Cobalt is a commonly known sensitiser in industrial settings and has been classified by the IARC as a possible group (2B) human carcinogen. Workers at a South African base metal refinery are potentially exposed to cobalt in the cobalt packaging area. The respiratory and dermal exposure to cobalt is a possible health risk. Quantifying the exposures levels assists in determining the degree of the risk as well as the management thereof. The objectives of this study were to assess dermal and respiratory exposure of workers at a cobalt packaging area and to assess their skin condition by measuring transepidermal water loss (TEWL) and skin hydration indices. The skin hydration index was measured on the back of the hand, forehead, wrist and palm at the start, during and end of the shift. The TEWL index was measured at the start and end of the shift on the same areas as the hydration index. Ghostwipes was chosen as preferred wipe sampling media to collect dermal and surface samples. Wipe samples were also taken on suspected contaminated workplace surfaces. Respiratory samples were taken by using the Institute of Occupational Medicine (IOM) inhalable aerosol sampler at a flow rate of 2 l/min. Wipes and respiratory samples were analysed for cobalt according to NIOSH method 9102 using inductively coupled plasma–atomic emission spectrometry (ICP–AES). The hydration indices indicated that worker’s skin are slightly dry to normal at the beginning of the shift. Hydration on the wrist increased significantly during the shift. TEWL indices increased significantly on the back of the hand, wrist and forehead during the shift. TEWL indices of the palm showed a low barrier function before the shift and deteriorated further to a very low barrier function at the end of the shift. Significant dermal cobalt loading occurred on the back of the hand, forehead, wrist and palm during the shift. The palm was the most exposed and the forehead least. The barrier function of the skin is most likely to be affected by exposure to cobalt. The skin condition of workers put them at greater risk to develop adverse health effects of cobalt. Workplace surfaces were contaminated with cobalt. Airborne cobalt was visible at different working stations. Cobalt exposure is due to numerous sources in the packaging area, thus contributing to the dermal exposure. Respiratory exposure exceeded the 8 hour occupational exposure limit for most of the workers. The guidance limit for short term exposure was exceeded by half of the workers. It is important to minimise the exposure to cobalt in packaging area. Manifestation of the adverse health effects are usually not visible in the short term, the necessary precautions have to be taken to protect the workers. / Thesis (M.Sc. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Cobalt is a commonly known sensitiser in industrial settings and has been classified by the IARC as a possible group (2B) human carcinogen. Workers at a South African base metal refinery are potentially exposed to cobalt in the cobalt packaging area. The respiratory and dermal exposure to cobalt is a possible health risk. Quantifying the exposures levels assists in determining the degree of the risk as well as the management thereof. The objectives of this study were to assess dermal and respiratory exposure of workers at a cobalt packaging area and to assess their skin condition by measuring transepidermal water loss (TEWL) and skin hydration indices. The skin hydration index was measured on the back of the hand, forehead, wrist and palm at the start, during and end of the shift. The TEWL index was measured at the start and end of the shift on the same areas as the hydration index. Ghostwipes was chosen as preferred wipe sampling media to collect dermal and surface samples. Wipe samples were also taken on suspected contaminated workplace surfaces. Respiratory samples were taken by using the Institute of Occupational Medicine (IOM) inhalable aerosol sampler at a flow rate of 2 l/min. Wipes and respiratory samples were analysed for cobalt according to NIOSH method 9102 using inductively coupled plasma–atomic emission spectrometry (ICP–AES). The hydration indices indicated that worker’s skin are slightly dry to normal at the beginning of the shift. Hydration on the wrist increased significantly during the shift. TEWL indices increased significantly on the back of the hand, wrist and forehead during the shift. TEWL indices of the palm showed a low barrier function before the shift and deteriorated further to a very low barrier function at the end of the shift. Significant dermal cobalt loading occurred on the back of the hand, forehead, wrist and palm during the shift. The palm was the most exposed and the forehead least. The barrier function of the skin is most likely to be affected by exposure to cobalt. The skin condition of workers put them at greater risk to develop adverse health effects of cobalt. Workplace surfaces were contaminated with cobalt. Airborne cobalt was visible at different working stations. Cobalt exposure is due to numerous sources in the packaging area, thus contributing to the dermal exposure. Respiratory exposure exceeded the 8 hour occupational exposure limit for most of the workers. The guidance limit for short term exposure was exceeded by half of the workers. It is important to minimise the exposure to cobalt in packaging area. Manifestation of the adverse health effects are usually not visible in the short term, the necessary precautions have to be taken to protect the workers. / Thesis (M.Sc. