The PCB Baby Studies - Part 2
(PCB effects are summarized at the top of each study.)
The Japan and Taiwan Rice-Oil Poisoning Studies ---
Yusho and Yu-Cheng
In Japan in 1968 and in Taiwan in 1979, accidental mass poisoning incidents occurred from cooking oil contaminated by PCBs. The 1,788 Japanese people affected are referred to as "Yusho" (Japanese for "rice oil") disease patients, and the 1,843 Taiwanese people affected are said to suffer from "Yu-Cheng" (Chinese for "oil disease.")
It appears that in both cases, the rice-bran oil was being deodorized by a heating process that involved heat-exchange coils filled with circulating PCB oil. When pinholes developed in the coils, PCBs leaked into the cooking oil, and merchants distributed the contaminated oil in markets over wide areas. The oil contained variable levels of PCBs, plus the heated products of PCB degradation: polychlorinated dibenzofurans [furans] and polychlorinated quaterphenyls. (These degradation products are also found in the Fox River and Green Bay. In general, the PCB and furan exposure levels were higher in Taiwan and Japan than we’ve seen in Northeast Wisconsin, though heavy fish consumers on the Fox River and Bay might approach some of these levels.)
In Taiwan, the rice-oil contaminant concentrations were estimated to range from 4.8 to 204.9 ppm PCBs, with a mean of 52 ppm plus or minus 38.7 ppm. Blood measurements within the first year of the outbreak showed a range from 3 to 1,156 ppb PCBs, with a mean of 89.14 plus or minus 6.9 ppb. Four years later, the mean value of PCB blood levels varied from 39 to 101.7 ppb, which was much higher than that of the Japanese Yusho outbreak [mean of 5.9 plus or minus 4.5 ppb.] (Hsu et al, 1985) The PCBs levels were slow to drop. In 59 patients with Yusho, 52.5% still had PCB levels higher than the range found in the general population 13 years after the accident. (Akagi et al, 1985) This has implications for children born to PCB exposed victims many years later.
Roughly half of the 1,843 Taiwanese affected were between the ages of 11 and 30. (Hsu et al, 1985)
Several studies by several different researchers have been conducted on the PCB-exposed women, their newborns and directly-exposed children, over a period of several years:
Of 36 babies known to be born to Yusho mothers in Japan, all showed dark brown hyperpigmentation (termed "Coca-Cola" or "Cola Babies") though this effect tended to fade over time. Studies of roughly half of these babies found they also suffered from gingival hyperplasia (gum disease), exophthalmic edematous eye (puffy eyes with discharge), dentition (teeth) at birth, abnormal calcification of the skull as demonstrated by X-ray, and rocker bottom heel. There were 2 stillbirths. (Yamashita et al, 1985) Low birth weight was common (Higuchi 1976, Wong et al, 1981, Nicholson et al, 1994, and Yamashita et al, 1995) and premature births, also. (Higuchi 1976 and Wong et al, 1981) The children also suffered retarded growth, and abnormal tooth development (Nicholson et al, 1994). In both the Yusho and Yu-Cheng incidents, slowed nerve conduction, especially of sensory nerves was documented in children born to exposed mothers (Longnecker et al, 1997, and Rogan et al, 1992 and Hsu et al, 1994). In follow up studies, growth deficiencies were evident. Autonomic disturbances were observed; sluggish, clumsy, and jerky movements were exhibited; and the average intelligence quotient was in the low 70s. (An average IQ is 100.)
Effects on the immune system were also reported in the Yusho and Yu-Cheng populations (Tryphonas 1995). These were in the form of a) persistent respiratory distress (e.g., bronchitis and upper respiratory infections) in half of the persons with Yu-Cheng disease, b) significant decreases in IgA and IgM antibody levels 2 years after exposure but normal after 3 years, c) significant decline in the percentage of total T-lymphocytes in persons with Yu-Cheng disease and a slight increase in T-helper cells and a slight decrease in T-suppressor cells in persons with Yusho disease 14 years after exposure, and d) enhanced responses to mitogens (i.e., pokeweed and concavalin) (Guo et al. 1995).
