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Abstract from Report I10157 on 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Abstract

Range-Finding Report on the Immunotoxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6)

Report Date: August 2012

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.


Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin is the most potent polychlorinated dioxin (Schecter et al., 2006), and it is classified as a known human carcinogen (Group 1) by the International Agency for Research on Cancer (IARC). TCDD is well known as a contaminant of the herbicide Agent Orange used in the Vietnam War.

Human exposure to TCDD occurs almost exclusively through the consumption of meat, fish, and dairy products (Startin and Rose, 2003; EPA, 2004). In addition to being a human carcinogen, TCDD demonstrates potent immunosuppressive properties (Kerkvliet, 1995). Inhibition of the antibody forming cell response to sheep red blood cells in mice following an acute single dose of dioxins has been shown to be one of the most sensitive indicators of exposure to these compounds (Harper et al., 1995; Johnson et al., 2000).

The National Toxicology Program requested that a dose range-finding study be performed to establish an appropriate dose of TCDD to use as a positive control for subsequent studies evaluating other halogenated aromatic hydrocarbons. These studies were conducted in female B6C3F1/N mice. Five TCDD dose levels were utilized (0.1, 0.3, 0.5, 1, and 3 µg/kg), given in a single oral administration. Corn oil was used as the vehicle for TCDD administration.

Administration of TCDD did not adversely affect body weight or body weight gain. No effects were observed on the weights of the major organs of the immune system, the thymus and the spleen. Liver weights were significantly increased in animals receiving the high dose of TCDD (3 µg/kg) when expressed as both absolute (wet) weight and relative weight (percent of body weight) on both day 3 and day 11. Sporadic effects on hematological parameters were observed, but these effects were not dose responsive. Treatment with TCDD decreased the T-dependent IgM AFC response to sRBC at all dose levels. Furthermore, serum anti-sRBC IgM antibody titers evaluated by enzyme-linked immunosorbent assay were significantly decreased at TCDD doses greater than or equal to 0.5 µg/kg.

In conclusion, TCDD suppressed the humoral immune response, as measured by the T-dependent antibody response and ELISA, when administered in a single exposure to female B6C3F1/N mice at doses ranging from 0.1 to 3 µg/kg.

References

Startin J. & Rose M. (2003). Dioxins and dioxin-like PCBs in food. In: Dioxins and Health, Schecter A, Gasiewicz TA (Eds). Wiley, Hoboken, NJ. pp. 89-136.

Kerkvliet N.I. (1995). Immunological effects of chlorinated dibenzo-p-dioxins. Environ Health Perspect 103(Suppl 9):47-53.

Harper N., Connor K., Steinberg M., & Safe S. Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners: nonadditive (antagonistic) interactions. Fundam Appl Toxicol. 1995 Aug;27(1):131-9.

Johnson C.W., Williams W.C., Copeland C.B., DeVito M.J., & Smialowicz R.J. Sensitivity of the SRBC PFC assay versus ELISA for detection of immunosuppression by TCDD and TCDD-like congeners. Toxicology. 2000 Dec 7;156(1):1-11.


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