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Aims and objectives: The research aims and objectives of this thesis were: (i) to review literature pertaining to different dermal exposure assessment methods; (ii) to assess dermal exposure of refinery workers to nickel and/or cobalt by making use of skin wipes as a removal method; (iii) to assess concurrently the skin condition of the above mentioned workers by measuring skin hydration, transepidermal water loss (TEWL) and skin surface pH, and (iv) to compare South African skin notations and sensitisation notations with those of other developed countries. Methods: Refinery workers from two base metal refineries participated in this study. Skin condition and dermal exposure was measured on different anatomical areas before, during and at the end of a work shift. Dermal exposure to nickel and/or cobalt was assessed with Ghostwipes TM as a removal method. Wipe samples of potentially contaminated surfaces in the workplace were also collected. Wipes were analysed for nickel and/or cobalt according to NIOSH method 9102, using Inductively Coupled Plasma-Atomic Emission Spectrometry. The assignment and use of skin notations and sensitisation notations in South African legislation and six other developed countries were compared. Results: To date, occupational dermal exposure has been reported for numerous substances by making use of surrogate skin methods (interception methods), removal methods and fluorescent tracer methods (in situ detection methods). From published literature it is evident that skin (dermal) wipes, as a removal method, are the most appropriate method to assess dermal exposure to metals. Varying degrees of skin dryness (low hydration indices) and impaired barrier function (high TEWL indices) are reported, with the hands being implicated the most. However, normal skin condition is also reported for some anatomical areas. Skin surface pH for all anatomical areas sampled decreased significantly during the shift, but remained in normal range. Dermal exposure to nickel occurred during the shift at the electro-winning plant of one refinery, while dermal co-exposure to cobalt and nickel occurred at the cobalt plant of the other refinery. At both of the refineries, cobalt and/or nickel was collected from the workers’ skin even before the shift. Also, dermal exposure to these metals was highly variable between individual workers. Skin notations in South African legislation had a mean agreement of between 42.9% and 45.8% with other countries, while agreement for sensitisation notations was only 3.6% between countries. / Thesis (Ph.D. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Acne is a multifactorial skin disease affecting about 80 % of people aged 11 to 30. Several systemic and topical treatments are used to treat existing lesions, prevent scarring and suppress the development of new lesions. Topical therapy is often used as first line treatment for acne, due to the location of the target organ, the pilosebaceous unit, in the skin. Retinoids are widely used as oral or topical treatment for this disease, with tretinoin and adapalene being two of the most used topical retinoids. The transdermal route offers several challenges to drug delivery, e.g. the excellent resistance of the stratum corneum to diffusion, as well as variable skin properties such as site, age, race and disease. Some additional difficulties are associated with the dermatological delivery of tretinoin and adapalene, which include suboptimal water solubility of the retinoids, isomerisation of tretinoin in the skin, mild to severe skin irritation, as well as oxidation and photo–isomerisation of tretinoin, even before crossing the stratum corneum. Researchers constantly strive to improve dermatological retinoid formulations in order to combat low dermal flux, skin irritation and instability. The release kinetics of tretinoin varies greatly according to the way in which it is incorporated into the formulation and according to the type of formulation used. Little research has been conducted regarding improved formulations for adapalene. Pheroid technology is a patented delivery system employed in this study in order to improve the dermal delivery of retinoids. Tretinoin and adapalene were separately incorporated into castor oil, vitamin F and Pheroid creams. The creams were evaluated in terms of their in vitro retinoid release, in vitro transdermal diffusion and stability. Castor oil and Pheroid creams were superior in terms of release and dermal delivery of adapalene. Tretinoin was best released and delivered to the dermis by castor oil cream. The castor oil creams were the most stable formulations, whereas the Pheroid creams were the most unstable. In terms of release, dermal diffusion and stability, castor oil cream proved to be the most suitable cream for both tretinoin and adapalene. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.

