Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
______________________________________________________________________________
06–JAN–1997 (93)
Remark: This is a textbook on occupational epidemiology. Chapters
are devoted to epidemiologic study design, conduct,
analysis, and interpretation. Examples of concepts are
illustrated with examples from the occupational
epidemiologyliterature.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (791)
Remark: This document presents results of a re–evaluation of the
carcinogenic potency of benzene. The authors develop a
mathematical model, consistent with a two–stage theory of
carcinogenesis, that takes variable exposure and latency
period into account. This model evolved by substituting in
a sequential manner more plausible and scientifically
defensible assumptions than those originally employed by
EPA(1985). Two factors have the most pronounced effect
upon
the alteration of the unit risk estimate. These are the
useof new statistical methods, primarily estimation
techniques,and the requirement that two molecules of a
benzene metabolite are needed to cause the transforming
event. Since exposure for the pliofilm cohort was most
probably underestimated and strong empirical and
theoretical
evidenceexists suggesting that the relationship between
benzene metabolites and the cell transforming event is
non–linear, the linear model should be viewed as a highly
conservative upper bound. The authors also present
evidence
that very distant benzene exposures (e.g. > 30 years before
disease) may be irrelevant in determining risk.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (1129)
Remark: Chromosome changes are studied in 21 cases of chronic
benzene poisoning (avg 6 years exposure; range 1–28 years),
both hypodiploid and hyperdiploid cells are significantly
increased. Controls comprised 20 healthy subjects. Among
the hypodiploid cells, deletion of Group C, E and G
chromosomes is observed. Analysis of hyperdiploid cells
reveals extra Group C and E chromosomes. The chromatid
gapsand breaks are mostly found in poisoned cases, but
fragmentsand minutes are less common. However, the finding
of aneuploidy may not indicate that aneuploidy is a
sensitive effect indicator of benzene because some subjects
had simultaneous or previous benzene haemopathy.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (300)
Appendix D: Benzene SIDS Dossier
– 708/957 –