For definition of Groups, see Preamble Evaluation.
VOL.: 56 (1993) (p. 165)
Chem. Abstr. Name: 3-Methyl-3H-imidazo[4,5-f]quinolin-2-amine
IQ (2-Amino-3-methylimidazo[4,5-f]quinoline) has been found in cooked meat and fish. A few determinations indicated that the levels of IQ were lower than those of MeIQx (2-amino-3,8-dimethyl- imidazo[4,5-f]-quinoxaline) and PhIP (2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine). IQ was reported in the only sample of cigarette smoke condensate tested.
No data directly relevant to an evaluation of the carcinogenicity to humans of IQ were available; however, several studies that were potentially relevant were considered.
The only cohort study in which detailed results were presented showed a significantly increased risk for cancers at all sites and for gastric cancer associated with the consumption of broiled fish.
Two case-control studies, in Sweden and the USA, in which consumption of meat cooked in different ways was addressed and in which consumption of a number of nutrients was controlled did not show increased risks for colorectal cancer associated with consumption of fried meat; however, the study from Sweden showed an association with a preference for browned meat. One case-control study on gastric cancer in Japan showed no association with consumption of broiled fish or grilled meat.
The available information was insufficient to establish whether cooking methods that result in the formation of heterocyclic amines are a risk factor for cancer independent of the food item itself.
IQ was tested for carcinogenicity by oral administration in one experiment in mice, in two experiments in rats and in one study in monkeys. Hepatocellular adenomas and carcinomas, adenomas and adenocarcinomas of the lung and squamous-cell papillomas and carcinomas of the forestomach were produced in mice. In rats, hepatocellular carcinomas, adenocarcinomas of the small and large intestine, and squamous-cell carcinomas of the Zymbal gland were produced in animals of each sex. A high incidence of mammary adenocarcinomas was observed in females. In addition, squamous-cell carcinomas were found in the skin of males and in the clitoral gland of females. Hepatocellular carcinomas were produced in one study in monkeys.
Intraperitoneal injection of IQ to newborn male mice increased the incidence of hepatic adenomas.
Single dose or short-term oral treatment of rats with IQ followed by phenobarbital, with or without further modulating procedures, increased the numbers of foci of altered hepatocytes and of carcinomas in the liver. Sequential administration of IQ after N-nitrosodiethylamine enhanced the appearance of foci of altered hepatocytes in rats.
No data were available on the genetic and related effects of IQ in humans.
IQ bound to DNA in many organs of cynomolgus monkeys and rodents dosed in vivo. In rodents treated in vivo, IQ induced DNA damage, gene mutation and chromosomal anomalies. It induced chromosomal anomalies in human cells in vitro and chromosomal anomalies, gene mutation and DNA damage in animal cells in vitro. It induced mutations in Drosophila melanogaster and DNA damage and mutations in bacteria. Gene mutations in c-Ha-ras and p53 genes were found in some Zymbal gland carcinomas induced in rats by IQ.
There is inadequate evidence in humans for the carcinogenicity of IQ.
There is sufficient evidence in experimental animals for the carcinogenicity of IQ.
IQ (2-Amino-3-methylimidazo[4,5-f]quinoline) is probably carcinogenic to humans (Group 2A).
In arriving at the overall evaluation, the Working Group took into consideration the following contributory information:
IQ is comprehensively genotoxic, and this activity can be expressed in vivo in rodents. IQ can be metabolized by human microsomes to a species that damages bacterial DNA.
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluation: Suppl. 7 (1987) (p. 64)
See Also: Toxicological Abbreviations