Polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
and polychlorinated biphenyls (PCBs) are widespread environmental pollutants. The use
of these chemicals are currently banned or restricted in most developed countries.
However, because of the chemicals’ persistence in the environment, high background
concentrations are still found as seen in several large-scale epidemiologic studies in the
general population (Patterson et al. 2008; Patterson et al. 2009; Wong et al. 2008). Due
to the world-wide ubiquitous background exposure, PCDDs, PCDFs, and PCBs are still
a concern to human health.
PCBs, PCDFs, and dioxin-like chemicals are ubiquitous food contaminants in
developed countries around the world. However, only two major events of food
contamination by PCBs and PCDFs have occurred, 1968 in Japan, and 1979 in Taiwan.
In Japan, Yusho (oil-syndrome in Japanese) accident, involving more than 1800 people,
was caused by the use of Kanemi brand rice oil contaminated by Kanechlor-400, a
Japanese commercial brand of PCB mixture. In addition, the repeated heating partially
degraded the PCBs into PCDFs and polychlorinated terphenyls and quarterphenyls
(PCTs and PCQs) (Masuda et al., 1986). In 146 Yusho patients, the average amount of
Kanechlor 400 ingested was estimated to be about 2 g, with a minimum of 0.5 g
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(Kuratsune et al., 1972). Another study of 141 Yusho patients estimated the average
intake of PCBs, PCDFs and PCQs per patient to be 633, 3.4, and 596 mg, respectively
(Hayabuchi et al., 1979). In the Yusho victims, exposure levels have been studied in the
biological samples. PCB concentrations in the adipose tissue of Yusho patients were
estimated to have reached 46–76 ppm (wet weight basis; concentration of the analytes reported based on the sample’s wet weight) soon after the incident (Masuda et al.,
1996). The concentrations of non-ortho and mono-ortho PCBs in the blood of Yusho
patients about 34 years after the outbreak were 320 ± 187 (mean, standard deviation)
and 75651 ± 58264 pg/g lipid, respectively (Todaka et al., 2007). The concentrations of
residual PCDFs in the blood and adipose tissue of Yusho patients 20 years after
exposure remained 3-fold to 64-fold greater than those of the general population
(Masuda et al., 1997).
In Taiwan, an outbreak of severe acne, skin pigmentation, and conjunctivitis in
central Taiwan, and was later called Yucheng (oil-syndrome in Chinese). Most of the
victims consumed the same brand of cooking oil obtained from the same store (Hsu et
al., 1985). The illness, and its relation to cooking oil consumption, resembled Yusho.
Approximately 2000 persons registered with health agencies as being exposed. The
Yucheng rice oil was contaminated with PCBs (Kanechlor-500), and their pyrolytic
products PCDFs and PCQs (Hsu et al., 1985). Interview was carried out with 98
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Yucheng patients and each patient was estimated to consume an average of about 1 g
(range = 0.7–1.4) of PCBs and 3.8 mg (range = 1.8–5.6) of PCDFs (Lan et al., 1981).
Another estimation of the intakes of PCBs, PCDFs, and PCQs by Yucheng patients were
973, 3.8, and 490 mg, respectively.1 The concentrations of residual PCDFs in the blood
of Yucheng victims 14 years after exposure remained one to two orders of magnitude
higher than controls (Guo et al., 1997).
In Yucheng cohorts, for example, the concentrations of the PCBs ranged from 3 ppb
to 1156 ppb,7 with about 28% below 50 ppb, much above the 1-3 ppb tolerable daily
intake set in Germany (van Leeuwen et al., 2000), but still within the range of
dioxin-like PCB congeners reported in 187 studies regarding 29,687 subjects of 26 countries
world wide (Consonni et al., 2012). However, the initial call of these two events as
PCBs intoxication was overly simplified. Due to repeated heating of the rice oil,
pyrolytic products PCDFs became present, especially 2,3,4,7,8-penta-CDF and
1,2,3,4,7,8-hexa-CDF.( Guo et al., 1997; Masuda et la., 1979) The PCDFs contributed to
much higher levels of the toxic equivalencies (TEQs) than did PCBs.
The Yucheng and Yusho victims were exposed to comparable amount of PCBs and
PCDFs. In Yusho, the oil was estimated to be contaminated by 1000-3000 ppm of PCBs
and 5 ppm of PCDFs, and the victims were exposed for 1-2 months. On the other hand
in Yucheng, the oil was contaminated by 67 to 99 ppm of PCBs and 0.21 to 0.40 ppm of
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PCDFs, and the victims were exposed for 9-10 months (Guo et al., 2003; Masuda et al.,
2003).
Unlike the occupational cohorts, many of the victims of the Asian outbreaks were
symptomatic, and so it seemed likely that the doses to which they were exposed could
produce a detectable cancer excess. By 1998, although mortality studies of the Yusho
and Yucheng cohorts both showed excess mortality for non-malignant liver disease,
only the Yusho cohort showed an excess of liver cancer (Ikeda et al., 1987; Yu et al.,
1997). We anticipated that the discrepancy in findings between Yusho and Yucheng
would resolve with further follow-up. However, when we updated our report in 2007,
we did not observe any increase in liver cancer, but did see an unanticipated excess of
deaths from systemic lupus erythematosis (Tsai et al., 2007). These studies used the
Taiwan population as the referents, and we were concerned that regional or
socioeconomic variation might have biased the findings.
The statistical power for each cohort has been limited by the number of exposed
people. Here we conducted a meta-analysis of two cohorts to reevaluate the effects of
PCBs and PCDFs on major causes of mortalities.
PCBs have been suggested as neurotoxicants especially when exposed during
prenatal and early postnatal periods, and known to cause neurological effects including
neurocognitive deficits, behavioral problems, and auditory impairments (Boucher et al.,
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2010; Grandjean and Landrigan 2006; Schantz et al. 1996; Schantz et al. 2003; Tilson et
al. 1998). We and others have reported neurological adverse effects in the children
prenatally exposed to PCBs and PCDFs (Chen et al., 1992; Jacobson and Jacobson S,
1996; Lin et al., 2008). Our previous study showed that Yucheng children had a higher
incidence of otitis media than referent children (Chao et al. 1997). No auditory
assessment was performed during that time. We therefore conducted a follow-up study
to test the hypothesis whether children prenatally exposed to PCBs and PCDFs had
higher risk of developing auditory deficits, as compared to their referent children. We
also examined whether hearing effects were associated with gestational PCBs/PCDFS
exposure or exposure to specific congeners in the Yucheng children. Table 1 shows the
whole picture of current studies.
Therefore, the aim for this study were:
1. To examine the overall and cause-specific mortalities in Yucheng subjects as
compared to their age and gender matched neighborhood referents 30 years after
PCBs/PCDFs exposure.
2. To conducted a meta-analysis of two cohorts to reevaluate the effects of PCBs
/PCDFs on major causes of mortalities.
3. To examine the association between gestational PCBs/PCDFS exposure and auditory function in Yucheng children’s early adulthood.
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