In a study of 39 babies born early in the poisoning episode to Yu-Cheng mothers in Taiwan, all showed hyperpigmentation. The fatality rate was high. Eight babies died of pneumonia, bronchitis, sepsis, prematurity or congenital weakness. (Hsu et al, 1985) Other researchers also found skin pigmentation and low birth weight were common (Nicholson et al, 1994, and Hsu et al, 1994)
Another study examined 128 Yu-Cheng children, their parents and siblings who were directly exposed, and 115 control children. Direct exposure of mothers stopped in 1979 and children were born as late as 1985. At birth, exposed children had increased rates of hyperpigmentation, eyelid swelling and discharge, deformed nails, acne, and swollen gums compared to controls. Some were born with teeth. On examination, they had a much higher rate of dystrophic finger-nails and pigmented or dystrophic toe-nails than controls. They also had an increased rate of acne. In addition they had more generalized itching, localized skin infections and hair loss. The findings seen in babies exposed in the womb differ from those seen in people directly exposed (who have a higher prevalence of acne.) (Gladen et al, 1990)
In both the Yusho and Yu-Cheng incidents, slowed nerve conduction, especially of sensory nerves was documented in children born to exposed mothers (Longnecker et al, 1997, and Rogan et al, 1992 ).
In 1985, NIEHS scientists studied 117 offspring of Yu-Cheng mothers. The children showed cavity-prone teeth, poor nail formation, and short stature. Another study also showed exposed children were shorter and weighed less than normal (Hsu et al, 1984) A 1995 study of children of Yu-Cheng mothers found they were born growth retarded, with dysmorphic physical findings, and delayed cognitive (brain) development compared with unexposed children. (Yueliang et al, 1995)
In 1991, 55 Yu-Cheng children were studied and compared to age- and sex-matched control subjects. The children's growth profiles, bone mineral density and soft tissue composition, joint laxity, and serum parathyroid hormone, vitamin D, calcium, alkaline phosphatase, and phosphate were compared. The Yu-Cheng children were 3.1 cm (p < .05) smaller and had less total lean mass and soft tissue mass as compared to the matched control subjects. All other measure were similar in both groups. The shorter height and decreased total lean mass and soft tissue content were only seen in the Yu-Cheng children who were the first born after the PCB ingestion, but not in subsequent children. This was most likely due to decreased body burdens of the PCBs and related contaminants over time in the mothers. (Guo et al, 1994)
Since environmental chemicals have been shown to alter endocrine function, including sexual maturation, in wildlife and laboratory animals; another study examined whether PCBs and furans might alter sexual maturation in humans. A group of adolescent Yu-Cheng children were compared to a closely matched-control group of adolescents not exposed to PCBs or furans. On periodic physical exam the children's Tanner stage of sexual maturation was assessed. In the boys, size of testes and length of the penis were measured using standard techniques. There was no statistical difference in timing of the Tanner stages in either gender. However in the 55 pairs of boys between the ages of 11 and 15 years old, the penis length was decreased in the boys exposed in utero to PCBs and furans. Testicular size was similar in both groups. Future studies will determine if these effects will persist when the boys are sexually mature, and the mechanism(s) of the observed changes. (Guo et al, 1996)
All prenatally exposed Yu-Cheng boys and appropriate controls were contacted for medical examination in 1998. Sperm of exposed children were found to have increased abnormal morphology, reduced motility, and reduced capacity to penetrate hamster oocytes. (Guo et al, 2000)
In 1993, otolaryngologists examined the middle ear of Yu-Cheng children with a pneumatic otoscope, and measured the middle-ear pressure by tympanometry with a Rion RS20 impedance audiometer. The exposed children had a significantly higher prevalence of middle-ear diseases than their matched controls. The exposed children who had ear disease had higher serum levels of PCBs and furans than the children who did not. (Chao et al, 1997)
In 1995 studies, effects on the immune system were reported in the Yu-Cheng and Yusho populations (Tryphonas 1995). These included a) persistent respiratory distress (e.g., bronchitis and upper respiratory infections) in half of the persons with Yu-Cheng disease, b) significant decreases in IgA and IgM antibody levels 2 years after exposure but normal after 3 years, c) significant decline in the percentage of total T-lymphocytes in persons with Yu-Cheng disease and a slight increase in T-helper cells and a slight decrease in T-suppressor cells in persons with Yusho disease 14 years after exposure, and d) enhanced responses to mitogens (i.e., pokeweed and concavalin) (Guo et al. 1995).
