one week of tropical chamber, both fungicides performed more or less equally. However, after two weeks, Zenith 399 clearly outperformed TCMTB 30. Figure 5 shows photographs of the treated leathers after completion of the four-week tropical chamber test. Tannery trial results Zenith 399 was introduced commercially in selected leather markets in late 2006. Samples of the product were given to many tanneries to enable them to conduct trial batches for comparison to the standard fungicide used by each tannery. Zenith encouraged tanneries to submit cuttings from the trials as ‘blind' samples for fungal resistance testing, ie without disclosing which fungicide was used. The identities of fungicides used in the samples as well as the dosage levels were then subsequently disclosed to Zenith after completion and submission of the fungal resistance test report. Countless trials of this type have been performed since 2006 and the results have been extremely favourable for Zenith 399. One particularly interesting case involved a wet-bluing operation that started experiencing outbreaks of mould growth in the wet-blue stock after only a few days of storage and despite the proper use of a leading TCMTB 30 fungicide. The tannery consulted Zenith for assistance. The problem was identified as being caused by Trichoderma, a less common strain of fungus, against which TCMTB has limited effectiveness. The Zenith 399 product was tried in production and was found to effectively prevent all fungal growth on the wet-blue hide. The tannery then switched all of their production to the new product and the fungal problem was solved. In the relatively short time in which Zenith 399 has been commercially available on a limited basis, it has proven to be very successful. In those areas where it has been made available, the product has progressively overtaken Zenith's TCMTB fungicides as well as competitor products. Eco and people friendliness Zenith 399 was formulated utilising the latest formulation technology borrowed from the pharmaceutical industry, using a non-toxic and eco-neutral liquid carrier. This renders a liquid product that is more eco-friendly than traditional industrial solvent-based fungicide products, and which minimises the generation of volatile organic compounds (VOC).  Eco-toxicity test results show that Zenith 399 is less toxic to ecosystems than TCMTB 30. Furthermore, the product does not have a strong irritating or lachrymating odour and is therefore very user-friendly in terms of tannery staff who may work in proximity to open containers of the chemical. Oral toxicity tests conducted on animals, which are frequently used as a general indicator of a substance's acute toxicity and allow the relative toxicity of different chemicals to be compared, show Zenith 399 has lower toxicity than TCMTB 30. The product has also been found to be less aggressive to the skin. Although Zenith 399 in concentrated form is expected to irritate the skin upon extended direct exposure, short-term accidental exposure of the skin to concentrated Zenith 399 produced no irritant effects during the course of exposure and left no irritation or observable effects after removal of the product by rinsing with water. Nevertheless, the use of appropriate protective equipment such as rubber gloves and goggles when handling this and other chemicals is recommended. Responding to customer requests to use Zenith 399 in upholstery leather, Zenith commissioned the independent laboratory BLC Leather Technology Centre to evaluate the fungicide's suitability for such skin-contact applications. BLC submitted crust leather containing a high level of 0.3% Zenith 399 to their standard battery of tests for skin irritation potential, which included testing for TCMTB, OIT, PCP, formaldehyde, NPEO, VOC etc. The leather passed all of the tests and complied with BLC's requirements.  Conclusion With the development and commercial launch of Zenith 399, the industry now has a new alternative for fungal control in leathermaking that provides important benefits over the previous standards: improved fungicidal performance, safer handling and better eco-friendliness. Overall results and experience with this new generation fungicide indicate it is a definite advancement in the continuing quest for better, safer and eco-friendlier fungicides. However, it should be noted that the product remains an industrial fungicide designed to kill living cells, albeit fungal cells. Therefore, the product should always be handled with care, taking proper precautions and following the recommended handling procedures. N References 1. J A Zarn, B J Bruschweiler and J R Schlatter (2003). Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14[alpha]-demethylase and aromatase. Environmental Health Perspectives. 2. D J Sheehan, C A Hitchcock and C M Sibley (1999). Current and Emerging Azole Antifungal Agents. Clinical Microbiology Reviews. 3. D L Dalton (2008). Case Study: New Generation Fungicide Outperforms TCMTB. Leather Age. 4. D L Dalton et al (1996). United States Patent 5,571,443. About the author Dennis L Dalton is managing director of Zenith Industrial Chemicals. Dalton's expertise and career have been focused on speciality chemicals and industrial microbiological control in particular. He has authored numerous papers as well as patents. He co-authored a patent in 1996 covering TCMTB fungicides for the control of mould in leather. Prior to joining Zenith, Dalton held management positions with Cosan Chemical Corporation, Caschem and Buckman Laboratories. Dalton has worked in product development, technical service, marketing and general management in Europe, USA and Asia