Non-cancer effects in adults
Several persistent, exposure-related effects occurred in two or more adult populations exposed to PCDDs, PCDFs and PCBs. These populations include the industrial cohorts previously described: US Air Force Ranch Hands (exposed to TCDD during spraying of Agent Orange, median serum TCDD levels back-extrapolated at time of exposure around 50 pg/g lipid), Centers for Disease Control Vietnam Experience Study (exposed to TCDD during a one year tour in Vietnam, mean serum TCDD levels at time of study in 1987, 4 pg/g lipid), and the Seveso, Yusho and Yucheng cohorts.
The effects are elevated GGT in the NIOSH, Ranch Hands and Vietnam Experience cohorts (NIOSH: out-of-range GGT levels, OR=2.27, 95%CI, 1.17-4.39: Vietnam Experience Study: OR 1.3, 95%CI, 1.0-1.8: Ranch Hand mean GGT concentration in highest exposed group 33.3 pg/g lipid TCDD compared to referent group, p <0.001); statistically nonsignificant dose-related increases in Triglyceride levels in the NIOSH cohort (and significant increases in Ranch Hands with serum TCDD concentrations above 15 pg/g lipid; significantly increased mean fasting plasma glucose levels among Ranch Hands with 2,3,7,8-TCDD concentrations > 94 pg/g lipid (OR=1.5, 95%CI 1.2, 2.0), an increased prevalence of diabetes among workers in the NIOSH cohort with serum concentrations above 1500 pg/g lipid and mortality from diabetes among females in all zones of Seveso, particularly in zone B (Zone A, Obs=2, RR=1.8, 95%CI 0.4-7.3; Zone B, Obs=13, RR=1.9, 95%CI 1.1-3.2; Zone R, Obs=74, R.R. 1.2, 95%CI 1.0-1.6). Increased mortality from cardiovascular diseases occurred in multiple industrial cohorts and in males of Zones A and R of the Seveso cohort. Positive dose-response trends were also observed for ischaemic heart disease in the heavily exposed German occupational cohort study, the Dutch occupational cohort and the IARC multicenter study. Among Yusho and Yucheng adults, chronic exposure-related effects included chloracne, conjunctivitis, and sebaceous cysts and inflammation, decreased nerve conduction velocity, fatigue and malaise, hyperpigmentation and hyperkeratosis, and increased mortality from non-malignant liver disease.
In summary, noncancer endpoints were evaluated among groups exposed to dioxins, dioxin-like and non-dioxin-like polychlorinated aromatic compounds in a variety of exposure scenarios, from background to extremely high exposures. Among children exposed in utero to background levels, effects include subtle developmental delays (U.S.and Dutch children) and subtle thyroid hormone alterations (Dutch infants to age 3 month). Multiple, persistent effects occurred among highly exposed children in Yusho and Yucheng who had transplacental exposure. Of the many effects evaluated in exposed adult study populations, many were transient effects disappearing after the end of exposure. A few conditions appear to be in excess among the exposed cohorts when compared to unexposed referent groups including alterations in lipid, fasting plasma glucose and GGT concentrations as well as mortality from cardiovascular disease. Both of the Asian cohorts showed excess death from non-malignant liver disease.