S148 Abstracts / Toxicology Letters 189S (2009) S57–S273

J16Evaluation of spermatotoxicity of halogenated propanes by uti-lizing of mitochondrial metabolism in rat and comparison withthe other test methods

Katsumi Ohtani ∗, Hisayo Kubota

National Institute of Occupational Safety and Health, HazardEvaluation and Epidemiology Research, Kawasaki, Japan

Several reproductive hazard incidents due to halogenatedpropanes: Dibromochloropropane (DBCP) and 2-bromopropane(2BP), evidenced by exposure in the workplace, have suggested theimportance of testicular toxicity testing in the industrial toxicology.In order to develop simple and rapid sperm analysis methods forevaluation of reproductive toxicity of industrial chemicals, we haveapplied the assays of four tetrazolium salts (MTT//WST-1,-3,-8),the substrates of mitochondrial reductase, to assessment of spermquality, comparing these assays with other instrumental methods,such as the uses of Sperm Quality Analyzer (SQA) and Computer-Assisted Sperm Analyzer (CASA; HTM-IVOS).The epididymal fluidderived from male F344 rats treated with DBCP or 2BP in the doserange of 25–100 or 500–2000 mg/kg/day (s.c.) respectively 8 timesfor one month was examined by all these assays. Significant changesin absorbance levels by MTT and WST-3 assays were observed in theDBCP 75 and 100 mg/kg treated groups and the 2BP 2000 mg/kgtreated group as well as in the Sperm Count by CASA, while nosignificant difference was evident only in WST-1 assay. Further-more, significant decreases in the sperm motility index obtainedby SQA was observed in the similar DBCP groups, while no suchdecrease was observed in all the 2BP treated groups. These resultssuggest that some tetrazoliums except WST-1 are effective for theassessment of male reproductive toxicity.

doi:10.1016/j.toxlet.2009.06.821

J17Effects of gestational and lactational exposure to bisphenol A on

development and reproduction in F1 rat offspring�

Kenichi Kobayashi ∗, Katsumi Ohtani, Hisayo Kubota, MuneyukiMiyagawa

National Institute of Occupational Safety and Health, Kawasaki, Japan

Bisphenol A (BPA) is widely used in the manufacturing of poly-carbonate and epoxy resins, dental sealants, and other chemicallyderived products. BPA, a xenoestrogen, has been reported to mimicthe actions of estrogen and to affect the endocrine glands in vivoand in vitro. However, the effects of low-dose exposure to BPA onpostnatal development and reproduction remain controversial. Wethus performed a one-generation toxicity study using rat offspring.Pregnant CD (SD) IGS female rats (F0) were given free access to dietthat contained low doses of BPA (0, 0.3, 3.3, or 33 ppm) from ges-tation day 6 through lactation day 21. The weanlings from each F0dam group were fed control (0 ppm) diet ad libitum until sacrifice.F1 offspring were scarified at age 5- and 13-weeks for subsequentanalyses of developmental parameters and reproductive function.At age 5 weeks, vaginal opening was verified in all F1 females. F1offspring exhibited no treatment-related changes in body weight,anogenital distance, weight of any of the reproductive organs, orplasma sex hormone concentrations of both sexes. There were notreatment-related effects of BPA on sperm motility in 13-week-oldF1 males. These findings suggest that dietary exposure to low lev-

els of BPA has no apparent adverse effects on development andreproduction in F1 generation of rats.

� Selected for Oral Presentation.

doi:10.1016/j.toxlet.2009.06.822

J18Transcriptional response to neurotoxicants: Impact of gender,developmental stage and co-exposure on rat cerebellum and

hippocampus gene expression following perinatal exposure�

Guillaume Pelletier 1,∗, Bhaja Krushna Padhi 1, Andrew Williams 2

1 Health Canada, Hazard Identification Division, Tunney’s Pasture,Ottawa, Canada, 2 Health Canada, Population Studies Division,Tunney’s Pasture, Ottawa, Canada

Although human populations are simultaneously exposed to mul-tiple environmental contaminants, our knowledge of the effectsof such co-exposures on brain gene expression and neurodevel-opment is still limited. In order to investigate this question, theNorthern Contaminants Mixture (NCM) was formulated to con-tain methylmercury (MeHg), polychlorinated biphenyls (PCBs, 14congeners), and organochlorine pesticides (OCs, 12 compounds,including pesticide isoforms and metabolites) in the same pro-portion measured in the blood of Canadian Arctic populations.Published comparisons of the effects of perinatal exposure to NCMor to its MeHg, PCBs, and OCs components administered sepa-rately revealed that co-exposure significantly masks the effectsof individual components on rat brain gene and protein expres-sion. Building on the knowledge generated from these previousstudies performed at high contaminant doses, we selected 10 tox-icologically relevant genes for further investigation by Real-TimeqPCR following perinatal exposure to the same contaminant mix-tures at toxic and sub-toxic doses. Gene expression was assessedin rat pup cerebella and hippocampii at two developmental timepoints (post-natal days 14 and 21) and in both genders. Com-parison of gene expression patterns confirms that transcriptionalperturbation following exposure to a mixture of toxicants cannotbe accurately predicted from exposure to its components admin-istered separately, at both toxic and sub-toxic exposure levels. Wealso report that toxicant effects on brain gene transcription at highdoses cannot be directly extrapolated to low dose exposures andthat gender, developmental stage and brain structure are crucialvariables affecting transcriptional response to toxicants.

� Selected for Oral Presentation.

doi:10.1016/j.toxlet.2009.06.823

J19Withdrawn

doi:10.1016/j.toxlet.2009.06.824