Atrophy, testicular

The reproductive toxicity of some phthalate esters has been reviewed by the Commission of the European Communities (45). This review concludes that testicular atrophy is the most sensitive indicator of reproductive impairment and that the rat is the most sensitive species. 

In men, administration of an androgen may result in breast enlargement (gynecomastia), testicular atrophy, inhibition of testicular function, impotence, enlargement of the penis, nausea, jaundice, headache, anxiety, male pattern baldness, acne, and depression. Fluid and electrolyte imbalances, which include sodium, water, chloride, potassium, calcium, and phosphate retention, may also be seen. 

Virilization in the woman is the most common reaction associated with anabolic steroids, especially when higher doses are used. Acne occurs frequently in all age groups and both sexes. Nausea, vomiting, diarrhea, fluid and electrolyte imbalances (the same as for the androgens, discussed previously), testicular atrophy,... 

Pain, headache, asthenia, abdominal pain, chest pain, flu symptoms, fever, liver toxicity, insomnia, nausea, constipation, testicular atrophy, dyspnea, pain, asthenia... 

Headache, dizziness, intolerance to contact lens, edema, thromboembolism, hypertension, nausea, weight changes, testicular atrophy, acne, breast tenderness, gynecomastia... 

In experimental animals, vitamin E deficiency results in resorption of femses and testicular atrophy. Dietary deficiency of vitamin E in humans is unknown, though patients with severe fat malabsorption, cystic fibrosis, and some forms of chronic fiver disease suffer deficiency because they are unable to absorb the vitamin or transport it, exhibiting nerve and muscle membrane damage. Premamre infants are born with inadequate reserves of the vitamin. Their erythrocyte membranes are abnormally fragile as a result of peroxidation, which leads to hemolytic anemia. 

Testicular atrophy Testes Walleye No Increased Friedmann et al. 

Changes in steroidal hormone production, conversion, and handling are also prominent features of cirrhosis. These changes can result in decreased libido, gynecomastia (development of breast tissue in men), testicular atrophy, and features of... 

Nonspecific signs on physical exam include jaundice, tea-colored urine, bruising, hepatomegaly, splenomegaly, spider angiomata, caput medusae, palmar erythema, gynecomastia, and testicular atrophy. 

Rat (Fischer- 344) 90 d 10.3 101 M (testicular atrophy) MacEwen and Vernot 1983 Durad MP280... 

Testicular atrophy was observed upon gross necropsy after male rats were continuously exposed for 90 days to an aerosol concentration of 101 mg/m3 Durad MP280, but not in rats exposed to 10.3 mg/m3 (MacEwen and Vemot 1983). Testicular atrophy was not observed in male rats continuously exposed for 90 days to an aerosol concentration of 100 mg/m3 Fyrquel 220 (MacEwen and Vemot 1983). 

There are insufficient data to derive hydraulic fluid-specific acute-duration inhalation MRLs. No systemic effects were observed in rats exposed to 6,350 mg/m3 of Durad MP280 for 4 hours (Gaworski et al. 1986). Mild lethargy was observed 1-3 hours post-exposure to 6,190 and 6,350 mg/m3. Longer-term inhalation exposure to Durad MP280 resulted in testicular atrophy in rats (MacEwen and Vemot 1983). 

Following a 90-day continuous exposure to 101 mg/m3 of Durad MP280, leukocytosis, kyphosis, and testicular atrophy were observed in rats and 100% mortality, cachexia, head droop, anorexia, and lethargy were observed in rabbits. No effects were observed in either species at 10.3 mg/m3 Durad MP280 (MacEwen and Vemot 1983). Continuous exposure to 100 mg/m3 of Fyrquel 220 for 90 days resulted in kyphosis in rats (MacEwen and Vemot 1983) the NOAEL for this effect was 10.1 mg/m3. No adverse effects were observed in rabbits exposed to 100 mg/m3 Fyrquel 220 continuously for 90 days (MacEwen and Vemot 1983). At the lowest tested concentration of Cellulube 220 (2,000 mg/m3, 4 hours/day,... 

Organophosphate ester hydraulic fluids may cause adverse reproductive effects based on observations of testicular atrophy in rats after continuous inhalation exposure to 101 mg/m3 Durad MP280 for 90 days (MacEwen and Vemot 1983), loss of spermatic elements and degeneration in the seminiferous tubules in dogs given 20 subcutaneous injections of Cellulube 220 at doses ranging from 100 to 500 mg/kg/day... 

