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Acrylamide (AA) is an important industrial chemical used mainly in the production of polymers. It can be absorbed through the skin. AA was shown to be a germ cell clastogen that entails a genetic risk for exposed workers. The genetic risk calculation was based on mouse heritable translocation test data obtained after acute intraperitoneal (ip) exposure (Adler et al., 1994). To obtain a correction factor between ip and dermal exposure, dominant lethal and heritable translocation tests were carried out with dermal exposure of male mice to AA. In the dominant lethal test, male (102/El × C3H/El)F1 mice were exposed by dermal application to the shaved backs of 50 mg/kg AA per day on five consecutive days or to five daily ip injections of 50 mg/kg AA. One day after the end of exposure, the males were mated to untreated females of the same hybrid stock for four days and females were changed every four days for a total of five matings. Dominant lethal effects were found during matings 1–3. For ip exposure, these values were 81.7, 85.7 and 45.4%, respectively; for dermal exposure the corresponding values were 22.1, 30.6 and 16.5%, respectively. In the heritable translocation assay, male C3H/El mice were treated with five dermal exposures of 50 mg/kg AA and mated 1.5–8.5 days after the end of exposure to untreated female 102/El mice. Pregnant females were allowed to come to term and all offspring were raised to maturity. Translocation carriers among the F1 progeny were selected by a sequential fertility testing and cytogenetic analysis including G-band karyotyping and M-FISH. A total of 475 offspring were screened and 41 translocation carriers were identified. The observed translocation frequency after dermal exposure was 8.6% as compared to 21.9% after similar ip exposure (Adler, 1990). The calculated ratio of ip vs. dermal exposure of 0.39 can be applied to obtain a more realistic calculation of genetic risk for dermally exposed workers. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In this study, we describe the ability of hybrid mouse monoclonal antibody (mAb) to induce monocyte-mediated cytotoxicity towards human IgA1-coated E (HuIgAl-E), and the effect of mAb binding valency on FcγRI-mediated ADCC. All hybrid monospecific (ms) anti-HulgAl and bispecific (bs) anti-HuIgA1/HRP mAb were capable of inducing monocyte-mediated lysis of HuIgAl-E, in spite of differences in mAb densities essential for optimal lysis. The cytotoxicity induced by hybrid mAb which consist of one or more mlgG2a H chains was predominantly mediated via FcγRI, as shown by inhibition studies on monocytes with FcγRI-blocking mAb TB-3 (≈80% inhibition). However, partial inhibition of mtgGl-2a and mlgG2a-2b-induced cytotoxicity (20-50%) was observed by using FcγRll-blocking mAb IV.3 or CIKM5. For hybrid mIgGl-l mAb the opposite was true; the cytotoxicity was predominantly mediated via FcαRlI (70-80%) and less via FcγRl (20-30%). Comparing the hybrid ms anti-HulgA 1 mAb-induced cytotoxicity with the cytotoxicity induced by hybrid bs anti-HuIgAl/HRP mAb of the same isotype, we observed a decrease in cytotoxicity towards HuIgAl-E sensitized with univalently bound bs anti-HuIgAl/HRP mAb. This decrease was only found for FcγRI-mediated ADCC (mlgG2ae2a, mlgGl -2a and mIgG2a-2b). This diminished recognition of univalently bound IgG relative to bivalently bound IgC by FcγRI was also observed with U937 effector cells. In conclusion, this work shows that hybrid mAb are able to induce monocyte-mediated cytotoxicity towards E-HuIgA1 and that there appears to be an effect of Ag-IgG binding valency on FcγRI-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]