Document B5mGdXJ1mO1a46Q69mVxV87y4

PCDDs are In progress. The carcinogenic potentials of PCDFs have not been studied. 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 (IAFC> 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 (Honc'nar and Halperin, 1981). 28 Table 7. Toxic Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin In Man.a Effects________________ ____ ~ ________________ DERMATOLOGICAL Chloracne Porphyria cutanea tarda Hyperpigmentation and hirsutism -- INTERNAL Liver damageb Elevated serum hepatic enzyme levels Disorders of fat metabolism Disorders of carbohydrate metabolism 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 OCCUPATIONAL EXPOSURES IN CHLORINATED PHENOLS RESULTING IN HUMAN ILLNESSa Yea r,Place,and chemical(s) Type of exposure and no. of cases 1936 Michigan Produc tion Tetrachlorophenol 21 2- (2-chloropheny1) pheno1 Effects on the skin Chloracne, hyperkeratos is Neurological effects Effects on the liver and serum lipids Other effects Fatigue, weight loss Re ferences Butler, 193 1936 Mississippi Wood treatTet rachlorophenol ment 300-600 Chloracne,fac ial erythema, vesculation, ulceration, hyperkeratosis, hyperpigmentation Fatigue, colored urine, urinary problems, venous thrombos is Anonymous, 19 36: St ing 1960 1969 West Virginia Tr icliloro phenol 2,6,5-T Explosion 117 Produc tion 111 O CvJ Chloracne, facial erythema, hyperpigmentation, melano8 is Nervousness, Hepatomegaly, ab- Fatigue, weight - irritability, normal liver 1os8, weakness, insomnia, function, toxic decreased libido, personality hepatitis, elevat- impotence, intol cliange.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) Ashe and Susk ind, 1< 1930; Susk: 1953; Susk 1977 1969 Germany Tr ichlorophenol Tet rachlorophenol Pentachlorophenol Product ion, Industrial Labora tory 17 Chloracne, hyperpigment ation, scarring Lower extremity Abnormal liver pain and weak- function, ness, paresis cirrhosis without atrophy, paresthesia, polyneurit is Fatigue, severe bronchitis, decreased libido, impotence, bursi tis, myocardial damage Baoder 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 Production 17 Explosion 21 Production 29 1963 Holland Trichlorophenol 2,4,5-T Explosion 106 Chloracne Chloracne, hyperpigmen tation, hy pertrichosis , acquired porphy ria cutanea tard, 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 blepharoconjunctlvitis, myocardial dam age, intolerance to alcohol Suskind, 1 Sensory impair- Toxic hepatitis ment of smell.taste, hearing; tendency to orthostatic collapse, limited paresis, peripheral neuropathy, reading difficulties Fatigue, drowsiness bronchitis, laryn gitis, blepharoconj unctivit is, hemorrhagic pleu ritis, myocardial damage, increased susceptibility to infect ion Coldman, Peripheral neuropathy Toxic hepatitis, elevated tryglycierides and choles terol Dugois et 1956; Dug et al, 19 Clinical examination normal , No Information Abnormal liver Right upper function, abnor- quadrant pain mal liver biopsies (parenchymal cell degeneration, fluorescence) Liver function normal Fatigue Bielberg 1964 Vos et al 1964 USSR Trichlorophenol 2,4,5-T Production 128 Chloracne 1968 England Trichlorophenol Explos ion 79 Cloracne, facial erythema 1965-1968 Czechoslovakia Trichlorophenol Pentachlorophenol 2,4,5,-T Production 80 Chloracne, hyperpigmentation, hyper trichosis , scarring, ac quired porphyria cutanea tarda 1969 New Jersey Trichlorophenol 2,4,5-T 2,4-D 1.978 England Trichlorophenol no longer in production Production 73 Followup of plant studied by Bleiberg (above) Followup of 41 workers in'1968 explosion (above) 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 an Bikbulatova 1970 Abnormal liver function Transient glyco suria , mild con junctivitis May, 1973; Jensen and Walker, 19f Jensen et t 1972 Lower extremity Hepatomegaly, ab- Fatigue, weight weakness and normal liver func- loss, abnormal pain,somnolence, tion, abnormal blucose tolerance, headache, insom- liver biopsies no evidence of nia, emotional (mild steatosis, myocardial or and psychiatric periportal fibro- renal damage or disorders, peri- sis, fluorescence) . of increased eye- pheral neuro- Elevated trlglyc- inflammation or pathy (confirmed erides, phospho- respiratory in by abnormal. EMG) lipids, and fection cholesterol Jiraskek et 1964; Pazdt Vejlupkova al, 1980; PazderovaVejlupkova 1981 Lower extremity No significant weakness, corre- abnormalities lation between chloracne and hypomania scale on MMFI Eye irritation, mild uroporphyrinuria in one worker Poland et \ 1971 (see Bleiberg e 1964) .Elevated GGT, elevated tri glycerides , elevated urinary D-glucarlc 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 ABhe 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: Hoses et al, 1984 Elevated GOT in those with chloracne Decreased libido, Moses et al sexual dysfunction 1984 History of GI ulcer Lower pulmonary function in exposed smokers Suskind anc Hertzberg, 1984 Elevated Aik. Phos. Elevated urinary porphyrins Chezzi et al, 1984