Another immunity study in 1995 had different results: Researchers examined 105 Yucheng children and 101 control children, with a thorough physical examination and blood draw. The Yucheng children were reported by their parents to have higher frequencies of influenza attacks than the control children during the six months prior to the examination. The frequencies of other symptoms were similar between the two groups. The serum levels of various immunoglobulins were similar between the two groups. Fifty-one serum samples, 29 of Yucheng and 22 of control children, were available for cell-mediated immunologic analysis. The percentages of various T cell markers, CD3, CD4, and CD8, and B cell and NK cell markers were not different between the Yucheng and the control children. No dose-response relationship was found between 27 Yucheng children's serum PCB/PCDF levels and any of their immunologic markers. These researchers concluded that 16 years after the Yucheng incident, children exposed to high doses of PCBs/PCDFs in utero did not show, with the serum immunologic marker analyses, suppressed immunity when compared to their controls. To explain the consistent higher frequencies of upper respiratory tract infection in the Yucheng children, immune functional tests such as delayed hypersensitive skin reaction, in vitro lymphocyte proliferation, and antibody synthesis following immunization may be necessary. (Yu et al, 1998)
Neurological Study #1 --- In 1985, NIEHS scientists studied 117 offspring of Yu-Cheng mothers. They displayed behavioral problems and developmental delays that average 5-8 points on standard IQ scales. In addition, researchers discovered that children born up to six years after the exposure exhibit delays as severe as those in children born in 1979.
Neurological Study #2 --- Researchers used data from a project that began in 1985 in Taiwan, in which 117 children (mean age, 2.7 years in 1985) born to mothers in a PCB/PCDF poisoning registry and controls were followed, and they examined whether the developmental delay in the children was related to the severity of exposure to the mother or child. Blood samples from 38 children were analyzed and none had detectable furans. More exposed children (14/21) than control children (6/15) had detectable PCBs; the highest median concentration was among the breast-fed exposed children (4.5 ppb), but bottle-fed exposed controls (0.44) and breast-fed controls (0.53) were about the same. Among the exposed children, those with detectable PCBs had mean IQ scores 15 points lower than those without detectable PCBs when tested in the fall of 1986. A simple count of PCB-associated symptoms among the mothers was weakly related to IQ score (P = 0.01, R2 = 0.05). There were no strong relations between either measure of exposure and signs or symptoms in the children or between symptoms in the mother and level in the child. The authors conclude that there is some evidence for dose-response in the expression of the syndrome in the children, but small numbers and the imprecision in measuring both IQ and exposure make quantification difficult. (Yu et al, 1990)
Neurological Study #3 --- Cognitive testing (Bayley mental and psychomotor developmental indices, Stanford-Binet test, and the Wechsler Intelligence Scale for Children [WISC-R]) indicated significantly lower overall age-adjusted developmental scores among the exposed Yu-Cheng children. Developmental delays were seen at all ages and were greater in children who were smaller in size, had neonatal signs of intoxication, and/or had a history of nail deformities. Results of follow-up testing (Stanford-Binet test and WISC-R), when the children were 4–7 years of age, indicated that effects on cognitive development persisted for several years after exposure (Chen et al. 1992).
