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Handbook of Solvents - George Wypych - ChemTech - Ventech!

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1376 Nachman Brautbar<br />

ation in cytogenic changes between subjects suggested varying degrees <strong>of</strong> exposure to<br />

mutagenic agents. Brandt et al. 13 studied the effects <strong>of</strong> exposure to organic solvents and<br />

chromosomal aberrations. Ten patients had a history <strong>of</strong> daily handling <strong>of</strong> organic solvents<br />

for at least one year preceding the diagnoses <strong>of</strong> non-Hodgkin�s lymphoma. All have been<br />

exposed to a variety <strong>of</strong> solvents to include aromatic and aliphatic compounds. Forty-four<br />

patients for only a shorter period <strong>of</strong> time worked with organic solvents, and therefore served<br />

as the control group. There was a statistically significant increase in chromosomal changes<br />

in the exposed group compared to the non-exposed group. The authors suggested based on<br />

their results, that at diagnosis <strong>of</strong> non-Hodgkin�s lymphoma, patients with a history <strong>of</strong> significant<br />

occupational exposure to organic solvents tends to have a larger number <strong>of</strong> chromosomal<br />

aberrations in the lymphoma cells. Furthermore, certain aberrations may be<br />

characteristic for the exposed patients. They have concluded that the over representation <strong>of</strong><br />

certain chromosome aberrations in non-Hodgkin's lymphoma patients occupationally exposed<br />

to organic solvents supports the concept that these exposure may be relevant for the<br />

subsequent development <strong>of</strong> non-Hodgkin's lymphoma. Their data are in agreement with the<br />

studies published previously, indicating that workers handling organic solvents and other<br />

petroleum products have an increased frequency <strong>of</strong> chromosomal aberrations in lymphocytes.<br />

12,14,15,16 Indeed, association between exposure to solvents and other chromosomal<br />

changes in the cells have been studied by other investigators, describing chromosomal<br />

changes in acute non-lymphocytic leukemia. 3,17,18,19 In cultured cells, Koizumi 20 examined<br />

the effects <strong>of</strong> benzene on DNA syntheses in chromosomes <strong>of</strong> cultured human lymphocytes.<br />

They have shown an increased incidents <strong>of</strong> chromatoid gaps and breaks in cultures treated<br />

with benzene, compared to those who were untreated with benzene. They also showed<br />

changes in DNA metabolism in the form <strong>of</strong> inhibition <strong>of</strong> syntheses in those samples which<br />

were treated with benzene. This observation was confirmed by other investigators 21 who<br />

have shown an increased chromosomal aberrations in cultured human leukocytes exposed<br />

to benzene. From the in vitro to the in vivo experimental animals, it was shown that treated<br />

rats with benzene, were found to have increased chromosomal changes taken from the bone<br />

marrow as compared to the non-treated animals. 22 It was <strong>of</strong> interest that the degree <strong>of</strong> chromosomal<br />

changes that were induced by benzene, were similar to that induced by toluene 23<br />

(probably secondary to the benzene in toluene). Experimental rabbits treated with benzene<br />

also showed a significant amount <strong>of</strong> bone marrow chromosomal changes persisting up to 60<br />

days after the end dosing with benzene. 24<br />

A patient who has developed aplastic anemia after exposure to benzene, was shown to<br />

have significant chromatoid fragments. 25 A cytogenic study which was carried out later, 26<br />

on a patient who developed leukemia after 22 years <strong>of</strong> continuous exposure to a high concentration<br />

<strong>of</strong> benzene, showed that later in the process there were changes in 47 chromosomes<br />

in the bone marrow. Sellyei et al. 27 studied patients who developed pancytopenia<br />

after having been exposed for 18 months to benzene. Significant chromosomal changes<br />

were detected even 7 years after remission from the anemia and the presentation <strong>of</strong> leukemia.<br />

In line with these changes, Forni et al. 28 have studied 25 subjects with a history <strong>of</strong><br />

hematopoietic abnormalities and benzene exposure, and compared these to 25 matched controls.<br />

They have shown that 18 years after clinical and hematological symptoms chromosomal<br />

aberrations were increased as compared to the control group. In 1965, Tough et al. 29<br />

have studied chromosomes <strong>of</strong> workers exposed to benzene for periods varying from 1 to 18<br />

years. They have also shown a small but significant increase in chromosomal changes com-

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