Liver dysfunction among workers handling 5-nitro-o-toluidine

Abstract

Background: 5-Nitro-o-toluidine is an aromatic nitro amino compound. While other aromatic compounds are known to damage the human liver and are registered as toxic substances, toxicity information concerning 5-nitro-o-toluidine is lacking.

Aims: To investigate the hepatotoxicity of 5-nitro-o-toluidine.

Patients and methods: Of 15 workers in the same factory who handled 5-nitro-o-toluidine, three were hospitalised with symptoms of acute liver dysfunction. Suspecting a link between liver dysfunction and working conditions, we correlated workplace factors with clinical findings in all 15 workers.

Results: Blood biochemistry tests indicated liver damage in seven of 15 study subjects. Workers who handled 5-nitro-o-toluidine and nitrosyl sulphuric acid often loosened their respiratory protective equipment shortly after 5-nitro-o-toluidine powder had been dispersed into the air of the room. No potential hepatotoxins were present except for 5-nitro-o-toluidine. Six of the affected workers had handled 5-nitro-o-toluidine 12 to 20 times; the seventh worker had handled the powder three times; and the other eight workers without liver dysfunction had handled the material once or twice. No other significant differences in background were evident between the affected and unaffected workers, such as age, sex, or protective measures. Histological findings during recovery from liver damage were similar to those of acute viral hepatitis. None of the 15 subjects has demonstrated liver damage since the factory was closed.

Conclusions: A link between liver dysfunction and 5-nitro-o-toluidine exposure is suggested by greater severity of liver dysfunction associated with more episodes of handling.

Figure 1

Reaction sequence for producing hair dye. Workers manually loaded 5-nitro-o-toluidine, sulphuric acid (H₂SO₄), and nitrosylsulphuric acid (HOSO₃NO) into a closed mixing vessel where these compounds reacted with one another.

Figure 2

Liver function tests over time in two hospitalised patients. All values for aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were normal one month prior to exposure. Patient Nos 2 (A) and 3 (B) handled 5-nitro-o-toluidine 20 and 18 times, respectively, as indicated by the arrows. All values for AST, ALT, and ALP after handling of 5-nitro-o-toluidine initially were high, gradually decreased, and were finally normalised.

Figure 3

Histological findings in the cases shown in fig 2 ▶. (A) Case No 2 showed ceroid accumulation in Kupffer cells (arrowheads) (haematoxylin and eosin; original magnifications ×40). (B) Case No 3 showed fatty change and mild fibrosis surrounding the central veins, with no apparent damage to the biliary ducts (haematoxylin and eosin; original magnifications ×20).