Nickel is one of the most commonly known sensitisers and has been classified by the International Agency for Research on Cancer (IARC) as a possible carcinogen to humans (group 2B). Workers at a South African base metal refinery packaging area are potentially exposed to many hazardous chemicals that include nickel. Aims and Objectives: The aim and objectives of this study were to assess dermal and respiratory exposure of workers exposed to nickel in a packaging section at a South African base metal refinery and to assess the change in skin barrier function during a work shift by measuring percentage change in trans epidermal water loss (TEWL), skin hydration and skin surface pH. Skin health was established with a skin questionnaire. Surfaces that workers may come into contact with were also assessed. Method: Respiratory and dermal exposure assessment was done concurrently. Respiratory exposure was assessed and analysed by using the National Institute for Occupational Safety and Health (NIOSH) method 7300. The Institute of Occupational Medicine (IOM) inhalable aerosol sampler was used for personal air sampling. The TEWL index, skin hydration and skin surface pH of the index finger, palm, forearm and forehead were measured before and at the end of the shift with a Derma Measurement Unit, EDS 12 and Skin-pH-Meter® pH 905. These measurements were reported as percentage change in skin barrier function during the shift. Dermal exposure samples were collected with Ghostwipes™ from the index finger and palm of the dominant hand before, during and at the end of the shift, while samples from the forearm and forehead were only collected before and after the shift. Surface sampling was collected and all wipes were analysed for nickel according the NIOSH method 9102, using inductively coupled plasma-atomic emission spectrometry. Results: Respiratory exposure for the whole group of workers in a packaging section was well below the eight hour Time Weighted Average (TWA) respiratory Occupational Exposure Limit (OEL) of 0.5 mg m-3 for nickel. Dermal nickel loading was detected for all the job categories on all the anatomical areas even before the shift had commenced. During the shift more nickel was detected on the index finger and palm of the hand. Levels on the forearm and forehead were much lower in comparison with the index finger and the palm of the hand. Workplace surfaces, which workers may come into contact with on a daily basis, were also contaminated with nickel. Forklift drivers showed high exposure on the index finger and palm of their hands, and this can be attributed to them not wearing any gloves for hand protection. An increase in percentage change for TEWL was seen for most of the job categories on all anatomical areas measured during the shift. Percentage change in skin surface pH and skin hydration varied among job categories. Conclusion: The research addressed the problem statement, with the stated objectives. It was hypothesised that workers at a packaging section of a base metal refinery are exposed to quantifiable levels of nickel through the dermal exposure route. The hypothesis was accepted and control measures together with future studies were recommended. The results confirmed that all workers at a base metal refinery are exposed to quantifiable levels of nickel through the dermal exposure route. Dermal exposure was evident on all anatomical areas for all job categories before the shift had commenced. Personal protective equipment was provided to all employees, but forklift drivers did not wear gloves when operating the forklift. Respirable exposure to nickel was below the OEL. Changes in TEWL and to a lesser extent skin hydration, suggest a deterioration in skin barrier function during the shift. Forklift drivers as well as plate washers may be the highest risk job categories in developing allergic contact dermatitis. Several measures to lower respiratory and dermal exposure to nickel are also recommended. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2014

Nickel is one of the most commonly known sensitisers and has been classified by the International Agency for Research on Cancer (IARC) as a possible carcinogen to humans (group 2B). Workers at a South African base metal refinery packaging area are potentially exposed to many hazardous chemicals that include nickel. Aims and Objectives: The aim and objectives of this study were to assess dermal and respiratory exposure of workers exposed to nickel in a packaging section at a South African base metal refinery and to assess the change in skin barrier function during a work shift by measuring percentage change in trans epidermal water loss (TEWL), skin hydration and skin surface pH. Skin health was established with a skin questionnaire. Surfaces that workers may come into contact with were also assessed. Method: Respiratory and dermal exposure assessment was done concurrently. Respiratory exposure was assessed and analysed by using the National Institute for Occupational Safety and Health (NIOSH) method 7300. The Institute of Occupational Medicine (IOM) inhalable aerosol sampler was used for personal air sampling. The TEWL index, skin hydration and skin surface pH of the index finger, palm, forearm