Neurological Study #4 --- The Rutter Child Scale A, a parent interview questionnaire that detects behavioral disorders, was used in this study. Higher scores represent more behavior disorders. At each year since 1985, combining children of different ages, the Yu-Cheng children scored 9-43% higher (worse) (mean = 22%) on the Rutter scale; differences were significant except for the 2.5-year follow-up. There was no consistent trend toward decreased differences in score with increasing time between the outbreak and year of birth. There were similar results from a Child Activity Checklist. This exposure appears to cause a behavior disorder and perhaps increased activity; the effect is persistent over time and appears to be similar in children born up to 6 years after the mother was exposed. (Chen et al, 1992)
Neurological Study #5 --- 118 children, referred to as 'the early-born Yucheng children', and matched controls were followed with the Chinese version of Rutter's Child Behavior Scale A annually from 1985 to 1991. At any fixed age, the early-born Yucheng children had mean Rutter behavior scores 1.75 to 2.40 points higher (14-38% worse) than that of their controls. The effects were similar in the health, habit, and behavioral subscores and persistent as the children aged. (Yu et al, 1994)
Neurological Study #6 --- Another researcher started a 12-year follow-up study in August 1985, 118 Yucheng children were assigned a non-exposed child matched by sex, age, locality of residence, mother's age, socio-economic status of the family. A consistent tendency indicates that Yucheng children score lower in each kind of measurement tool at each age level. This implies that congenital exposure to PCBs and their contaminants has long-term adverse effects on the cognitive development of human beings. (Lai et al, 1994)
Neurological Study #7 --- Starting in 1985, a group of 117 Yu-Cheng children and 117 controls were assessed annually for neurocognitive functioning. The Yucheng children scored approximately 5 points lower than their matched controls at ages 4-5 by Stanford-Binet test, and at ages 6-7 by Wechsler Intelligence Scale for Children, revised. In Raven's Colored Progressive Matrices (CPM) at ages 6-8, Yucheng girls scored similarly as control girls, but Yucheng boys' scores were lower than those of control boys and were similar to those of the girls. The Yucheng children scored higher than their matched controls on both Rutter Child Behavior Scale and Werry-Weiss-Peters Activity scales from 1985 to 1991, indicating higher frequencies of disordered behavior and higher activity levels. (Guo et al, 1995)
Studies of the Yusho and Yu-Cheng victims contribute to the weight of evidence that man-made chemicals can disrupt normal endocrine (hormone) function and are associated with neurobehavioral deficits. (Harada 1976; Wong and Huang 1981; Hsu et al. 1985)
Conclusions --- Although these neurobehavioral deficits were similar to the findings of the Jacobsons on Lake Michigan, they were much more pronounced and, according to several scientists, could have resulted primarily from the presence of furans as co-contaminants in the rice oil. They believe: "For this reason, and based predominantly on comparisons with Japanese workers who had higher PCB blood levels and few or none of the symptoms present in the rice oil poisonings, furans were generally considered to be the primary causal agent" (Bandiera et al. 1984; Kunita et al. 1984; Masuda and Yoshimura 1984; Ryan et al. 1990; Safe 1990; Takayama et al. 1991; Tanabe et al. 1989; ATSDR 1997).
However, the results of the Japan Occupational Exposure Study below show that PCB-exposed worker’s children suffered the same symptoms, except that no neurological tests were performed on the children to determine whether they suffered the same learning and behavior deficits. In addition, several of the Yu-Cheng neurological studies cited above are based on the same 117 children used in "Neurological Study #2 cited above, where the researchers state that among their selected 38 children "none had detectable PCDFs (furans)" in their blood samples. Even so, the children suffered serious intelligence declines of 15 IQ points (mean).
Furthermore, commercial mixtures of PCBs frequently contain significant furan contamination. And when PCBs degrade over time or are exposed to heat, additional furans are formed. As a result, worldwide human PCB exposures frequently involve furans as well. To say that Yu-Cheng neurological effects are due only to furans (and are therefore irrelevant to PCB risk assessment) isn’t plausible given this information and the results of the numerous studies cited in this report from other parts of the world.