Carcinogenicity study of 3-monochloropropane-1, 2-diol (3-MCPD) administered by drinking water to B6C3F1 mice showed no carcinogenic potential.

3-Monochloropropane-1, 2-diol (or 3-chloro-1,2-propanediol, 3-MCPD) is a well-known food processing contaminant found in a wide range of foods and ingredients. It has been classified as non-genotoxic carcinogen but its carcinogenic potential in the rodents has been controversial. The carcinogenicity to B6C3F1 mice by drinking water administration was assessed over a period of 104 weeks. Three groups, each comprising 50 male and 50 female mice received 3-MCPD at dosages of 30, 100 or 300 ppm up to Day 100 and 200 ppm onward (4.2, 14.3 and 33.0 mg/kg for males; 3.7, 12.2, and 31.0 mg/kg for females), were allocated. Survival was good, with at least 80% of males and 72% of females in each group surviving 104 weeks. Body weights and body weight gain were decreased in males and females receiving 200 ppm. Water and food consumptions of both sexes at 300/200 ppm were lowered. Emaciated or crouching position was observed for animals of both sexes exposed to 200 ppm. There were some differences in hematology and serum biochemistry compared with controls, although there was no histopathological evidence to support those changes. Histopathological examination did not reveal any neoplastic or non-neoplastic findings attributable to treatment with 3-MCPD. It is concluded that drinking water administration of 3-MCPD for 104 weeks revealed no evidence of carcinogenic potential.

Pathological features of bone marrow transplantation-related toxicity in a mouse.

In this case report, we present a mock-transduced bone marrow (BM) transplantation in a mouse, which was found moribund and autopsied to evaluate pathogenesis. Macroscopically, red discoloration of systemic organs was observed. Hematological values revealed a decrease in white blood cells, red blood cells, hematocrit, hemoglobin, and platelets, but an increase in reticulocytes. In BM cytology, hematopoietic cell lines were severely depleted. Histopathologically, hemorrhage in the cerebellar parenchyma, hemosiderin deposition and hemorrhage in the heart, necrosis and telangiectasia in liver, pulmonary parenchymal cysts, spermatogenic germ cells necrosis, atrophy and hemorrhage in testis, oligospermia and hemorrhage in the epididymis, and atrophy of BM, thymus and spleen were observed. In conclusion, autoimmune-like complications such as hematological value change, BM dysplasia and systemic hemorrhage appear to be the lethal cause of the mouse transplanted with mock-transduced BM.

Lack of a co-promotion effect of 60 Hz rotating magnetic fields on N-ethyl-N-nitrosourea induced neurogenic tumors in F344 rats.

The present study was conducted to investigate the possible effect of 60 Hz magnetic fields as promoters of brain tumors initiated transplacentally by ethylnitrosourea (ENU) in F344 rats. One hundred twenty mated animals were divided into six different groups and exposed in utero on day 18 of gestation to a single intravenous dose of either Saline (vehicle control, Group I), or ENU 10 mg/kg (Groups II-VI). In the present study, a total of 480 offspring was used. The offspring in group II were given no further treatment while the offspring in Groups III-VI were exposed to four different intensities of magnetic fields. Animals received exposure to 60 Hz magnetic field at field strengths of 0 Tesla (sham control, T1, Group III), 5 muT (T2, Group IV), 83.3 muT (T3, Group V), or 500 muT (T4, Group VI), for 21 h/day from the age of 4 weeks to the age of 32 or 42 weeks. At histopathological examination, tumors of the nervous system were seen in all the ENU-treated groups. The tumor incidence of the ENU group at 32nd and 42nd week necropsy was higher than that of the vehicle control group. The incidence of glial tumors at 42nd week necropsy was higher than the 32nd week necropsy. However, there were no differences in the tumor incidence between the sham control (T1) and ENU + magnetic field exposure groups (T2-T4). In conclusion, there was no evidence that exposure of offspring to 60 Hz at magnetic field strengths up to 500 muT to the age of 32 or 42 weeks promoted ENU-initiated brain tumors in rats.

Potential side effects of dendritic cells pulsed with allogenic melanoma cell lysate in mice.

An attempt has been made to investigate the toxicity of cancer immunotherapy based on the dendritic cells pulsed with lysate of allogenic melanoma cell, DM401. Dendritic cells pulsed with lysate of clone M3 were subcutaneously administered once a week eight times to C57BL/6 mice at 0, 2.5, 5, and 10 x 10(7) cells/kg. No changes attributable to the administration were observed in clinical signs and food and water consumption. The administration induced slight increases in body weights, white blood cells, total protein, total cholesterol, triglyceride, phospholipids, and absolute spleen weights, but a slight decrease in albumin/globulin ratio. Microscopic examinations revealed the infiltration of inflammatory cells in the lung, mainly in the pulmonary arteriole, in which the tunica media thickened, and in the pulmonary alveoli and alveolar space. Thickened tunica media of pulmonary arteriole was observed in both males and females at all selected doses. In addition, the subcutis at the test substance-application site showed inflammation and fibrosis. In conclusion, lung is a target organ of DM401, and most of the changes including the findings in lung are considered as the immunomodulatory functions of dendritic cells.

Hematological and serum biochemical values in cynomolgus monkeys anesthetized with ketamine hydrochloride.

The effects of ketamine anesthesia on both hematological and serum biochemical variables were investigated in 19 male and 15 female cynomolgus monkeys. Blood samples were obtained from the cephalic vein within 30 minutes of an intramuscular injection of ketamine hydrochloride (10 mg/kg). Ketamine anesthesia caused a reduction in leukocyte counts and a significant reduction in lymphocytes percentages. Ketamine anesthesia also increased the serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine phosphokinase (CPK), but reduced the serum concentrations of glucose, inorganic phosphate, sodium and potassium. The alterations of hematological and serum biochemical values will be discussed. These alterations should be considered when designing studies for and interpreting data from cynomolgus monkeys.

Zearalenone induces male germ cell apoptosis in rats.

Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin, is known to cause toxicity of testis in male rats. To investigate whether apoptosis is involved in ZEA-induced testicular toxicity and to identify the stage and target germ cell type, 10-week-old Sprague-Dawley male rats were treated with a single intraperitoneal (i.p.) dose of ZEA (5 mg/kg) and euthanized at 3, 6, 12, 24, or 48 h subsequently. Histopathologically, germ cell degeneration was found at stages I-VI 12 h after dosing. Degenerating germ cells were shown to undergo apoptosis as revealed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The frequency of TUNEL-labeled germ cells increased in a stage-specific manner, the peak frequency gradually progressing at stages I-VI of seminiferous tubules with time after dosing, suggesting that the damaged germ cells, especially spermatogonia and spermatocytes, gradually underwent the processes leading to apoptosis. DNA laddering on gel electrophoresis was apparent 12 h after dosing. The results demonstrated that a single dose of ZEA induces testicular germ cell apoptosis in a time-dependent and stage-specific pattern. This study has established that apoptosis is the principal mechanism contributing to germ cell depletion and testicular atrophy following ZEA exposure.