Toluidines

About: Toluidines is a research topic. Over the lifetime, 139 publications have been published within this topic receiving 1780 citations.

The Carcinogenic Action of 4-Aminodiphenyl and 3:2'-Dimethyl-4-Aminodiphenyl

Abstract: Tumours of the bladder in dyestuff workers have been recorded with increasing frequency during the last 50 years. A high proportion of the recorded cases are attributable to exposure to b-naphthylamine or benzidine ; experimental evi dence of their carcinogenicity has accumulated during recent years. Hueper and Wolfe (1937), Hueper, Wiley, and Wolfe (1938), and Bonser (1943) have produced malignant bladder tumours in dogs with b-naphthylamine. With benzidine, Spitz, Maguigan, and Dobriner (1950) have obtained tumours of the acoustic gland, liver, and large bowel in rats as well as one bladder tumour in a dog, and we have confirmed their results in rats. The term " aniline cancer " was applied to this hazard in the dyestuffs industry because a number of the early cases of bladder tumours were asso ciated with the manufacture of aniline (Wendel, 1900 ; Rehn, 1905 ; Seyberth, 1907), and with dyestuffs from aniline (Rehn, 1895 ; Bardenheuer, 1904 ; Seyberth, 1907 ; Cesa-Bianchi, 1911 ; Leuen berger, 1912). Owing to the poor fractionation of crude benzol in these early days " anilines " at that time contained considerable amounts of toluidines and xylidines. It was in fact the presence of p-toluidine as an impurity that enabled Perkin in 1856 to discover mauveine, the first synthetic dyestuff. Recent reports tend to dis count aniline as a cause of tumours arising during the last 20 years, although a variety of other aromatic compounds have been suspected (Gehrmann, Foulger, and Fleming, 1949 ; Goldblatt, 1949 ; Barsotti and Vigliani, 1949 ; M?ller, 1951 ; Scott, 1952). Hergt (personal communication), who has records of a number of early cases in Germany, finds that they were rare in aniline makers but not uncommon in workers making toluidines and xylidines. He believes that these early "aniline tumours" are attri butable to toluidines and that their complete absence in men starting work in Germany during the last 40 years is due to improved working conditions, resulting in considerably reduced exposure. The first tumours described by Rehn (1895) were in fuchsine workers, who would be heavily exposed to aniline, toluidines, and xylidines in the course of their work. There is, however, no reliable experimental evidence that either aniline, toluidines, or xylidines are carcinogenic. In an attempt to find an explanation for the early tumours attributed to these bases, a survey was made of the literature relating to the manufacture ot aniline in Germany before 1900. This revealed that in 1862 Hofmann isolated a new based, 4-aminodiphenyl (xenylamine), from the distillation residues of " heavy aniline " (anilin f?r rot). Loring Jackson, a collaborator of Hofmann, continued this work, and apart from isolating naphthylamines from similar residues,, found therein a monomethyl homologue of amino diphenyl melting at 46-5?-47-5?C. (acetyl derivative, m.p.H4-2?C.) (Loring Jackson, 1875). This latter amine has not been identified but it would not appear to be any of the known isomers.* Hofmann (1862) thought that the 4-aminodiphenyl in the residues arose from the cracking of aniline, but Loring Jackson's finding of naphthylamines suggests that these bases were formed by the nitration and reduction of naphthalene, diphenyl, and methyl diphenyl (as well as of toluene and xylenes) all occurring as impurities in the benzene used for making aniline. Kruber (1932) has in fact isolated 2-methyldiphenyl and 3-methyldi phenyl from coal tar and Loring Jackson's amine is possibly a derivative of one of these hydro carbons. Kruber isolated 4 : 4/-dimethyl and 3 : 4'