Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An historical prospective study was undertaken of 262 men who had worked on an isopropyl alcohol plant and 446 men who had worked on two MEK dewaxing plants. All of the former have been traced, and only one man from the latter group was lost to follow-up. These studies linked occupational records with cause of death data for those who had died; the average follow-up was 15.5 years for the IPA plant workers and 13.9 years for those on the MEK dewaxing plants. For the IPA workers the observed deaths (26) were slightly above the expected (23.6), and there was a non-significant excess of deaths from neoplasms (0 = 9, E = 6.19). One person died from nasal cancer (E = 0.02, p = 0.017); though based on small numbers this finding is unlikely to be due to chance and agrees with the original hazard. For those who had worked on the MEK dewaxing plants the observed deaths (46) were below the expected (55.51) and there was also a slight deficiency of deaths from neoplasms (0 = 13, E = 14.26). When the seven sites of malignancy, which had been examined in a recent American study, were compared there were significantly more deaths from buccal cavity and pharynx cancers (0 = 2; E = 0.13; p = 0.008) and significantly fewer from lung cancer (0 = 1; E = 6.02; p less than 0.045). After reviewing the American and present results, it was concluded that there is no clear evidence of a cancer hazard in these workers, though further follow-up of larger numbers is necessary for a more precise estimate of the confidence limits of these findings.
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PMID:Mortality of workers on an isopropyl alcohol plant and two MEK dewaxing plants. 737 Jan 97

It is well recognized in industrial and environmental health that man is exposed simultaneously to more than one chemical. Interaction may take place in the metabolism of chemicals absorbed in combination or in sequence, especially when the chemicals share similar chemical structures. It is further conceivable that the extent of possible metabolic interaction will depend on the intensity of exposure. Moreover, the metabolism of chemicals may be modified by social habits, especially smoking. No systemic and comprehensive studies however have been reported in literature, possibly because the combinations of the chemicals are various and the exposure intensities vary greatly. In a survey of factories where workers were exposed to either benzene alone (20 ppm as GM and 86 ppm as max.), toluene alone (38 and 86 ppm) or a combination of both, the urinary levels of phenol (a metabolite of benzene) and hippuric acid (that of toluene) were significantly lower among the co-exposed workers as compared with the levels in workers who were exposed to either benzene or toluene alone (Inoue et al. (1988) Int. Arch. Occup. Environ. Health 60, 15-20). In contrast, a similar factory survey on the workers exposed to a mixture of toluene (3 ppm as GM) and xylenes (3 ppm for the sum of the 3 isomers) revealed that increments in urinary hippuric acid and methylhippuric acid levels were equal to the values after individual exposure (Huang et al. (1994) Occup. Environ. Med. 51, 42-46). Furthermore, the hippuric acid levels in the urine of workers exposed to toluene (18 ppm as GM) were not reduced by the co-exposure to MEK (16 ppm) or IPA (7 ppm) (Ukai et al. (1994) Occup. Environ. Med. 51, 523-529). In a human volunteer study with repeated exposures, metabolic interaction took place when the subjects were exposed to a combination of 95 ppm toluene and 80 ppm xylenes (mostly m-isomer), whereas no interaction was detected after the exposure to a combination of 50 ppm toluene and 40 ppm xylenes (Tardif et al. (1991) Int. Arch. Occup. Environ. Health 63, 279-284). From the observation it appears likely that due caution should be exercised when the intensity of the combined exposure is high but not necessarily so when the exposure is low. The threshold remains yet to be established.
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PMID:Exposure to complex mixtures: implications for biological monitoring. 761 72

Exposure monitoring by personal diffusive samplers, biological monitoring of toluene exposure by urinary hippuric acid determination, haematology, serum biochemistry for liver function, and a subjective symptom survey by questionnaire were conducted on 303 male solvent workers. They were exposed to a mixture of solvents including toluene (geometric mean 18 ppm), methyl ethyl ketone (MEK; 16 ppm), isopropyl alcohol (IPA; 7 ppm), and ethyl acetate (9 ppm). The intensity was mostly below unity using the additiveness formula based on current Japanese occupational exposure limits, but more than eight times unity at the maximum. The results were compared with the findings in 135 non-exposed male workers of similar ages. Haematology and liver function tests did not show any exposure related abnormality, and subjective symptoms were mostly related to central nervous system depression and local irritation. Further analysis suggested that the irritation effects were not related to exposure to MEK. Analysis of the relation between toluene exposure and hippuric acid excretion in urine showed that there was no metabolic interaction between MEK and toluene, or between IPA and toluene. Overall, therefore, it is concluded that there was no sign or symptom detected to suggest anything other than toluene toxicity, that there was no evidence to indicate any modification of toluene toxicity or metabolism due to coexposure, and that the additiveness assumption is reasonable for risk assessment for the combination of solvents under these exposure conditions.
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PMID:Occupational exposure to solvent mixtures: effects on health and metabolism. 795 76