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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↗

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↗

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↗

PubMed1975