Chromium has proved effective in counteracting the deleterious effects of cadmium in rats and of vanadium in chickens. High mortality rates and testicular atrophy occurred in rats subjected to an intraperitoneal injection of cadmium salts however, pretreatment with chromium ameliorated these effects (Stacey et al. 1983). The Cr-Cd relationship is not simple. In some cases, cadmium is known to suppress adverse effects induced in Chinese hamster (Cricetus spp.) ovary cells by Cr (Shimada et al. 1998). In southwestern Sweden, there was an 80% decline in chromium burdens in liver of the moose (Alces alces) between 1982 and 1992 from 0.21 to 0.07 mg Cr/kg FW (Frank et al. 1994). During this same period in this locale, moose experienced an unknown disease caused by a secondary copper deficiency due to elevated molybdenum levels as well as chromium deficiency and trace element imbalance (Frank et al. 1994). In chickens (Gallus sp.), 10 mg/kg of dietary chromium counteracted adverse effects on albumin metabolism and egg shell quality induced by 10 mg/kg of vanadium salts (Jensen and Maurice 1980). Additional research on the beneficial aspects of chromium in living resources appears warranted, especially where the organism is subjected to complex mixtures containing chromium and other potentially toxic heavy metals. 

Weight gain, acne, hirsutisrrt dyslipide-mia, hepatic consequences, gynecomastia, priapism, prostate disorders, testicular atrophy, sleep apnea, and skin reactions with patches... 

Reproductive Effects. Reproductive effects have not been examined in humans after exposure to -hexane. A dominant-lethal test in mice showed no effect on male fertility (Litton Bionetics 1980). No effects were seen on reproductive tissues in male rats after intermediate-duration inhalation exposure at 500 ppm (IRDC 1981) or in either sex of mice after intermediate-duration inhalation exposure to up to 10,000 ppm -hexane (Dunnick et al. 1989 NTP 1991). However, inhalation exposure in male rats to higher concentrations of -hexane showed effects after acute-duration exposure to 5,000 ppm (spermatid and spermatocyte degeneration and exfoliation) and atrophy of testicular germinal epithelium after intermediate-duration exposure to 1,000 ppm (De Martino et al. 1987 Nylen et al. 1989). Testicular atrophy in rats was also noted after intermediate-duration oral exposure at 4,000 mg/kg/day (Krasavage et al. 1980). Similar to -hexane neurotoxicity after inhalation exposure, effects on the testes in rats can be reproduced by oral administration of the w-hexane metabolite 2,5-hexanedione (Chapin et al. 1982 ... 

Co-exposure to approximately equal concentrations of xylene or toluene (Nylen et al. 1989) has also prevented 77-hexane-induced testicular atrophy in Sprague-Dawley rats. The protective effects of xylene and toluene on peripheral neuropathy and testicular atrophy caused by 77-hexane may result from competition for metabolism, resulting in a slowing of 77-hexane conversion to 2,5-hexanedione. 

Gillies PJ, Norton RM, Baker TS, et al. 1981. Altered lipid metabolism in 2,5-hexanedione-induced testicular atrophy and peripheral neuropathy in the rat. Toxicol Appl Pharmacol 59 293-299. 

Nylen P, Ebendal T, Eriksdotter-Nilsson M, et al. 1989. Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to -hexane and a protective effect of simultaneous exposure to toluene or xylene. Arch Toxicol 63 296-307. 

Some cardiovascular effects observed after high doses seem less important than testicular atrophy observed in juvenile rats. It seems possible that the latter effect is species-specific. Respective investigations are being carried out. 

No studies were located regarding reproductive effects in animals after dermal exposure to mirex. The only animal study that referred to reproductive effects following dermal exposure to chlordecone was conducted in rabbits by Allied Chemical. This study was not available for review. A published review of the study (Epstein 1978) indicated that chlordecone applied to shaved skin at dose levels of 5 or 10 mg/kg for 8 hours/day, 5 days/week, for 3 weeks induced testicular atrophy in two of six rabbits at 5 mg/kg and in one of six rabbits at 10 mg/kg. No other toxic effects were noted. This study is limited by the lack of dose response and lack of a NOAEL for the effect observed. 

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