Zajdela F, Croisy A, Barbin A, Malaveille C, Tomatis L, & Bartsch H (1980) Carcinogenicity of chloroethylene oxide, an ultimate reactive metabolite of vinyl chloride, and bis(chloromethyl)ether after subcutaneous administration and in initiation-promotion experiments in mice.
These differences are most likely attributed to relative rates of absorption versus metabolic conversion and the many non-specific reactions in which chloroacetaldehyde would be expected to be involved in the gastrointestinal tract and on the skin.
Evidence was presented suggesting that some of the carbon monoxide arose from the oxidative metabolism of bromoform to a dibromocarbonyl and subsequent reactions with GSH.
Greater lipophilicity and reactivity of this compound or its metabolites (i.e., the bromochlorocarbonyl metabolite) may also prevent it from reaching critical target sites.
This compares with a Vmax value for chloroform of 6.8 mg/h (Corley et al., 1990), providing additional evidence for more rapid metabolism and greater generation of reactive intermediates from BDCM than from chloroform.
Although it is often claimed that the whites invented scalping as evidence of having killed an Indian, words for ceremonial scalping (as well as other forms of dismemberment) existed in many Indian languages prior to the white man's arrival.
To the extent they are metabolized, the principal reactions of the trihaloacetic acids occur in the microsomal fraction, whereas more than 90% of the dihaloacetic acid metabolism, principally by glutathione transferases, is observed in the cytosol.
In rats, P450-mediated metabolism of BDCM (Figure 1) is believed to proceed by the same two pathways established for chloroform: oxidation with phosgene the proposed active metabolite, and reduction with the dichloromethyl free radical proposed as the reactive product (Tomasi et al., 1985; IPCS, 1994; Gao et al., 1996).
Metabolic activation to reactive intermediates is required for THM toxicity, and the three brominated species are all metabolized more rapidly and to a greater extent than chloroform.
Most investigations of THM metabolism and reaction mechanisms have focused on chloroform, and a detailed review of chloroform biotransformation has been published recently (IPCS, 1994).
1.2 Kinetics and metabolism in laboratory animals and humans 1.2.1 Disinfectants Residual disinfectants are reactive chemicals that will react with organic compounds found in saliva and stomach content, resulting in the formation of by-products.
Metabolism was characterized directly by measuring production of bromide ion, which is liberated by all known biotransformation reactions of BDCM, and indirectly by gas uptake techniques.
intraperitoneal IPCS International Programme on Chemical Safety JECFA Joint FAO/WHO Expert Committee on Food Additives LD50 median lethal dose LDH lactate dehydrogenase LDL low-density lipoprotein LOAEL lowest-observed-adverse-effect level MA 3,4-(dichloro)-5-hydroxy-2(5H)-furanone MBA monobromoacetic acid/monobromoacetate MCA monochloroacetic acid/monochloroacetate MNU methylnitrosourea MOR mortality odds ratio MRI magnetic resonance imaging MTBE methyl tert-butyl ether MX 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone NADP nicotinamide adenine dinucleotide phosphate NOAEL no-observed-adverse-effect level NOEL no-observed-effect level NOM natural organic matter NTP National Toxicology Program (USA) 8-OH-dG 8-hydroxy-2-deoxyguanosine OR odds ratio PAS periodic acid/Schiff's reagent PBPK physiologically based pharmacokinetic model PFBHA O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine p Ka log acid dissociation constant PPAR peroxisome proliferator activated receptor PPRE peroxisome proliferator responsive element RR relative risk SCE sister chromatid exchange SD standard deviation SDH sorbitol dehydrogenase SE standard error SGOT serum glutamate-oxaloacetate transaminase SGPT serum glutamate-pyruvate transaminase SMR standardized mortality ratio SSB single strand breaks TBA tribromoacetic acid/tribromoacetate TBARS thiobarbituric acid reactive substances TCA trichloroacetic acid/trichloroacetate TCAN trichloroacetonitrile TCPN trichloropropanone TDI tolerable daily intake TGF transforming growth factor THM trihalomethane TOC total organic carbon TOX total organic halogen TPA 12- O-tetradecanoylphorbol-13-acetate UDS unscheduled DNA synthesis UV ultraviolet UVA254 UV absorbance at 254 nm Vmax maximum rate of metabolism WHO World Health Organization 1.
As a consequence, an exaggeration of those effects of chloral hydrate that are secondary to metabolism through reactive intermediates might be expected (Hoz et al., 1991).