A tubular pattern of intraductal components in IDC of the pancreas indicates intraductal invasion, while a low papillary pattern indicates CIS or carcinoma in another location to which it has spread.

To assess the validity and limitations of 2-week repeated daily dosing to detect toxic effects on male reproductive organs in rodents, a comparative 2- and 4-week oral repeated dosing study of boric acid, a known testicular toxicant, was given to 6- or 8-week-old Crj:Wistar rats at daily levels of 0, 125, 250 and 500 mg/kg. The ages of the rats were selected so that they were all sacrificed at 10 weeks of age. The testes and epididymides were weighed at necropsy; histopathological specimens were prepared in a routine manner and stained with H&E or PAS-H. In addition, the sperm number and motility rates were evaluated. There were no boric acid-induced effects on reproductive organ weights and on gross behavior/appearance in any groups in either the 2- or 4-week studies. The sperm number and motility rate were not decreased in any group after 2 weeks, while both decreased in the 250 and 500 mg/kg groups after 4 weeks. Histopathologically, as evidence of toxicity at the early stage of boric acid exposure, retention of step 19 spermatids of stages IX-XI was observed in the testes of almost all rats treated with 500 mg/kg after both 2 weeks and 4 weeks. Degenerative/necrotic germ cells and multinucleated giant cell formation were observed in 2 weeks, though to a lesser extent than in 4 weeks. On stage analysis of germinal cells in 2 weeks, spermatogonia and spermatids of stage VII were found to be decreased, and pachytene spermatocytes of stage X were increased. In conclusion, the results indicate that if the selection of doses is appropriate, testicular toxicity of boric acid can be detected even after only 2 weeks of repeated daily oral treatment.

No abstract

N-Ethyl-N-nitrosourea (ENU) is known to induce a wide spectrum of tumors in various organs in adult experimental animals. The renal and neuroectdermal tumors are known as representative lesions by transplacental exposure to ENU in the offspring animals. However, little information is available about tumorigenicity in other organs and tissues in offspring when their mother animals are treated with ENU during gestation. Thus, the purpose of this study was to evaluate the effects of transplacentally treated-ENU on the various organ tumorigenicity in offspring rats. ENU was injected intraperitoneally to female Sprague-Dawley (SD) rats with a single dose at 50 mg/kg on the 18th day of gestation. After spontaneous delivery, 44 male and 64 female offspring, including moribund and dead after birth, were subjected to the evaluation of carcinogenicity. At the 54th to 55th week of birth, all surviving offspring were euthanized under ether anesthesia for histopathology. ENU showed a wide spectrum of transplacental tumorgenesis in the kidney, central nervous system, peripheral nervous system, thyroid gland, and teeth. The tumors of the thyroid and teeth were characteristic in particular in this study. The thyroid tumors included various histopathological types (follicular cell adenoma and adenocarcinoma, C-cell adenoma and carcinoma, squamous cell carcinoma, and fibroma). As a characteristic tumor of the teeth, ameloblastic odontoma was detected in 3 (one male and 2 females) of 108 offspring. In conclusion, the results indicate that the transplacental exposure of a single ENU dose induces various types of thyroid gland tumors and odontogenic tumors as well as the renal or neuroectodermal tumors in rat offspring. (J Toxicol Pathol 2004; 17: 7-16)

In order to assess the safety of cefmetazole, preclinical multiple-dose parenteral studies, varying from one to three months in length, were conducted in Sprague-Dawley rats and beagle dogs. Although the largest doses used were in multiples of several times the weight-adjusted doses intended for humans, cefmetazole was generally well tolerated. The principal adverse effect noted in the adult rats receiving the largest doses (2000 and 2500 mg/kg/day) of cefmetazole was slight elevation of serum alanine aminotransferase. Infant rats injected subcutaneously with 300 mg/kg/day or more of cefmetazole for 35 consecutive days had reversible reductions in testicular weight and maturation of spermatogenesis, but not lasting discernible effect on reproductive function. The most consistent effects of longterm multiple dosing with cefmetazole in dogs consisted of vomiting and retching during dosing and reversible haematological changes (mild regenerative anaemia, positive Coombs' test, clinically-silent thrombocytopenia) in a number of the dogs. These findings supported the interpretation that cefmetazole was acceptably safe for clinical studies in humans.