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Skin Absorption and Damage
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Skin Damage Caused by PCBs
This is not a complete list of all studies on this topic. For more studies,
visit the TOXNET database operated
by the National Library of Medicine (the source of these abstracts).
Study #1
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PCBs are absorbed through the skin
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PCBs cause chloracne and chemical burns on contact with the
skin
Chemical safety information sheet. Highly toxic. Is absorbed
through the skin. Suspected carcinogen. Acute toxicity: irritation
of the eyes and the respiratory tract; chemical burns on contact,
chloracne,
edema
of the face and hands. Chronic toxicity: liver damage. Exposure
limits (United Kingdom): for PCB (42% chlorine) 8h TWA = 1.0mg/m|3| and
10min TWA = 2.0mg/m|3|; for PCB (54% chlorine) 8h TWA = 0.5mg/m|3| and
10min TWA = 1.0mg/m|3|. (NIOSH, 1987)
Study #2
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dermal application of PCB causes lesions of liver, kidneys,
and lymphoid tissue, along with effects on the skin
The effects of polychlorinated biphenyls (PCBs) on dermal
toxicity were studied in female New-Zealand-rabbits. Clophen-A60 (11096825),
Phenoclor-DP6, and Aroclor-1260 were applied to the back skin of the animals
in doses of 118 milligrams (mg) each, 5 times weekly for 38 days. Animals
received water and pelleted food ad libitum. The animals were distributed
at random into four groups of four animals and were weighed weekly. Animals
surviving the 38 day test period were sacrificed. At necropsy, a pathologic
examination was performed, including macroscopic examination in ultraviolet
light. Feces collected from the cecum were analyzed. Hematologic examinations
and chemical determinations of blood serum were performed. In general,
the test animals showed a gradual loss of weight. All test animals, except
one rabbit of the Clophen-A60 group, showed fluorescence in ultraviolet
light. Liver and bone fluorescence was observed most frequently. Results
of the hematologic analyses were similar for the three substances. The
number of leukocytes was significantly reduced in the test animals. Skin
lesions were hyperplasia and hyperkeratosis of the epidermal and follicular
epithelium. Livers of treated animals showed degeneration of the centrolobular
region, cell atrophy, focal necrosis, and cytoplasmic hyalin degeneration.
Treatment with Phenoclor-DP6 and Clophen-A60 resulted in definite hyperplasia
and hyperkeratosis of the follicular epithelium of the ear skin. However,
Aroclor-1260 caused minimal hyperplasia and hyperkeratosis in this area.
PCB induced kidney lesions, thymus atrophy, and lymphopenia; there also
was an increase in fecal coproporphyrin and protoporphyrin excretion. The
authors conclude that dermal application of PCB causes lesions of liver,
kidneys, and lymphoid tissue, along with effects on the skin. (Vos
et al, 1971)
Study #3
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acneiform eruptions and enlargement of the follicular openings;
pigmentation of the nails, gums, and lips
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dermal changes appeared to be caused by hyperkeratinization
associated with abnormal lipid metabolism
Polychlorinated-biphenyl (1336363) (PCB) poisoning and pollution
are outlined in a study of 138 Yusho patients in Japan. The patients are
classified by sex, age, and grade according to the severity of their dermal
symptoms. The data suggested the major outbreak occurred between May and
August. Ocular discharge and dysfunction; acneiform eruptions and enlargement
of the follicular openings; pigmentation of the nails, gums, and lips;
edema of the limbs; general fatigue, nausea, and vomiting characterized
the disease's incipient stage. The dermal changes appeared to be caused
by hyperkeratinization associated with abnormal lipid metabolism. Epidemiological
findings verified Kanechlor-400 (a commercial brand of polychlorinated-biphenyls
with 48% chlorine (7782505) content) as the toxic agent. Furthermore, it
was also demonstrated that contamination by copper (7440508), nickel (7440020),
zinc (7440666), cobalt (7440484), arsenic (7440382), mercury (7439976),
or pentachlorophenol (87865), was negligible. Most components of Kanechlor-400
were found in the serum, subcutaneous fat, mesenterium, mesenteriolum,
extraperitoneal adipose tissue, appendix vermiformis, heart, sternal marrow,
duodenum, trachea, and in fetal tissues. The Kanechlor was used to heat
the oil at reduced pressure to remove odorous matter. Analyzed oil samples
revealed the presence of polychlorinated-dibenzofurans (PCDF) and the absence
of polychlorinated-dibenzo-para-dioxins (PCDD). Therefore it is suggested
that the role of PCDF in the pathology of Yusho should not be dismissed.
(Higuchi, 1976)
Study #4
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skin lesions are one of the most striking change in mammals
exposed to PCBs
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PCB poisoning was associated with chloracne and skin discoloration
in infants
The status of the toxicologic, carcinogenic, teratogenic,
and mutagenic aspects of the PCBs of greatest relevance to man is reviewed.
Summaries of oral and dermal toxicity of Aroclors to rats and rabbits
indicate that they are of low acute toxicity. Lethal affects appear to
be cumulative. Summaries of PCB-induced pathologic changes show liver alterations
and skin lesions to be the most striking change in mammals, whereas
fluid in the pericardial sac, kidney damage, and reduced spleen are found
in birds. The toxic nature of contaminating polychlorodibenzofurans is
pointed out. Effects of low level feeding show reduced rate of weight gain,
increased kidney and liver weights, and elevated serum alkaline phosphatase.
Morphological and ultrastructural changes in livers of treated rats are
described. Acute and chnroic feeding studies resulted in fewer and smaller
offspring, decreased weanling survival, and lowered mating indices in rats;
and body weight loss, eggshell thinning, and poor egg hatchability in chickens.
