Disposition of 4-methylimidazole in goats and heifers

Nielsen, Poul; Friis, Christian; Kraul, Inge; Olsen, Carl Erik

doi:10.1016/0034-5288(93)90014-7

Cited by 15 publications

(13 citation statements)

References 10 publications

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“…The reason why female F344/N rats are more sensitive to the neurobehavioral effects of 4MI than male F344/N rats is unclear. The neurobehavioral effects displayed by female rats are consistent with those observed in farm animals fed ammoniated hay (Wiggins 1956;Nishie et al 1970;Edwards 1986a, 1986b;Nielsen et al 1993;Weiss et al 1986;Perdok and Leng 1987). In male albino mice, a single dose of 4MI induced tremors, restlessness, running, sialorrhea, opisthotonus, Straub tail, and tonic extensor seizure (Nishie et al 1969).…”

Section: Discussionsupporting

confidence: 74%

“…Ewes fed ammoniated hay showed facial twitching and general body tremors initially, followed by opisthotonus and convulsion (Weiss et al 1986). In goats and heifers 4MI administered intravenously induced coughing, salivation, urination, defecation, and convulsions or clonic seizure (Nielsen et al 1993). Neurologic effects similar to those in cattle have been observed in mice administered 4MI (Nishie et al 1969;1970).…”

Section: Introductionmentioning

confidence: 86%

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Toxicity and carcinogenicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice

et al. 2007

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4-Methylimidazole (4MI) is used in the manufacture of pharmaceuticals, photographic chemicals, dyes and pigments, cleaning and agricultural chemicals, and rubber. It has been identified as a by-product of fermentation in foods and has been detected in mainstream and side stream tobacco smoke. 4MI was studied because of its high potential for human exposure. Groups of 50 male and 50 female F344/N rats were fed diets containing 0-, 625-, 1,250-, or 2,500 ppm 4MI (males) or 0-, 1,250-, 2,500-, or 5,000 ppm 4MI (females) for 106 weeks. Based on the food consumption the calculated average daily doses were approximately 30, 55, or 115 mg 4MI/kg body weight to males and 60, 120, or 250 mg 4MI/kg to females. Survival of all exposed groups of males and females was similar to that of the control groups. The mean body weights of males in the 1,250- and 2,500 ppm groups and females in the 2,500- and 5,000 ppm groups were less than those of the control groups throughout the study. Feed consumption by 5,000 ppm females was less than that by the controls. Clonic seizures, excitability, hyperactivity, and impaired gait were observed primarily in 2,500- and 5,000 ppm females. The incidence of mononuclear cell leukemia in the 5,000 ppm females was significantly greater than that in the controls. The incidences of hepatic histiocytosis, chronic inflammation, and focal fatty change were significantly increased in all exposed groups of male and female rats. The incidences of hepatocellular eosinophilic and mixed cell foci were significantly increased in 2,500 ppm males and 5,000 ppm females. Groups of 50 male and 50 female B6C3F1 mice were fed diets containing 0-, 312-, 625-, or 1,250 ppm 4MI for 106 weeks. Based on the food consumption the calculated average daily doses were approximately 40, 80, or 170 mg 4MI/kg body weight to males and females. Survival of all exposed groups of males and females was similar to that of the control groups. Mean body weights of males and females in the 1,250 ppm groups and that in the 312- and 625 ppm females were less than those of the control groups. Feed consumption by exposed groups of male and female mice was similar to that by the controls. The incidences of alveolar/bronchiolar adenoma in all exposed groups of females, alveolar/bronchiolar carcinoma in 1,250 ppm males, and alveolar/bronchiolar adenoma or carcinoma (combined) in 1,250 ppm males and 625- and 1,250 ppm females were significantly greater than those in the control groups. The incidence of alveolar epithelial hyperplasia was significantly increased in the 1,250 ppm females. 4MI is carcinogenic inducing alveolar/bronchiolar adenoma and carcinoma in male and female mice. 4MI may also induce mononuclear cell leukemia in female rats.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 86%

Toxicity and carcinogenicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice

et al. 2007

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“…Judging from published studies on the pharmacokinetics of 4-Mel in ruminants (Karangwa et al 1990, Nielsen et al 1993 and from feeding experiments with heifers (Friis Kristensen et al 1991), our observed levels of 4-Mel in ewe plasma compared with the levels in the feed are lower than expected. This might be due to different degrees of rumen metabolism of 4-Mel under different conditions.…”

supporting

confidence: 49%

Further Arguments against 4-methylimidazole as Causal Factor in Ammoniated Forage Toxicosis: Experimental Seed-hay Poisoning in Young Lambs

Sivertsen

Langseth

et al. 1993

Acta Vet Scand

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“…An early study reported that animals exposed to 4‐MI developed anemia and convulsion . Following that study, convulsant activity has also been observed in cattle fed with ammoniated molasses, in calves that received milk from cows fed ammoniated hay and in goats and heifers receiving 4‐MI via intravenous administration . In mice, 4‐MI treatment induces similar convulsant activity to those found in cattle .…”

Section: Introductionmentioning

confidence: 67%

“…6 Following that study, convulsant activity has also been observed in cattle fed with ammoniated molasses, 7,8 in calves that received milk from cows fed ammoniated hay 9,10 and in goats and heifers receiving 4-MI via intravenous administration. 11 In mice, 4-MI treatment induces similar convulsant activity to those found in cattle. 8,12 In 2007, the National Toxicology Program (NTP) published a result of 2-year study regarding the toxicological testing of 4-MI conducted in laboratory animals.…”

mentioning

confidence: 79%

Embryonic exposure to 4‐methylimidazole leads to zebrafish myofibril misalignment

Tsai

Sun

Ding

et al. 2018

Environmental Toxicology

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4‐methylimidazole (4‐MI) is an imidazole‐derived organic chemical compound that can be used as a raw material in the manufacture of diverse chemicals and has been identified as an ingredient of caramel color in soybean sauce, beers, and other soft drinks. The aim of the present study was to investigate the teratogenic effects of 4‐MI during zebrafish embryogenesis. Zebrafish embryos were treated with different dosages of 4‐MI (0‐120 mM) for different exposure durations (12‐60 hours). The percentages of embryos with malformed phenotypes increased as the exposure dosages and duration time of 4‐MI increased. We also used immunofluorescence and transmission microscopy to evaluate the subtle changes in the myofibril alignment and ultrastructure of muscle organization. Our data showed that 4‐MI treatment disturbs muscle fiber alignment. Electron microscopy data indicated that Z‐lines were undetectable in the 4‐MI‐treated embryos. Although the thick and thin filaments were visible, they were all disorganized. In addition, zebrafish embryos treated by 4‐MI exhibited aberrant expression of 2 muscle‐specific genes, myod and myogenin. Taken together, we concluded that early exposure to 4‐MI affects zebrafish myogenesis, especially in myofibril alignment.

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Disposition of 4-methylimidazole in goats and heifers

Cited by 15 publications

References 10 publications

Toxicity and carcinogenicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice

Toxicity and carcinogenicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice

Further Arguments against 4-methylimidazole as Causal Factor in Ammoniated Forage Toxicosis: Experimental Seed-hay Poisoning in Young Lambs

Embryonic exposure to 4‐methylimidazole leads to zebrafish myofibril misalignment

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