Testosterone toxicity

A dose-related depression in testosterone production at doses not producing any general toxic or significant cytotoxic action... 

Androgenic deficiency in male rats given a single oral dose of 15 pg 2,3,7,8-TCDD/kg BW was evident as early as 2 days posttreatment, with persistence up to 12 days. These deficiencies may account for male reproductive pathology and dysfunction in rats treated with overtly toxic doses of TCDD. Findings included depression in plasma testosterone concentrations, as well as decreased weight of seminal vesicles (by 68%), ventral prostate gland (by 48%), testes, and epididymis (Moore et al. 1985). 

As would be expected, khat overuse produces symptoms similar to those of other monoamine stimulants, such as cocaine or amphetamine, including signs of sympathetic overarousal. In the extreme this can involve a toxic psychosis. Disorders more frequently associated with chronic khat use in males are headaches, anorexia, insomnia, constipation, and respiratory illnesses (Kennedy et al. 1983). Females report higher incidences of acute gastritis, jaundice, bronchitis and hepatic diseases. Also, cathinone has toxic reproductive effects in humans and experimental animals (Islam et al. 1990). It decreases sperm count and motility, and increases the number of abnormal sperm cells. It also decreases plasma testosterone in rats. 

Plasma hormones and enzymes of testicular origin were used as markers for evaluation of acute testicular toxicity in rats treated with 1,3-DNB. Lactate dehydrogenase isozyme C4 (LDH-C4) and ABP were both elevated after treatment with doses between 10 and 25 mg/kg of 1,3-DNB (Reader et al. 1991). Testosterone levels were reduced after treatment with 10 and 32 mg/kg of 1,3-DNB (Reader etal. 1991 Rehnberg et al. 1988). 

In rats ammonium perfluorooctanoate induced hepatomegaly that was more pronounced in the male than in the female. Male rats are thought to be more sensitive to the toxic effects of ammonium perfluorooctanoate because of their slower excretion rate. The rapid excretion by female rats is due to active renal tubular secretion, which is considered to be hormonally controlled by estradiol and testosterone levels. The hepatomegaly was hypertrophic rather than hyperplastic and involved proliferation of peroxisomes. 

Adverse effects include changes in libido and the occurrence of oedema, weight gain and gynecomastia, may occur. Androgens are potentially hepato-toxic, testosterone less than methyltestosterone and fluoxymesterone. Androgens can potentiate anticoagulant action. 

Goetz AK, Ren HZ, Schmid JE, Blystone CR, ThiUainadarajah I, Best DS, Nichols HP, Strader LE, Wolf DC, Narotsky MG, Rockett JC, Dix DJ (2007) Disruption of testosterone homeostasis as a mode of action for the reproductive toxicity of triazole fimgicides in the male rat. Toxicol Sci 95 227-239... 

Males had inhibited testosterone levels and reduced growth, while females had increased uterine weights Lowest toxic dose... 

The involvement of testosterone in the testicular atrophy caused by di(2-ethyl-hexyl) phthalate was examined by co-administration of testosterone (1 mg/kg bw) subcutaneously with 2000 mg/kg bw di(2-ethylhexyl) phthalate [purity not specified] in groundnut oil to adult male Wistar rats for 15 days (Parmar et al., 1987). Administration of di(2-ethylhexyl) phthalate reduced the sperm count and also significantly increased the activity of y-GT, lactate dehydrogenase and P-glucuronidase and decreased the activity of sorbitol dehydrogenase and acid phosphatase. Co-adminis-tration of testosterone seemed to normalize the sperm count and the activity of testicular enz5mies. The role of testosterone in the testicular toxicity of di(2-ethylhexyl) phthalate has not been fully elucidated. Several reports refer to increased or decreased testosterone levels in plasma and testicular tissue. 

Steroids that aid in muscle development are called anabolic steroids. They are synthetic derivatives of testosterone, thus have the same muscle-building effect as testosterone. There are more than 100 different anabolic steroids which, vary in structure, duration of action, relative effects and toxicities. Androstenedione, stanozolol and dianabol are anabolic steroids. They are used to treat people suffering from traumas accompanied by muscle deterioration. The use of anabolic steroid can lead to a number of dangerous side-effects, including lowered levels of high density lipoprotein cholesterol, which benefits the heart, and elevated levels of harmful low density lipoprotein, stimulation of prostate tumours, clotting disorders and liver problems. 

Thyroid Effects. Limited information is available on thyroid effects in PBDE-exposed humans. There are suggestive occupational data as shown by effects that included increased serum FSH, low or borderline low serum T4, and increased thyroid antimicrosomal antibody titers in workers exposed to decaBDE and/or unspecified PBBs. There was no clear association between plasma levels of 2,2, 4,4-tetraBDE and thyroid hormone levels (free and total T3 and T4, TSH, free testosterone, follicle-stimulating hormone, lutenizing hormone, and prolactin) in men who consumed varying amounts of fatty fish from the Baltic Sea. Based on consistent evidence in animals, as summarized below, the thyroid is particularly sensitive to PBDEs and is a likely target of toxicity in exposed humans. 

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