Abstract  BARBER(1 934) reported the death of five factory workers, who were employed in processes involving the use of dioxan. The principal lesions found at autopsy were a central zonal necrosis of the liver and a symmetrical necrosis of the cortex of the kidneys. The similarity of the renal condition to that found in the cortical necrosis of pregnancy first prompted the present investigation.

Abstract  The present study investigated the toxicokinetics of 1,4-dioxane in humans exposed at rest and during physical stress. Eighteen volunteers were divided into three groups of six individuals each, who were exposed separately in three experiments to 20 ppm (73 mg/m(3)) 1,4-dioxane for 8 h. The first group was exposed at rest (Experiment 1), whereas the other groups performed exercises on a bicycle ergometer for 10 min every hour, corresponding to a physical exercise of 50 W (Experiment 2) and 75 W (Experiment 3), respectively. Blood samples were collected after 4 and 8 h, and all urine samples were collected over 24 h. The samples were analysed for 1,4-dioxane and its metabolite 2-(2-hydroxyethoxy)acetic acid (HEAA). The amount of urinary-eliminated HEAA increased during exposure and showed its maximum 9.8 ± 1.9 h after the beginning of exposure. The levels of 1,4-dioxane in blood and urine, however, barely rose above the limit of detection. Depending on the physical stress of the volunteers, the maximum elimination rate of HEAA in urine was significantly increased with 23.2 ± 7.7, 30.4 ± 7.2 and 41.8 ± 23.8 mg/h for Experiments 1, 2 and 3, respectively. Likewise, the cumulative HEAA excretion over 24 h increased with increasing physical stress; 53 ± 15 % of the theoretical inhaled 1,4-dioxane dose was excreted as HEAA in urine during the first 24 h. The average maximum level of HEAA ranged between 378 and 451 mg/g creatinine and increased with the applied physical stress. The half-life of HEAA was found to be 3.4 ± 0.5 h. Twenty-four hours after the beginning of the exposure, 31-51 mg HEAA/g creatinine were still detected in urine, indicating only a low accumulation of the metabolite during a working week. The study results revealed an increasing effect of the applied physical stress on the total eliminated amounts of HEAA as well as on the maximum HEAA levels at the end of exposure. For the estimation of biomonitoring equivalents to occupational exposure limits, this effect should be taken into account.

Abstract  Information on the acute effects associated with the handling of 1,4-dioxane is sparse. Our aim was to evaluate the acute effects of 1,4-dioxane vapours. In a screening study, six healthy volunteers rated symptoms on a visual analogue scale (VAS), while exposed to stepwise increasing levels of 1,4-dioxane, from 1 to 20 ppm. The initial study indicated no increased ratings at any of the exposure levels; we decided to use 20 ppm (72 mg/m3) as a tentative no observed adverse effect level (NOAEL). In the main study, six female and six male healthy volunteers were exposed to 0 (control exposure) and 20 ppm 1,4-dioxane vapour, for 2 hours at rest. The volunteers rated 10 symptoms on VAS before, during, and after the exposure. Blink frequency was monitored during exposure. Pulmonary function, and nasal swelling, was measured before, and at 0 and 3 hours after exposure. Inflammatory markers in plasma (C-reactive protein, and interleukin-6) were measured before and at 3 hours after exposure. In conclusion, exposure to 20 ppm 1,4-dioxane for 2 hours did not significantly affect symptom ratings, blink frequency, pulmonary function, nasal swelling, or inflammatory markers in the plasma of the 12 volunteers in our study.

Abstract  This public health statement tells you about 1,4-dioxane and the effects of exposure to it. The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for long-term federal clean-up activities. 1,4-Dioxane has been found in at least 31 of the 1,689 current or former NPL sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility exists that the number of sites at which 1,4-dioxane is found may increase in the future as more sites are evaluated. This information is important because these sites may be sources of exposure, and exposure to this substance may be harmful. When a substance is released either from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance, or by skin contact. If you are exposed to 1,4-dioxane, many factors will determine whether you will be harmed. These factors include how much (the dose), how long (the duration), and how you come in contact with it. You must also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and state of health.

Abstract  As a result of recent interest in the carcinogenic effect of dioxane, a mortality study was conducted on employees exposed to this compound at a major chemical company plant. Standard follow-up techniques were used to ascertain the vital status of a total of 165 employees ever exposed to dioxane since 1954. Observed deaths from overall cancer were not significantly different from the expected number of deaths. The observations were based on small numbers of deaths of employees who were apparently exposed at low levels and for relatively short exposures.

Abstract  A.M.A. archives of industrial health e field[29]: 1,4-Dioxane

Abstract  Sensory response limits for 18 industrial solvents were determined. An average of 12 persons were used for each solvent test. The cohort was exposed to solvent vapors for 15 minutes. Air vapor concentrations producing irritation to ears, eyes, nose, or throat were determined. The solvents tested included ketones, alcohols, esters, ethers, and several miscellaneous solvent. Seven of the solvents had previously suggested maximum allowable limits. In each case, new lower sensory limits were observed. Methyl-isobutyl-ketone (108101) was found to have a sensory limit of 100 parts per million (ppm), one half the previously suggested limit. Acetaldehyde (75070) in concentrations of 50ppm produced eye irritation in a majority of the cohort. A limit of 200ppm was formerly thought appropriate. Diisobutylcarbinol (108827) produced eye irritation at less than 5ppm. No limit had been determined previously. Other solvents whose limits were determined to be lower than those previously suggested were isophorone (78591), mesityl-oxide (141797), isopropyl-acetate (108214), isopropyl-ether (108203), and dioxane (123911). Over 50 percent of the solvents tested had no previous maximum limits associated with them. The authors suggest that this new data be used as guidelines for new maximum allowable limits.