Risk assessment for the harmful effects of UVB radiation on the immunological resistance to infectious diseases.

Abstract

Risk assessment comprises four steps: hazard identification, dose-response assessment, exposure assessment, and risk charcterization. In this study, the effects of increased ultraviolet B (UVB, 280-315 nm) radiation on immune fiuctions and the immunological resistance to infectious diseases in rats were analyzed according to this strategy. In a parallelogram approach, nonthreshold mathematical methods were used to esismate the risk for the human population after increasd exposure to UVB radiation. These data demontrate, using a worst-case strategy (sensitive individuals, no Risk assessment is a process of analyzing relevant biological, dose-response, and exposure data for a particular agent in an attempt to establish qualitative and quantitative estimates of adverse effects on human health (1). As defined by the frequently cited National Academy of Science Report (2), risk assessment comprises four steps: hazard identification, dose-response assessment, exposure assessment, and risk characterization. This general framework covers the process of assessing risk of cancer as well as noncancer endpoints, including decreased resistance to infections. The present study is not aimed at the determination or calculation of the maximal tolerable dose of UV radiation humans are advised or allowed to be exposed to. This study only serves as an estimation of the effect of exposure to increased levels of UVB with respect to the immune system and related resistance to infections in comparison to humans that are not exposed to increased UVB levels due to ozone depletion.The first step, hazard identification, involves a largely qualitative evaluation of available human and animal data to determine whether a chemical or physical agent is a potential hazard. Consideration is given to the dose, route, and duration of exposure in the test species. Any possible change in immune function, due to the agent studied, indicates that this agent is a potential hazard. Many studies indicate that suberythemal doses of ultraviolet light can affect the immune system in rodents as well as in humans. The major effect of UV exposure is suppression of the cellular immune system and of natural killer cell (NK) function, which is found in humans as well as in rodents. In rodent studies it has been demonstrated that UV-induced immunomodulation can lead to a lowered resistance to certain infections and tumors (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).Following hazard identification, doseresponse studies (step 2 of risk assessment)give quantitative information, which is the basis for obtaining the no-observed adverse effect level (NOAEL) and the lowest adverse effect level (LOAEL), which are threshold values. This information is also necessary to determine the effective dose, which induces a certain level of suppression of an immune function, e.g., 50% suppression (ED50), for which it is assumed that there is no threshold dose value. The ED50, the dose that inhibits the response by 50%, can be calculated using linear or nonlinear regressio...

UV-B induced immunomodulation: a health risk

“…Because experimental data on the effects of UVR on infectious diseases, easily obtainable in laboratory animals, cannot be acquired using human subjects for ethical reasons, and because epidemiological data regarding the incidence of infectious diseases are not readily available, the only way to estimate the risk for humans is to extrapolate from the animal data. The parallelogram approach was used for this, as published earlier (Garssen, Norval et al 1998;Goettsch, Garssen, Slob et al 1998;Goettsch, Hurks et al 1998). In rodent models the effects of UV-B exposure on immune responses to systemic infections with L. monocytogenes and HSV were investigated.…”

“…Artificial UV exposure was extrapolated to solar exposure using 3 different action spectra and I absorption spectrum. CHS = action spectrum for contact hypersensitivity (De Fabo & Noonan 1983); DNA = action spectrum for DNA damage (Matsunaga et al 1991); UCA = Urocanic acid absorption spectrum (De Fabo & Noonan 1983); MSLR = action spectrum for mixed skin lymphocyte reaction (Hurks, 50% in human subjects was 6.8 x 3.85 x 0.5 = 13.1 H/m2 cumulative (Goettsch, Garssen, Slob et al 1998;Goettsch, Hurks et al 1998).…”

“…In earlier risk assessment studies, the output of the lamp was extrapolated to solar exposure using an action spectrum for suppression of contact hypersensitivity in mice and biological effective irradiance for 50% immunosuppression in mice at certain latitudes as published by De Fabo &Noonan (1983) andDe Fabo et al (1990). The exposure times necessary for 50% suppression of immunity to L. monocytogenes in people at different latitudes were calculated for different amounts of ozone depletion (Garssen, Norval et al 1998;Goettsch, Garssen, Slob et al 1998;Goettsch, Hurks et al 1998). In the present study we performed additional calculations taking other action or absorption spectra into account.…”

“…Based on our data with respect to the L. rnonocytogenes model and studies by De Fabo et al (1990), an estimation of the risk of exposure of human subjects to increasing UV-B due to a decrease in the ozone layer thickness was calculated (Garssen, Norval et al 1998;Goettsch, Garssen, Slob 1998;Goettsch, Hurks et al 1998). The mathematical model included information on the action spectrum for the suppression of contact hypersensitivity (De Fabo & Noonan 1983) and dose response studies for suppression of T cell activity in the Listeria infection model, and the estimated biological effective irradiance at certain latitudes (De Fabo et al 1990).…”

“…Immune function parameters such as contact hypersensitivity, delayed-type hypersensitivity, mixed lymphocyte reactions, mixed skin lymphocyte reactions and antigen presentation, as well as changes in cutaneous phenotypes, have been examined extensively (Hurks, Garssen et al 1994). In addition, some studies have focused on the consequences of this immunomodulation for resistance to UV induced skin tumours and skin associated infections, such as herpes simplex (Norval et al 1994;Garssen, Norval et al 1998;Goettsch, Garssen, Slob et al 1998;Goettsch, Hurks et al 1998). Immune response and resistance to herpes simplex virus (HSV) was suppressed by suberythemal doses of UV-B in rodent models and in human subjects.…”