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Abstracts / Toxicology Letters 205S (2011) S180–S300
hexyl-, di-n-hexyl-, di-iso-heptyl-, di-2-ethylhexyl-, di-n-heptyl-, di-n-octyl-, and di-iso-nonyl-phthalate. Adverse effects on various endpoints of male fertility and offspring development were compared. Results: Selected phthalates with side chain lengths of 4–6 C-atoms adversely affect male fertility with comparable potential and potency. Overall, impairment of male development was more pronounced compared to the impairment of male fertility. Concerning fertility, adverse effects on sperm parameters and Sertoli cells were the most sensitive endpoints. Concerning development, reduction of anogenital distance and changes in testosterone levels in serum or testes were the most sensitive endpoints. Concerning development, doses inducing adverse effects were lower for phthalates with 4–6 C-atoms in the side chain when compared to phthalates with longer or shorter side chains. doi:10.1016/j.toxlet.2011.05.844
P2221 Evaluation of the embryotoxicity of misoprostol using the whole embryo culture assay M.F. Cavieres ∗ , C.A. Campos Faculty of Pharmacy, Universidad de Valparaíso, Valparaíso, Chile Purpose: Misoprostol, a synthetic analog of prostaglandin E1, is indicated for pregnancy termination. Misoprostol-inducedabortions may not be successful leading to in utero exposure to the drug. A strong epidemiological relationship has been found between in utero exposure to misoprostol and the induction of developmental defects. However, reports of experimental studies are practically non-existent, probably indicating lack of experimental models suitable for the study of the teratogenicity of the drug. Here we used the whole embryo culture assay (WEC) to examine the effect of misoprostol on development. Methods: Embryos were collected from Sprague Dawley rats on gestation day 9.5 and cultured according to the ECVAM method. In brief, embryos with attached yolk sacs and ectoplacental cones were cultured for 48 h at 37 ◦ C in rat serum supplemented with streptomycin and penicillin and a gas mixture of CO2 , O2 and N2 . Misoprostol concentrations were 200, 2000 and 20,000 pg/ml. At the end of culture, embryonic growth was assessed by measurement of crown–rump length, head length, and yolk sac diameter. Development was evaluated by counting the number of somites and arches. Rotation, forelimb bud, optic and otic vesicles, and other embryo structures were evaluated for stage of development. Heartbeat and presence of functional blood vessels in the visceral yolk sac were also determined. Results: Misoprostol resulted in concentration-dependent induction of morphologic abnormalities and in the decrease of embryo growth parameters. The data confirms that WEC is an experimental alternative suitable for the study of mechanisms that mediate misoprostol teratogenicity. doi:10.1016/j.toxlet.2011.05.845
P2222 Protective effect of Spirulina (Arthrospira) maxima against cadmium-induced genotoxicity and teratogenicity in mice G.A. Chamorro-Cevallos 1,∗ , N. Argüelles-Velázquez 1 , I. Alvarez González 2 , E. Madigal-Bujaidar 2 1
Pharmacy, Escuela Nacional de Ciencias Biològicas, IPN, Mèxico D.F., Mexico, 2 Morphology, Escuela Nacional de Ciencias Biològicas, IPN, Mèxico D.F., Mexico The role of Spirulina (Arthrospira) maxima (SP) in preventing cadmium (Cd) genotoxicity and teratogenicity in ICR mice was studied. Cd was administered intraperitoneally to pregnant female mice at 1.5 mg/kg on gestation day (GD) 7 and SP was given by gastric intubation at 0, 200, 400 or 800 mg/kg from GD-0 through GD-17 (until sacrifice). For the genotoxicity study, blood samples were collected through a neck incision in each fetus and a micronucleous assay was used. The frequency of micronucleated polychromatic erythrocytes (MNPE) was counted among 1000 polychromatic erythrocytes (PE). Cytotoxicity was also determined as the PE/NE (normochromatic erythrocyte) index. On the other hand, for the teratogenic study, the fetuses were weighed and inspected for external malformations. Total implantations sites and reabsorptions were noted in the uterus. One third of the offspring was designed for skeletal analysis. The remaining fetuses were fixed in Bouin’s solution and prepared for Wilson serial slices. The group treated with Cd showed a significant increase in the quantity of MNPE. The SP treatment at the three doses diminished genotoxic damage in a dose-dependent manner. The cytotoxic assay revealed no alterations in the evaluated index. SP significantly decreased the frequency of fetuses with exencephaly, micrognathia, micropthalmia and skeletal abnormalities at these doses. The results of the present study clearly demonstrate the therapeutic potential of SP in Cd-induced mutagenicity and teratogenicity. It is possible that the mechanism of action of SP could be related to its antioxidant capacity, which has been clearly demonstrated in previous experiments. doi:10.1016/j.toxlet.2011.05.846 P2223 Impact of food products from crude oil polluted area of Nigeria on the reproductive organs of male rats A.P. Ebokaiwe ∗ , E.O. Farombi Biochemistry, University of Ibadan, Ibadan, Nigeria This study was designed to investigate the effect of the secondary exposure of Bonny Light crude oil (BLCO) via food chain on the reproductive system of male rats. Four weeks old male rats were fed with food products from crude oil contaminated area (Imiringi, Bayelsa State) and non contaminated area (Ibadan, Oyo State) for 90 days. Normal commercial rat feed served as control. The food products include 20% fish meal, 33% corn starch, 33% whole grain (corn), 07% fluted pumpkin, 06% vegetable oil, 1% CaCl2 , 0.4% NaCl, 0.6% mixture of minerals and vitamins. Weights and histology of reproductive organs, serum Leutenizing Hormone (LH), Follicle Stimulating Hormone (FSH) and testosterone levels, sperm analysis and morphology, antioxidant system status, and levels of bio-metals were evaluated. The result showed significant increase in weights of seminal vesicle and prostate gland with no effect in testes and epididymal weight. BLCO contaminated food products increased FSH level, whereas LH and testosterone decreased significantly. Although there was a significant increase in bio-metals with