THE SCIENTIFIC BACKGROUND
This is not the place for a thorough discussion of the issue of carcinogenicity, but
in short a set of early Swedish reports (6-8) indicated a cancer risk and initiated
several studies from different countries during the last decade. Many, but not all,
of these subsequent studies provided epidemiological evidence of an increased
risk of soft-tissue sarcoma and malignant lymphoma in persons exposed to
phenoxy herbicides, chlorophenols, or their contaminating dioxins and
dibenzofurans (9, 10). It is especially noteworthy that two case-control studies
in the United States have also found an association between exposure to the
phenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and non Hodgkin's
lymphoma (11, 12).
Two cohort studies also support the association between exposure to the
aforementioned chemicals and soft-tissue sarcoma (13, 14). Some additional
case-control studies from Sweden corroborate the earlier Swedish indications of
a carcinogenic effect in humans (15-19). Furthermore, a meta-analysis of four of
the Swedish case-control studies on soft-tissue sarcoma (6, 7, 15, 16)
demonstrated a dose-dependent risk associated with exposure ta phenoxyacetic
acids or the chemically related chlorophenols contaminated with TCDD as well
as other dioxins (20).
A general carcinogenic effect by TCDD-that is, an effect on all cancer sites
combined-also seems likely based on three cohort studies (13, 21-23), as
concluded in the evaluation by IARC (1). These findings corroborate earlier
observations (24-26) and might be explained by a TCDD contamination of the
pesticides used.
A follow-up of the population in Seveso, which was exposed to TCDD due to a
chemical plant accident in 1976, shows an increased incidence of soft-tissue
sarcoma and hematopoietic malignancies (i.e., a priori expected tumor types)
and hepatobiliary cancer (27).
The report by the Institute of Medicine of the U.S. National Academy of
Sciences was initially published in 1993 (5) and has recently been updated.
It concluded that there is sufficient evidence for an association between
exposure to Agent Orange, including the phenoxy herbicides 2,4-D and
2,4,5trichlorcphenoxyacetic acid (2,4,5-T) and soft-tissue sarcoma,
non-Hodgkin's lymphoma, and Hodgkin's disease (28). As mentioned above, in
our Swedish studies these tumor types were associated with exposure to
phenoxy herbicides.
Finally, toxicological studies have been supportive insofar as they show that of
the dioxins, TCDD and two congeners of hexachlorinated dioxins are
carcinogenic in experimental animals (29-34).
This is not the place for a thorough discussion of the issue of carcinogenicity, but
in short a set of early Swedish reports (6-8) indicated a cancer risk and initiated
several studies from different countries during the last decade. Many, but not all,
of these subsequent studies provided epidemiological evidence of an increased
risk of soft-tissue sarcoma and malignant lymphoma in persons exposed to
phenoxy herbicides, chlorophenols, or their contaminating dioxins and
dibenzofurans (9, 10). It is especially noteworthy that two case-control studies
in the United States have also found an association between exposure to the
phenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and non Hodgkin's
lymphoma (11, 12).
Two cohort studies also support the association between exposure to the
aforementioned chemicals and soft-tissue sarcoma (13, 14). Some additional
case-control studies from Sweden corroborate the earlier Swedish indications of
a carcinogenic effect in humans (15-19). Furthermore, a meta-analysis of four of
the Swedish case-control studies on soft-tissue sarcoma (6, 7, 15, 16)
demonstrated a dose-dependent risk associated with exposure ta phenoxyacetic
acids or the chemically related chlorophenols contaminated with TCDD as well
as other dioxins (20).
A general carcinogenic effect by TCDD-that is, an effect on all cancer sites
combined-also seems likely based on three cohort studies (13, 21-23), as
concluded in the evaluation by IARC (1). These findings corroborate earlier
observations (24-26) and might be explained by a TCDD contamination of the
pesticides used.
A follow-up of the population in Seveso, which was exposed to TCDD due to a
chemical plant accident in 1976, shows an increased incidence of soft-tissue
sarcoma and hematopoietic malignancies (i.e., a priori expected tumor types)
and hepatobiliary cancer (27).
The report by the Institute of Medicine of the U.S. National Academy of
Sciences was initially published in 1993 (5) and has recently been updated.
It concluded that there is sufficient evidence for an association between
exposure to Agent Orange, including the phenoxy herbicides 2,4-D and
2,4,5trichlorcphenoxyacetic acid (2,4,5-T) and soft-tissue sarcoma,
non-Hodgkin's lymphoma, and Hodgkin's disease (28). As mentioned above, in
our Swedish studies these tumor types were associated with exposure to
phenoxy herbicides.
Finally, toxicological studies have been supportive insofar as they show that of
the dioxins, TCDD and two congeners of hexachlorinated dioxins are
carcinogenic in experimental animals (29-34).
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