immediately dangerous to life and health (idlh) concentration for benzene to 500 ppm. the current niosh definition for an idlh condition, as given in the niosh respirator selection logic, is one that poses a threat of exposure to airborne contaminants when that exposure is likely to cause death or immediate or delayed permanent adverse health effects or prevent escape from such an environment. the purpose of establishing an idlh value is (1) to ensure that the worker can escape from a given contaminated environment in the event of failure of the respiratory protection equipment and (2) is considered a maximum level above which only a highly reliable breathing apparatus providing maximum worker protection is permitted. in september 1995, niosh issued a new policy for developing recommended exposure limits (rels) for substances, including carcinogens. as benzene can cause cancer, niosh recommends that all workers wear special breathing equipment when they are likely to be exposed to benzene at levels exceeding the rel (10-hour) of 0.1 ppm. the niosh short-term exposure limit (stel – 15 min) is 1 ppm. american conference of governmental industrial hygienists (acgih) adopted threshold limit values (tlvs) for benzene at 0.5 ppm twa and 2.5 ppm stel. biomarkers of exposure several tests can determine exposure to benzene. benzene itself can be measured in breath, blood or urine, but such testing is usually limited to the first 24 hours post-exposure due to the relatively rapid removal of the chemical by exhalation or biotransformation. most people in developed countries have measureable baseline levels of benzene and other aromatic petroleum hydrocarbons in their blood. in the body, benzene is enzymatically converted to a series of oxidation products including muconic acid, phenylmercapturic acid, phenol, catechol, hydroquinone and 1,2,4-trihydroxybenzene. most of these metabolites have some value as biomarkers of human exposure, since they accumulate in the urine in proportion to the extent and duration of exposure, and they may still be present for some days after exposure has ceased. the current acgih biological exposure limits for occupational exposure are 500 μg/g creatinine for muconic acid and 25 μg/g creatinine for phenylmercapturic acid in an end-of-shift urine specimen. biotransformations even if it is not a common substrate for metabolism, benzene can be oxidized by both bacteria and eukaryotes. in bacteria, dioxygenase enzyme can add an oxygen to the ring, and the unstable product is immediately reduced (by nadh) to a cyclic diol with two double bonds, breaking the aromaticity. next, the diol is newly reduced by nadh to catechol. the catechol is then metabolized to acetyl coa and succinyl coa, used by organisms mainly in the citric acid cycle for energy production. the pathway for the metabolism of benzene is complex and begins in the liver. several enzymes are involved. these include cytochrome p450 2e1 (cyp2e1), quinine oxidoreductase (nq01 or dt-diaphorase or nad(p)h dehydrogenase (quinone 1)), gsh, and myeloperoxidase (mpo). cyp2e1 is involved at multiple steps: converting benzene to oxepin (benzene oxide), phenol to hydroquinone, and hydroquinone to both benzenetriol and catechol. hydroquinone, benzenetriol and catechol are converted to polyphenols. in the bone marrow, mpo converts these polyphenols to benzoquinones. these intermediates and metabolites induce genotoxicity by multiple mechanisms including inhibition of topoisomerase ii (which maintains chromosome structure), disruption of microtubules (which maintains cellular structure and organization), generation of oxygen free radicals (unstable species) that may lead to point mutations, increasing oxidative stress, inducing dna strand breaks, and altering dna methylation (which can affect gene expression). nq01 and gsh shift metabolism away from toxicity. nq01 metabolizes benzoquinone toward polyphenols (counteracting the effect of mpo). gsh is involved with the formation of phenylmercapturic acid. genetic polymorphisms in these enzymes may induce loss of function or gain of function. for example, mutations in cyp2e1 increase activity and result in increased generation of toxic metabolites. nq01 mutations result in loss of function and may result in decreased detoxification. myeloperoxidase mutations result in loss of function and may result in decreased generation of toxic metabolites. gsh mutations or deletions result in loss of function and result in decreased detoxification. these genes may be targets for genetic screening for susceptibility to benzene toxicity. molecular toxicology the paradigm of toxicological assessment of benzene is shifting towards the domain of molecular toxicology as it allows understanding of fundamental biological mechanisms in a better way. glutathione seems to play an important role by protecting against benzene-induced dna breaks and it is being identified as a new biomarker for exposure and effect. benzene causes chromosomal aberrations in the peripheral blood leukocytes and bone marrow explaining the higher incidence of leukemia and multiple myeloma caused by chronic exposure. these aberrations can be monitored using fluorescent in situ hybridization (fish) with dna probes to assess the effects of benzene along with the hematological tests as markers of hematotoxicity. benzene metabolism involves enzymes coded for by polymorphic genes. studies have shown that genotype at these loci may influence susceptibility to the toxic effects of benzene exposure. individuals carrying variant of nad(p)h:quinone oxidoreductase 1 (nqo1), microsomal epoxide hydrolase (ephx) and deletion of the glutathione s-transferase t1 (gstt1) showed a greater frequency of dna single-stranded breaks. biological oxidation and carcinogenic activity one way of understanding the carcinogenic effects of benzene is by examining the products of biological oxidation. pure benzene, for example, oxidizes in the body to produce an epoxide, benzene oxide, which is not excreted readily and can interact with dna to produce harmful mutations. inhalation outdoor air may contain low levels of benzene from automobile service stations, wood smoke, tobacco smoke, the transfer of gasoline, exhaust from motor vehicles, and industrial emissions. about 50% of the entire nationwide (united states) exposure to benzene results from smoking tobacco or from exposure to tobacco smoke. after smoking 32 cigarettes per day, the smoker would take in about 1.8 milligrams (mg) of benzene. this amount is about 10 times the average daily intake of benzene by nonsmokers. inhaled benzene is primarily expelled unchanged through exhalation. in a human study 16.4 to 41.6% of retained benzene was eliminated through the lungs within five to seven hours after a two- to three-hour exposure to 47 to 110 ppm and only 0.07 to 0.2% of the remaining benzene was excreted unchanged in the urine. after exposure to 63 to 405 mg/m3 of benzene for 1 to 5 hours, 51 to 87% was excreted in the urine as phenol over a period of 23 to 50 hours. in another human study, 30% of absorbed dermally applied benzene, which is primarily metabolized in the liver, was excreted as phenol in the urine. exposure from soft drinks under specific conditions and in the presence of other chemicals benzoic acid (a preservative) and ascorbic acid (vitamin c) may interact to produce benzene. in march 2006, the official food standards agency in united kingdom conducted a survey of 150 brands of soft drinks. it found that four contained benzene levels above world health organization limits. the affected batches were removed from sale. similar problems were reported by the fda in the united states. contamination of water supply in 2005, the water supply to the city of harbin in china with a population of almost nine million people, was cut off because of a major benzene exposure. benzene leaked into the songhua river, which supplies drinking water to the city, after an explosion at a china national petroleum corporation (cnpc) factory in the city of jilin on 13 november 2005. when plastic water pipes are subject to high heat, the water may be contaminated with benzene. genocide the nazi german government used benzene administered via injection as one of their many methods for killing.