eONTENTS NOTE TO THE READER . 9 LIST OF PARTICIPANTS . Il PREAMBLE .......................................................... 17 Background ........................................................ 17 Objective and Scope ................................................. 17 Selection of Topics for Monographs . 18 Data for Monographs ................................................ 19 The Working Group ................................................. 19 Working Procedures ................................................. 19 Exposure Data. " 20 Studies of Cancer in Humans ... 21 Studies of Cancer in Experimental Animais .............................. 25 Other Data Relevant to an Evaluation of Carcinogenicity and Its Mechanisms . 27 Summary of Data Reported ........................................... 29 Evaluation ......................................................... 30 References ......................................................... 34 GENERA REMARKS .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 39 THE MONOGRAHS Infection with schistosomes (Schistosoma haematobium, S. mansoni and S. japonicum). 45 1. Exposure data .................................................... 45 1. 1 Structure and biology of schistosomes ............................. 45 1.1.1 Taxonomy.............................................. 45 1.1.2 Structure............................................... 45 1. 1.3 Life cycle and biology of the adult worm . .. 46 1.2 Methods for detection of infection . .. 48 1.2.1 History taking . .. 48 1.2.2 Clinical diagnosis ........................................ 48 1.2.3 Parasitological tests ...................................... 49 1.2.4 Immunological tests . .. .. 49 1.2.5 Establishment of absence of infection ....................... 50 CONTENTS 1.3 Epidemiology of infection . " 50 1.3.1 Geographical distribution ................................. 50 1.3.2 Risk factors for infection . " 55 1.3.3 Aggregation of infection .................................. 55 1.3.4 Prevalence and intensity of infection ........................ 55 1.3.5 Sex-related patterns of infection . .. 58 1.3.6 Relationship of morbidity to intensity of infection ............. 58 1.3.7 Relationship of morbidity to mortality from infection. " 58 1.4 Clinical disease in humans (other than cancer) ................... .. 59 1.5 Treatment and control ....................................... " 61 1.5.1 Treatment.............................................. 61 1.5.2 Control ................................................ 62 2. Studies of cancer in humans . .. 63 2.1 Descriptive studies . .. 63 2.1.1 Schistosoma haematobium ................................... 63 2.1.2 Schistosoma mansoni ....................................... 66 2.1.3 Schistosoma japonicum . ; . 67 2.2 Case reports and case series .................................. .. 70 2.2.1 Schistosoma haematobium ................................... 71 2.2.2 Schistosoma mansoni ....................................... 72 2.2.3 Schistosoma japonicum . 73 2.3 Cohort study . .. 73 2.4 Case-control studies (with retrospective exposure assessment) ......... 74 2.4.1 Schistosoma haematobium ................................... 74 2.4.2 Schistosoma japonicum . 77 3. Studies of cancer in animais. .. 81 3.1 Infection wi th Schistosoma haematobium alone . .. 81 3.1.1 Mouse................................................. 81 3.1.2 Rat.................................................... 81 3.1.3 Hamster................................................ 82 3.1.4 Opossum............................................... 82 3.1.5 Nonhuman primate ...................................... 82 3.2 Infection with Schistosoma haematobium in combination with administration of known carcinogens .......................................... 83 3.2.1 2-Acetylaminofluorene.................................... 83 3.2.2 ortho-Aminoazotoluene................................... 84 3.2.3 N-Nitrosamines.......................................... 84 3.3 Infection with Schistosoma mansoni alone .. .. 84 3.3.1 Mouse................................................. 84 3.3.2 Mastomys natalensis ........................................ 85 3.3.3 Hamster................................................ 85 3.3.4 Nonhuman primate ...................................... 85 CONTENTS 3.4 Infection with Schistosoma mansoni in combination with administration of known carcinogens .......................................... 86 3.4.1 2-Amino-5-azotoluene.................................... 86 3.4.2 2-Naphthylamine and 2-acetylaminofluorene . .. 86 3.5 Infection with Schistosoma mansoni in combination with administration of compounds used or evaluated in the past as antischistosomal agents " 87 3.6 Infection with Schistosoma japonicum al one ........................ 