[' ', ' ', ' ', 'Personal', 'Notes', ' ', '891207', 'GSE/RPE', 'PAGE', '3', 'methylene', 'chloride', 'for', 'man,', 'there', 'are,', 'according', 'to', 'Green,', '2', 'path-', 'ways', 'considered', 'to', 'be', 'involved', 'in', 'the', 'metabolism', 'of', 'methylene', 'chloride.', 'These', 'are', 'the', 'cytochrome', 'P-450', 'pathway', 'with', 'high', 'sub-', 'strate', 'affinity', 'and', 'the', 'glutathione-S-transferase', 'pathway', 'with', 'low', 'affinity.', 'The', 'former', 'is', 'a', 'detoxifying', 'pathway', 'which', 'is', 'quickly', 'saturated.', 'At', 'high', 'doses,', 'the', 'substrate', 'is', 'mainly', 'metabolized', 'by', 'the', 'glutathione-S-transferase', 'pathway.', 'There', 'is', 'evidence', 'which', 'suggests', 'that', 'the', 'lung', 'and', 'liver', 'cancer', 'seen', 'in', 'exposed', 'mice', 'is', 'due', 'to', 'high', 'rates', 'of', 'metabolism', 'of', 'methylene', 'chloride', 'by', 'the', 'glutathione-S-transferase', 'pathway.', 'The', 'mechanism', 'by', 'which', 'metabo-', 'lites', 'from', 'this', 'pathway', 'induce', 'cancer', 'are', 'unknown.', 'The', 'existence', 'of', 'competitive', 'metabolic', 'pathways', 'depending', 'on', 'the', 'presence', 'and', 'activity', 'of', 'different', 'enzymes', 'would', 'also', 'provide', 'an', 'explanation', 'for', 'the', 'observed', 'species', 'differences', 'with', 'regard', 'to', 'the', 'car-', 'cinogenicity', 'of', 'this', 'chemical.', 'Interspecies', 'scaling', 'and', 'comparisons', 'with', 'respect', 'to', 'animal', 'biokinetics', 'were', 'also', 'addressed', 'in', 'the', 'talk', 'given', 'by', 'Ings', '(Slough,', 'U.K.).', 'He', 'said', 'that', 'an', 'interspecies', 'comparison', 'based', 'on', 'a', 'similar', 'metabolism', 'is', 'often', 'possible,', 'whereas', 'similar', 'biokinetics', 'were', 'nearly', 'impossible', 'to', 'find.', 'He', 'argued', 'that.', 'physiological', 'models', 'which', 'could', 'compensate', 'for', 'interspecies', 'differences', 'may', 'have', 'severe', 'limitations.', 'The', 'models', 'may', 'be', 'costly,', 'time', 'consuming,', 'and', 'prone', 'to', 'frequent', 'failures.', 'He', 'said', 'they', 'were', 'becoming', 'more', 'and', 'more', 'unwieldy', 'as', 'their', 'complexity', 'increases.', 'As', 'a', 'more', 'pragmatic', 'approach,', 'he', 'proposed', 'the', 'method', 'of', 'allometric', 'scaling,', 'in', 'which,', 'e.g-,', 'body', 'weight,', 'body', 'surface', 'area,', 'bone', 'thickness,', 'hepatic', 'blood', 'flow,', 'lifetime,', 'or', 'other', 'suitable', 'parameters', 'are', 'used', 'to', 'scale', 'interspecies', 'variations', 'with', 'regard', 'to', 'biokinetics.', 'Ings', 'gave', 'an', 'example', 'of', 'a', 'new', 'parameter', 'called', '"neoteny"', 'in', 'order', 'to', 'describe', 'the', 'interspecies', 'variations', 'in', 'metabolic', 'rates', 'which', 'can-', 'not', 'be', 'sufficiently', 'scaled', 'by', 'interspecies', 'clearance', 'differences.', '1789', 'oS286CEZ02']