Document bBjENdovKE788LDevEYOEaY03

27 PCDDs are in progress. The carcinogenic potentials of PCDFs have not beenstudied. 2,3,7,8-TCDD is teratogenic in mice and hamsters. The threshold teratogenic dose in mice was estimated to be 0.1 meg per day (Smith et al, 1976). 2,3,7,8-TCDD has been shown to be fetotoxic in a wide variety of species, including primates. HCDD was teratogenic in rats at a dose of I 100 meg'/kg per day (IARC 1977) There is as yet no data on the fetotoxic potentials of PCDFs in animals. The toxic effects of 2,3,7,8-TCDD in man are summarized in Table 7. The toxic effects most consistently observed in occupational studies are chloracne, liver dysfunction, neuropsychiatric disturbances, and abnormalities in porphyrin metabolism. Table 8 summarizes the findings of the morbidity studies of workers exposed to 2,3,7,8-TCDD to date. The few follow-up studies which have been done show resolution of gross liver dysfunction and porphyrin abnormalities following removal from exposure. (Pazderova-Vijlupkova et al, 1981; Suskind, 1984). Several of the occupational exposures occurred as the result of uncontrolled exothermic reactions during the production of trichlorophenol. A similar process accident at Seveso, Italy in 1976 resulted in widespread community exposure to 2,3,7,8-TCDD. Health effects included chloracne, primarily in children, and peripheral neuropathy in a small percent of those exposed (Pocchiari et al, 1979). The epidemiologic studies on the carcinogenecity of TCDD are summarized in Table 9- While individual occupational mortality studies reveal no excess of cancer, the pooled data suggest an excess of soft tissue sarcoma (Honchar and Halperin, 1981). 28 Table 7. Toxic Effects of 2,3,7,8-Tetrachlorodlbanzo-p-dioxin in Man.a E f f e c t s ____ _______ _______________________________ _________ _ ________ DERMATOLOGICAL Chloracne Porphyria cutanea tarda Hyperpigmentation and hirsutism INTERNAL Liver damage^ Elevated serum hepatic enzyme levels Disorders of fat metabolism Disorders of carbohydrate metabolism I Cardiovascular disorders Urinary tract disorders Respiratory disorders Pancreatic disorders NEUROLOGICAL Polyneuropathies (perpheral neuritis) Lower extremity weakness Sensory impairments (sight, hearing, smell, taste) PSYCHIATRIC Neurasthenic or depressive syndromes____ ____ ______ ^Source: Huff, Moore, Saracci, and Tomatis, 1980 ^Mild fibrosis, fatty changes, hemofuscin deposition and parenchymal-cell degeneration were observed in a few cases. TABLE 8. REPORTED OCCU?ATIONAL EXPOSURES IN CHLORINATED PHENOLS RESULTING IN HUMAN ILLNESSa Type of Year,Place,and exposure and chemical(s)_______ no. of cases Effects on the Effects on Neurological liver and the skin__________effects__________ serum lipids_______Other effects________ References 1936 Michigan Production Tetrachlorophenol 21 2- (2-chlorophenyl) phenol Chloracne, hyperkeratosis Fatigue, weight loss Butler, 193 1936 Mississippi Wood treat Tetrachlorophenol ment 300-600 Chloracne,facial erythema, vsicula tion, ulceration, hyperkeratosis, hyperpigmentation Fatigue, colored urine, urinary problems, venous thrombosis Anonymous, 1936: Sting I960 1969 West Virginia Trichlorophenol 2,4,5-T Explosion 117 Production 111 Cvl 1969 Germany Trichlorophenol Tetrachlorophenol Pentachlorophenol Production, Industrial Laboratory 17 Chloracne, facial erythema, hyper pigmentation, melanosis Nervousness, Hepatomegaly, ab- Fatigue, weight > irritability, normal liver loss, weakness, insomnia, function, toxic decreased libido, personality hepatitis, elevat- impotence, intol change,de-*- ed triglycerides erance to cold, pression, and cholesterol increased sus headache, ceptibility to vertigo, pain infection (es and weakness pecially respir lower extrem- atory) eties, paresis, peripheral neuro pathy, abnormal nerve biopsy (loss of myelin) Chloracne, hyperpigment ation, scarring Lower extremity Abnormal liver pain and weak- function, ness, paresis cirrhosis without atrophy, paresthesia, polyneuritiB Fatigue, severe bronchitis, de creased libido, impotence, bursi tis, myocardial damage Ashe and Suskind, 19 1950; Suski 1953; Suski 1977 Baader and Bauer, 195! 