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The skin allergenic properties of chemicals may depend on contaminants
S106
Abstracts / Toxicology Letters 164S (2006) S1–S324
P3-07 Effect of phenol and hydroquinone associated exposure on leukocyte migration into allergic inflamed lung Alexandre Ferreira, Sandra Manoela Dias Macedo, Suellen Cristine Moreira Vaz, Wothan Tavares Lima, Sandra Helena Poliselli Farsky University of S˜ao Paulo, Sao Paulo, Brazil Benzene is metabolized by the liver generating phenol (PHE) and hydroquinone (HQ), which is substrate to myeloperoxidase in the bone marrow resulting in 1,4 p-benzoquinone. These metabolites are linked to immunotoxic effects, however, their effects on leukocyte mobilizations during inflammatory processes are not fully understood. We previously showed that in vivo HQ exposure for an extended period of time (50 mg/kg, i.p., 16 daily doses, with 2-day intervals every 5 doses) impairs the leukocyte migration into lung during an allergic response in rats. Now, we investigated the effect of lower doses of HQ, PHE or association of both on leukocyte mobilization into inflamed lungs. Adult, male Wistar rats were sensitized with OA (10 mg; aluminum hydroxide solution, i.p. route) at the 10th day after beginning phenolic compounds (5 mg/kg, i.p., 16 daily doses, with 2-day intervals every 5 doses) or vehicle (ethanol:saline solution 1:20) exposures. Twenty-four hours after last doses, animals were challenged (1% PBS solution; 15 min inhalation). Broncheoalveolar lavage (BAL) was collected 24 h after challenge. HQ or PHE exposure induced impairment on number of polymorphonuclear (PMN, 50%) cells into BAL. The reduced cell migration was not modified by HQ and PHE associated exposure. These data suggest that in vivo lower dose of both phenolic compounds impairs the PMN recruitment to inflamed lung and PHE/HQ association does not promote synergic effect. Financial support: FAPESP grants 03/04013-8; 04/11412-9. doi:10.1016/j.toxlet.2006.06.222 P3-08 The skin allergenic properties of chemicals may depend on contaminants Evidence from studies on coumarin Francois E. Floch ITEConsult, Lyon, France Background/aims: Positive patch tests are considered as representative of a contact allergy to the tested chemi-
cal. However, contaminants and derivatives rather than the suspected chemical itself could be responsible for the skin allergic reactions. Here, we tested the importance of contaminants in the sensitizing and allergenic properties of coumarin in mice and humans. Coumarin, an ingredient of cosmetics and fragrances, was chosen as the reference chemical since conflicting results have been obtained regarding its ability to induce contact allergy. This could be explained by the presence, in some chemical preparations, of coumarin derivatives endowed with allergenic properties. Methods: In mice, three different coumarin preparations were tested in the local lymph node assay. In humans, we assessed the irritant and allergenic properties of highly pure coumarin in non allergic and fragrance allergic patients. Results: Pure coumarin did not exhibit irritant or sensitizing properties in the LLNA. In contrast, two other commercially available coumarins and three contaminants that were detected in these coumarin preparations were identified as weak and moderate sensitizers, respectively. In humans, pure coumarin was extremely well tolerated since only 1 out of 512 patients exhibited positive patch test to the chemical. Conclusions: These results indicate that coumarin cannot be considered as a common contact allergen and further emphasize that purity of chemicals is mandatory for assessment of their allergenicity. doi:10.1016/j.toxlet.2006.06.223 P3-09 The KLH-assay as alternative to the PFC-assay: A comparative study with cyclophosphamide Andr´e Hendrikus Penninks, Jolanda H.M. van Bilsen, Mary-lene M.H. Brouwer, Karin - Junker, Frieke C. Kuper TNO Quality of Life, Zeist, Utrecht, The Netherlands To date the T cell-dependent antibody response (TDAR) is regarded to be the most predictive assay for immunotoxicity testing. The IgM-plaque forming cell (PFC) assay using sheep red blood cells (SRBC) as antigen is a widely accepted and validated standard test. However, this assay has a number of drawbacks. Therefore, alternative assays like the KLH-assay using Keyhole Limpet Hemocyanin (KLH) as antigen are being developed and validated. In an Immunotoxicity Inter-Laboratory Project (IILP), a common design for a KLH-assay was established using well known immunosuppressive compounds. In this study we assessed for cyclophosphamide (CY) the robustness and sensitivity of the KLH-assay
