Male adolescent exposure to endocrine-disrupting pesticides: vinclozolin exposure in peripubertal rabbits.

Adolescence is a time of dramatic neuroendocrine changes that are required for sexual maturation. Hormonal mimicking or inhibiting chemicals can cause significant impairment during this critical period. Vinclozolin (Vin) has been shown to be an anti-androgen affecting male offspring in rats in utero, and its mechanism of action may be mediated by inhibition of androgenic receptor action. The majority of teenagers working on farms are male, and therefore a systemic fungicide, vinclozolin, was selected for study. The rabbit has proved to be an excellent species for modelling reproductive toxicant effects in the male and was selected as the test species. The peripubertal phase for the rabbit was determined to be between the 3rd and 4th months. A 2-month dosing period was therefore initiated at 3 months of age and carried through to the 4th month. Vin was administered by dermal application (100 mg kg(-1) in 100 microl of dimethylsulphoxide) daily. Body weights were determined weekly. The rabbits were then held until fully mature (6 months of age). Semen was collected and evaluated from sexually mature males on a weekly schedule for 5 weeks to maximize sperm output. An automated solid phase extraction procedure for monitoring exposures through isolation and quantification of Vin and its metabolic products was developed. Increased plasma levels of Vin and M2 were found throughout the experimental period. The exposed rabbits had a smaller weight gain during pubertal growth (approaching significance; P=0.059). At maturity, the accessory sex glands of the exposed animals weighed less than those of the controls (P=0.016). Surprisingly, the pooled sperm count of the exposed animals was significantly higher (P=0.017) than that of the unexposed animals. The anti-androgenic effects of Vin may have blocked the negative feedback mechanism of testosterone on the hypothalamus or pituitary gland, allowing for an increase in gonadotrophin release, and consequently increasing sperm production at puberty.

Male reproductive effects of lead, including species extrapolation for the rabbit model.

The effects of elevated blood lead on semen quality were evaluated in the rabbit model and compared to published effects in humans. Mature, male rabbits were given lead acetate by subcutaneous injection in the dose range of 0 to 3.85 mg/kg on a Monday-Wednesday-Friday basis. In each of eight treatment groups, a dosing regimen was developed to produce blood lead levels of 0, 20, 40, 50, 70, 80, 90, and 110 microg/dL. A 5-week pre-exposure period was followed by a 15-week exposure testing period allowing for response through six cycles of the seminiferous epithelium. Semen analyses revealed that increased blood lead levels were associated with adverse changes in the sperm count, ejaculate volume, percent motile sperm, swimming velocities, and morphology. Hormonal responses were minimal. Testicular pathology revealed a dose-dependent inhibition of spermiation. For six measures of semen quality, threshold estimates ranged from 16 to 24 microg/dL. Using the species extrapolation factor derived in this study, a rabbit dose would have to be divided by 1.56 to obtain the equivalent human dose for an equal percentage decrease in sperm concentration; however, rabbits are 3.75 more sensitive in terms of absolute decrease in sperm count for a given blood lead level.

Exogenous human growth hormone reduces body fat in obese women.

The effects of biosynthetic methionyl human growth hormone (met-hGH) on body composition and endogenous secretion of insulin-like growth factor I (IGF-I) were studied in obese women ranging between 138 and 226% of ideal body weight. Following double-blind procedures, 12 subjects were assigned at random to either treatment with met-hGH (n = 6, 0.08 mg/kg desirable body weight) or placebo (n = 6, bacteriostatic water diluent). Treatments were delivered intramuscularly three times per week for a period of 27-28 days. Subjects were instructed to follow a weight-maintaining diet and their pre- and posttreatment kilocaloric intake was monitored for verification. The baseline peak serum GH response to L-dopa/arginine stimulation for the study population as a whole, was in the hyposecretory range (9.6 +/- 1.9 ng/ml), accompanied by a low level of circulating IGF-I (0.56 +/- 0.09 U/ml). Hydrodensitometry revealed that the met-hGH-treated subjects had a significant reduction in body fat, while an observed mean increase in fat-free mass (FFM) approached significance. The percent change in body fat was unrelated to pretreatment levels of body fat, total body weight, or initial endogenous GH status. Changes in circulating IGF-I were similar to those for FFM, with increases approaching significance. There were no significant changes in body composition or IGF-I in the placebo-treated subjects. No significant differences were observed in the self-reported dietary intake of kilocalories during the experimental period between the two groups. We conclude that exogenous GH reduces body fat in obese women in the apparent absence of significant kilocaloric restriction. The effect appears to be unrelated to endogenous GH secretion or body composition.

Heating of basalts with a carbon dioxide laser.

Basalts heated strongly with focused infrared laser radiation vaporized and splattered. Electron microprobe analyses of condensate, ejecta, and residue show strong vapor fractionation trends which, for some elements, are different from what would be expected theoretically and from previously reported data on more siliceous materials. It appears that solution effects can account for these differences. Heating of materials by a powerful focused laser beam for the purpose of study of vapor fractionation is a convenient technique that is more versatile than previous methods such as heating in solar or arc image furnaces.