Immunomodulatory effects of mono-, di-, and trimethylphenols in mice.

The relationship of air pollutants with the increasing prevalence of allergic diseases is a matter of concern in developed countries. In this study, the immunomodulatory effects of mono-, di-, and trimethylphenols in mice were examined as regards two aspects. First, whether or not these chemicals act as sensitizers was evaluated by local lymph node assay. Of the 13 methylphenols tested, three dimethylphenol isomers (2,4-DMP, 2,5-DMP, and 3,4-DMP) were found to induce auricular lymphocyte proliferation after dermal application on both ears of mice. Cytokine production patterns in the supernatants of cultured auricular lymphocytes from mice showed these methylphenols to be contact sensitizers. Second, the effects of methylphenols on cytokine production profiles were examined using cultured splenocytes from immunologically naive mice. Under subtoxic conditions, eight methylphenols inhibited interferon-gamma (IFN-gamma) production significantly, while the effect on intreluekin-4 (IL-4) production was moderate, resulting in higher IL-4/IFN-gamma ratios in all of the tested chemicals, with the most prominent effect shown by 2,6-DMP. These results suggest that several methylphenols, especially dimethylphenol isomers, have potencies that affect the immune system, being immunogens themselves or modulators of the Th1/Th2 cytokine balance.

Allergenicity evaluation of p-chloro-m-cresol and p-chloro-m-xylenol by non-radioactive murine local lymph-node assay and multiple-dose guinea pig maximization test.

p-Chloro-m-cresol (PCMC) and p-chloro-m-xylenol (PCMX) are known to cause allergic contact dermatitis. For risk assessment of skin sensitizers, information on dose-response profiles in the induction and elicitation phases and cross-reactivity with analogous chemicals are important. In the non-radioactive local lymph-node assay (LLNA) using 5-bromo-2'-deoxyuridine instead of 3H-methyl thymidine, significant effect on lymph node cell proliferation was detected at 10% PCMC and 25% PCMX, while in the multiple-dose guinea pig maximization test (GPMT) at least one animal tested in the group was sensitized at a 5 ppm induction dose of either chemical. When mean skin reaction score in an animal group maximally sensitized with each allergen with the GPMT was plotted against log challenge concentration, linear regression lines with high correlations were obtained in both cases. The calculated elicitation threshold was lower for PCMC than PCMX. The area under the linear regression line between the threshold point and 1% of the elicitation concentration, another index of relative elicitation potency, was also greater for PCMC. Bidirectional cross-reactivity between PCMX and PCMC was detected in the GPMT. PCMC was thus identified in both LLNA and GPMT as a stronger sensitizer than PCMX in both the induction and elicitation phases. These results suggest that the non-radioactive LLNA is a simple and useful method for evaluating allergenicity in the induction phase, while the GPMT using a maximally sensitized animal group is more suitable for assessing the dose-response profile and cross-reactivity in the elicitation phase.

Evaluation of a commercially available ELISA kit as a tool to determine BTEX in groundwater.

The reliability of enzyme-linked immunosorbent assay (ELISA) tests as a screening technique to address groundwater contamination was tested in an area following leakage of gasoline from a petrol station. Immunoassay data of benzene, toluene, ethylbenzene, and o-, m- and p-xylene (BTEX) were compared with results obtained using capillary gas chromatographic analysis. Detection limits were of 20 microg l(-1) for ELISA and 0.3 microg l(-1) for gas chromatography with flame ionization and photoionization detectors (GC-FID/PID) determination. Despite an observed overestimation of BTEX concentrations as given by ELISA, the tests responded reliably to different levels of contamination.

Enhanced mortality and liver damage in virus-infected mice exposed to p-xylene.

This study assessed effects of exposure to p-xylene, a ubiquitous air pollutant, on mice infected with murine cytomegalovirus (MCMV), a mouse model for a common human virus. It was postulated that adverse health effects could occur as a result of (1) enhanced infection due to xylene-induced immune suppression, (2) increased p-xylene toxicity due to viral suppression of cytochrome P-450 (P-450), and/or (3) additive or synergistic effects on liver function due to tissue injury by both p-xylene and MCMV. Mice were exposed to filtered air, 600 or 1200 ppm p-xylene 6 h/d for 4 d and infected with a sublethal dose of MCMV after the first exposure. No deaths occurred among uninfected, p-xylene-exposed mice or infected, air-exposed mice; 34% and 0% mortality occurred respectively in infected mice exposed to 1200 and 600 ppm p-xylene. Virus titers in the liver and splenic natural killer cell activity were unaffected by exposure to 1200 ppm p-xylene. Small but significant increases in serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities, indicators of liver damage, were observed at 4 d postinfection. p-Xylene exposure had no effect on these serum enzyme activities in uninfected mice, but 1200 ppm potentiated this effect in infected mice. MCMV significantly suppressed and p-xylene significantly increased total P-450 levels in the liver, but there was no significant interaction between the two. Isozymes 1A1, 2B1/B2, and 2E1 were decreased to a similar degree, suggesting that the virus does not target specific isozymes. Enhanced mortality was not due to immune suppression. While p-xylene potentiated liver damage was caused by the virus, the magnitude of serum enzyme activities indicates that this damage was not a likely cause of death. The cause of deaths is unclear, results were consistent with the hypothesis that enhanced mortality was related to enhanced xylene toxicity due to suppression of P-450, although additive or synergistic damage to tissues other than liver cannot be ruled out.

Contact sensitivity to topical antimicrobials. (II). Sensitizing potentials of some topical antimicrobials.

A predictive study comparing the sensitizing potentials of some topical antimicrobials, using a modified Beuhler's technique, showed that over-the-counter (OTC) antimicrobials were more sensitizing than prescribed topical antibiotics. Among OTC antimicrobials, proflavine was the most potent sensitizer (4/10 guinea pigs); parachlorometaxylenol, benzalkonium chloride and propamidine isethionate moderate sensitizers (2/10 guinea pigs); iodine a weak sensitizer (1/10 guinea pigs); and chlorhexidine and cetrimide very weak sensitizers (0/10 guinea pigs). Among prescribed topical antibiotics, neomycin was a moderate sensitizer (2/10 guinea pigs); gentamycin and chloramphenicol weak sensitizers (1/10 guinea pigs); kanamycin, clioquinol, polymyxin B, bacitracin, tetracycline, sodium fusidate and fusidic acid very weak sensitizers (0/10 guinea pigs). There was good correlation between sensitizing potentials in animal studies and clinical experience of contact allergy to these topical antimicrobials.