Toxicity of N-methyl-4-methoxynaphthalimide, a fluorescent whitening agent

Abstract

Toxicological studies onN-methyl-4-methoxynaphthalimide (MMNI), a water pollutant, were performed on mice for acute toxicity, and on rats for distribution and subacute toxicity. The mutagenicity of MMNI and its metabolites in bacteria was also investigated. Seven days of consecutive administration with MMNI to male rats caused accumulation of MMNI in the adipose tissue, large intestine, and liver. Small amounts of MMNI were detected in the kidneys, spleen, thymus, and serum, and the metabolites of MMNI (C-hydroxide and conjugate) were detected primarily in the serum and liver, although they were rapidly excreted from the body by urinary routes. The LD50 value in male mice by intraperitoneal administration of MMNI was 7,700 mg/kg. No growth retardation was found in rats orally administered for 21 days. Male rats fed on 30,000 ppm and female rats fed on 6,700 or 30,000 ppm of MMNI exhibited slight growth retardation after a 40-day feeding trial. Enlargement of rat livers was seen in the high dose groups (100 mg/day, 6,700 and 30,000 ppm), along with moderate histological changes in liver (such as fatty infiltration, focal necrosis, proliferation of endoplasmic reticulum, and Mallory's bodies). Histological changes were also detected in kidneys (vacuolation and numerous hyalin droplets in the tubules) and pancreas (vacuolation). In these groups, mean amounts of serum protein were elevated, and serum glutamic pyruvic transaminase (SGPT) activities were decreased. Atrophy of thymus was seen in 6,700 and 30,000 ppm group, but immunosuppressive effect was not observed. An increase in the amounts of liver cytochrome P-450 was found in the rats given 10 and 100 mg daily doses of MMNI for 21 days. There was no mutagenic activity of MMNI on theSalmonella typhimurium TA98 and TA 100 with or without S-9 mix, whereas its metabolites present in the urine of rats had slight mutagenic activity on TA100.