1952 Germany Trichlorophenol Production 31 Chloracne, hyperpigmen tation 1953 Germany Trichlorophenol Explosion 55 Chloracne 1956 France Trichlorophenol 1966 France Trichlorophenol 1956 New Jersey Trichlorophenol Product ion 17 Explosion 21 Production 29 1963 Holland Trichlorophenol 2,4,5-T Explosion 106 Chloracne Chloracne, hyperpigmentation, hy pertrichosis, acquired porphy ria cutanea tarda Chloracne, facial erythema Lower extremity Toxic hepatitis, pain and weak- abnormal liver ness,paresthesia, biopsy memory and con centration defi cits, sleep disturbances,' hy persomnolence, abnormal psycho logical tests (apathy, dulled emotional response) Fatigue, chronic bronchitis, per sistent blepharoconjunctivitis, myocardial dam age, intolerance to alcohol Suskind, 19 Sensory impair- Toxic hepatitis ment of smell,taste, hearing; tendency to orthostatic collapse, limited paresis, peripheral neuropathy, reading difficulties Fatigue, drowsiness, bronchit is, laryn gitis, blepharoconj unctivitis, hemorrhagic pleu ritis, myocardial damage, Increased susceptibility to infection Coldman, ] Peripheral neuropathy Toxic hepatitis, elevated tryglycerides and choles terol Dugois et 1956; Dugo et al, 196 Clinical exam ination normal No information Abnormal liver Right upper function, abnor quadrant pain mal liver biopsies (parenchymal cell degeneration, fluorescence) Liver function normal Fatigue Bleiberg e 1966 Vos et al, 1964 USSR Trichlorophenol 2,4,5-T Production 128 Chloracne 1968 England Trichlorophenol Explosion 79 Cloracne, facial erythema 1965-1968 Czechoslovakia Trichlorophenol Pentachlorophenol 2,4,5,-T Production 80 Chloracne, hyperpigmenta- v tion, hyper trichosis , scarring, ac quired porphyria cutanea tarda 1969 New Jersey Trichlorophenol 2,4,5-T 2,4-D 1978 England Trichlorophenol no longer in production Production 73 Followup of plant studied by Bleiberg (above) Followup of 41 workers in 1968 explosion (above) 41 Chloracne in 48, hypertrichosis in 16, hyperpig mentation in 30, no overt por phyria cutanea tarda Chloracne Headache, loss of memory, somnolence, sleeplessness, Increased sweating Fatigue, joint pain, stomach pain Telegina and Bikbulatova, 1970 Abnormal liver function Transient glyco suria, mild con junctivitis May, 1973; Jensen and Walker, 196' Jensen et al 1972 Lower extremity Hepatomegaly, ab weakness and normal liver func pnin,somnolence, tion, abnormal headache, insom liver biopsies nia, emotional (mild steatosis, and psychiatric periportal fibro disorders, peri sis, fluorescence) pheral neuro Elevated triglyc pathy (confirmed erides, phospho by abnormal EMC) lipids, and cholesterol Fatigue, weight loss, abnormal blucose tolerance, no evidence of myocardial or renal damage or of increased eye inflammation or respiratory in fection Jiraskek et 1964 ; Pazdei Vejlupkova t al, 1980; PazderovaVejlupkova e 1981 Lower extremity No significant weakness, corre abnormalities lation between chloracne and hypomania scale on MMPI Eye irritation, mild uroporphyrinuria in one worker Poland et a 1971 (see Bleiberg et 1964) Elevated CGT, elevated tri glycerides , elevated urinary D-glucaric acid May, 1982 1949 West Virginia Trichlorophenol 2,3,5-T . 1949 West Virginia Trichlorophenol 2,4,5-T 226 Followup of plant studied by Ashe and Suskind (above) 204 Followup of plant studied by Ashe and Suskind and Moses et al (above) Chloracne 70-residual 47-by his tory Abnormal sensory findings in those with chloracne Chloracne in 107 Actinic Elastosis ^ 1976 Seveso Trichlorophenol No. not given ICMESA workers follow-up five years after explosion a Source: Moses et al, 1984 Elevated GGT In those with chloracne Decreased libido, Moses et al sexual dysfunction 1984 History of GI ulcer Lower pulmonary function in exposed smokers Suskind and Hertzberg, 1984 Elevated Aik. Phos. Elevated urinary porphyrins Ghezzi et al, 1984