Assessment of long-term health risks after accidental exposure using haemoglobin adducts of epichlorohydrin.

On September 9th, 2002, two goods trains collided in Bad Münder, Lower Saxony, causing the release of more than 40 metric tonnes of epichlorohydrin (1-chloro-2,3-epoxypropane) into the environment. A human biomonitoring study was performed to evaluate the accidental exposure to epichlorohydrin and to assess the possible long-term, i.e. carcinogenic health effects. This was done on the basis of a biochemical effect monitoring using the N-(3-chloro-2-hydroxypropyl)valine and the N-(2,3-dihydroxypropyl)valine haemoglobin adducts of epichlorohydrin in blood to respond to missing ambient monitoring immediately after the crash. N-(3-chloro-2-hydroxypropyl)valine adduct levels above the LOQ (25 pmol/g globin) ranged from 32.0 to 116.4 pmol/g globin in 6 out of 628 samples. The N-(2,3-dihydroxypropyl)valine adduct was not detected above the LOD (10 pmol/g globin) in any of the blood samples. Based on the quantified N-(3-chloro-2-hydroxypropyl)valine adduct values, the body doses after two days of exposure were estimated to be in the range of 1.7-6.2 nmol/kg body weight. The reverse estimation of the external exposure leads to cumulative additional lifetime cancer risks ranging from 2.61×10(-8) to 9.48×10(-8). The estimated excess lifetime cancer risks have to be assessed as extremely low. Our biomonitoring study facilitated the dialogue between individuals and groups concerned and authorities, because suspected or occurred exposures and risks to human health could be quantified and interpreted in a sound manner.

A method for the simultaneous determination of mercapturic acids as biomarkers of exposure to 2-chloroprene and epichlorohydrin in human urine.

We developed and validated an analytical method for the simultaneous determination of several chlorine and non-chlorine containing mercapturic acids in urine as specific metabolites of the hazardous chemicals 2-chloroprene and epichlorohydrin. The method involves an online column switching arrangement for online solid phase extraction of the analytes with subsequent analytical separation and detection using LC-MS/MS. The developed method enables for the first time the determination of Cl-MA-I (4-chloro-3-oxobutyl mercapturic acid), Cl-MA-II (4-chloro-3-hydroxybutyl mercapturic acid), Cl-MA-III (3-chloro-2-hydroxy-3-butenyl mercapturic acid) and HOBMA (4-hydroxy-3-oxobutyl mercapturic acid) as potential biomarkers of 2-chloroprene in urine. Additionally, CHPMA (3-chloro-2-hydroxypropyl mercapturic acid) as a specific metabolite of epichlorohydrin in urine and DHBMA (3,4-dihydroxybutyl mercapturic acid) can be determined. The analytical method proved to be both sensitive and reliable with detection limits ranging from 1.4 µg/L (for Cl-MA-III) to 4.2 µg/L (for HOBMA). Intra- and interday imprecision was determined to range from 4.7 to 11.8%. Due to the good accuracy and precision and the low limits of detection the developed method is well suited for application in biomonitoring studies in order to determine occupational exposure to 2-chloroprene and epichlorohydrin.

Geographical distribution of acute symptoms after a train collision involving epichlorohydrin exposure.

In September 2002, two freight trains collided in a northern German town. The inhabitants were potentially exposed to the probable human carcinogen epichlorohydrin. As no objective data on the level of exposure were available, we aimed to assess the geographical distribution of acute symptoms among local residents and subjects occupationally involved in the accident (e.g., firemen). A random sample of 932 adult local residents and 342 occupationally involved subjects were invited to answer a mail-in questionnaire. The main outcome measures were self-reported acute symptoms potentially associated with combustion products (e.g., irritation of the eyes, nose, or throat) and stress-related nonspecific symptoms. The main location during the first 26 h after the accident served as exposure proxy. For occupationally involved subjects, the time spent at the accident site was also used. The overall prevalence of symptoms potentially associated with combustion products was 9.8% for residents and 25.4% for occupationally involved subjects. After adjustment, subjects whose main location was close to the accident site had an increased risk for such symptoms. Among occupationally involved subjects the risk increased with duration at the accident site. Neither main location nor time at the accident site was significantly associated with non-specific symptoms. We could provide an example for designing and carrying out an epidemiologic study shortly after a local accident with potential public health impact. We could define parts of the population at increased risk for symptoms potentially specific for the exposure under study.

Exposure to epichlorohydrin and central nervous system neoplasms at a resin and dye manufacturing plant.

This study evaluated the relationship between central nervous system neoplasms (CNSN) and exposure to epichlorohydrin (ECH) among 11 CNSN cases and 44 controls who were members of a cohort of chemical workers. Information on area of employment and potential exposure to ECH was obtained from plant personnel and medical records and from interviews with long-term employees. An elevated odds ratio (OR) for CNSN was observed for subjects who worked in the epoxy resin process line (OR = infinity, 95% confidence interval [CI] = 1.2-infinity), and in the production of anthraquinone intermediate dyes (OR = infinity, 95% CI = 1.7-infinity) and azo dyes (OR = 3.6, 95% CI = 0.6-41). Routine potential exposure to ECH was associated with CNSN (OR = 4.2, 95% CI = 0.7-26). Dose-response relationships were found with duration and with cumulative routine potential exposure to ECH (p = .11 and .08, respectively). Acute exposure to ECH requiring treatment at the plant infirmary also was associated with subsequent CNSN (OR = infinity, 95% CI = 1.5-infinity).

Fulminant hepatitis following exposure to dichlorohydrin--report of two cases.

A 34-year-old man suffered from fulminant hepatitis after cleaning a tank in which there were traces of dichlorohydrin. In spite of daily plasma exchanges, he died 10 days after exposure. A 27-year-old man with much lighter exposure showed only slight liver dysfunction. This is the first report of lethal injury following exposure to dichlorohydrin.

[Organ and tissue cyclic adenosine-3', 5'-monophosphate during the process of the body's adaptation to extreme factors]. / Tsiklicheskii adenozin-3'5'-monofosfat v organakh i tkaniakh v protsesse adaptatsii organizma k ekstremal'nym vozdeistviiam.

Various by nature extreme factors (hypoxic hypoxia, CO intoxication, chemical influence, noise and hypokinesia) caused similar changes in cAMP levels in different organs of albino rats (liver, the great cerebral hemispheres, heart). There was a significant increase in cAMP concentrations during the first stages of the influence and a progressive fall when the influence was continued. This fall was particularly expressed when the extreme factors used were of marked intensity. The authors consider the universality of the ascertained regularity to be a reflection of one of the central adaptive mechanisms of cell and the organism as a whole.