Exposures to TCDD

Alderfer R, Sweeney M, Fingerhut M, et al Measures of depressed mood in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Chemosphere 25 247-250, 1992 

Bond GG, McLaren EA, Cartmill JB, et al Cause-specific mortality among male chemical workers. Am J Ind Med 12 353-383,1987 Bond GG, Wetterstroem NH, Roush GJ, et al Cause specific mortality among employees engaged in the manufacture, formulation, or packaging of 2,4-dichloro-phenoxyacetic acid and related salts. British Journal of Industrial Medicine 45 98-105, 1988 

Bond GG, McLaren EA, Lipps TE, et at Update of mortality among chemical workers with potential exposure to the higher chlorinated dioxins. Journal of Occupational Medicine 31 121-123, 1989 

Gilioli R, Genta P, Cotroneo L, et al Electroencephalographic spectral analysis in chemical and engineering workers, in Neurobehavioral Methods in Occupational ffealth. Edited by Gilioli R, Cassitto MG, Foa V. Oxford, UK, Pergamon, 1983, pp 219-229 

Green LM Suicide and exposure to phenoxy acid herbicides (letter). Scand J Work Environ Health 13 460, 1987 

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TCDD causes bone marrow hypocellularity, with specific decreases in the total number of hematopoietic stem cells (HSC) and lymphocyte precursors.42 16 Exposure to TCDD also diminishes mRNA levels of recombination activating gene-1 and terminal deoxy-nucleotidyl transferase in bone marrow cells.47 The best characterized effect of TCDD on bone marrow is the impaired maturation of B cells. A single dose of TCDD causes a transient, time- and dose-dependent, and developmental stage-specific impairment in B cell maturation, with mature B cells affected first, followed by depletion of B cell progenitors.45-46... 

In contrast to adaptive immune function, fewer studies have examined effects of TCDD on the innate immune system. Furthermore, of the limited data available, much of it is inconsistent. For example, natural killer (NK) cell activity has been reported to be unaffected,80,93 diminished,94 and increased95 following exposure to TCDD. Although a thorough assessment of AhR expression in all innate cell lineages has not been conducted, neutrophils and macrophages express the AhR,8,96 and neutrophils are affected... 

Effects of TCDD on macrophages have also been examined. When assessed ex vivo, macrophage functions such as tumor cell lysis, phagocytosis and oxidative burst were not suppressed by exposure to TCDD.9396 101 In other experimental systems, exposure to TCDD increases IL-1 and TNF production by macrophages.99 102 103 However, the ability of TCDD to alter IL-1 and TNF production is likely organ- or stimulus-specific, because in the context of respiratory viral infection, exposure to TCDD had no effect on IL-1 or TNF-a levels.80... 

The sensitivity of the developing immune system to TCDD has been recognized for quite some time.105 106 However, the period of time during immune ontogeny that is most sensitive to disruption by TCDD has not been identified, and differences in the endpoints examined, the dose of TCDD, and the time period of exposure to TCDD (continuous,... 

Compared to people in a noncontaminated area, plasma IgG levels were also significantly decreased in proportion to increasing plasma levels of TCDD in a cohort exposed in an industrial accident in Seveso, Italy.118 There was no effect on IgM or IgA levels, or on complement levels IgE was not measured. In separate studies, in vitro exposure to TCDD enhanced the spontaneous production of IgE by B cells isolated from atopic but not non-atopic individuals, but did not affect the levels of other isotypes.119 Other recent studies have reported small changes in immune cells from individuals exposed occupationally to PHAH.120121 For example, compared to unexposed controls, a cohort of men exposed occupationally to TCDD had diminished IFNy production in a recall response to tetanus toxin, while IFNy production following polyclonal activation was unaffected.120 This observation is consistent with mouse studies, in which antigen-specific responses are highly suppressed by TCDD, but mitogen-driven T cell responses are less susceptible to impairment.83 88122123... 

Holladay, S., et. al., Perinatal thymocyte antigen expression and postnatal immune development altered by gestational exposure to TCDD, Teratolog,y 44, 385, 1991. 

Vorderstrasse, B., Cundiff, J., and Lawrence, B.P, A dose-response study of the effects of prenatal and lactational exposure to TCDD on the immune response to influenza A virus, J. Toxicol. Environ. Health,69, 445. 

Reggiani G Acute human exposure to TCDD in Seveso, Italy. J Toxicol Environ Health 6 27, 1980... 

April 1977 to December 1984 there was a decrease in the male/ female sex ratio (26/48) in contrast, from 1985 to 1994, this ratio increased to normal values (60/64). These results suggest that high-level exposure to TCDD may affect birth sex ratios however, no changes in sex ratios have been observed as a result of parental occupational exposure to relatively high doses of TCDD,31 and no other data corroborate the Seveso findings. 

The one-compartment approach has been used to estimate background exposure to TCDD in the general population on the basis of serum or adipose measurements with the following equation (EPA 2003) ... 

Ultimate proof of the widespread exposure to TCDD is exemplified by the fact that virtually all human adipose tissue samples contain TCDD at trace levels of 6 ppt.60 Adipose tissue of non-occupationally exposed humans has been found to contain concentrations of 18-122 pg TEQ g 1 fat, with a mean value of 56pg TEQ g 1 fat,43 a value 22 times higher than the concentration in beef fat (2.6 pg TEQ g 1 fat). 

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. 

One of the major hallmarks of acute exposure to TCDD and related compounds is the development of chloracne and other dermal problems which have been identified in highly exposed workers.67,68 In animal studies, TCDD can cause... 

Upon ocular exposure to TCDD, the eye should be immediately washed well with plenty of tap water. Skin exposed to TCDD should be immediately washed with soap and water. Get immediate medical attention in the event of ingestion or inhalation of TCDD. 

Creighton LIniversity Studying products of altered lipid metabolism, including formaldehyde, associated with exposures to TCDD, endrin, and lindane in pregnant mice. Specifically, they are concerned with the exposures of the fetus to these products and will be determining formaldehyde concentrations in maternal serum and amniotic fluid. NIEHS... 

Schantz SL, Seo B-W, Moshtaghian J, et al. 1996b. Effects of gestational and lactational exposure to TCDD or coplanar PCBs on spatial learning. Neurotoxicol Teratol 18 305-313. 

Smith DA Germolec DR (2000) Developmental exposure to TCDD and mercuric chloride in autoimmune-prone MRL/lpr mice. Toxicologist, 54 8. 

Exposures to TCDD also resulted from industrial wastes or accidents that contaminated entire communities such as Times Beach, Missouri, and Seveso, Italy. Although TCDD is no longer commercially available, it remains a hazard for several occupations and occupants of certain geographical localities (Table 1-5). Cocaine abusers can encounter cocaine derived from coca plants treated with phenoxy herbicides in countries without herbicide regulation (Elsohly et al. 1984). 

In addition to chloracne, acute or chronic health effects, or both, may occur. Acute effects are noticed soon after heavy exposure to TCDD, as after the explosions ( ). In such cases, workers usually become ill within 1 week. If workers are continually exposed to lower levels of TCDD, however, signs of illness may not occur for several months. Under such circumstances, the overriding sign is the chloracne. Although in Nitro, West Virginia exposure and occupational illness occurred as early as 1947, it was not until 1957 that TCDD was identified as the culprit (19). 

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