Abstracts / Toxicology Letters 164S (2006) S1–S324
P3-07 Effect of phenol and hydroquinone associated exposure on leukocyte migration into allergic inflamed lung Alexandre Ferreira, Sandra Manoela Dias Macedo, Suellen Cristine Moreira Vaz, Wothan Tavares Lima, Sandra Helena Poliselli Farsky University of S˜ao Paulo, Sao Paulo, Brazil Benzene is metabolized by the liver generating phenol (PHE) and hydroquinone (HQ), which is substrate to myeloperoxidase in the bone marrow resulting in 1,4 p-benzoquinone. These metabolites are linked to immunotoxic effects, however, their effects on leukocyte mobilizations during inflammatory processes are not fully understood. We previously showed that in vivo HQ exposure for an extended period of time (50 mg/kg, i.p., 16 daily doses, with 2-day intervals every 5 doses) impairs the leukocyte migration into lung during an allergic response in rats. Now, we investigated the effect of lower doses of HQ, PHE or association of both on leukocyte mobilization into inflamed lungs. Adult, male Wistar rats were sensitized with OA (10 mg; aluminum hydroxide solution, i.p. route) at the 10th day after beginning phenolic compounds (5 mg/kg, i.p., 16 daily doses, with 2-day intervals every 5 doses) or vehicle (ethanol:saline solution 1:20) exposures. Twenty-four hours after last doses, animals were challenged (1% PBS solution; 15 min inhalation). Broncheoalveolar lavage (BAL) was collected 24 h after challenge. HQ or PHE exposure induced impairment on number of polymorphonuclear (PMN, 50%) cells into BAL. The reduced cell migration was not modified by HQ and PHE associated exposure. These data suggest that in vivo lower dose of both phenolic compounds impairs the PMN recruitment to inflamed lung and PHE/HQ association does not promote synergic effect. Financial support: FAPESP grants 03/04013-8; 04/11412-9. doi:10.1016/j.toxlet.2006.06.222 P3-08 The skin allergenic properties of chemicals may depend on contaminants Evidence from studies on coumarin Francois E. Floch ITEConsult, Lyon, France Background/aims: Positive patch tests are considered as representative of a contact allergy to the tested chemi-
cal. However, contaminants and derivatives rather than the suspected chemical itself could be responsible for the skin allergic reactions. Here, we tested the importance of contaminants in the sensitizing and allergenic properties of coumarin in mice and humans. Coumarin, an ingredient of cosmetics and fragrances, was chosen as the reference chemical since conflicting results have been obtained regarding its ability to induce contact allergy. This could be explained by the presence, in some chemical preparations, of coumarin derivatives endowed with allergenic properties. Methods: In mice, three different coumarin preparations were tested in the local lymph node assay. In humans, we assessed the irritant and allergenic properties of highly pure coumarin in non allergic and fragrance allergic patients. Results: Pure coumarin did not exhibit irritant or sensitizing properties in the LLNA. In contrast, two other commercially available coumarins and three contaminants that were detected in these coumarin preparations were identified as weak and moderate sensitizers, respectively. In humans, pure coumarin was extremely well tolerated since only 1 out of 512 patients exhibited positive patch test to the chemical. Conclusions: These results indicate that coumarin cannot be considered as a common contact allergen and further emphasize that purity of chemicals is mandatory for assessment of their allergenicity. doi:10.1016/j.toxlet.2006.06.223 P3-09 The KLH-assay as alternative to the PFC-assay: A comparative study with cyclophosphamide Andr´e Hendrikus Penninks, Jolanda H.M. van Bilsen, Mary-lene M.H. Brouwer, Karin - Junker, Frieke C. Kuper TNO Quality of Life, Zeist, Utrecht, The Netherlands To date the T cell-dependent antibody response (TDAR) is regarded to be the most predictive assay for immunotoxicity testing. The IgM-plaque forming cell (PFC) assay using sheep red blood cells (SRBC) as antigen is a widely accepted and validated standard test. However, this assay has a number of drawbacks. Therefore, alternative assays like the KLH-assay using Keyhole Limpet Hemocyanin (KLH) as antigen are being developed and validated. In an Immunotoxicity Inter-Laboratory Project (IILP), a common design for a KLH-assay was established using well known immunosuppressive compounds. In this study we assessed for cyclophosphamide (CY) the robustness and sensitivity of the KLH-assay