Patient attitudes toward issues of environmental health.

OBJECTIVE: Although the place of environmental health in medical education has been cautiously explored, patient attitudes toward environmental issues have been largely ignored in the medical literature. The purpose of this study was to evaluate the baseline level of family practice patient concerns about a variety of environmental issues, including their major sources of information and their level of trust in each source. Patient desire for more environmental education was also assessed. METHODS: This cross-sectional, descriptive study was based on a confidential, 14 question survey administered to a convenience sample of 373 adult family medicine patients at 4 University of Wisconsin-Madison Department of Family Medicine affiliated clinics, including 2 urban, 1 suburban, and 1 rural site. Of 496 patients approached, 415 accepted, and 373 returned complete and acceptable questionnaires. The level of patient concern for each environmental issue, patient trust in each source of information, and the amount of education patients felt they had received from their physician were measured. RESULTS: A high level of concern for environmental issues existed among the study sample patients. Although only 18% of patients reported utilizing their physician as a major source of environmental information, physicians were considered the most trustworthy source. In general, patients felt that they had received an inadequate amount of environmental education from their physician regarding all environmental issues presented. CONCLUSIONS: Patients desire and would be receptive to more environmental education from their physicians.

Use of an in vitro test battery as a prescreen in the assessment of ocular irritancy.

The current OECD guideline for the assessment of eye irritation recommends, in initial considerations, the use of data from skin irritation tests as a prescreen to detect the most severely irritating materials, assuming that materials that are severely irritating to the skin are also significantly irritating to the eyes. However, analysis of data for 179 materials tested in this laboratory for both dermal and ocular irritancy, revealed that, at most, only 36% of severe eye irritants were also severe skin irritants. This resulted in a significant number of rabbits developing severe ocular effects that had not been predicted from the dermal responses. This study reports the results of an alternative approach for predicting severe eye irritants. The approach was a two-stage test battery in vitro: the first stage was a cytotoxicity assay utilizing the K562 cell line; the second was the isolated rabbit eye test. In contrast to the use of skin irritation tests, the in vitro battery was significantly more predictive (83% of severe eye irritants were detected). Although the incidence of false positive responses in each of the assays precludes their routine use as a replacement from the in vivo rabbit eye test they provide a powerful aid to reducing animal use and guiding in vivo studies to minimize the severity of effects. The need for an interlaboratory assessment to confirm and extend these findings is discussed.

Development of an in vitro test battery for use within a stepwise approach to the assessment of ocular irritancy in vivo.

The current OECD guideline for the assessment of eye irritation recommends, within its initial considerations, the use of data from skin irritation tests as a pre-screen to detect the most severely irritating materials, its being assumed that materials that are severely irritating to the skin are also significantly irritating to the eyes. However, analysis of data for 223 materials, tested in this laboratory for both dermal and ocular irritancy, revealed that only 23% of severe eye irritants were also severe skin irritants. This resulted in a significant number of rabbits developing severe ocular effects that had not been predicted from the dermal responses. This study reports the results of an alternative approach for predicting severe eye irritants. The approach was a two-stage in vitro test battery; the first stage was a cytoxicity assay using the K562 cell line; the second was the isolated rabbit eye test. In contrast to the use of skin irritation tests, the in vitro battery was significantly more predictive (83% of severe eye irritants were detected). Although the indicence of false positive responses in the assay precludes its routine use as a replacement for the in vivo rabbit eye test, the test battery provides a powerful aid to reducing animal use and guiding in vivo studies to minimize the severity of effects.

A comparison of two cytotoxicity tests for predicting the ocular irritancy of surfactants.

In vivo rabbit eye tests have attracted criticism on both scientific and ethical grounds. Consequently, there is a need to develop new approaches that still provide the necessary information on eye irritation hazard but that minimize or even avoid the use of whole laboratory animals. Cytotoxicity models have been used to predict the ocular irritancy of surfactants, since this class of chemicals has an essentially common action on cell membranes which involves membrane disruption. The aim of the present studies was to compare the predictive ability of two in vitro cytotoxicity tests, the K562 and the red blood cell lysis tests, in the assessment of the in vivo eye irritancy of surfactants. The results of these studies on 14 selected surfactant materials showed that the K562 assay was only modestly predictive of the in vivo response, with a specificity of 86% but a sensitivity of only 57%. In contrast, the red blood cell lysis test was more predictive, correctly identifying all irritants tested. In addition, all non-irritant surfactants examined were predicted and a high (89%) ability to rank irritant effect was demonstrated. The red blood cell lysis test could be a powerful addition to a testing strategy or pre-screen for the evaluation of surfactant chemicals.

A comparison of two cytotoxicity tests for predicting the ocular irritancy of surfactants.

