8. EFFECT OF PCDDs ON HUMAN BEINGS - EPIDEMIOLOGICAL AND CASE STUDIES
Dioxinnz.com is campaigning for this to take place in New Zealand concerning victims of exposure to dioxin which was in 2,4,5t and 2,4D herbicides manufactured and sold in New Zealand.
8.2 General Population Studies
USA Environmental exposures have occurred in a small area of Missouri, USA (Carter et al., 1975; Kimbrough et al., 1977; Kimbrough, 1984). In the summer of 1971 many birds, rodents, cats, dogs, insects, and horses died after exposure in a horse arena in eastern Missouri.
The incident followed the spraying of "waste oil" on the horse arena for dust control. Within 3 weeks of the spraying of this arena, two other arenas were sprayed. In all, 57 adult horses died, 26 abortions occurred among the horses at the most heavily exposed farm and many foals died soon after birth. At the time, the nature of the chemical that had caused the problem was unknown.
The arenas were excavated and the contaminated dirt dumped at other sites. After many fruitless attempts to identify the cause of this outbreak, it was discovered in 1973-1974 that the original soil from one of the arenas contained 5600-6500 mg trichlorophenol/kg, 31.8-33.0 mg TCDD/kg, and 1350-1590 mg polychlorinated biphenyls/kg. Because of this finding, the episode was reinvestigated. It was found that the salvage oil company that sprayed the three arenas routinely collected discarded motor oil and lubricants from over 2000 service stations in eastern Missouri and southwestern Illinois.
It also collected, from various sources, a limited amount of used organic solvents such as transformer oils and other compounds. A company in southwestern Missouri was finally identified as a source of TCDD. This company had manufactured trichlorophenol as an intermediate for hexachlorophene. The production of 2,4,5-tri-chlorophenol had generated a distillate residue which was emptied once a week into a residue storage tank. Initially this chemical waste was collected and incinerated but, in 1971 when the trichlorophenol producer experienced a financial crisis, he arranged for the chemical wastes to be disposed of by a chemical supplier.
The chemical supplier subcontracted the chemical waste disposal to the salvage oil dealer. The salvage oil dealer added the toxic chemical waste to his salvage oil storage tank, having collected a total of 18 000 gallons. This material, mixed with salvage oil and other chemicals, was sprayed on the riding arenas and some of it was taken to re-refining companies. Soil samples from arenas where contaminated dirt had been dumped in 1974 contained trichlorophenol levels that ranged from 1.5-32.6 mg/kg, TCDD levels that ranged from 0.22-0.85 mg/kg, and polychlorinated biphenyl levels that ranged from 10-25 mg/kg.
A 6-year-old girl, who had used one of the arenas for sandbox-like play in 1971, developed epistaxis, headache, diarrhoea and lethargy, haemorrhagic cystitis, and signs of pyelonephritis. She had an uneventful recovery. Three other females exposed to the same arena had recurring headaches, skin lesions, and polyarthralgias. Two 3-year-old boys in another arena developed chloracne on the exposed skin surfaces which lasted for more than a year. Evaluation of the three female patients 5.4 years after exposure to TCDD-containing oil showed them to be in good health (Beale et al., 1977).
A comprehensive medical examination of 154 residents exposed to TCDD, and 155 unexposed residents in similar type housing in eastern Missouri, revealed no consistent differences between the two groups. The examination included a medical history, physical examination, serum and urinary chemistries, and immunological and neurological tests. The findings may suggest that long-term TCDD exposure is associated with depressed cell-mediated immunity (decreased delayed-type hypersensitivity skin reactions to standard antigens) (Hoffman et al., 1986; Stehr et al., 1986). Urinary concentrations of glucaric acid were not significantly different between persons identified as being at high or low risk (Steinberg et al., 1985).
The scientific follow-up on the population of Seveso, N. Italy, which had been accidentally exposed to TCDD in 1976 (see sections 4.1.1 and 8.1), was guided by an international steering group headed by Professor M.A. Klingberg. The group completed its work in February 1984 and concluded that "it is obvious that no clear-cut adverse health effects attributable to TCDD, besides chloracne, have been observed" (Regione Lombardia, 1984). A total of 193 people had displayed symptoms of chloracne, but at the beginning of 1984 only 20 presented active symptoms. After 15-20 days exposure to TCDD soil levels of 270-1200 µg/m2, there was a marked incidence of chloracne.
No disturbance of biochemical functions were seen when the exposure had been limited to soil with TCDD levels at or below 30-70 µg/m2. Later evaluations failed to confirm earlier findings of a decrease in motor nerve conduction velocity in some individuals. A significant increase in urinary glucaric acid levels, indicating increased microsomal enzyme activity, was found 3 years after exposure in 67 exposed children, as compared to 86 non-exposed children (Ideo et al., 1982, 1985). The steering group found the data difficult to evaluate as analytical and individual biological variabilities were not explained (Regione Lombardia, 1984).
Studies performed on the rate of spontaneous abortions and birth defects in the Seveso area do not allow any conclusions to be drawn (Tognoni & Bonaccorsi, 1982). The hypothesis that low exposure might cause pre-pregnancy or pregnancy effects that adversely affect the outcome was tested using several exposure models. The only finding was a slightly higher rate of haemangioma among newborns in the exposed group. However, this showed up only with one of the exposure models. It was considered doubtful that this was due to TCDD exposure (Regione Lombardia, 1984).