Aims and objectives: The research aims and objectives of this thesis were: (i) to review literature pertaining to different dermal exposure assessment methods; (ii) to assess dermal exposure of refinery workers to nickel and/or cobalt by making use of skin wipes as a removal method; (iii) to assess concurrently the skin condition of the above mentioned workers by measuring skin hydration, transepidermal water loss (TEWL) and skin surface pH, and (iv) to compare South African skin notations and sensitisation notations with those of other developed countries. Methods: Refinery workers from two base metal refineries participated in this study. Skin condition and dermal exposure was measured on different anatomical areas before, during and at the end of a work shift. Dermal exposure to nickel and/or cobalt was assessed with Ghostwipes TM as a removal method. Wipe samples of potentially contaminated surfaces in the workplace were also collected. Wipes were analysed for nickel and/or cobalt according to NIOSH method 9102, using Inductively Coupled Plasma-Atomic Emission Spectrometry. The assignment and use of skin notations and sensitisation notations in South African legislation and six other developed countries were compared. Results: To date, occupational dermal exposure has been reported for numerous substances by making use of surrogate skin methods (interception methods), removal methods and fluorescent tracer methods (in situ detection methods). From published literature it is evident that skin (dermal) wipes, as a removal method, are the most appropriate method to assess dermal exposure to metals. Varying degrees of skin dryness (low hydration indices) and impaired barrier function (high TEWL indices) are reported, with the hands being implicated the most. However, normal skin condition is also reported for some anatomical areas. Skin surface pH for all anatomical areas sampled decreased significantly during the shift, but remained in normal range. Dermal exposure to nickel occurred during the shift at the electro-winning plant of one refinery, while dermal co-exposure to cobalt and nickel occurred at the cobalt plant of the other refinery. At both of the refineries, cobalt and/or nickel was collected from the workers’ skin even before the shift. Also, dermal exposure to these metals was highly variable between individual workers. Skin notations in South African legislation had a mean agreement of between 42.9% and 45.8% with other countries, while agreement for sensitisation notations was only 3.6% between countries. / Thesis (Ph.D. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Acne is a multifactorial skin disease affecting about 80 % of people aged 11 to 30. Several systemic and topical treatments are used to treat existing lesions, prevent scarring and suppress the development of new lesions. Topical therapy is often used as first line treatment for acne, due to the location of the target organ, the pilosebaceous unit, in the skin. Retinoids are widely used as oral or topical treatment for this disease, with tretinoin and adapalene being two of the most used topical retinoids. The transdermal route offers several challenges to drug delivery, e.g. the excellent resistance of the stratum corneum to diffusion, as well as variable skin properties such as site, age, race and disease. Some additional difficulties are associated with the dermatological delivery of tretinoin and adapalene, which include suboptimal water solubility of the retinoids, isomerisation of tretinoin in the skin, mild to severe skin irritation, as well as oxidation and photo–isomerisation of tretinoin, even before crossing the stratum corneum. Researchers constantly strive to improve dermatological retinoid formulations in order to combat low dermal flux, skin irritation and instability. The release kinetics of tretinoin varies greatly according to the way in which it is incorporated into the formulation and according to the type of formulation used. Little research has been conducted regarding improved formulations for adapalene. Pheroid technology is a patented delivery system employed in this study in order to improve the dermal delivery of retinoids. Tretinoin and adapalene were separately incorporated into castor oil, vitamin F and Pheroid creams. The creams were evaluated in terms of their in vitro retinoid release, in vitro transdermal diffusion and stability. Castor oil and Pheroid creams were superior in terms of release and dermal delivery of adapalene. Tretinoin was best released and delivered to the dermis by castor oil cream. The castor oil creams were the most stable formulations, whereas the Pheroid creams were the most unstable. In terms of release, dermal diffusion and stability, castor oil cream proved to be the most suitable cream for both tretinoin and adapalene. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.

