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Results for “Epichlorohydrin”

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At least 19 recordsLinked to original sources

PubMed1977

Mutagenic effect of epichlorohydrin. II. Analysis of chromosomal aberrations in lymphocytes of persons occupationally exposed to epichlorohydrin.

A prospective cytogenetic study was conducted in 35 workers occupationally exposed to epichlorohydrin (ECHH). Blood samples for cytogenetic analysis were collected before the exposure (to serve as a control) and after the first and second years of ECHH exposure; the cultivation time was 56--58 h. Four slides from each worker were prepared, coded and two of them separately analysed in two collaborating cytogenetic laboratories. About 50 cells were analysed on each slide, giving a total 16,674 scored cells. The percentage of cells with chromosomal aberrations in blood samples of workers was 1.37 before exposure, 1.91 after the first year and 2.69 after the second year of exposure. The difference between percentages of aberrant cells before and after two years of occupational exposure was highly significant (P less than 0.0001). There was particularly observed an increase of chromatid and chomosomal breaks after exposure, simultaneously with an increased number of breaks per 100 cells. These results are concordant with previously reported cytogenetic data found in experiments with mammals and human cells in vitro.

Adult↗

PubMed1990

Acute inhalation exposure to epichlorohydrin transiently decreases rat sperm velocity.

The effect of inhaled epichlorohydrin on rat sperm motility characteristics was evaluated. Male F-344 rats were exposed to 100 ppm epichlorhydrin via inhalation for 4 hr in the morning of Day 0 and killed immediately and on Days 1, 2, 6, and 14 postexposure. Videotapes of cauda epididymal sperm were analyzed (300-350 sperm/sample) with a Hamilton Thorn motility analyzer (HTM-2000, Hamilton Thorn Research, Danvers, MA). Epichlorohydrin did not affect the percentage of motile sperm at any time. However, transient changes in sperm velocity were found. On Day 1 postexposure mean progressive (straight line) and mean path (smoothed curvilinear) velocity were significantly decreased to 80 and 85% of control, respectively. The progressive velocities of sperm from both control and treated rats were normally distributed, indicating a general effect of epichlorohydrin on all sperm as opposed to a more severe effect on a specific sperm subpopulation. Sperm velocity was not significantly affected at later times. Other endpoints (testis and epididymis weights, testicular spermatid counts, and cauda epididymal sperm reserves) were unaltered by epichlorohydrin. Thus, inhaled epichlorohydrin at 100 ppm produced specific, transient decreases in rat sperm velocity. Furthermore, computer-assisted sperm analysis was able to detect these relatively subtle, toxicant-induced changes in rat sperm velocity, demonstrating the utility of this technology in reproductive toxicology studies.

Administration, Inhalation↗

PubMedDate not supplied

The automated analysis of rat sperm motility following subchronic epichlorohydrin administration: methodologic and statistical considerations.

The automated analysis of sperm motion endpoints is potentially useful in identifying male reproductive toxicants and ultimately in predicting fertility in humans. The present study was designed to evaluate the automated analysis of rat sperm motility characteristics following subchronic administration of epichlorohydrin. This type of validation is a prerequisite for inclusion of sperm motion measurements in the process of reproductive risk assessment. In the present studies videotapes were made of cauda epididymal spermatozoa from Long-Evans rats, both untreated and treated with epichlorohydrin. From analysis of videotapes of control epididymal spermatozoa, the relationship of various sperm motion endpoints and settings of the CellSoft computer-assisted sperm motion analysis system (Cryo Resources, Ltd., New York, NY) is described. Optimal settings of the system for analysis of rat spermatozoa are detailed. Employing data from both control and epichlorohydrin-treated animals, a statistical methodology is described that evaluates: (1) the distributions of CellSoft generated sperm motion endpoints, (2) the correlations between these endpoints, and (3) techniques for detection of dose-related effects.

Animals↗

PubMed1991

Characterization of the epoxide hydrolase from an epichlorohydrin-degrading Pseudomonas sp.

An epoxide hydrolase was purified to homogeneity from the epichlorohydrin-utilizing bacterium Pseudomonas sp. strain AD1. The enzyme was found to be a monomeric protein with a molecular mass of 35 kDa. With epichlorohydrin as the substrate, the enzyme followed Michaelis-Menten kinetics with a Km value of 0.3 mM and a Vmax of 34 mumol.min-1.mg protein-1. The epoxide hydrolase catalyzed the hydrolysis of several epoxides, including epichlorohydrin, epibromohydrin, epoxyoctane and styrene epoxide. With all chiral compounds tested, both stereoisomers were converted. Amino acid sequencing of cyanogen bromide-generated peptides did not yield sequences with similarities to other known proteins.