and forehead were measured before and at the end of the shift with a Derma Measurement Unit, EDS 12 and Skin-pH-Meter® pH 905. These measurements were reported as percentage change in skin barrier function during the shift. Dermal exposure samples were collected with Ghostwipes™ from the index finger and palm of the dominant hand before, during and at the end of the shift, while samples from the forearm and forehead were only collected before and after the shift. Surface sampling was collected and all wipes were analysed for nickel according the NIOSH method 9102, using inductively coupled plasma-atomic emission spectrometry. Results: Respiratory exposure for the whole group of workers in a packaging section was well below the eight hour Time Weighted Average (TWA) respiratory Occupational Exposure Limit (OEL) of 0.5 mg m-3 for nickel. Dermal nickel loading was detected for all the job categories on all the anatomical areas even before the shift had commenced. During the shift more nickel was detected on the index finger and palm of the hand. Levels on the forearm and forehead were much lower in comparison with the index finger and the palm of the hand. Workplace surfaces, which workers may come into contact with on a daily basis, were also contaminated with nickel. Forklift drivers showed high exposure on the index finger and palm of their hands, and this can be attributed to them not wearing any gloves for hand protection. An increase in percentage change for TEWL was seen for most of the job categories on all anatomical areas measured during the shift. Percentage change in skin surface pH and skin hydration varied among job categories. Conclusion: The research addressed the problem statement, with the stated objectives. It was hypothesised that workers at a packaging section of a base metal refinery are exposed to quantifiable levels of nickel through the dermal exposure route. The hypothesis was accepted and control measures together with future studies were recommended. The results confirmed that all workers at a base metal refinery are exposed to quantifiable levels of nickel through the dermal exposure route. Dermal exposure was evident on all anatomical areas for all job categories before the shift had commenced. Personal protective equipment was provided to all employees, but forklift drivers did not wear gloves when operating the forklift. Respirable exposure to nickel was below the OEL. Changes in TEWL and to a lesser extent skin hydration, suggest a deterioration in skin barrier function during the shift. Forklift drivers as well as plate washers may be the highest risk job categories in developing allergic contact dermatitis. Several measures to lower respiratory and dermal exposure to nickel are also recommended. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2014

Background: Platinum group metal (PGM) mining and refining is a large constituent of the mining sector of South Africa and contributes significantly to the gross domestic product. The PGMs include the rare metals platinum (Pt), palladium (Pd), rhodium (Rh), ruthenium (Ru), iridium (Ir) and osmium (Os). During the refining process workers are potentially exposed to various chemical forms of the PGMs via the respiratory and dermal exposure routes. Historically, emphasis has been on respiratory exposure while the extent of skin exposure is still unknown. Among the different forms of PGMs, the salts are potential sensitisers, with platinum being a known respiratory sensitiser. Workers occupationally exposed to platinum and rhodium have reported respiratory as well as skin symptoms. However, it is unknown if these metals in the salt form are permeable through human skin, and whether dermal exposure could contribute to sensitisation. Evidence regarding differences between African and Caucasian skin anatomy and structure, as well as permeation through skin is contradictory, and no information is available on metal permeation through African skin. The in vitro diffusion method has been utilised successfully in occupational toxicology to demonstrate that metals such as chromium, cobalt and nickel, to name a few, permeate through human skin. The permeability of platinum and rhodium has not been investigated previously. Aims and objectives: The research aim was to obtain insight into the permeability of platinum and rhodium through intact human skin and to provide information needed to determine the potential health risk following dermal exposure to these metals. The specific objectives included: (i) to critically review the in vitro diffusion method that is used to determine the permeability of metals through human skin, (ii) to investigate the permeation of potassium tetrachloroplatinate (K2PtCl4) and rhodium chloride (RhCl3) as representative PGM salts through intact human skin over a 24-hour period, (iii) to evaluate the difference in permeability of platinum and rhodium through intact human skin, (iv) to evaluate the difference in permeability of platinum through intact African and Caucasian human skin. Methods: Abdominal skin obtained after cosmetic procedures was obtained from five female Caucasian and three female African donors between the ages of 28 and 52 with ethical approval from the