Copper exposure is known to be a rare cause of skin irritation and allergic reactions and according to our knowledge occupational dermal exposure to copper sulphate has not yet been characterised. As a result, the objectives of this study were to assess the dermal exposure of workers at a chemical industry to copper sulphate and to characterise the change in the their skin barrier function from before to the end of the work shift, as the skin’s barrier function can greatly influence the permeation of chemical substances. Methods: The change in skin barrier function of reactor workers, crystal and powder packaging workers at the chemical industry were assessed by measuring their dominant hand’s palm, back and wrist as well as their foreheads’ skin hydration, transepidermal water loss (TEWL) and skin surface pH before and at the end of the work shift. Commercial GhostwipesTM were used to collect dermal exposure samples from the same four anatomical areas before and at the end of the shift. Additional dermal exposure samples were collected from the palm and back of hand, prior to breaks 1 and 2. Surface wipe sampling was also conducted at several work and recreational areas of the chemical industry. Wipe samples were analysed by an accredited analytical laboratory, according to NIOSH method 9102 by means of Inductively Coupled Plasma-Atomic Emission Spectrometry. Results: Changes in skin hydration of the workers and anatomical areas at the end of the work shift were highly variable, while in general TEWL increased and skin surface pH decreased. Copper was collected from the skin of all workers before the shift commenced, and dermal exposure increased throughout the work shift. All of the work and recreational areas from which surface samples were taken, were contaminated with copper. Conclusion: As a result of intermittent use of inadequate protective gloves and secondary skin contact with contaminated surfaces and work clothing, workers at the chemical industry are exposed to copper sulphate via the dermal exposure route. The decrease in the workers’ skin barrier function (increased TEWL) and skin surface pH is most likely the result of their dermal exposure to sulphuric acid, and may lead to enhanced dermal penetration. The low account of skin irritation or reaction incidences among these workers is contributed to their ethnicity as well as to the low sensitisation potential of copper. Recommendations on how to lower dermal exposure and improve workers’ skin barrier function are made. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2014

Copper exposure is known to be a rare cause of skin irritation and allergic reactions and according to our knowledge occupational dermal exposure to copper sulphate has not yet been characterised. As a result, the objectives of this study were to assess the dermal exposure of workers at a chemical industry to copper sulphate and to characterise the change in the their skin barrier function from before to the end of the work shift, as the skin’s barrier function can greatly influence the permeation of chemical substances. Methods: The change in skin barrier function of reactor workers, crystal and powder packaging workers at the chemical industry were assessed by measuring their dominant hand’s palm, back and wrist as well as their foreheads’ skin hydration, transepidermal water loss (TEWL) and skin surface pH before and at the end of the work shift. Commercial GhostwipesTM were used to collect dermal exposure samples from the same four anatomical areas before and at the end of the shift. Additional dermal exposure samples were collected from the palm and back of hand, prior to breaks 1 and 2. Surface wipe sampling was also conducted at several work and recreational areas of the chemical industry. Wipe samples were analysed by an accredited analytical laboratory, according to NIOSH method 9102 by means of Inductively Coupled Plasma-Atomic Emission Spectrometry. Results: Changes in skin hydration of the workers and anatomical areas at the end of the work shift were highly variable, while in general TEWL increased and skin surface pH decreased. Copper was collected from the skin of all workers before the shift commenced, and dermal exposure increased throughout the work shift. All of the work and recreational areas from which surface samples were taken, were contaminated with copper. Conclusion: As a result of intermittent use of inadequate protective gloves and secondary skin contact with contaminated surfaces and work clothing, workers at the chemical industry are exposed to copper sulphate via the dermal exposure route. The decrease in the workers’ skin barrier function (increased TEWL) and skin surface pH is most likely the result of their dermal exposure to sulphuric acid, and may lead to enhanced dermal penetration. The low account of skin irritation or reaction incidences among these workers is contributed to their ethnicity as well as to the low sensitisation potential of copper. Recommendations on how to lower dermal exposure and improve workers’ skin barrier function are made. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2014

