In this article, we provide a brief summary of study design of case-control study within a cohort and an introduction of two case-control studies within a cohort conducted in Japan recently using antihypertensive drug database based on the post-marketing surveillance data of pharmaceutical companies. In the case-control study within a cohort, it is possible to avoid bias caused in a case-control study and conduct more efficiently than cohort study. Therefore the case-control study within a cohort widely has been used in pharmacoepidemiological studies with a database. (Jpn J Pharmacoepidemiol 2013; 18(2): 77-83)

OBJECTIVESystemic and myelotoxic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) were examined by the single administration of TBDD by gavage to rats.

METHODSFifteen Wistar rats of both sexes per group received 0, 10, 30, 100 or 300 μg TBDD/kg body weight. Rats surviving to the scheduled necropsy on Days 2, 7 and 36 after TBDD administration were examined for growth rate, organ weight, hematology, histopathology and adipose tissue levels of TBDD.

RESULTSThree 300 μg/kg-dosed females died on Days 21, 23 and 27, and exhibited a marked decrease in body weight, severe thymic atrophy, decreased bone marrow hematopoiesis and hemorrhage in the subarachnoid space of brain and spinal cord. TBDD-dosed surviving rats exhibited growth retardation, decreased bone marrow hematopoiesis, decreases in red blood cell counts, hemoglobin concentrations, and hematocrit values, an increase in reticulocytes and decreases in platelet counts, white blood cell counts and eosinophils. These signs suggested TBDD myelotoxicity. Splenic extramedullary hematopoiesis was increased in both sexes given TBDD, whereas atrophy of the splenic white pulp occurred only in TBDD-dosed females. Marked decreases in body weights and the size and weight of the thymus, severe thymic atrophy and death in TBDD-dosed females suggested a wasting syndrome. The adipose tissue level of TBDD culminated on Day 7 and decreased to 20-30% of the Day 7 level on Day 36.

CONCLUSIONSThe TBDD-induced effects were characterized by a wasting syndrome and myelotoxicity that appeared at the dose levels of 30 μg/kg and higher and caused death in 300 μg/kg-dosed females.