Effect of low-dose 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) on influenza A virus-induced mortality in mice

• Published in: Toxicology (Amsterdam) 2002-01, Vol.170 (1), p.131-138
• Main Authors: Nohara, Keiko, Izumi, Hiroyuki, Tamura, Shin-ichi, Nagata, Ryoichi, Tohyama, Chiharu
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Body Weight - physiology; Chemical and industrial products toxicology. Toxic occupational diseases; Environmental Pollutants - toxicity; Female; Influenza A virus; Influenza virus; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mortality; Orthomyxoviridae Infections - mortality; Orthomyxoviridae Infections - virology; Polychlorinated Dibenzodioxins - toxicity; Sex Characteristics; Species Specificity; Survival Analysis; TCDD; Toxicology; Various organic compounds
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(01)00535-2

Dioxins, including the most toxic congener, 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), exert diverse biological effects in humans and animals. Host resistance, especially to virus infections, is considered one of the most sensitive targets of TCDD-toxicity, while a recent study showed that the vulnerability to TCDD of host resistance to viruses varied form experiment to experiment. Burleson et al. [Fundam. Appl. Toxicol. 29 (1996) 40] reported that a single oral dose as low as 10 ng TCDD/kg increased the mortality of mice infected with influenza A virus. If this value had been adopted as the basis for the tolerable daily intake (TDI) of dioxins, the TDI of 1–4 pg toxic equivalent (TEQ)/kg per day recommended by WHO would have to be lower. In the present study, we used the same experimental protocol described by Burleson et al. to determine whether low-dose TCDD consistently compromises the host resistance of mice infected with influenza A virus. To do so, we investigated the effect of TCDD in the dose range of 0–500 ng/kg on the mortality of virus-infected female B6C3F1 mice. We also investigated the sex- and strain-dependency of host resistance in male B6C3F1 mice and in female C57Bl/6, Balb/c, and DBA/2 mice by administering the same dose range of TCDD. The results showed that TCDD doses up to 500 ng/kg did not increase the mortality of virus-infected mice in any of the strains. Further studies on the mechanism underlying the toxicity of TCDD are needed to assess the risk of exposure to this compound in influenza A virus infection.