Die in dieser Arbeit isolierten und hochaufgereinigten, humanen dermalen Mastzellen wurden mit UVB, UVA-1 und PUVA-1 bestrahlt und anschließend entweder mit Substanz P oder anti-IgE stimuliert. Dadurch sollten Einblicke in die unterschiedlichen Wirkmechanismen der bei zahlreichen mastzellassoziierten Erkrankungen eingesetzten UV Licht Therapie gewonnen werden. Ein Schwerpunkt dieser Arbeit lag in der Erforschung der Histamin-, Tryptase- und Zytokinfreisetzung von menschlichen Mastzellen. Zusätzlich wurde die Expression von Lysosomen-assoziierten Membran Proteinen (LAMPs) auf der Oberfläche dieser Zellen untersucht. Im Gegensatz zu der durch UV Licht induzierbaren spontanen Histaminfreisetzung zeigte sich die anti-IgE stimulierte Histaminausschüttung durch UVB, UVA-1 und PUVA-1 signifikant und dosisabhängig inhibierbar. Auch die durch Substanz P stimulierten Mastzellen gaben nach UVA-1 Bestrahlung deutlich weniger Histamin ab. Demgegenüber blieb die sezernierte Menge des Mediators nach UVB und PUVA-1 konstant. Analog zu den erhobenen Histaminergebnissen konnte eine signifikante Inhibition der anti-IgE induzierten Tryptasefreisetzung nachgewiesen werden. Ebenso zeigte sich eine signifikante Verringerung, der innerhalb von vierundzwanzig Stunden basal freigesetzten Menge an Interleukin-6 und Interleukin-8, nach UV Bestrahlung. Die spontane Ausschüttung vom Tumornekrosefaktor-a verblieb in dem Untersuchungszeitraum auf sehr geringem Niveau, so dass eine relevante Beeinflussung durch UV Licht nicht stattfand. Des weiteren konnte eine vermehrte basale Expression von CD107a und CD63 auf der Mastzellmembran durch UV Bestrahlung demonstriert werden. Auch die anti-IgE induzierte Mehrexpression der LAMPs konnte bei den drei Bestrahlungsarten nachweisbar supprimiert werden. Die in dieser Arbeit gewonnenen Erkenntnisse zeigen, dass die Auswirkungen der UV Licht Therapie auf Mastzellen sehr komplex sind. Zu beachten ist, dass unter physiologischen Bedingungen nicht nur isolierte Mastzellen, sondern auch weitere bestrahlte Zellverbände eine Veränderung erfahren. Erst durch das Zusammenspiel aller Zellen lassen sich Rückschlüsse auf Krankheitsbilder und die anzuwendende Therapien ziehen. Letztendlich soll diese Arbeit dazu beitragen, dass das Verständnis der unterschiedlichen Wirkungen von UV Licht begriffen und so ein sinnvolles und gezieltes Einsetzen im klinischen Alltag ermöglicht wird. / For all experiments highly purified dermal mast cells were used. The aim of the current study was to systematically investigate the effects of UVB, UVA-1 and PUVA-1 on skin derived human mast cells. Baseline and stimulated release of histamine, tryptase and of the proinflammatory cytokines IL-6, IL-8 and TNF-a were examined. Furthermore, the CD 107a and CD 63 surface levels in UV treated cells were investigated representing two members of lysosome associated membrane proteins which were found to appear on mast cell surface during degranulation. Prior treatment with UV resulted in a striking suppression of the anti-IgE induced release of preformed mediators such as histamine and tryptase in a dose dependent manner. This inhibition was accompanied by a diminished, anti-IgE mediated increase in CD 107a and CD 63 surface expression. In sharp contrast, UV-light slightly preactivates mast cells as indicated by a marginal but statistically significant direct UV-caused histamine release. Theses findings matched the observation of slightly enhanced CD 107a and CD 63 surface levels in UV treated but unstimulated cells. After UVA-1 treatment the histamine release of substance P stimulated mast cells is statistically significant reduced which contrasts to the unchanged liberation of this preformed marker after UVB and PUVA-1 irradiation. Furthermore the release of mediators that are not or only partially preformed was examined. In the present study all types of UV-irradiation inhibits baseline IL-6 and IL-8 secretion from mast cells. The very low baseline level of TNF-a remained unaffected. Taken together, the present findings identify cutaneous human mast cells as important targets of UV-induced immunomodulation. They help explain both the dose-dependent adverse effects of UV-light and the beneficial and desired antiinflammatory effects during therapy.