Amino Acid Sequence↗

PubMed1991

The effect of deuterium labeling on the genotoxicity of N-nitrosodimethylamine, epichlorohydrin and dimethyl sulfate.

Deuterated and non-deuterated N-nitrosodimethylamine, epichlorohydrin and dimethyl sulfate were evaluated for the ability to induce DNA single-strand breaks in rat hepatocytes as measured by alkaline elution. Non-deuterated nitrosodimethylamine induced twice the amount of DNA-strand breaks as the deuterated form. No evidence of a deuterium isotope effect was seen for the direct-acting alkylating agents epichlorohydrin and dimethyl sulfate.

Animals↗

PubMed1979

Activation of Sepharose with epichlorohydrin and subsequent immobilization of ligand for affinity adsorbent.

The optimal conditions for the activation of Sepharose by epichlorohydrin and subsequent immobilization of ligands were investigated. Under the optimal conditions for activation, namely, 30% Sepharose-5% epichlorohydrin-0.4 M NaOH, 40 degrees C, 2 h, the maximum amount of epoxy group was introduced into Sepharose with low cross-linking. The absorbents obtained by using N-acetyl-D-glucosamine, tri-N-acetylchitotriose, and glycoprotein as a ligand exhibited no nonspecific adsorption and good permeability for the high molecular substance to be purified, and were stable in an alkaline solution. Solanum tuberosum agglutinin was specifically adsorbed on a tri-N-acetylchitotriose-Sepharose column and was quantitatively recovered by elution with 0.2 M ammonia solution. Furthermore, the column could be repeatedly used under these conditions without reduction of its capacity.

Acetylglucosamine↗

PubMed1986

Sensitization to epichlorohydrin and epoxy system components.

In an epoxy resin manufacturing plant, 26 of 228 (11.4%) workers had work-related eruptions; 19 were patch tested. The test series consisted of chemicals used in the manufacturing process, a standard battery and some other sensitizers. The prevalence of sensitization to epichlorohydrin and/or epoxy resins in the whole group was 6.1%. A relatively high prevalence (3.5%) of epichlorohydrin sensitization was found. 10 cases of sensitization to liquid epoxy resin (MW about 385) were observed, in 7 cases combined with allergy to solid epoxy resin (MW 980). Sensitization to Bisphenol A was not seen.

Adult↗

PubMed1978

Tissue distribution and excretion of 14C-epichlorohydrin in male and female rats.

The tissue distribution and excretion of 14C-epichlorohydrin was studied in both male and female rats following an oral dose of 10 mg/kg. Organs containing the highest concentrations of radioactive label per unit weight were the kidneys, liver, pancreas, ann spleen. With the exception of the pancreas, these are the same organs in which epichlorohydrin-induced pathologic changes have been reported by a number of investigators, indicating a direct correlation between tissue levels and target organ toxicity. The principal route of excretion was via the kidneys, 38-40% of the dose appearing in the urine during the 72 hour period of study. Fecal excretion was relatively insignificant, representing less than 4% of the administered dose. It was found that 18-21% of the administered dose appeared as 14CO2 in the expired air, the majority being excreted in the first 4 hours, suggesting a rapid and extensive biotransformation of the compound.

Animals↗

PubMed1976

Mutagenic effect of epichlorohydrin. I. Testing on human lymphocytes in vitro in comparison with TEPA.

The mutagenic effect of the monofunctional alkylating agent epichlorohydrin was tested on human lymphocytes in vitro and compared with the mutagenic effect of the polyfunctional alkylating agent TEPA. The same descending concentrations were used for both mutagens: 10(-4), 10(-5), 10(-6), 10(-7), 10(-8), 10(-9), 10(-10) and 10(-11) M. Similar types of chromosomal aberration were found, but the effect of ECHH was 4-5 times lower than that of TEPA. ECHH was found to be a mild mutagen. Different timing of mutagen application was used in the course of 56 h of cultivation of lymphocytes: 1 h before cultivation, one hour between the 24th and 25th h of cultivation and 24 h before the end of cultivation. From the results presented we conclude that the application of the chemical for the last 24 h of human lymphocyte cultivation should be recommended for routine mutagenicity testing.

Azirines↗

PubMed1976

Banding technique used for the detection of chromosomal aberrations induced by radiation and alkylating agents TEPA and epichlorohydrin.