87 3.7 Infection with Schistosoma japonicum in combination with administration of known carcinogens .......................................... 87 3.7.1 Dimethylaminobenzene................................... 87 3.7.2 2-Acetylaminofluorene.................................... 88 4. Other data relevant for evaluation of carcinogenicity and Its mechanisms . .. 88 4.1 Pathology of infection .......................................... 88 4.1.1 Humans................................................ 88 4.1.2 Experimental systems . " 92 4.2 Other observations relevant to the interpretation of carcinogenicity and mechanisms of carcinogenesis . .. 93 4.2.1 Humans................................................ 93 4.2.2 Experimental systems. .. 95 5. Summary of data reported and evaluation ............................. 96 5.1 Exposure data. .. 96 5.2 Human carcinogenicity data ..................................... 97 5.3 Animal carcinogenicity data ..................................... 99 5.4 Other relevant data ............................................ 99 5.5 Evaluation.................................................... 99 6. References ............................................. .. 100 Infection with liver flukes (Opisthorchis viverrini, O. jelineus and Clonorchis sinensis). 121 1. Exposure data ................................................... 121 1. 1 Structure and biology of liver flukes . .. 121 1.1.1 Taxonomy ............................................. 121 1.1.2 Structure.............................................. 121 1.1.3 Life cycle and biology of the adult worm . .. 122 1.1.4 Immune response to infection. .. 124 1.2 Methods for detection of infection . .. 124 1.2.1 Qualitative faecal examination for eggs .. .. 124 1.2.2 Quantitative faecal assessment of intensity of infection ........ 125 1.2.3 Serological tests for helminth-specific antibody and antigen .... 125 1.2.4 Intradermal tests. .. 126 1.3 Epidemiology of infection . .. 126 1.3.1 Geographical distribution ................................ 126 1.3.2 Risk factors for infection .... .. 130 CONTNTS 1.3.3 Age- and sex-related patterns of infection ................ " 132 1.3.4 Aggregation of infection ................................. 132 1.4 Clinical disease in humans (other than cancer) ..................... 134 1.5 Treatment and control .. " 135 2. Studies of cancer in humans . " 136 2.1 Descriptive studies . " 136 2.1.1 Opisthorchis viverrini . .. 136 2.1.2 Opisthorchis feIineus . .. 137 2.2 Case reports and case series .................................... 13 7 2.2.1 Opisthorchis viverrini . .. 137 2.2.2 Opisthorchis felineus . " 137 2.2.3 Clonorchis sinensis . .. 141 2.3 Case-control studies .......................................... 141 2.3.1 Opisthorchis viverrini . .. 141 2.3.2 Clonorchis sinensis . " 143 3. Studies of cancer in animais. " 144 3.1 Infection with Opisthorchis viverrini alone .............. " 144 3.2 Infection with Opisthorchis viverrini in combination with administration of known carcinogens ......................................... 146 3.2.1 N-Nitrosodimethylamine................................. 146 3.2.2 N-Nitrosodiethylamine................................... 148 3.2.3 N-Nitrosodihydroxydi-n-propylamine....................... 148 3.3 Infection with Opisthorchis viverrini in combination with administration of other modifyng factors . .. 149 3.4 Infection with Opisthorchis feIineus . .. 150 3.5 Infection with Clonorchis sinensis alone . .. 150 3.5.1 Rat................................................... 150 3.5.2 Cat................................................... 150 3.5.3 Dog.................................................. 150 3.6 Infection with Clonorchis sinensis in combination with administration of known carcinogens ......................................... 150 3.6.1 AfatoxIn Bi ........................................... 150 3.6.2 N-Nitrosodimethylamine................................. 151 3.6.3 2-Acetylaminofluorene................................... 152 4. Other data relevant for evaluation of carcinogenicity and its mechanisms . " 152 4.1 Pathology of infection ......................................... 152 4.1.1 Humans............................................... 152 4.1.2 Experimental systems. .. 155 4.1.3 Comparison of hum ans and experimental animais ............ 157 4.2 Other observations relevant to the interpretation of carcinogenicity and mechanisms of carcinogenesis . .. 157 4.2.1 Humans............................................... 157 CONTENTS 4.2.2 Experimental systems. .. 158 5. Summary of data reported and evaluation ............................ 159 5.1 Exposure data. .. 159 5.2 Human