A major corn-related mycotoxin, fumonisin B1 (FB1), continues to attract attention of researchers as well as risk-assessors due to the diverse toxicological characteristics, including distinct target tissues in different animal species and opposite susceptibility in males and females in mice and rats. More than thirty years passed since the structure identification as a sphingoid-like chemical, but the causal mechanism of the toxicity remains obscure in spites of extensive studies. Considerable amounts of knowledge have been accumulated on the biochemical/toxicological actions of FB1, but the influence on lipid dynamics and mobilization in the body has not been focused well in relation to the FB1-mediated toxicity. Considerable influences of this toxin on mobilization of sphingolipids and phospholipids and also on adaptive changes in their compositions in tissues are implicated from recent studies on FB1-interacting ceramide synthases. Accumulated patho-physiological data also suggest a possible role of hepatic phospholipid on FB1-mediated toxicity. Thus, a mechanism of FB1-mediated toxicity is discussed in relation to the mobilization of phospholipids and sphingolipids in the body in this context.

High hydrostatic pressure (HP) treatment is used in food processing owing to its sterilization effect. Meat or meat products are sterilized and become tender by HP processing. Therefore, the variety of HP-processed meat products has increased worldwide. However, little is known about the safety of HP-processed meat products. The aim of this study was to determine the effects of HP processing and HP combined with 0.4 M sodium carbonate treatment (HP-Na) on pork loins and to evaluate the subacute toxicity and cytotoxicity of these processing methods. In an in vivo study, we performed 90- and 180-day feeding tests in mice and did not detect any adverse effects in HP-processed and HP-Na-processed pork loins. In addition, we evaluated the cytotoxicity of HP-processed meats, and did not observe any obvious toxicity associated with pork loin extracts in vitro. These results suggest that HP is not associated with risk factors during processing.

Food Safety Commission of Japan (FSCJ) conducted a risk assessment of fenquinotrione (CAS No. 1342891-70-6), a triketone herbicide, based on results from various studies. A major adverse effect of fenquinotrione was observed in ocular toxicity characterized as keratitis in rats, which is often observed with other 4-hydroxyphenylpyruvate dioxygenase (4-HPDDase) inhibitors in this species. Other effects included were centrilobular hepatocytes hypertrophy, and also cholecystolithiasis in mice. No effects were observed on neurotoxicity, fertility, teratogenicity and genotoxicity. A corneal squamous cell carcinoma found in a male rat, at a sub-highest dose in a two-year carcinogenicity study, was judged to be treatment-related, because this tumor is rare in rats. The occurrence was considered to be attributed to persistent stimulation of inflammation including keratitis. In addition, negative results were obtained from all of the genotoxicity studies. Therefore, a genotoxic mechanism was unlikely involved in the tumor development, and it enabled FSCJ to establish a threshold in the assessment. Fenquinotrione (parent compound only) was the residue definition for dietary risk assessment in agricultural products. The lowest no-observed-adverse-effect level (NOAEL) obtained from all the studies was 0.166 mg/kg bw/day in a two-generation reproductive toxicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.0016 mg/kg bw/day by applying a safety factor of 100 to the NOAEL. The lowest-observed-adverse-effect-level (LOAEL) for potential adverse effects of a single oral administration of fenquinotrione was 2,000 mg/kg bw based on soft feces and staining of perianal fur observed within one day after the oral administration in an acute toxicity study in rats. Thus the acute reference dose (ARfD) is not necessary, since the LOAEL was adequately above the cut off level (500 mg/kg bw).

Food Safety Commission of Japan (FSCJ) conducted a risk assessment of flometoquin (CAS No. 875775-74-9), a quinoline insecticide, based on results from various studies. Major adverse effects of flometoquin observed were suppressed body weight and hepatocellular steatosis in rats, and ovarian atrophy with decreased numbers of small follicle in rats and mice. Neither teratogenicity nor genotoxicity relevant to human health was detected. Increased incidences of gonadal stromal tumor in female rats and of small intestine adenocarcinomas in male mice were identified in carcinogenicity studies. Genotoxic mechanisms were, however, unlikely involved in their tumor developments, and these enabled FSCJ to establish a threshold in the assessment. Mechanism and toxicity studies suggested that ovarian atrophy triggered the development of gonadal stromal tumor, through continuous stimulation of gonadotropin to the gonadal stroma, via negative feedback. A reproductive study showed the decreases in numbers of small follicle, implantation and also in litter size. Based on the results from various studies, flometoquin (parent compound only) was the residue definition for dietary risk assessment in agricultural products. The lowest no-observed-adverse-effect level (NOAEL) obtained from all the studies was 0.8 mg/kg bw/day in a developmental toxicity study in rabbits. FSCJ specified an acceptable daily intake (ADI) of 0.008 mg/kg bw/day by applying a safety factor of 100 to the NOAEL. FSCJ recognized that in considering the ambiguity of the underlying mechanism, the adverse effect on small follicle possibly occurred after single oral administration of flometoquin. Thus FSCJ specified an acute reference dose (ARfD) to be 0.044 mg/kg bw by applying a safety factor of 100 to the NOAEL of 4.45 mg/kg bw per day in a two-generation reproductive toxicity study in rats, based on a comprehensive evaluation of NOAEL for ovarian toxicity.

Food Safety Commission of Japan (FSCJ) conducted a risk assessment of pyraziflumid (CAS No.942515-63-1), a carboxamide fungicide of pyrazine-biphenyl type, based on results from various studies. Major adverse effects of pyraziflumid observed were of single-cell necrosis hepatocytes and hypertrophy of follicular epithelial cell in the thyroid. No adverse effects were detected in fertility, teratogenicity and genotoxicity relevant to human health. Increased incidences of thyroid follicular cell adenomas and carcinomas in males, and also of hepatocellular adenomas in females were identified in a two-year combined chronic toxicity/carcinogenicity study in rats. Genotoxic mechanisms were, however, unlikely involved in the tumor developments, and these enabled FSCJ to establish a threshold in the assessment. Based on various studies, pyraziflumid (parent compound only) was the residue definition for dietary risk assessment in agricultural products. The lowest no-observed-effect level (NOAEL) obtained from all the studies was 2.15 mg/kg bw/day in a two-year combined chronic toxicity/carcinogenicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.021 mg/kg bw/day by applying a safety factor of 100 to the NOAEL. FSCJ considered it unnecessary to specify an acute reference dose (ARfD) in view of the absence of adverse effects that would be likely to be elicited by a single oral administration of pyraziflumid.