Blood samples from two healthy donors were exposed, (1) to 200 R of X-rays in G0 and G1S phases of the cell cycle, and (2) to epichlorohydrin 10(-6) M and TEPA 10(-4) M in G0 and/or in G1S and G2 phases. Part of the cells was processed for chromosome studies conventionally and the other part by the trypsinization banding technique. Detailed chromosomal analysis showed that, after irradiation, 38.2% of aberrations in G0 and 18.7% in G1S phases escaped cytogenetic detection when the conventional technique was used. After exposures to TEPA and ECHH, 10.9% of aberrations were undectable in G0 and 3.3% in G1S and G2 phases. The distribution of chromosome breaks was non-random both after irradiation and after exposure to alkylating agents. However, it differed according to the mutagen used. Some chromosomal segments were broken significantly more frequently than the others (e.g. 9q12), some were resistant to breakage (e.g. the whole Y chromsome). The segments represented by G-negative bands were more fragile than the G-positive and G-variable segments.

Chromosome Aberrations↗

PubMed1979

Cytogenetic investigation of occupational exposure to epichlorohydrin.

Cytogenetic evaluation of peripheral lymphocytes from 93 workers currently exposed to epichlorohydrin has revealed an increase in aberration rates as compared to that of a 75-person group seen for preemployment examination. Statistically significant differences were found in the distribution of individuals with chromatid breaks, chromosome breaks, severely damaged cells, and total abnormal cells. These results confirm the observations of Kucerova et al. in a similar occupational group.

Adult↗

PubMed1990

Enhancement of cyclosporin production in a Tolypocladium inflatum strain after epichlorohydrin treatment.

Following treatment of conidia of the cyclosporin producer fungus, Tolypocladium inflatum, with 0.15 M epichlorohydrin, strain M6 was isolated. The new strain exhibited a similar growth rate to the parent organism but more extensive conidiation and several-fold higher overall cyclosporin production. Strain M6 reached titres of 318 mg l-1 cyclosporin A in agar cultures, whereas in liquid medium it produced 140 mg l-1 cyclosporin A and 68 mg l-1 cyclosporin C. It also maintained a steady volumetric productivity of 0.48 mg l-1 h-1 cyclosporin A over 2 weeks of submerged cultivation in maltose-based semisynthetic medium. The new strain holds potential for improved cyclosporin production due to the superior titres and demonstrated capacity to sustain elevated production of cyclosporin for periods greater than the wild type.

Chlorohydrins↗

PubMed1989

Effects of epichlorohydrin on male and female reproduction in Long-Evans rats.

Male and female Long-Evans rats were treated with epichlorohydrin (ECH) by oral gavage (males: 12.5, 25, and 50 mg/kg/day; females: 25, 50, and 100 mg/kg/day) for 21 and 14 days, respectively, prior to mating trials with untreated animals. Treated females were further dosed until delivery. Fertility was assayed in the high-dose males only and was found to be totally impaired. No measured parameters of female reproduction were changed relative to controls. Treated males showed normal copulatory behavior. Sperm morphology and percentage motile sperm were not statistically different from control values in both ejaculated and cauda epididymal samples from ECH-treated animals. The number of sperm in ejaculates was normal while cauda epididymal sperm count was slightly decreased in males at the 50 mg ECH/kg dose level. Mean curvilinear velocity, straight-line velocity, and amplitude of lateral head displacement of cauda epididymal sperm were significantly reduced by ECH at 12.5 mg/kg/day and above. Sperm track linearity was also reduced, but only at 50 mg/kg/day. Beat/cross frequency of sperm was significantly increased at 12.5 mg/kg/day and above. All of the above sperm motion parameters showed dose-dependent trends. These effects are consistent with the spermatozoal metabolic lesions reported for alpha-chlorohydrin, a metabolite of ECH.

Animals↗

PubMed1988

Occupational sensitization to epichlorohydrin and epoxy resin.

Sensitization to epichlorohydrin (ECH) is reported in 6 patients with occupational contact allergy. In 2 cases, an isolated positive test to ECH was found. In the remaining 4 cases, concomitant positive reactions were seen to "ICDRG epoxy resin" (MW 385) and to liquid epoxy resin (MW 370). Allergy to bisphenol A was not seen in the patients. 5 patients worked in an epoxy resin plant. Adequate preventive measures to avoid skin contact with ECH are required to prevent ECH sensitization becoming a more serious industrial hazard.

Adult↗

PubMed1990

Mortality of workers potentially exposed to epichlorohydrin.

