Humans TCDD exposure

Hepatotoxic effects, such as elevated GGT levels and small alterations in lipid profile, have sometimes been observed in humans after exposure to high 2,3,7,8-TCDD levels. In general, the effects have been mild and in some cases appear to have been transient."... 

Most, if not all, occupational illnesses associated with 2,4,5-T (such as chloracne) have been found to be the result of product contamination with TCDD. TCDD is extremely toxic to animals, and exposure has also been associated with liver function impairment, peripheral neuropathy, personality changes, porphyria cutanea, hypertrichosis, and hyperpigmentation in humans. TCDD is a chlorinated dioxin, one of a large number of related compounds referred to as dioxins it has no functional use and is not intentionally produced. It has been identified as the responsible toxic agent in several industrial disasters, such as accidental releases at Nitro, WV in 1949, and at Seveso, Italy in 1976. " The role of dioxin contaminants must also be considered in the discussion of 2,4,5-T toxicology. 

TCDD exposure levels and health effects. A common problem with most of the human studies is that the people are exposed to a number of chemicals at the same time. In most human health studies, we do not know how much 2,3,7,8-TCDD people were exposed to or how long the exposure lasted. In other studies, the people were examined many years after they were exposed and some of the effects may have not have been present at the time of examination or the effects observed may not have been caused by 2,3,7,8-TCDD. Some of the more recent studies have measured 2,3,7,8-TCDD levels in the blood or fat tissue of exposed populations. The levels of... 

The effects of 2,3,7,8-TCDD exposure in humans exposed in occupational or environmental settings have been described in several studies. Few studies provided precise exposure levels. However, for some cohorts, blood lipid 2,3,7,8-TCDD levels in samples collected shortly after exposure and stored frozen for several years have been analyzed. In other studies, the original blood levels of 2,3,7,8-TCDD were estimated using 2,3,7,8-TCDD levels measured in recent blood samples, the amount of time between exposure and blood sample collection, and a mean serum half-life of 5-12 years. 2,3,7,8-TCDD body burdens calculated from available serum lipid 2,3,7,8-TCDD levels are presented in Table 2-1. 

Dermal Effects. The most commonly observed effect of 2,3,7,8-TCDD exposure in humans is chloracne (Jirasek et al. 1976 Kimbrough et al. 1977 May 1973 Oliver 1975 Reggiani 1980). Chloracne is characterized by follicular hyperkeratosis (comedones) occurring with or without cysts and pustules... 

In conclusion, dermal effects, particularly chloracne, are the most commonly reported effects of 2,3,7,8-TCDD exposure in humans because they are easy to identify. Additional information is needed to determine the level and frequency of 2,3,7,8-TCDD exposure needed to cause chloracne and whether individual susceptibility plays a role in the etiology. Also, chloracne in humans indicates CDD exposure, but lack of chloracne does not indicate that exposure has not occurred. Other dermal conditions reported include hypertrichosis, hyperpigmentation, and solar elastosis. 

Psychological effects have been associated with 2,3,7,8-TCDD exposure in some human studies. Personality changes were reported following acute exposure (Oliver 1975). Depression (Levy 1988 ... 

A number of studies have investigated the possible association between 2,3,7,8-TCDD exposure and reproductive toxicity in humans. A common limitation of many of these studies, particularly those... 

TCDD or 2,3,7,8-TCDD-contaminated chemicals, workers involved in manufacturing or application of phenoxy herbicides and/or chlorophenols, and Vietnam veterans. In most of the human studies, exposure was poorly characterized. 

The results of the available developmental studies in humans were inconclusive. The lack of exposure data, small sample sizes, and the lack of reliable data for birth defect rates prior to 2,3,7,8-TCDD exposure limit the power of the human studies to determine if an association between 2,3,7,8-TCDD exposure and developmental toxicity exists. 

TCDD exposure. It should be emphasized that some of the human studies do not provide adequate exposure data and were confounded by concomitant exposure to other chemicals. 

There is sufficient evidence that 2,3,7,8-TCDD is carcinogenic in animals, and the overall epidemiological database suggests that the incidence of certain types of cancer may be increased in humans by exposure to 2,3,7,8-TCDD (Hardell et al. 1994 Lucier et al. 1993a). The mechanism of... 

TCDD in the workplace (Jirasek et al. 1976 Oliver 1975). However, due to the lack of data from controlled studies, the role of 2,3,7,8-TCDD, if any, is difficult to ascertain. Although weight loss has not been well documented in humans following exposure to 2,3,7,8-TCDD, numerous animal studies provide evidence that exposure to CDDs causes the wasting syndrome. Acute oral exposure to... 

The animal database provides strong evidence that developmental toxicity is a sensitive end point following 2,3,7,8-TCDD exposure. Structural malformations, functional alterations (including impaired development of reproductive system), decreased growth, and fetal/newbom mortality have been observed in several animal species. Limited human data on the developmental toxicity of CDDs is available. Most of these studies examined the occurrence of birth defects in children of males exposed to 2,3,7,8-TCDD. Deficiencies in the human data preclude drawing firm conclusion on the potential of 2,3,7,8-TCDD to induce developmental effects in humans. However, the animal data suggest that 2,3,7,8-TCDD is a likely human developmental toxicant. 

In vitro genotoxicity studies are summarized in Table 2-17. Eukaryotic cell systems were used for detecting the effects of 2,3,7,8-TCDD exposure on DNA. Exposure to 2,3,7,8-TCDD did not stimulate the unscheduled DNA synthesis in cultural human cells (Loprieno et al. 1982), but inhibited DNA, ribonucleic acid (RNA), and protein synthesis in mouse lymphocytes (Luster et al. 1979) caused gene mutations in mouse lymphoma cells (Rogers et al. 1982) and induced sister chromatid exchanges in Chinese hamster cells (Toth et al. 1984). 

KnutsenAP. 1984. Immunologic effects of TCDD exposure in humans. Bull Environ Contam Toxicol 33 673-681. 

The food chain is the primary pathway of human exposure to dioxin, with meat (38%) and dairy products (28%) dominating. Fish ingestion can be a significant contributor in countries with high fish consumption (26% of total intake in the Netherlands), but is not an important factor in the US. The exact contribution of fruits and vegetables is unclear, but vegetable oil does appear to play a role in human dioxin exposure. Inhalation and consumption of contaminated water and soil are not major sources of human exposure to TCDD. 

Aylward LL, Hays SM. 2002. Temporal trends in human TCDD body burden decreases over three decades and implications for exposure levels. J Expo Anal Environ Epidemiol 12 319-328. 

TCDD, the most toxic of the 75 dioxin isomers and possibly the most toxic manufactured chemical, contaminates phenoxy herbicides during the production process (Demers and Perrin 1995 Klaassen 1985). Conflicting literature addresses TCDD lethality in humans. Some reviews deny that human deaths result from systemic effects of TCDD (Demers and Perrin 1995). Others describe successful suicides with phenoxy herbicides (Nielsen et al. 1965). Despite extensive reports of numerous medical conditions from TCDD, the literature confirms only chloracne and transient mild hepatotoxicity in humans. Table 1-6 lists the various, but unconfirmed, signs and symptoms associated with human poisonings. Table 1-7 lists the unconfirmed psychiatric symptoms attributed to TCDD exposure. 

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