Bladder cancers, heptaomas, lung abscesses, pneumonia, spleen atrophy,
intracranial abscesses, hyperplasia and dysplasia of gastric mucosa, fetotoxicity,
abortions, maternal deaths, and stillbirths have been observed in mammalian
species. A high incidence of chromosomal aberrations has been reported
in ring doves, but none was observed in human lymphocyte cultures, rat
bone marrow or spermatogonia. Suppressed immunological responses have been
observed in ducks, guinea pigs, rabbits, and chickens. An outbreak of PCB
poisoning in Japan in 1968 resulted in 1081 patients being affected by
chloracne,
blindness, gastrointestional symptoms, skin discoloration in infants
of poisoned mothers, decreased birth weights, increased urinary 17-ketosteriods,
respiratory distress, a hematological picture suggesting inflammation,
and elevated blood-serum triglycerides. (Fishbein, 1974)
Study #5
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elevated PCB levels and exposures were associated with dermatotoxicity
Study of 120 male workers in a railway locomotive and carriage
maintenance works, in which there had been exposure to transformer fluids
containing PCBs for nearly 40 years, to determine the prevalence of increased
PCB absorption and the presence of potentially related clinical and metabolic
abnormalities. Workers were categorised as "exposed", "nominally exposed"
and "non-exposed". Evidence of dermatotoxicity and elevated PCB
levels was found most frequently in the "exposed group", correlating well
with age and duration of employment; significant correlations were found
between plasma PCB and STG and SGOT levels; no significant correlations
were found between PCB levels and levels of cholesterol, high-density lipoprotein
cholesterol of levels studied on liver function tests other than SGOT.
Further analysis relating frequency of reported direct contact with PCB
levels suggested a dermal route of exposure. (Chase et al, 1982)
Study #6
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PCBs exposure is unequivocally associated with chloracne,
skin hyperpigmentation and chronic skin irritation
Health effects associated with exposure to polychlorinated
biphenyls (PCBs) were reviewed. Workers with the greatest PCB exposure
have been employed in the manufacture or repair of electrical capacitors
or transformers in which PCBs have been used as heat transfer fluids. The
health
effects unequivocally associated with PCB exposure were chloracne, skin
hyperpigmentation, and chronic eye and skin irritation. These effects
have only been seen in workers with relatively high dermal or inhalation
exposures. The possibility that the skin problems could have been caused
by polychlorinated dibenzofuran contaminants, some of which are potent
chloracnegens, cannot be excluded. Clinical studies of the health effects
of PCB exposure have shown that the skin is the only organ system affected
by PCB exposure and that the skin disorders, primarily chloracne, occurred
only in persons occupationally exposed to relatively high PCB concentrations.
In contrast to experimental animal studies, other organ systems such as
the liver and immune and hematopoietic systems of humans are not affected.
The divergence between the effects observed in humans and animals may reflect
differences in interspecies susceptibility and exposure. The authors conclude
that there appears to be little basis for the concern for internal organ
system toxicity, especially since use and disposal of PCBs is now strictly
controlled. (James et al, 1993)
Study #7
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the great majority of workers handling PCB had dermatologic
complaints.
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discontinuance of contact with PCB led to gradual improvement
of these lesions
A follow-up study of capacitor manufacturing workers exposed
to polychlorinated biphenyls (PCB) and their children was conducted since
1973. PCB levels in whole blood of workers as well as in breast milk of
the exposed lactating mothers were approximately 10 to 100 times those
of nonexposed Japanese. Blood PCB levels had a statistically significant
correlation with the duration of PCB handling and breast milk PCB levels.
The rate of decline of blood PCB levels, as well as the changes of the
gas chromatograph of blood PCB over 7 years was found to vary with the
kind of PCB handled. The levels of blood PCB tended to be higher in the
children fed PCB -contaminated breast milk for a long period. The great
majority of workers handling PCB had dermatologic complaints. Discontinuance
of contact with PCB led to gradual improvement of these lesions. Abnormal
results in the blood chemistry of the workers were rare, while serum triglyceride
concentration was significantly correlated with blood PCB levels in 1974.
In the questionnaire study, the number of complaints in children born from
mothers who had handled PCB, especially those fed breast milk for a long
period, was conspicuously higher than that in control groups. Several children
were found to have the same medical findings as in yusho; however, they
have not been diagnosed as PCB -poisoning, because these findings were
neither so serious nor related to the blood PCB levels. (Hara, 1985)
Study #8
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PCB contaminants (furans and quaterphenyls) may contribute
to skin effects
Yusho and Yu-Cheng syndrome (contaminated rice oil poisoning)
were compared with simple polychlorinated-biphenyl (1336363) (PCB) toxicity
with respect to disease etiology. Rice oil samples and patient tissues
were analyzed for PCBs, dibenzofurans (PCDFs), and quaterphenyls (PCQs)
by gas chromatography and mass spectrometry. Five rice oil samples involved
in Yu-Cheng, the Taiwan outbreak in 1979, were roughly 1/10 as contaminated
by PCBs, PCDFs, and PCQs as samples of oil involved in the 1969 Yusho outbreak
in Japan. Both Yusho and Yu-Cheng specimens contained numerous isomers
of trichlorinated and hexachlorinated dibenzofurans. The oils involved
in both incidents contained similar compositions of PCQs; they appeared
to have similar ratios of the six types of PCQ in their basic makeup. In
general, Yusho and Yu-Cheng samples were composed of similar congeners;
the tissue levels of PCQs, PCDFs, and PCBs remained elevated and clinical
symptoms persisted for over 10 years. In occupationally PCB exposed workers,
on the other hand, dermal lesions and other symptoms disappeared rapidly
after discontinuation of PCB handling, although PCB levels remained high.