An epidemiological study was undertaken to determine whether the animal carcinogen, epichlorohydrin (ECH), produces cancer in man. A total of 863 workers with probable exposure to ECH at two chemical plants during 1948-65 were followed up for deaths up to 1983. Twenty years or more after first exposure the all cancer SMR was 112.2 (22 deaths) and the SMR for leukaemia was 500.0 (three deaths), which is statistically significant. All cancer, leukaemia, and most other causes of death were related to estimated levels of exposure to ECH, except violence. The most consistent (both plants) relation was between exposure level and heart disease. Overall, the heart disease SMR 20 years or more after first exposure was 39.2 (five deaths) for low exposure and 105.4 (17 deaths) for high exposure. Limited evidence of a cardiovascular disease relation to ECH production in one other epidemiological study is supported by this study. Allyl chloride used in the production of ECH may play a part. The relation of heart disease and exposure does not appear to be an artifact, although the fact that many other causes of death were also related to exposure argues against a causal relation.

Cardiovascular Diseases↗

PubMed1990

Morbidity prevalence study of workers with potential exposure to epichlorohydrin.

This study examined the morbidity experience from 1981 to 1988 of two cohorts (Shell cohort and Enterline cohort) of workers who had potential exposure to epichlorohydrin (ECH). The morbidity prevalence data for this study were extracted from the morbidity section of the Shell health surveillance system which included all illness and absence records in excess of five days. For both cohorts, the standardised morbidity ratios (SMRs) for all causes and all neoplasms were similar to an internal comparison group. There were no increases in heart disease morbidity for the Shell cohort (SMR = 97) or the Enterline cohort (SMR = 90). The SMRs for heart disease in the lower exposure group of the Shell cohort were 101 and 93 for the corresponding Enterline cohort. They were 92 and 87, respectively, in the higher exposure group. The increased risk of heart disease mortality reported by Enterline et al in workers more heavily exposed to ECH was not confirmed in this morbidity study. Morbidity from skin and subcutaneous tissue disorders, however, was found to be increased significantly in the Shell cohort. The SMR was 98 for the lower exposure group and 195 for the higher exposure group. A review of the original morbidity reports for each case suggested that factors unrelated to exposure to ECH such as the physical demands of a particular job, amount of time outside--for example, exposure to poison ivy--and other underlying medical conditions may be of greater importance than exposure to ECH.

Adult↗

PubMedDate not supplied

[Specific features of the pathogenesis of epichlorohydrin eye burns and their treatment (an experimental clinico-morphological study)].

Specific features in the pathogenesis of ocular burns with a solution of an organic product, epichlorohydrin, are analyzed. Abnormalities in the vascular system anterior portion were revealed, related to the toxic effect of the agent on tissue vessels and to enhanced permeability and involvement of not only the cornea, but (and even more so) of the iris, where necrotic changes and hemorrhages eventuating in iris atrophy were detectable. Contrykal (hordox) therapy promoted a drastic inhibition of leukocytic and lymphocytic migration into burnt tissue, this resulting in a month in the formation of gentle cicatricial tissue with negligible residual inflammatory infiltration in the burn wound. Iris changes still persisted, since the drug appeared to have no effect on this process.

Animals↗

PubMedDate not supplied

Correlation of sperm motion parameters with fertility in rats treated subchronically with epichlorohydrin.

We investigated the relationship between fertility and sperm motin endpoints in rats treated subchronically with the male reproductive toxicant, epichlorohydrin (ECH). Male rats were given ECH orally for 23 days at dosages of 0, 6.25, 12.5, or 25 mg/kg/day. They were mated twice (at 19 and 22 days) to estimate fertility by (1) detection of fertilized ova (presence of sperm head and tail or two pronuclei) 18 hours after mating and by (2) counting implants on day 14 of gestation. Both indices showed dose-related reductions (P less than 0.001). Motion parameters of cauda epididymal sperm were assessed using the CellSoft computer-assisted sperm motion analysis (CASA) system after the rats were asphyxiated on day 25. Curvilinear velocity, straight-line velocity, linearity, and amplitude of lateral head displacement were reduced in a dose-related manner. The fertility indices, percent fertilized ova, and percent implantation on day 14 of gestation were correlated significantly (r = 0.68; P = 0.0001). The following motion parameters were also correlated significantly with fertility (P less than 0.0003; r1 = percent fertilized ova and r2 = percent implantation): linearity (r1 = 0.42; r2 = 0.40), amplitude of lateral head displacement (r1 = 0.54; r2 = 0.48), curvilinear velocity (r1 = 0.53; r2 = 0.50), straight-line velocity (r1 = 0.55; r2 = 0.50), and percent motile sperm (r1 = 0.42; r2 = 0.32). These results suggest a relationship between toxicant-induced reductions in sperm motion and fertility.

Animals↗