Carcinogenicity testing of herbicide 2,4,5-trichlorophenoxyethanol containing dioxin and of pure dioxin in Swiss mice

Abstract

SERIOUS environmental contamination is a hazard in the use of derivatives of 2,4,5-trichlorophenol (TCP) as weedkillers¹ or defoliants² and in accidents during the manufacture of TCP³ (as in Seveso, Italy in 1976^4–6). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is an inevitable toxic⁷ teratogenic⁸ and weakly mutagenic^9,10 by-product which is always present as a contaminant. When TCP derivatives, including 2,4,5-tri-chlorophenoxyacetic acid (2,4,5-T), were tested for carcinogenicity in (C57BL/6 × C3H/Anf)F₁ and (C57BL/6 × AKR)F₁ mice (experiments lasting 18 months) none increased tumour incidence¹¹, while in another study there was a significant increase in the incidence of tumours in C3Hf mice treated with 2,4,5-T¹². During a chronic toxicity study with TCDD (a potent inducer of microsomal enzymes¹³) in Sprague-Dawley rats some tumours were observed¹⁴. In another 2-yr study TCDD ingested at 0.1 µg per kg body weight per day caused an increased incidence of hepatocellular and squamous carcinomas in Sprague-Dawley rats, but reduced the incidence of some other tumours. Smaller doses of dioxin did not affect tumour incidence¹⁵. We report here that both 2,4,5-trichlorophenoxyethanol (TCPE), a derivative of TCP, and dioxin enhance liver tumours in male mice in a dose-dependent manner. Amyloidosis is a long term complication often associated with severe skin lesions induced by TCDD.