The authors conclude that PCDFs and PCQs appear to be strongly associated
with the development of Yusho and Yu-Cheng. (Miyata et al, 1985)
Study #9
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PCB treated animals showed no dermal symptoms, but furan
treated animals did [PCBs are generally contaminated with furans]
The toxicity of the polychlorinated-biphenyls (1336363) (PCBs),
polychlorinated dibenzofurans (PCDFs), and polychlorinated quaterphenyls
(PCQs) found in contaminated rice oil and associated with Yusho and Yu-Cheng
syndromes was studied in rats and monkeys. Male Sprague-Dawley-rats were
orally administered daily doses of PCBs (1 milligram per day (mg/day)),
PCDFs (10 micrograms per day (microg/day)), PCQs (1mg/day), an additive
mix (Mix-1), or no compounds (control) for 22 days. Subgroups of six rats
from each treatment group were sacrificed at 5, 10, and 22 days of treatment,
and 10 and 24 days after cessation of treatment. Female Cynomolgus-monkeys
were orally administered 6 day a week doses of PCBs (5mg/day), PCDFs (20microg/day),
PCQs (5mg/day), an additive mix of PCBs and PCDFs (Mix-2), or no compounds
(control) for 20 weeks. The monkeys were observed daily and bled at 4 week
intervals; they were examined by autopsy for pathologic assessment.
PCB treated animals showed hepatic hypertrophy, immunosuppression,
and increased drug metabolizing enzyme activities of hepatic microsomes,
but no dermal symptoms characteristic of Yusho. PCQs caused an increase
in drug metabolizing enzyme activities of hepatic microsomes and immunosuppression,
but to a lesser degree than PCBs. PCDFs alone and the mixes caused liver
hypertrophy, immunosuppression, weight loss, thymic atrophy, and increase
in drug metabolizing enzyme activities of hepatic microsomes; effects were
100 fold greater than those detected with PCBs alone. Monkeys fed PCDF
or Mix-2 showed the dermal lesions characteristic of Yusho. The authors
conclude that PCDFs appear to be the primary causal agent of Yusho and
Yu-Cheng. (Kunita et al, 1985)
Study #10
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dermal toxicity is a response to PCB exposure
Recent studies on the hazards of polychlorinated biphenyls
(PCBs) were reviewed and discussed. Specific topics reviewed include the
PCB analysis and environmental impact, role of metabolism in the toxicity
of PCBs, biochemical and toxic responses to PCB mixtures, metabolic process
for PCBs, structure and function relationships for PCB congeners, PCBs
that exhibit dioxin like activity (including coplanar congeners and monoortho
coplanar congeners), human health effects of PCBs, and the risk assessment
of PCBs on a congener specific basis through the development of toxic equivalency
factors. Current findings were that metabolic activation is not required
for PCB toxicity, and that the parent hydrocarbons are responsible for
most of the biochemical and toxic responses elicited by these compounds.
Some of the responses included developmental and reproductive toxicity,
dermal
toxicity, endocrine effects, hepatotoxicity, carcinogenesis, and the
induction of diverse phase-I and phase-II drug metabolizing enzymes. The
short term effects of PCBs on humans occupationally exposed appeared to
be reversible. No consistent changes in overall mortality and cancer mortality
have been reported. (Safe, 1993)
Study #11
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dermal lesions are typical sequelae of human PCB poisoning
Environmental contamination by polychlorinated biphenyls
(PCBs) was reviewed. Topics included fundamental terminology, production
and application, characterization of mixtures and related compounds, pollution
aspects, dose effects, and analytical methods. Emphasis was placed on environmental
pollution from the perspective of the analytical chemist. The distribution
of PCB congeners in environmental samples was discussed using the occurrence
of the components of aroclor-1260 (11096825) in human milk and birds eggs
as examples. Time trends of environmental PCB contamination were considered.
Laboratory animal studies indicated that PCBs cause: body weight loss,
chloracne, hepatomegaly, liver hemorrhage, porphyria, and bile duct, gall
bladder, urinary tract, endocrine system, and reproductive system dysfunction,
teratogenesis, and carcinogenesis. Liver damage, dermal lesions,
respiratory system disorders, eye problems, immunodeficiency, and reproductive
system dysfunction were typical sequelae of human PCB poisoning.
Chloracne was the most common manifestation of occupational exposure. Definite
evidence of human PCB carcinogenicity was not presented. Diagnostic difficulties
were associated with contamination with polychlorinated dibenzo-p-dioxins
and dibenzofurans. The biochemical effects of PCBs were discussed with
respect to coplanar and noncoplanar PCBs. Benefits and drawbacks of chromatographic
and spectrometric analyses were considered. Other procedures were also
discussed. (Lang, 1992)
Study #12
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humans exposed to PCBs showed skin discoloration and dermal
abnormalities
Data concerning the reproductive toxicity of polychlorinated-biphenyls
(1336363) (PCBs) were reviewed. Data have been obtained from animal experiments
as well as the accumulated reports on the intoxications among humans through
the accidental contamination of their environment with PCBs. Aroclor-1254
(11097691) inhibited spermatogenesis in rodents. Clorphen-A60 (11096994)
demonstrated a lengthening effect on estrous cycles in mice. Rats demonstrated
a significant reduction in plasma progesterone. PCBs with less than 48
percent chlorine have been associated with inherent estrogenic activity.
Some PCBs may not have any significant estrogenic activity themselves,
but may potentiate the effects of natural estrogens. Chronic dosing with
Aroclor-1248 (12672296) in the diet of rhesus-monkeys was lethal for some
and among survivors caused various reproductive problems, including abnormal
menses, infertility, increased abortion, and low birth weight of offspring.
A number of animal species have demonstrated the placental transfer of
PCBs. Rhesus-monkeys bred after exposure to Aroclor-1248 for six months
demonstrated a high rate of abortion and fetal death. Reproductive effects
among humans accidentally exposed to PCBs included overt abnormalities
in the offspring, fetal loss, skin discoloration, dermal abnormalities,
developmental deficits, behavioral problems, thick secretions from the
eyes, cysts of the Meibomian glands, and edema of the eyelids and face.