Lymphocytes from inhabitants of Seveso were examined for chromosomal aberrations by Regianni (1980a,b) and Mottura et al. (1981). In 17 TCDD-exposed individuals examined within two weeks of the accident, no increase in chromosomal aberrations was observed (Regianni, 1980). In the abstract by Mottura et al. (1981), chromosomal aberration analysis was performed on subjects distributed into three classes: acute exposure, chronic exposure, and a control group of non-exposed subjects. No significant difference in the frequency of chromosomal aberrations in the three exposure categories was reported. Data on number of subjects, chromosomal aberrations, and exposure level and time were not given.
Tenchini et al. (1983) published a comparative cytogenetic study on induced abortions from women exposed to TCDD after the Seveso accident, and in non-exposed subjects. Chromosome analysis was performed on maternal peripheral blood, placental and umbilical cord tissues, and fetal tissues. No significant differences were found in the level of chromosomal aberrations in the blood of placenta and umbilical cord from TCDD-exposed and non-exposed women. The exception was fetal samples from non-exposed women, in which a significant increase in chromosomal aberrations was obtained, possibly an artefact due to experimental techniques. The effect of TCDD on fetal chromosomes is therefore still unclear. Several epidemiological follow-up studies are continuing in and around Seveso.
From 1960 to 1969 a mixture of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid (Agent Orange), which was contaminated with TCDD (concentrations ranging from 0.5 to 47 mg/kg) (Kearny et al., 1972), was sprayed over areas of Viet Nam as a defoliant. The spraying from 1960 to 1965 was minimal; in 1966 it covered slightly more than 800 000 acres, in 1967 almost 1.7 million acres, in 1968 over 1.3 million acres, and in 1969 1.2 million acres.
Studies have been carried out since the early 1970s to ascertain whether the exposure of the general population in Viet Nam to this herbicide could have resulted in an increased incidence of birth defects. However, the results of such investigations have not been published in readily available peer-reviewed journals, making it difficult to assess the scientific significance of the findings.
Such studies have been reviewed by Westing (1984) and Constable & Hatch (1985). Those studies reviewed indicate a range of effects including spontaneous abortions, infertility, and birth defects. However, there are marked deficiencies in experimental design in most, if not all, studies, including potential bias in the selection of populations, poor record-keeping of populations and biological effects, such as congenital malformations, and a lack of control over possible confounding factors. These deficiencies make it difficult, if not impossible, to use this body of data in assessing the human health risks from exposure to phenoxyherbicides contaminated with TCDD and other PCDDs.
Tung (1973) reported an increased incidence of liver tumours in Viet Nam. From 1955 to 1961 there were 159 cases of liver cancer out of a total of 5492 cancer cases, and from 1962 to 1968, 791 out of a total of 7911 cancer cases. Van (1984) continued Tung's investigation. Previous exposure to herbicides of 21 male cases of primary liver cancer and 42 controls was ascertained. Six of the 21 cases and three of the controls had lived or worked in areas sprayed with herbicides or had moved there shortly after spraying ceased. Residence time varied from 8 to 77 months. There is a lack of information on confounding factors and there was a chance for bias in these studies. In general, the possibility of exposure to multiple chemicals and the short latency period noted make the study by Van (1984) of little value for assessing risk (IARC, 1986).
In 1979, the United States Air Force (USAF) initiated an epidemiological study into the possible health effects from chemical exposure of Air Force personnel who conducted aerial dissemination of herbicide in Viet Nam (Operation Ranch Hand) (Lathrop et al., 1984). The purpose of this investigation was to determine whether long-term health effects exist and can be attributed to occupational exposure to herbicides. This study used a matched cohort design in a non-concurrent prospective setting, incorporating mortality, morbidity, and follow-up studies.
The report presented the results of health information on 2706 Ranch Handers and comparison individuals obtained by questionnaire and 2269 Ranch Handers and comparison individuals undergoing an extensive physical examination. It was concluded that there was insufficient evidence to support a cause and effect relationship between herbicide exposure and adverse health in the Ranch Hand group at this time. The study disclosed numerous medical findings, mostly of a minor or undetermined nature, that require detailed follow-up.
In a study of 15 soldiers in Australia exposed to Agent Orange, no increases in structural chromosomal aberrations or sister chromatid exchanges were noticed, compared to a control group of 8 subjects (Mulcahy, 1980). In 1980 the Australian Commonwealth Institute of Health agreed to conduct a series of scientific investigations into the health of Viet Nam veterans and their families. After considerating the most appropriate study programme, it was decided in 1981 to conduct, as part of that programme, a case-control study of congenital anomalies and Viet Nam service (Donovan et al., 1984). The report is largely negative, as is that of Erickson et al. (1984) which reported a similar study of American veterans.Table 64-01
A. Skin Manifestations 1. Chloracne 2. Hyperkeratosis 3. Hyperpigmentation 4. Hirsutism 5. Elastosis
C. Neurological Effects 1. Sexual dysfunction 2. Headache 3. Neuropathy 4. Sight disturbance 5. Loss of hearing, taste,and smell
D. Psychiatric Effects 1. Sleep disturbance 2. Depression 3. Loss of energy and drive 4. Uncharacteristic bouts of anger