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A novel antimitotic compound named Nostodione A (Nd A) was isolated from a terrestrial blue-green alga Nostoc commune. Nostodione A disturbed the mitotic spindle formation of sea-urchin eggs and gave small spindles with low birefringence density. Nostodione A. how­ever, had no phytotoxicity on the germination of a dicotyledonous plant Medicago sativa. Based on the spectral analysis and chemical degradation, the structure of Nostodione A was elucidated

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Skin sensitization resulting in allergic contact dermatitis is a common occupational health issue. In this study, the effect of mixing two skin sensitizers on the skin sensitization response was investigated. Skin sensitizers are generally classified into T helper type 1 (Th1) or T helper type 2 (Th2), depending on the induced cytokine profile. Dinitrochlorobenzene (DNCB) and oxazolone (Oxa) are Th1 skin sensitizers and phthalic anhydride (PA) and toluene diisocyanate (TDI) are Th2 skin sensitizers. We investigated the effect on skin sensitization response to mixtures of three pairs of these sensitizers: DNCB and Oxa, DNCB and PA, and PA and TDI, using guinea pig maximization test and mouse ear swelling test. In guinea pigs sensitized with the mixture of DNCB and Oxa or PA and TDI, there were changes of skin sensitization response to DNCB and Oxa, and that to PA. On the other hand, there was no mixture effect in guinea pigs sensitized with the mixture of DNCB and PA. The skin sensitization responses were decreased in mice sensitized with the mixtures of DNCB and Oxa or PA and TDI, whereas the mixture effect was not observed in mice sensitized with the mixture of DNCB and PA. The present findings revealed that mixture effect on the skin sensitization response was observed after simultaneous exposure to two skin sensitizers, and the effect was determined by combinations of mixed skin sensitizers.

The aim of the present study was to develop a quantitative evaluation method for detecting antiandrogenic activity of chemicals in rabbits that are regularly used for developmental toxicity studies. Kbl: New Zealand White rabbits (n = 8-9) were injected intramuscularly with an antiandrogen, cyproterone acetate (CA; 10 mg/kg body weight [BW]/day), on gestation days (GD) 13-24. On GD 29, live fetuses were obtained by cesarean section and sexed by examination of the internal genitalia. The external genitalia were evaluated in cross-section measurements of the phallus by both diameter and width of the ventral gap of the preputial lamella with a micrometer under a stereoscopic microscope. The diameters of the preputial lamella were 1015 Ϯ 83.5, 856 Ϯ 64.0, and 865 Ϯ 72.6 mm in control males, control females, and CAtreated males, respectively. The ventral gaps of the preputial lamella were 26 Ϯ 8.2, 437 Ϯ 72.3, and 318 Ϯ 59.4 mm in the control males, control females, and CA-treated males, respectively. There were statistically significant differences in both parameters between control males and control females or CA-treated males. The lower fetal BW in CA-treated males did not disturb the detection of the feminization of the ventral gap of the preputial lamella; however, the diameter of the preputial lamella might be influenced by fetal BW because no difference in the relative diameter of the preputial lamella was found between control males and CA-treated males.These results demonstrated that this approach could detect the antiandrogen activity of CA quantitatively by feminization of male external genitalia in rabbit fetuses.

INTRODUCTIONProcymidone, N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide (hereafter PCM), is a fungicide used to control plant diseases such as sclerotinia rot and gray mold on a range of vegetables, fruits, soya bean, sunflowers, tobacco, and oil seed rape, as well as on ornamental plants and flower bulbs. The mechanism of pesticidal action involves the inhibition of triglyceride synthesis in fungi.The toxicities of PCM were evaluated by the Joint FAO/WHO Meeting on Pesticide Residues (FAO and WHO, 2007). The Meeting established an acceptable daily intake (ADI) of 0-0.1 mg/kg body weight (bw) based on a no-observed-adverse-effect-level (NOAEL) of 12.5 mg/kg bw per day in a two-generation study of reproductive toxicity and a study of developmental toxicity in rats, on the basis of hypospadias and alterations in testes, prostate, and epididymis weights, and safety factor of 100. PCM is an active anti-androgen (Hosokawa et al., 1993) and the androgen receptor antagonism is the likely to be the mechanism of those toxicities described above.Although PCM alters sexual differentiation of male offspring in rats, no alterations in rabbit male fetuses were observed in a conventional teratology study in rabbits receiving up to 1,000 mg/kg bw (FAO and WHO, 2007). These results suggest that species difference of developmental effects of PCM on sexual differentiation exists. However, in the conventional teratology study in rabbits (FAO and WHO, 2007), some concerns were raised regarding a shorter treatment period (gestation day (GD) 7 to 19) and an observation method of external genitalia development. In rats, Ostby et al. (1999) reported that PCM alters sexual differentiation of male offspring in rats receiving 25 mg/kg bw and above from GD 14 to postnatal day (PND) 4. It seems that the critical period of sexual differentiation such as external genitalia development is late in gestation, and the treatment period in the rabbit study described above might not have included the critical period of external genitalia development in rabMaternal exposure to procymidone has no effects on fetal external genitalia development in male rabbit fetuses in a modified developmental toxicity study Kunifumi Inawaka, Noriyuki Kishimoto, Hashihiro Higuchi and Satoshi KawamuraEnvironmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-8558, Japan (Received December 25, 2009; Accepted January 12, 2010) ABSTRACT -This study was conducted to evaluate the effects of procymidone (PCM) on development of male rabbit fetal external genitalia. PCM was administered once daily by gavage at dose levels of 0 (control) and 125 mg/kg/day to pregnant rabbits from gestation day 6 through 28 and fetal external genitalia was observed in detail. This treatment period covered the critical stage of sexual differentiation of fetal external genitalia in rabbits. In the maternal animals, food consumption was reduced in the PCM group. There were no effects of PCM on maternal caesarean section...

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