Changes observed in lympho-hematopoietic organs in rats given piperonyl butoxide may be attributable either to direct toxic effects or to undernutrition. Male F344 rats were therefore fed diet containing 2.5% piperonyl butoxide or subjected to a 64% restriction of food intake for 2 weeks. Marked inhibition of body weight gain, decreased white blood cell count, depletion of T/B lymphocytes in lymphoid tissues, hypoplasia of the bone marrow, and decreased proliferating cell nuclear antigen (PCNA) labeling indices in these tissues were seen in both dietary restriction and 2.5% piperonyl butoxide groups. The depletion of T lymphocytes in the thymus and spleen was stronger in the 2.5% piperonyl butoxide group, as indicated by PCNA labeling indices and image analysis of T lymphocyte areas of the spleen, however, the toxicological profile observed for the chemically treated group was essentially the same as for animals on the restricted diet. These results suggest that the lympho-hematopoietic findings in rats receiving 2.5% piperonyl butoxide are probably due to undernutrition resulting from a reduced food intake.

No abstract

In order to examine whether kojic acid (KA) exerts a promoting effect on thyroid carcinogenesis, male F344 rats were initiated with N-bis(2-hydroxypropyl)nitrosamine (BHP; 2800 mg/kg body wt, single s.c. injection) and, starting 1 week later, received pulverized basal diet containing 2 or 0% KA for 12 weeks. Untreated control rats were given basal diet for 13 weeks. As an additional experiment, two groups without BHP initiation received basal diet or diet containing 2% KA for 20 weeks. The serum triiodothyronine (T3) and thyroxine (T4) levels were significantly decreased (half to one-third of values of the BHP alone group) and serum thyroid-stimulating hormone (TSH) was markedly increased (13-19 times higher than the values of the BHP-alone group) in the BHP + KA group at weeks 4 and 12. Similar changes in serum thyroid-related hormones were observed in the group with 2% KA alone at week 4, but not at week 20. Thyroid weights were significantly increased in the BHP + KA and KA-alone groups. Focal thyroid follicular hyperplasias and adenomas were observed in 4/5 and 3/ 5 rats in the BHP + KA group at week 4, respectively. At weeks 12, these lesions were observed in all rats in the BHP + KA group. Animals of the KA alone group showed marked diffuse hypertrophy of follicular epithelial cells at weeks 4 and 20. No changes in thyroid-related hormone levels or thyroid histopathological lesions were observed in either the BHP alone or the untreated control groups. Measurement of liver T4-uridine diphosphate glucuronosyltransferase (UDP-GT) activity at week 4 revealed no significant intergroup differences. These results suggest that thyroid proliferative lesions were induced by KA administration due to continuous serum TSH stimulation through the negative feedback mechanism of the pituitary-thyroid axis, with decreases of T3 and T4 caused by a mechanism independent of T4-UDP-GT activity.

In a 2-year carcinogenicity study of potassium iodide (KI) in F344/DuCrj rats, squamous cell carcinomas (SCCs) were observed in the salivary glands of 4/40 males and 3/40 females receiving 1000 ppm KI in the drinking water. Ductular proliferation with lobular atrophy was observed at high incidence in the submandibular glands of the high-dose animals, and squamous metaplasia was frequently evident within the proliferative ductules and the larger interlobular ducts. A transition from metaplasia to SCC was apparent. The results suggest that squamous metaplasia in proliferative ductules, occurring secondarily to lobular impairment induced by KI, may develop into SCCs via a non-genotoxic, proliferation-dependent mechanism.

No abstract