Exposure to neonates may occur through the breast milk of nursing mothers.
(Lione, 1988)
Study #13
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PCBs caused dermatosis --- Acneform eruptions, prominent
enlargement and elevation of the follicular openings, pigmentation and
flattening of the nails, and pigmentation of the integument
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hyperpigmentation of the epidermis, mild hyperkeratosis,
severe keratotic plugs in hair follicles, and chronic inflammatory dermal
infiltrate with foreign body granulomas
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atrophic epidermis, cystic follicular dilatation, keratinization
of sebaceous epithelial ducts, and abnormal melanin deposition in basal
layers of the integument
The pathogenesis of Yusho (oil disease) in Japan is discussed
based on six autopsy case results. The main clinical findings of Yusho
patients concerned dermatosis. Acneform eruptions, prominent enlargement
and elevation of the follicular openings, pigmentation and flattening of
the nails, and pigmentation of the integument are considered the major
cutaneous changes. Histological findings included hyperpigmentation
of the epidermis, mild hyperkeratosis, severe keratotic plugs in hair follicles,
and chronic inflammatory dermal infiltrate with foreign body granulomas.
Gas chromatographic PCB (1336363) analysis was performed on the liver,
fatty tissue, kidney, and brain. The gas chromatographic patterns suggested
that large quantities of PCB with four chlorine (7782505) atoms per molecule
were ingested but discharged within 1 year, leaving PCBs with five to seven
chlorine atoms per molecule in the body. Biopsy studies indicated atrophic
epidermis, hyperkeratosis and cystic follicular dilatation, keratinization
of sebaceous epithelial ducts, and abnormal melanin deposition in basal
layers of the integument. Cutaneous Yusho changes closely resembled occupational
acne symptoms regardless of intake route, and PCB appeared to induce similar
cutaneous reactions. Liver disturbances were most noticeable in PCB poisoning.
Complete loss of liver cells, hemorrhage of central lobules, and prominent
proliferation of the bile duct characterized this degenerative state. Histological
changes in the stillborn showed differences from other cases particularly
in pigmentation, thus, two PCB induced types of changes, adult and fetal,
may be distinguished. Special gas chromatographic patterns, unexplained
cardiac changes, and calcium (7440702) metabolic disorders indicated late
PCB action. (Kikuchi et al, 1976)
Study #14
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chloracne cleared more quickly in occupationally-exposed
vs. Yusho-exposed PCB victims, possible due to differences in furan concentrations
A detailed examination was undertaken of the chromatographic
record that had accumulated through ongoing medical surveillance of a group
of capacitor workers with previous direct occupational exposure to polychlorinated
biphenyls (PCBs). The study group originally consisted of 194 individuals
directly exposed to dielectric fluids in a pair of capacitor facilities
where the fluids used included substantial levels of Aroclor-1254 (11097691)
during 1946 to 1954, Aroclor-1242 (53469219) during 1950 to 1971, and Aroclor-1016
(12674112) during 1972 to 1977. Exposure occurred via both inhalation and
dermal
contact. Results were compared with those for a group of yusho disease
patients. The clearance rates of the major lower PCB congeners from the
sera of this group were estimated from levels measured 7.7 years apart
and compared with corresponding rates for patients with chloracne.
Even though high levels of serum PCB had been observed in this group in
early 1976, the group showed no significant PCB related abnormalities in
spirometric, biochemical, hematological, or other indicators of health
status. No chloracne was observed and the gas chromatograms of the group
all showed normal patterns of residual PCB congener distribution. The monoortho
chlorinated congeners were cleared three to seven times as fast in the
chloracne patients as in the capacitor workers. The diortho chlorinated
congeners were cleared three to seven times more slowly in the yusho patients.
The authors attributed these alterations in the yusho patients' PCB metabolism
to a PCDF induced increase in the level of cytochrome-P-448 and a corresponding
depression in that of the ordinary type of cytochrome-P-450. The authors
conclude that the rates of PCB congener decay in this group could be taken
as representative of those in normal, as opposed to chloracnegenic, human
populations. (Brown et al, 1989)
Study #15
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acne like eruptions on the cheeks and chin characterized
by severe inflammation and cystic changes
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dilated and hyperkeratinized follicles with inflammatory
infiltration
A case of Yusho like skin eruptions resulting from exposure
to halogenated polychlorinated biphenyl (PCB) analogues was described.
A 28 year old male graduate student at Kyushu University, Japan, complaining
of skin eruptions on the face was examined at a dermatology clinic. The
lesions consisted of acne like eruptions on the cheeks and chin and were
characterized by severe inflammation and cystic changes. The patient reported
that he was involved in synthesizing polychlorinated dibenzofurans (PCDFs)
and polybrominated dibenzofurans (PBDFs). All clinical chemistry parameters
were within their normal ranges. No PCBs or PCDFs were detected in the
patient's blood. A biopsy specimen showed dilated and hyperkeratinized
follicles with inflammatory infiltration. The patient was treated with
oral corticosteroids for 2 weeks and then given an acne lotion containing
sulfur powder for 2 months. He was advised to avoid direct contact with
any experimental chemicals. The eruptions disappeared almost completely
within 6 months. The authors conclude that the patient's skin eruptions
resulted from direct contact with the PCDFs and PBDFs used in his work,
and that the eruptions are similar to those seen in Yusho patients. (Asahi
et al, 1987)
Study #16
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some occupationally-exposed PCB workers did show dermal effects
Surveys of workers occupationally exposed to polychlorinated
biphenyls (PCBs) in the production of thread or of paint, and of yusho
patients were carried out from 1973 to 1982. PCB concentrations in the
plasma of the workers ranged from 2 to 521 ppb, and some showed higher
PCB levels in the plasma than typical Japanese yusho patients. Gas chromatographic
patterns of plasma PCBs of the workers with high PCB levels were shown
to match the patterns of the PCBs to which they had been exposed in the
workplace. Japanese yusho children showed remarkable decrease with time,
but no such decrease was observed in the yusho adults and the workers.
