Is 1,3-Propane sultone carcinogenic to humans?

1,3-Propane sultone (1,3-PS) is a directly alkylating, genotoxic and carcinogenic substance. In rats, 1,3-PS induces local and systemic tumors at multiple sites, including the mammary gland, intestine, hematopoietic system, kidneys, and the central nervous system (CNS), especially in the form of gliomas. In one particular company, 1,3-PS had been manufactured in limited amounts in the 1950s and 1960s, and for a few purposes until the 1970s. The number of individuals having been in contact with the compound occupationally comprised 55 in total. Data were obtained from this group with an open question of legal compensation regarding an occupational disease. Particular emphasis was placed on malignancies occurring among the occupationally exposed persons.

Gliomas of the brain are the main systemic tumour induced experimentally by 1,3-Propane sultone, so the occurrence of glioblastomas in previously exposed persons is evident. Of the cases observed, three intestinal malignancies were recorded. Also noteworthy was a case of duodenal carcinoma, usually a rare human malignancy. Two haematopoietic/lymphoid malignancies of different nature have been observed and one case of renal cell carcinoma. These malignancies observed in a cohort of people exposed to 1,3-Propane sultone are strikingly consistent with the expectations of existing animal studies. The current case studies indicate a long latency period (up to 30-40 years or more) after limited past time exposure.

As cerebral gliomas are a major type of tumor induced by 1,3-PS experimentally, the occurrence of two glioblastomas among the previously exposed persons was significant. Three intestinal malignancies were recorded within the cases observed. It is also noteworthy that there was one case of a duodenal carcinoma, which is normally a rare human malignancy. Two hematopoietic/lymphatic malignancies were observed, and there was one case of a renal cell carcinoma. The types of malignancies within a group of only 55 exposed persons are surprisingly consistent with the results from rodent studies. Data clearly indicate that 1,3-PS is carcinogenic in humans. Evidence indicates that 12 cases with various neoplasms were legally compensated within the period of 1985-2010 as an occupational disease, based on the "opening clause" of § 9 (2) SGB VII of legislation in Germany.

Genotoxicological investigation of 1,3-propane sultone was undertaken using human lymphocyte cultures as the test system. Concentrations >1 mM induced appreciable chromosomal aberrations, which increased proportionally to the dose or the duration of treatment. It was also observed that treatment administered at 45°C produced almost 3 times more abnormal cells than at 37°C. The chemical also produced a significantly higher frequency of SCEs.

References:

[1] HERMANN M BOLT; Klaus G. 1,3-Propane sultone as an extremely potent human carcinogen: description of an exposed cohort in Germany.[J]. Journal of Toxicology and Environmental Health-Part A-Current Issues, 2012. DOI:10.1080/15287394.2012.675305.

[2] HERMANN M. BOLT; Klaus G. 1,3-Propane sultone, an extremely potent experimental carcinogen: what should be expected in humans?[J]. Toxicology letters, 2004. DOI:10.1016/j.toxlet.2003.12.073.

[2] KAUL B L. Induction of chromosomal aberrations and sister chromatid exchanges by propane sultone in human lymphocytes in vitro[J]. Toxicology letters, 1985. DOI:10.1016/0378-4274(85)90022-0.

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