In vivo rabbit eye tests have attracted criticism on both scientific and ethical grounds. Consequently there is a need to introduce methods that provide relevant information whilst avoiding the use of whole laboratory animals. Cytotoxicity models have been used to predict the ocular irritancy of surfactants since the action of this class of chemicals on cell membranes is essentially common and involves membrane disruption. The aim of the present studies was to compare the predictive ability of two in vitro cytotoxicity tests (the K562 and the red blood cell lysis tests) in the assessment of the in vivo eye irritancy of surfactants. The results of these studies on 14 selected surfactant materials showed that the K562 assay was less likely to over-estimate effect (when assessed over a wide range of surfactant concentration) than had previously been observed. This increased specificity (86%) was accompanied by a decrease in sensitivity (57%), the ability to correctly identify 'irritant' surfactants. In contrast, the red blood cell lysis test was more predictive, correctly identifying all irritants tested. In addition, all non-irritant surfactants examined were predicted by this test and a high (89%) ability to rank irritant effect was demonstrated. The red blood cell lysis test could be a powerful addition to a testing strategy or pre-screen for the evaluation of surfactant chemicals.

Investigation of TNF-alpha release as a measure of skin irritancy.

Contact dermatitis is by far the most frequently reported occupational disease, with irritant dermatitis accounting for up to 80% of all cases. A wide variety of materials are capable of causing skin inflammation including soaps, cosmetics, pesticides, organic dyes, solvents and industrial chemicals and wastes. Skin irritation results from a complex series of events involving the development of an inflammatory response at the site of exposure. Cytokines are a family of proteins and glycoproteins that regulate immune and inflammatory responses; many are produced by epidermal cells. The present study examines the response of mouse epidermal strips to the cutaneous irritant sodium dodecyl sulphate (SDS). A time-dependent relationship was established for the release of the cytokine tumour necrosis factor-alpha, from epidermal keratinocytes after treatment with 20% SDS. The potential value of this methodology for the detection of cutaneous irritants has been established. The utility of the approach for the identification in vitro of other materials of known in vivo irritant potential will be investigated.

Dopamine receptor abnormalities in the striatum and pallidum in tardive dyskinesia: a post mortem study.

Dopamine D1 and D2 receptors were determined in brain tissue taken post mortem from schizophrenic patients previously known to have had tardive dyskinesia and yet who had not received neuroleptic drug treatment for over one year prior to death. In comparison with age-matched control subjects, diminished D2 receptor density was observed in striatal regions, while these receptors appeared to be increased in the pallidum, an area of the brain particularly implicated in the production of dyskinesias. D 1 receptors showed similar tendencies to lower numbers in the striatum in tardive dyskinesia.

The skin corrosivity test in vitro. Results of an inter-laboratory trial.

The collaborative study reported here was performed to evaluate the reliability of the skin corrosivity test in vitro when performed in independent laboratories. Twenty substances were examined in each of three participating laboratories and the results were compared with existing data from standard assays in vivo. The skin corrosivity test is based on the assumption that corrosive substances destroy the skin's natural outer protective barrier, the stratum corneum. Corrosive action in vitro is measured by a fall in the transcutaneous electrical resistance (TER) below a predetermined threshold. A refined test using a MgSO(4) electrolyte solution for TER measurements has recently been shown to reduce the number of false positive results in the test, while maintaining excellent predictive value for skin corrosive substances. Although in the present study there was some variation between laboratories in terms of the absolute mean TER values obtained, all 6 substances corrosive in vivo were correctly predicted by the three laboratories. The other 14 substances ranged from being non-irritant to severe skin irritants in vivo, but the test was unable to discriminate between these different categories in any of the three laboratories. However, these inter-laboratory comparisons demonstrate that the refined skin corrosivity test is a robust and reliable method in vitro for identifying potential skin corrosive substances.

An interlaboratory assessment of the Eytex system.

Seventeen raw materials and chemical formulations were evaluated in the Eytex System to determine the ability of this assay in vitro to predict eye irritation potential in vivo. All the test samples, which represented a wide range of chemical types and eye irritancy potential in vivo, were provided by one of the participating laboratories. Historical data from tests in vivo were available for each of the test samples, so testing in vivo specifically for this study was not necessary. Samples were evaluated by both the membrane partition assay (MPA) and the rapid membrane assay (RMA). The sensitivity, specificity, predictivity and equivalence of the Eytex assay were determined by comparison with the rabbit eye irritation data, using each of the different Eytex Draize Equivalent (EDE) classification schemes. Regardless of the classification scheme used, the correlation between the scores in vivo and in vitro was poor. The Eytex System consistently overclassified materials of low irritancy in vivo and underclassified those test materials of moderate irritancy or above. On the basis of the results from the 17 materials tested in this study, the Eytex System appears unsuitable as a replacement in vitro for ocular irritancy testing of all types of chemical. However, Eytex may have a place as a pre-screening method used as part of a test battery.

The relationship between exposure to rats and antibody production in man: IgG antibody levels to rat urinary protein.

An ELISA procedure has been developed to measure specific IgG antibodies against rat urine. Using this method antibody levels in individuals with differing exposure levels to rat have been measured. Mean antibody titres in groups of workers regularly exposed to rats were higher than those in groups currently or totally non-exposed. However, only in the group of workers exposed and sensitized to rats were IgG levels significantly elevated. Despite this significant difference in mean antibody titres there was considerable overlap between individuals in each group, and there was no direct relationship between exposure to rats and levels of IgG anti-rat urine antibody. Our results suggest a stronger correlation between sensitization to rats and the levels of antigen-specific IgG antibodies.