Polychlorinated quaterphenyls (PCQs) were detected in the blood of typical
Japanese and Taiwanese yusho patients, but PCQ levels in the plasma of
the workers were below the detection limit of 0.02 ppb. Clinical findings
and subjective complaints of the workers were usually slight compared with
typical yusho patients, though some of them had mild dermal manifestations
a (incomplete abstract) (Takamatsu et al, 1985)
Study #17
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dermal effects were attributed to the mediation by an aryl
hydrocarbon (Ah) receptor mechanism of action.
The environmental and biological impacts of polychlorinated
dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated
biphenyls (PCBs) were discussed with specific emphasis on the application
of the toxic equivalency factor (TEF) concept. Primary sources of PCDDs,
PCDFs, and PCBs included chemical reactions, combustion processes, photochemical
reactions, source leakages, disposal of contaminated materials, and biochemical
processes, while secondary sources included food and water intake, inhalation,
and skin exposure. The analysis of PCDDs, PCDFs, and PCBs included
high resolution chromatographic/spectrometric and/or sample extraction
methods in addition to quality assurance and cell culture bioassays. PCDDs
and PCDFs were found primarily in abiotic samples such as air, water, snow,
soil, and sediments, and in biotic samples from aquatic organisms. Human
tissue levels and dietary intake of PCDDs and their congeners were mentioned
with reference to values from the World Health Organization. The dermal
effects, immunotoxicity and hepatotoxicity as well as biochemical,
teratogenic, carcinogenic, and neurobehavioral effects due to PCDD, PCDF,
and PCB exposure were attributed to the mediation by an aryl hydrocarbon
(Ah) receptor mechanism of action. The criteria for dioxin like activity
of a particular compound (Ah receptor binding, induction of dioxin specific
biochemical/toxic responses, and persistence and accumulation in the food
chain) were discussed in reference to risk management purposes and the
applicability of the TEF concept in relation to risk management. The neurobehavioral,
neurochemical, carcinogenic, and endocrine changes associated with nonAh
receptor mediated effects were distinguished from Ah receptor responses.
Short term experiments, bioassays, and interactive effects were mentioned
as components in the role of kinetics in the TEF concept. Adverse effects
resulting from occupational and accidental exposure in humans and environmental
exposure among animals were discussed. The authors conclude that the applicability
of the TEF concept is dependent on Ah receptor mediated toxic responses.
(Ahlborg et al, 1992)
Study #18
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dermal lesions improved after fasting
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acneform eruptions forming cysts or abscesses were difficult
to cure
The effects of fasting on polychlorobiphenyl (PCB) poisoned
patients were determined. Sixteen patients were examined and fasted for
7 or 10 days according to age and physical strength. Patients were given
a laxative on day 1. Vitamin tablets were regularly administered. Water
was administered in doses of 15 to 2.0 liters daily, and 200 milliliters
(ml) of mixed juice of vegetables and fruits were administered twice daily
from day 2. Those on a 7 day schedule were administered 200ml of milk twice
daily from day 4; those fasting until day 10 received the milk on day 7.
PCB concentrations in blood were determined from samples taken on days
1, 7, and 10 of fasting and from days 6 and 7 of recovery. All patients
showed some or dramatic improvements after completing the fasting. Dermal
lesions improved after fasting. Acneform eruptions forming cysts or
abscesses were difficult to cure. PCB concentrations in blood were elevated
during and after fasting. The authors conclude that fasting has beneficial
effects on PCB poisoning. (Imamura et al, 1984)
Study #19
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PCBs induced keatinization in mouse epithelial cells
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PCB toxicity in rabbits was initiated by dermal application
of PCBs
Health effects studies were made of polychlorinated dibenzofurans
(PCDF) and polychlorinated biphenyls (PCB) released during a transformer
fire that occurred in a building in 1981. Concentrations of these chemicals
and the soot matrix were collected from the fire site and analyzed. Their
toxicity was studied with in-vitro bioassays based on induction of keratinization
in mouse epithelial cells, acute oral dose experiments and 90 day feeding
studies with guinea-pigs, morphological examinations of liver tissues with
electron and light microscopy, and dermal application studies with rabbits.
