Dinitrotoluene (technical grade) (Benzene, methyldinitro-), 2,4-Dinitrotoluene (Benzene, 1-methyl-2,4-dinitro-), 2,6-Dinitrotoluene (Benzene, 2-methyl-1,3-dinitro-)
The oral acute toxicity of 2,4-DNT, 2,6-DNT and t-DNT is moderate to high. Based solely on the oral rat studies, 2,4-DNT, 2,6-1DNT and t-DNT appear to have a borderline acute toxicity between toxic (T) and harmful (Xn). However, in view of their ability to cause methaemoglobin formation at low doses in the cat, classification as toxic (T) with R25 seems reasonable in this case. Furthermore, since dinitrotoluenes have been reported to be absorbed from inhalation and dermal exposure at doses that cause acute toxicity it also seem reasonable to classify 2,4-DNT, 2,6-1DNT and t-DNT as toxic (T) by these other routes of exposure. The existing classification for the t-DNT is TR23/24/25. There is not enough documentation to show that 2,4-DNT, 2,6-1DNT and t-DNT have any local irritating effects or sensitisation properties. Following repeated exposure to DNTs, neurotoxic effects have been described in humans and in experimental animals. Thus, it is reasonable to classify 2,4-DNT, 2,6-1DNT and t-DNT with R48/22. 2,4-1DNT has caused renal tumours in one mouse study but not in another. 2,4-1DNT has been shown to cause hepatocellular carcinomas and fibroadenomas of the mammary gland in rats. 2,6-1DNT has caused hepatocellullar carcinomas with metastasis to the lungs in rats but not in mice. 2,4-DNT, 2,6-13DNT and t-DNT are genotoxic. Furthermore, IARC has evaluated the analogue 2,6-13NT to be a Group 2B carcinogen. Based on this information it seems reasonable to classify 2,4-DNT, 2,6-1DNT and t-DNT as Carc. Cat. 2 with R45. In tests for in vitro mutagenicity 2,4-DNT, 2,6-1DNT and t-DNT have given both positive and negative results. From mechanistic studies it is evident that DNTs must undergo nitro reduction in order to become a proximate mutagenic metabolite. Consequently, 2,4-1DNT and 2,6-1DNT appear to elicit a positive mutagenic response in test systems having an elevated level of nitroreductase. Furthermore, DNA binding and DNA adduct formation resulting from 2,4-1DNT and 2,6-1DNT exposure have been reported in vivo. t-DNT is also positive in in vivo/in vitro UDS studies in rats. Thus, 2,4-1DNT and 2,6-DNT satisfy the criteria for classification as Muta. Cat. 3 with R40. A similar classification for t-DNT seems reasonable. 2,4-DNT and 2,6-DNT have the ability to adversely affect spermatogenesis in animals and indications of similar effects in humans have been reported. The Sertoli cell has been suggested as the primary target leading to testicular atrophy and necrosis. These data warrant classification of 2,4-DNT and 2,6-DNT as Repr. Cat. 3 with R62. One study in rats indicates that t-DNT is embryotoxic at high, maternal toxic doses, but not teratogenic. In summary 2,4-DNT, 2,6-DNT and t-DNT should, according to EC-criteria, be classified toxic (T) with R23/24/25, harmful (Xn) following repeated oral exposure with R48/22, Carc. Cat.2 with R45, Muta. Cat.3 with R40 and Repr. Cat.3 with R62.