8. EFFECT OF PCDDs ON HUMAN BEINGS - EPIDEMIOLOGICAL AND CASE STUDIES
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8.3 Signs and Symptoms in Humans Associated With TCDD Exposure
Many signs and symptoms have been reported in studies of human exposures to PCDDs, both occupationally and from the general environment. These have been compiled from the various studies and are shown in Table 64.
8.3.1 Skin manifestations
Chloracne is a sign of exposure to several chlorinated cyclic organic compounds, the most potent being TCDD. Chloracne thus may serve as a marker of such exposure. The most distinctive lesion in chloracne is the so-called cyst, a skin-coloured elevation that may measure from 1 mm to 1 cm in diameter, with a central opening that may be difficult to detect. Comedones that contain black or black-appearing material in their openings are also present. There may be a secondary inflammatory reaction, melanosis, and hyperkeratosis, and these skin changes may be preceded by a "cable rash" or "cable itch".
These skin lesions resemble photosensitivity reactions and the bearers may suffer severe pruritus. Microscopic examination of the skin lesions shows marked dilatation of the hair follicles which are filled with keratinous material, the sebaceous glands may be partly or completely atrophied and, occasionally, hyperplasia of these glands has also been reported. Hyperkeratosis and acanthosis of the surrounding epidermis usually accompany these lesions.
Atrophy of the epithelium and thinning of the epithelial walls surrounding these keratinous cysts are observed at a later stage of the disease. If the follicular cysts rupture, foreign body granulomata may also be observed. Healing of these skin lesions usually results in deeply pitted scars. The distribution of chloracne is predominantly facial, affecting in particular the malar areas, the jaws, and the regions behind the ears. At times it may involve the ear canal and, with increasing severity, also the rest of the face and neck. In more extensive cases, the outer upper arms, neck, back, abdomen, outer thighs, and genitalia may also be involved (Crow, 1970).
While the absence of chloracne does not absolutely rule out exposure to TCDD, it usually indicates that there has been no exposure to a toxic dose of the substance. "Toxic" is used here to indicate both systemic and local effects. Where there has been exposure to TCDD and chloracne has resulted, it is the only known clinical sign that persists for a long period of time, even for the remainder of the exposed person's life time. In a large group of people exposed to mixtures containing TCDD, the absence of chloracne usually indicates that exposure to a toxic dose was unlikely and also makes it unlikely that severe, persistent systemic disorders will result.
Hyperkeratosis is a fairly common phenomenon whereas hyperpigmentation and hirsutism are rare. It should be noted that hyperkeratosis is prominent in the exposed Seveso children who have no affected sebaceous glands. These glands develop only at puberty. Elastosis of the skin has been noted as a long-term effect of TCDD exposure.
8.3.2 Systemic effects
Liver effects following exposure to PCDDs have been diagnosed even by histological examination, and account for temporarily raised transaminases in blood, hypercholesteraemia, and hypertriglyceridaemia. Bauer et al. (1961) and Risse-Sundermann (1959) do not however exclude viral hepatitis as a cause of such findings in their patients exposed to TCDD. Loss of appetite, weight loss, and digestive disorders are common complaints from humans exposed to either TCDD itself, or to technical mixtures containing TCDD. Muscular aches and pain and weakness in extremities have been reported, particularly after exposure to technical mixtures containing TCDD.
Swollen lymph nodes have also been reported, both after exposure to "pure" TCDD and to mixtures. The cardiovascular, urinary tract, respiratory, and pancreatic disorders reported are of doubtful significance with regard to a causal relationship to TCDD exposure.
Porphyria cutanea tarda has been reported in two cases of occupational exposure where chlorinated organic compounds were manufactured in addition to trichlorophenol. These were the incidents at the factory of Diamond Alkali, Newark, New Jersey, USA, in 1956 (Poland et al., 1971) and at Spolana, Czechoslovakia, between 1964 and 1969 (Pazerova-Vejlupkova et al., 1981). The porphyria cutanea tarda observed in these cases was very unlikely to have been induced by exposure to TCDD but rather by exposure to other chlorinated organic compounds manufactured in these plants (Jones & Chelsky, 1986).
8.3.3 Neurological effects
Sexual dysfunction (lack of libido and impotence) has been reported after acute exposure to both "pure" TCDD and technical mixtures (Schulz, 1968). The frequency of its occurrence may have been underestimated to date. Headache is a frequent symptom after exposures to technical mixtures containing TCDD.
Sensory neuropathy has been noted in many instances. Usually workers in the initial stages of exposure will complain of pains in their joints after they have very acute severe chloracne; however, there are usually no abnormal physical findings in the joints, but the complaints may continue. In early studies of workers affected by TCDD, no attempts were made to objectively measure the effects on the sensory nervous system.
Tests have now been developed that evaluate sensory nerves and that can be used in future field studies. The nerve conduction tests, which primarily have been used so far, are actually not very useful to measure neuropathy. Differences in nerve conduction were shown among residents from Seveso, Italy, who had chloracne and those who did not (Richert, von, 1962; Fillipini et al., 1981).
Sight disturbance may be related to alkaline exposure or to conjunctivitis related to effects on the glands of Meibom. Loss of hearing, taste, and smell have been reported in a few cases, but a causal relationship to TCDD exposure is doubtful.
8.3.4 Psychiatric effects
The symptoms have been listed in Table 64 in what is believed to be their order of frequency and degree of severity.