The acute oral feeding study made use of a soot sample that approximated
the mean value of soot contamination with PCDF and PCB, and a parallel
study was made with its benzene (71432) extract equivalent. Particulate
matter collected from ceiling panels in the building revealed PCDF concentrations
ranging from less than 1 to 1,200 parts per million (ppm), while PCB concentrations
varied from 23 to 2,300ppm. The PCDF ratio was about 0.067. In addition,
a concentration of 3ppm 2,3,7,8-tetrachloro-dibenzo-p-dioxin (1746016)
(TCDD) was detected in the soot. Particulate samples were effectively ranked
in order of their degree of chemical contamination by the keratinization
in-vitro bioassay studies. The acute oral lethal dose in guinea-pigs was
410 milligrams per kilogram (mg/kg), and its benzene equivalent was 327mg/kg,
indicating that the soot matrix had virtually no effect on the toxicity
of the chemical contaminants in the soot. Liver samples from animals receiving
the soot revealed morphological alterations. Local inflammatory reactions,
as well as evidence of hypertrophy and centrilobular hepatocytes, were
observed in rabbits after dermal application of the soot. Salivary
gland duct metaplasia and decreased relative thymus weights occurred in
animals fed 1.2mg/kg soot for 90 days. The authors estimate that the soot
produced by the fire had a toxicity equivalent to that of 44ppm TCDD. (O’Keefe
et al, 1985)
Study #20
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monkeys fed PCBs developed generalized dry and flaking skin,
and some hair loss
Results were presented from a study designed to provide information
about the response of female cynomolgus-monkeys and rhesus-monkeys to the
ingestion of polychlorinated biphenyls (PCBs). Eight female cynomolgus-monkeys
and eight female rhesus-monkeys were equally divided between a control
and a Aroclor-1254 (11097691) treated group. Aroclor-1254 ingestion affected
body weight. The rhesus monkeys gained weight while the cynomolgus monkeys
lost weight, although feed consumption was not dramatically affected by
treatment. The monkeys also experienced ocular effects, but nothing analogous
to chloracne. The major dermal change in this study may best be described
as generalized dry and flaking skin. Some hair loss was also noted, but
not to an extensive degree. Alterations were noted in the red and white
cell parameters. Pathological changes in the bone marrow of both species
were also noted. The authors conclude that the two species of monkey differ
somewhat in their response to Aroclor-1254 ingestion. Differences were
observed in clinical manifestations, serum chemistry, and apparent absorption/retention
of the ingested PCB. However, the data do not provide convincing support
for the assertion that rhesus-monkeys were more sensitive than cynomolgus-monkeys
to the ingestion of PCBs. Following mating all of the treated rhesus monkeys
aborted within 30 to 60 days of becoming pregnant, while all of the control
monkeys had viable offspring. (Arnold et al, 1990)
Study #21
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animal studies have demonstrated dermal changes
The chemical structure, sources, and adverse health effects
of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans
(PCDFs), and polychlorinated biphenyls (PCBs) were reviewed. PCDDs and
PCDFs have been found as by products in the synthesis of chlorophenolic
based chemicals and combustion processes. PCBs were produced for use in
dielectric fluids, heat exchange systems, lubricants, plasticizers, and
adhesives prior to 1977. A review of major episodes of environmental contamination
involving these substances was presented, and their environmental fate
and transport were discussed. The pharmacokinetics and biodistribution
of PCDDs, PCDFs, and PCBs in humans and experimental animals was examined.
Studies in experimental animals have demonstrated thymic atrophy, wasting,
hepatotoxicity, bone marrow effects, ascites or edema, and dermal changes
after acute exposures and hepatotoxic, carcinogenic, immunologic, and reproductive
and developmental effects following chronic exposures to these compounds.
Studies on the acute health effects in humans reported symptoms such as
nausea and vomiting, headaches, and mucosal membrane irritation. Cancer,
reproductive effects, hepatotoxicity, and immunological effects have been
reported following occupational exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin
(51207319) (TCDD) in herbicide applicators and chemical factory workers.
Problems encountered in risk assessments of TCDD exposures, particularly
in determining exposure and dose response levels, were discussed. (Nessel
et al, 1992)
Study #22
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dermal PCB application caused early macroscopic skin lesions
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hyperplasia and hyperkeratosis of the follicular and epidermal
epithelium
Three groups of rabbits were treated daily (5 times/wk for
28 days) with 120 mg polychlorinated biphenyl (PCB) mixture (Aroclor 1260)
and the solvent isopropanol, respectively. The dermal application
resulted in early macroscopic skin lesions in the Aroclor group.
The lesions in the 2,4,5,2',4,'5'- hexachlorobiphenyl group appeared later
on and were less severe. This difference was confirmed microscopically:
were more severe in the Aroclor group. Fecal coproporphyrin levels were
significantly increased in the experimental groups. Enhanced liver weights
were found in both test groups. Liver injury, as judged by light microscopic
lesions and elevated serum transaminase levels, was somewhat more severe
in the hexachlorobiphenyl group when compared with the Aroclor group, though
the mean liver content was about the same (respectively, 239 and 236 ppm).
Light microscopic findings included subcapsular necrosis, zonal necrosis,
hydropic degeneration, as well as a peripheral and perinuclear shift of
cell organelles, and focal cytoplasmic hyalin degeneration. In electron
microscopy the shift was due to a proliferation of smooth surfaced membranes
of the endoplasmic reticulum (SER), resulting in a displacement of rough
surfaced membranes (RER) and mitochondra. The hyalinized cytoplasm was
recognized as tightly packed tubules of proliferated SER, that is considered
as hypertrophic, hypoactive SER. The contribution of chlorinated dibenzofurans
and pure PCB in the toxicity of crude PCB mixtures is discussed. (Vos et
al, 1972)
Study #23
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skin contact and inhalation of PCBs could lead to nerve damage
Several capacitors containing polychlorinated biphenyls (PCB)
exploded in a cardboard plant. During the accident, and in the clearing
work, several workers were in probable contact with PCB and its degradation
products. Nausea, intense perspiration, and headache were acute symptoms,
which cleared quickly. The 15 men with the greatest exposure were studied
neurophysiologically twice, namely, two and six months after the explosion.
Motor conduction velocities (MCV) of the right median, ulnar, and peroneal
nerves; sensory conduction velocity (SCV) of the right sural nerve: and
distal SCVs of the right median and ulnar nerves were measured with skin
electrodes. Thirty male workers with a similar age distribution werved
as referents. Two months after the explosion all SCVs and distal SCVs were
slower in the exposed men, and still six months after the explosion the
distal SCV of the ulnar nerve and the SCV of the sural nerve were slightly
slower among the exposed. However, clear improvements occurred in the distal
SCVs during the follow-up. As in many toxic distal axonapathies, the distal
SCVs were reversibly impaired after an accidental exposure to PCB fumes.