North-West University. Full thickness skin tissue was mounted in a vertical Franz diffusion cell. Skin integrity was tested by measuring the electrical resistance across the skin before and after conclusion of the experiments, using a Tinsley LCR Data bridge Model 6401. The donor solution of 32.46 mg K2PtCl4 in 50 ml of synthetic sweat (pH 6.5), and 43.15 mg RhCl3 in 50 ml of synthetic sweat (pH 6.5) was prepared. The donor solution was applied to the stratum corneum side of the skin and physiological receptor solution (pH 7.35) was added to the receptor compartment. The concentration of the metals in the receptor solution was determined by high resolution inductively coupled plasma-mass spectrometry after extraction at various intervals during the 24 hours of the study. After completion of the study, the skin was rinsed four times to remove any platinum or rhodium remaining on the skin surface. The skin was digested using hydrogen peroxide, nitric acid and hydrochloric acid during different steps to determine the mass of the metals remaining in the skin by inductively coupled plasma-optical emission spectrometry. Results: The comparison of published in vitro skin permeation studies involving metals is impeded by the variations in the experimental design and dissimilarity in the reporting of results. Differences in experimental design included, most noticeably, the use of various donor and receptor solutions, different temperatures wherein the receptor compartment was placed, differences in skin thickness and variations in exposed skin surface areas. The metals considered in the review, namely chromium, cobalt, gold, lead, mercury, nickel, platinum, rhodium and silver, permeate through intact human skin under physiological conditions. Large variations in the permeability results were observed, with the notable differences in methodology as the probable reason. Results obtained from the in vitro experiments indicate that platinum and rhodium permeated through intact Caucasian skin with flux values of 0.12 and 0.05 ng/cm2/h, respectively. The cumulative mass of platinum (2.57 ng/cm2) that permeated after 24 hours of exposure was statistically significantly (p = 0.016) higher than rhodium permeation (1.11 ng/cm2). The mass of platinum (1 459.47 ng/cm2) retained in the skin after 24 hours of exposure was statistically significantly (p < 0.001) higher than rhodium retention (757.04 ng/cm2). The comparison of permeability between two different racial groups indicates that platinum permeated through the skin of both racial groups with the flux through African skin found as 1.93 ng/cm2/h and 0.27 ng/cm2/h through Caucasian skin. The cumulative mass of platinum permeated after 24 hours of exposure was statistically significantly (p = 0.044) higher through African skin (37.52 ng/cm2) than Caucasian skin (5.05 ng/cm2). The retention of platinum in African skin (3 064.13 ng/cm2) was more than twice the mass retained in Caucasian skin (1 486.32 ng/cm2). Conclusions: The in vitro diffusion method is an applicable method to determine skin permeability of metals. However, the experimental design and format of data reporting should be standardised to enable comparison of results from different studies. Platinum and rhodium permeated through intact human skin, with platinum permeation significantly higher. African skin was significantly more permeable by platinum than Caucasian skin. Both platinum and rhodium were retained inside the skin after 24 hours of exposure, possibly forming a reservoir which could contribute to continued permeation through the skin even after removal thereof from the skin. Platinum and rhodium permeated through full thickness skin and thereby could possibly contribute to local skin symptoms such as dermatitis and urticaria found in occupationally exposed workers. By permeating through the upper layers of the skin, these metals could potentially reach the viable epidermis and contribute to sensitisation. / PhD (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015

Background: Platinum group metal (PGM) mining and refining is a large constituent of the mining sector of South Africa and contributes significantly to the gross domestic product. The PGMs include the rare metals platinum (Pt), palladium (Pd), rhodium (Rh), ruthenium (Ru), iridium (Ir) and osmium (Os). During the refining process workers are potentially exposed to various chemical forms of the PGMs via the respiratory and dermal exposure routes. Historically, emphasis has been on respiratory exposure while the extent of skin exposure is still unknown. Among the different forms of PGMs, the salts are potential sensitisers, with platinum being a known respiratory sensitiser. Workers occupationally exposed to platinum and rhodium have reported respiratory as well as skin symptoms. However, it is unknown if these metals in the salt form are permeable through human skin, and whether dermal exposure could contribute to sensitisation. Evidence regarding differences between African and Caucasian skin anatomy and structure, as well as permeation through skin is contradictory, and no information is available on metal permeation through African skin. The in vitro diffusion method has been utilised successfully