Multiple Endocrine Disrupting Effects in Rats Perinatally Exposed to Butylparaben.

Parabens comprise a group of preservatives commonly added to cosmetics, lotions, and other consumer products. Butylparaben has estrogenic and antiandrogenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar rats (n = 18) were orally exposed to 0, 10, 100, or 500 mg/kg bw/d of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected. In the 2 highest dose groups, the anogenital distance of newborn male and female offspring was significantly reduced, and in prepubertal females, ovary weights were reduced and mammary gland outgrowth was increased. In male offspring, sperm count was significantly reduced at all doses from 10 mg/kg bw/d. Testicular CYP19a1 (aromatase) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group. Thus, butylparaben exerted endocrine disrupting effects on both male and female offspring. The observed adverse developmental effect on sperm count at the lowest dose is highly relevant to risk assessment, as this is the lowest observed adverse effect level in a study on perinatal exposure to butylparaben.

Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats.

Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development, even though the doses of the single compounds are below their individual NOAELs for anti-androgenic effects. Consequently, we have initiated a large project where the purpose is to study mixture effects of endocrine disrupting pesticides at low doses. In the initial range-finding mixture studies, rats were gavaged during gestation and lactation with five doses of a mixture of the fungicides procymidone, mancozeb, epoxyconazole, tebuconazole and prochloraz. The mixture ratio was chosen according to the doses of each individual pesticide that produced no observable effects on pregnancy length and pup survival in our laboratory and the dose levels used ranged from 25 to 100% of this mixture. All dose levels caused increased gestation length and dose levels above 25% caused impaired parturition leading to markedly decreased number of live born offspring and high pup perinatal mortality. The sexual differentiation of the pups was affected at 25% and higher as anogenital distance was affected in both male and female offspring at birth and the male offspring exhibited malformations of the genital tubercle, increased nipple retention, and decreased prostate and epididymis weights at pup day 13. The results show that doses of endocrine disrupting pesticides, which appear to induce no effects on gestation length, parturition and pup mortality when judged on their own, induced marked adverse effects on these endpoints in concert with other pesticides. In addition, the sexual differentiation of the offspring was affected. This as well as the predictability of the combination effects based on dose-additivity modelling will be studied further in a large dose-response study.

Similar serum lipoprotein reductions by lipid-lowering diets with different polyunsaturated:saturated fat values.

Lipid-lowering diets enriched in polyunsaturated fat decrease the serum cholesterol in hyperlipoproteinaemia, usually by reducing both the low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) cholesterol concentrations. The aim of the present study was to investigate whether the effects on LDL could be maintained but those on HDL cholesterol be diminished by reducing the ratio, polyunsaturated:saturated fat (P:S) of the diet. Twenty hyperlipoproteinaemic patients (six with type IIa, eight with type IIb and six with type IV) in a metabolic ward were given two fat-modified diets during two consecutive 3-week periods in a randomized order. The diets were identical with regard to nutrient composition but differed with regard to the P:S values, which were 2.0 and 1.3 respectively. The lipoprotein-lipid composition and serum apolipoprotein concentrations were similar at the end of the two dietary periods in type IIa and type IV patients but in type IIb patients a more pronounced reduction of the LDL-cholesterol concentration by 9% (P less than 0.05) was achieved on the diet with the higher P:S value. The HDL-cholesterol did not differ significantly. The results indicate that increasing the P:S value of lipid-lowering diets from 1.3 to 2.0 does not offer a great advantage with regard to the lipoprotein-lipid reductions achieved in moderate hyperlipoproteinaemia.

Reduction of low density and high density lipoprotein cholesterol by fat-modified diets. A survey of recent findings.

The aim of this review is to summarize recent findings concerning the effects of fat-modified diets on serum lipoproteins, especially on high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol concentrations. Generally, both HDL and LD cholesterol are reduced in subjects on diets enriched in polyunsaturated fatty acids (PUFA diets). The only exceptions to this rule are hypertriglyceridaemic patients with low HDL or LDL concentrations. The changes in HDL and LDL cholesterol are inversely related to the respective HDL and LDL concentrations before dietary treatment. Increasing HDL cholesterol concentrations are seen only during simultaneous body weight reduction. Low HDL cholesterol concentrations are not normalized on PUFA diets. The ratio of LDL cholesterol to HDL cholesterol shows only marginal changes during treatment with a PUFA diet. Thus we cannot clearly state how a lipid-lowering diet might contribute to the anti-atherogenic effect which seems to be characteristic of this type of diet, on the basis not of the change in fasting serum lipoprotein concentrations, but of epidemiological and experimental data.

Supplementation with vitamin E in hyperlipidemic patients treated with diet and clofibrate. Effects on serum lipoprotein concentrations, plasma fatty acid composition and adipose tissue lipoprotein lipase activity.

Twelve hyperlipidemic patients on long term treatment with a lipid lowering diet enriched in polyunsaturated fatty acids and with clofibrate were supplemented with vitamin E (400 mg/day). The effect on serum lipoprotein concentration, plasma lipid fatty acid composition, and adipose tissue lipoprotein lipase activity was studied. No additional lipid-lowering effect was registered during a treatment period of 4 months. A slight increase in total serum cholesterol concentration and in high density lipoprotein concentration was probably attributable to seasonal variations in serum lipoprotein concentrations. No major changes of fatty acid composition in plasma cholesteryl esters or triglycerides were recorded. However, an increased relative amount of arachidonic acid and a reduced amount of palmitic acid in the plasma phospholipids after 2 months was possibly caused by the vitamin E therapy.