PCBs seem to exhibit neurotoxic properties in humans. (Seppalainen et al,
1985)
Study #24
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chloracne is considered the most significant work related
acne problem
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chloracne is produced by exposure to chlorinated aromatic
compounds
-
furans are acnegenic and are contaminants in many PCB formulations
Occupational acne was reviewed. Occupational acne, a form
of exogenous acne, was considered one of the most frequent causes of work
related skin disease, second only to contact dermatitis. Three different
groups of acnegenic compounds were distinguished: petroleum and its derivatives,
coal tar products, and halogenated aromatic compounds. Oil acne was the
most common form of industrial acne and was caused mainly by greases and
insoluble cutting oils that contain a high percentage of mineral oil. Machine
tool operators in the metal industry were most commonly affected. Machine
tool operation using cutting oils and coolants was considered to be one
of the ten most hazardous processes when the contact dermatitis produced
by these compounds was taken into account. Clinical features and prevention
and treatment of oil acne were described. Coal tar derivatives have acnegenic
and photosensitizing (phototoxic) as well as carcinogenic properties. Coal
tar acne showed a marked predilection for the exposed areas of the body,
particularly the malar areas. This suggested an airborne distribution of
the compounds, such as the case of fumes generated when hot materials were
manipulated. Clinical features, prevention, and treatment were considered.
Chloracne
was a distinctive form of occupational acne produced by exposure to various
chlorinated aromatic compounds, which may be systemic toxic agents. Widespread
use of polychlorinated biphenyls (PCBs) has caused them to be dispersed
throughout the environment, causing great concern because of the hepatotoxic
and acnegenic potential of polychlorinated dibenzofurans that are contaminants
of many PCB formulations. The use of PCBs has been restricted to closed
system formulations. Chloracne was considered to be the most significant
work related acne problem. Clinical features and prevention and treatment
were reviewed. (Ancona, 1986)
Study #25
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railway electricians absorbed significant levels of PCBs
through handling dielectric fluid
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medical complaints included acneiform skin lesions
The occurrence of elevated polychlorinated-biphenyls
(1336363) (PCBs) in two women as a result of conjugal exposure was discussed.
The two cases discussed involved analytical chemical evidence of transmission
of PCBs from transformer maintenance workers to their wives. Both men had
been employed for 3 to 4 years as railway electricians and their jobs involved
handling dielectric fluid containing PCBs. Medical complaints included
fatigue and acneiform skin lesions. Complete blood counts and serum
biochemistries were normal for both men. Serum and adipose tissue PCBs
were analyzed in both couples. Neither of the women had any history of
occupational exposure to PCBs. PCB levels in the men ranged from 69 nanograms
per milliliter (ng/ml) to 101ng/ml in serum and 17.4 to 20.7 nanograms
per milligram (ng/mg) in adipose tissue. Serum levels in the women ranged
from 6 to 15ng/ml. The adipose PCB level in one of the women was 3.9ng/mg.
In the general population, serum levels were approximately 7ng/ml and adipose
levels were approximately 1ng/mg. The PCB patterns of both couples corresponded
to Aroclor-1254 (11097691). This suggested an industrial source. The authors
conclude that family contacts should be considered as a group at risk for
developing adverse health effects as a result of secondary exposure to
agents present in the occupational environment. (Fischbein et al, 1987)
Study #26
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PCBs are known to produce chloracne in humans
-
chloracne seems to have a predilection for the skin of the
face but involvement also occurs with the neck, shoulders, genitalia, chest,
and lower trunk in this order.
-
in severe cases the arms and legs are involved.
Chloracne is a relatively harmless skin disease caused by
contact with certain aromatic chlorinated hydrocarbons. However, the fact
that such an exposure to a potentially toxic chemical has taken place could
point to warnings of covert damages. Chlornaphthalenes, PCBs, polychlorinated
dibenzofurans, polychlorinated dibenzodioxins, tetrachloroazobenzenes,
and tetrachlorazoxybenzenes are the compounds known to produce chloracne
in humans, with the acneigenic potential of each compound being related
to its overall toxicity. The number of chlorines in the molecule has been
shown to determine the toxicity of the compond. The dioxins (especially
TCDD) with 4 chlorines have been proven to be great inducers of chloracne.
Many toxic chemicals will initiate the steps needed to undergo detoxification
by the induction of certain cellular enzymes. Chemical structures and steric
effects have also been shown to affect the toxicity of the chlorinated
compounds. Many of the chlorinated aromatic hydrocarbons have been proven
to be teratogenic and fetotoxic in animals and in humans. Data on the long
term effects of chloracneigens are limited to animal studies. There is
little hazard of contamination of commercial products with chloracneigens.
The only real risk of exposure to these compounds is in industry where
steps are being taken to control the occupational hazards involved with
handling these substances. (Crow, 1978a)
Study #27
Current knowledge on chloracne was assessed. With the exception
of chlorobiphenyls (PCBs) and chloronaphthalenes (CNs), the remaining
chloracneigens (chlorodibenzodioxins (PCDDs), chlorodibenzofurans (PCDFs),
chloroazo-benzenes (TCAB) and chloroazoxy-benzenes (TCAOB)), are contaminants
formed accidentally during manufacture. Rhesus-monkeys and hairless-mice
may be used to detect chloracne like changes, but rabbit ear is most sensitive
and particularly valuable for assessment of toxicity. The problem of long
term, low dose effects such as carcinogenicity and mutagenicity is currently
under investigation, particularly with respect of additive effects. Dose
related carcinogenicity of 2,3,7,8-tetrachlorodibenzodioxin (1746016) (TCDD)
has been demonstrated in rats, with signs of poisoning. In man, severe
chloracnes and general toxicity are so far confined to industrial workers
poisoned with TCDD as well as the 1200 victims of a Japanese accident in
1968. Isomerism is much more important that the degree of chlorination
in determining chloracneigenicity and general toxicity. Enzyme induction
(aryl-hydrocarbon-hydroxylase) is the most important technique for investigating
toxicity. This technique has recently revealed the apparent chemical basis
for the toxicity of chloracneigens. The authors suggest that the rabbit
ear test should become standard procedure in the evaluation of any new
halogenated aromatic compounds. (Crow, 1978b)
Study #28
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PCBs cause chloracne in humans
-
The position of the halogen atom on the molecule is vital
to the chloracnegenic characteristic
Chloracne is reviewed. Chloracne is an acneform eruption
due to poisoning by halogenated aromatic compounds having a specific molecular
shape. Substances which have unequivocally been proven to have caused
chloracne in humans are listed: chlornaphthalenes, polychlorinated
biphenyls, polychlorinated dibenzofurans, polychlorinated dibenzo-p-dioxins,
tetrachloroazobenzene, and tetrachloroazoxybenzene. Of these chloracnegens,
four are found mainly as contaminants formed accidentally in the manufacture
of other materials. Although the degree of halogenation of the compound
is not important, the position of the halogen atom on the outside of
the molecule is vital to the chloracnegenic characteristic. The distribution
of chloracne lesions is examined as a characteristic diagnostic of exposure
type and degree. The characteristic picture of typical chloracne is described.