in occupational toxicology to demonstrate that metals such as chromium, cobalt and nickel, to name a few, permeate through human skin. The permeability of platinum and rhodium has not been investigated previously. Aims and objectives: The research aim was to obtain insight into the permeability of platinum and rhodium through intact human skin and to provide information needed to determine the potential health risk following dermal exposure to these metals. The specific objectives included: (i) to critically review the in vitro diffusion method that is used to determine the permeability of metals through human skin, (ii) to investigate the permeation of potassium tetrachloroplatinate (K2PtCl4) and rhodium chloride (RhCl3) as representative PGM salts through intact human skin over a 24-hour period, (iii) to evaluate the difference in permeability of platinum and rhodium through intact human skin, (iv) to evaluate the difference in permeability of platinum through intact African and Caucasian human skin. Methods: Abdominal skin obtained after cosmetic procedures was obtained from five female Caucasian and three female African donors between the ages of 28 and 52 with ethical approval from the North-West University. Full thickness skin tissue was mounted in a vertical Franz diffusion cell. Skin integrity was tested by measuring the electrical resistance across the skin before and after conclusion of the experiments, using a Tinsley LCR Data bridge Model 6401. The donor solution of 32.46 mg K2PtCl4 in 50 ml of synthetic sweat (pH 6.5), and 43.15 mg RhCl3 in 50 ml of synthetic sweat (pH 6.5) was prepared. The donor solution was applied to the stratum corneum side of the skin and physiological receptor solution (pH 7.35) was added to the receptor compartment. The concentration of the metals in the receptor solution was determined by high resolution inductively coupled plasma-mass spectrometry after extraction at various intervals during the 24 hours of the study. After completion of the study, the skin was rinsed four times to remove any platinum or rhodium remaining on the skin surface. The skin was digested using hydrogen peroxide, nitric acid and hydrochloric acid during different steps to determine the mass of the metals remaining in the skin by inductively coupled plasma-optical emission spectrometry. Results: The comparison of published in vitro skin permeation studies involving metals is impeded by the variations in the experimental design and dissimilarity in the reporting of results. Differences in experimental design included, most noticeably, the use of various donor and receptor solutions, different temperatures wherein the receptor compartment was placed, differences in skin thickness and variations in exposed skin surface areas. The metals considered in the review, namely chromium, cobalt, gold, lead, mercury, nickel, platinum, rhodium and silver, permeate through intact human skin under physiological conditions. Large variations in the permeability results were observed, with the notable differences in methodology as the probable reason. Results obtained from the in vitro experiments indicate that platinum and rhodium permeated through intact Caucasian skin with flux values of 0.12 and 0.05 ng/cm2/h, respectively. The cumulative mass of platinum (2.57 ng/cm2) that permeated after 24 hours of exposure was statistically significantly (p = 0.016) higher than rhodium permeation (1.11 ng/cm2). The mass of platinum (1 459.47 ng/cm2) retained in the skin after 24 hours of exposure was statistically significantly (p < 0.001) higher than rhodium retention (757.04 ng/cm2). The comparison of permeability between two different racial groups indicates that platinum permeated through the skin of both racial groups with the flux through African skin found as 1.93 ng/cm2/h and 0.27 ng/cm2/h through Caucasian skin. The cumulative mass of platinum permeated after 24 hours of exposure was statistically significantly (p = 0.044) higher through African skin (37.52 ng/cm2) than Caucasian skin (5.05 ng/cm2). The retention of platinum in African skin (3 064.13 ng/cm2) was more than twice the mass retained in Caucasian skin (1 486.32 ng/cm2). Conclusions: The in vitro diffusion method is an applicable method to determine skin permeability of metals. However, the experimental design and format of data reporting should be standardised to enable comparison of results from different studies. Platinum and rhodium permeated through intact human skin, with platinum permeation significantly higher. African skin was significantly more permeable by platinum than Caucasian skin. Both platinum and rhodium were retained inside the skin after 24 hours of exposure, possibly forming a reservoir which could contribute to continued permeation through the skin even after removal thereof from the skin. Platinum and rhodium permeated through full thickness skin and thereby could possibly contribute to local skin symptoms such as dermatitis and urticaria found in occupationally exposed workers. By permeating through the upper layers of the skin, these metals could potentially reach the viable epidermis and contribute to sensitisation. / PhD (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015