Pigmentation is mainly confined to the face but may in the worst cases
extend more widely. A Japanese mass poisoning from cooking oil contaminated
with tetrachlorobiphenyl is described in which victims showed extensive
pigmentation. The appearance of hypertrichosis and phrynoderma is described.
Opthalmic changes are examined. The erythematous changes which may occasionally
be associated with the onset of chloracne are discussed. Skin reactions
in victims exposed to dioxin in a chemical explosion, particularly children
who showed the most serious chemical burns are described. Hyperhidrosis
of the palms and soles is also reported. Associated porphyria is discussed.
Histological changes associated with these toxic exposures begin within
5 days and involve replacement of the sebaceous gland by a keratinous cyst
with an attachment to the epidermis. The author concludes that whenever
chloracne is seen, however mild, chloracnegens must be sought. Histological
examination of lesions of more than 6 weeks duration will almost always
separate chloracne from other forms of acne. (Crow, 1982)
Study #29
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contact with contaminated flood water reportedly resulted
in skin burns
The MIDCO I site is a four-acre, abandoned industrial waste
recycling, storage, and disposal facility in Gary, Indiana. Twelve drinking
water wells have been identified within approximately one mile of the site.
The Calumet Aquifer, one of the two major aquifers underlying the site
and proving water to these wells, is highly susceptible to contamination
from surface sources. Within a three-year period, the site owners accepted
and stockpiled approximately 6,000-7,000 55-gallon drums containing bulk
liquid waste, and 4 bulk tanks, each 4,000-10,000 gallons. In June 1981
severe flooding caused water in the area to drain west into a neighboring
city; contact with the flood water reportedly resulted in skin burns.
In 1982 extensive surface wastes, an underground tank, and the top one
foot of contaminated soil were removed. The primary contaminants of concern
affecting the soil, sediment, and ground water are VOCs including benzene,
toluene, and TCE; other organics including PCBs, phenols, and PAHs;
(EPA Region 5, 1990)
Study #30
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chlorinated aromatic hydrocarbons (such as PCBs) cause chloracne
and another dermal lesions
Chloroorganic compounds, typified by the chlorinated aliphatic
and aromatic hydrocarbons, especially biphenyls, naphthalenes, dibenzo-p-dioxins,
dibenzofuranes and azo/xy/benzenes are, or were, manufactured as commercial
products /the chlorinated biphenyls and naphtalenes/, and occur
only as contaminants in commercial products /the chlorinated dibenzo- p-dioxins,
dibenzofurans, and azo/xy/benzenes/. They have all become widespread in
the environment. The chemical stability and lipophilicity of these compounds,
and their resistance to degradation results in their persistence in the
environment and concentration in the food chains. Their chemical structures
are similar, i.e. they are approximate isostereomers. They act by the common
receptor-mediated mechanism and produce similar toxic responses, although
they vary greatly in potency. All classes of chloroorganic compounds have
produced incidents of intoxication of industrial workers, the general population,
and farm or wild animals. Chlorinated aromatic hydrocarbons elicit a numerous
toxic effects which include body weight loss, thymic atrophy, immunotoxicity,
hepatotoxicity and porphyria, chloracne and another dermal lesions,
tissue-specific hypo- and hyperplastic responses, teratogenicity, reproductive
toxicity, and carcinogenesis. (Starek, 1996)
Study #31
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Lifetime prevalence of chloracne, abnormal nails, hyperkeratosis and skin
allergy were more frequent in PCB and furan poisoning victims
In 1979, a mass poisoning involving 2,000 people occurred in central Taiwan
from ingestion of cooking oil contaminated by polychlorinated biphenyls
(PCBs) and polychlorinated dibenzofurans (PCDFs). We studied the prevalence
of medical
conditions in the exposed individuals and in a neighborhood control
group. Starting with a registry of the exposed individuals from 1983, we
updated the addresses of exposed individuals and identified a control group
matched for age, sex, and neighborhood in 1979. In 1993, individuals 30
years of age or older were interviewed by telephone. We obtained usable
information from 795 exposed subjects and 693 control subjects. Lifetime
prevalence of chloracne, abnormal nails, hyperkeratosis, skin allergy,
goiter,
headache,
gum pigmentation, and broken teeth were observed more frequently in the
PCB/PCDF-exposed men and women. The exposed women reported anemia 2.3 times
more frequently than controls. The exposed men reported arthritis and herniated
intervertebral disks 4.1 and 2.9 times, respectively, more frequently than
controls.
There was no difference in reported prevalences of other medical conditions.
We conclude that Taiwanese people exposed to high levels of PCBs and PCDFs
reported more frequent medical problems, including skin diseases,
goiter, anemia, and joint and spine diseases. (Guo et al, 1999)
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