Testicular degeneration

Reproductive Toxicity. No data are available that impHcate either hexavalent or trivalent chromium compounds as reproductive toxins, unless exposure is by way of injection. The observed teratogenic effects of sodium dichromate(VI), chromic acid, and chromium (HI) chloride, adininistered by injection, as measured by dose-response relationships are close to the amount that would be lethal to the embryo, a common trait of many compounds (111). Reported teratogenic studies on hamsters (117,118), the mouse (119—121), and rabbits (122) have shown increased incidence of cleft palate, no effect, and testicular degeneration, respectively. Although the exposures for these experiments were provided by injections, in the final study (122) oral, inhalation, and dermal routes were also tried, and no testicular degeneration was found by these paths. 

A subacute study in rats treated intraperitoneally with deltamethrin showed testicular degeneration and an inhibition of spermatogenesis, which seemed to be mediated by an elevation of nitric oxide levels [148], Subcutaneous dosing also produced adverse testicular effects and reduced spermatogenesis [149],... 

Percutaneous absorption has been documented in rabbits. The liquid dropped into the eye of a rabbit caused severe but reversible conjunctivitis, iritis, and corneal opacity. Cytotoxic effects on rat bone marrow cells, with reduction in leukocyte counts, and testicular degeneration were observed after intramuscular injections at 400mg/kg/day. 

Daily exposure of male rats to 1500 ppm for 10 weeks caused severe testicular degeneration no males sired litters during a subsequent... 

Toxicology. Phenylphosphine is a respiratory and skin irritant multiple exposures in rodents causes hematologic changes and testicular degeneration in males. 

In 90-day inhalation studies (6 hours/day, 5 days/week) rats became hypersensitive to sound and touch and had mild hyperemia at 0.6ppm at 2.2ppm there was greater increase in splenic red blood cell formation, mild hemolytic anemia, and dermatitis. Severe testicular degeneration developed in the 2.2 ppm-exposed rats that did not return to normal during a 10-week postexposure observation period. Dogs similarly exposed at 0.6 and 2.2 ppm had some loss of appetite, diarrhea, lacrimation, and hind leg tremor. There was mild, reversible testicular degeneration in the males exposed at 2.2 ppm. 

Reproductive Toxicity. The effects of carbon tetrachloride on reproduction have not been well investigated. Inhalation of carbon tetrachloride caused testicular degeneration (Adams et al. 1952) and reduced fertility (Smyth et al. 1936) in rats. Oral exposure to carbon tetrachloride did not adversely affect reproduction in rats (Alumot et al. 1976). Additional studies in animals using modern techniques and protocols for measuring adverse effects on reproductive parameters in males and females would be valuable. In order to be maximally useful, such studies should involve both oral and inhalation exposures, and should include a range of doses extending below those that cause frank parental injury. 

Chatterjee A. 1966. Testicular degeneration in rats by carbon tetrachloride intoxication. Experientia 226 395-396. 

Testicular degeneration was observed in rats and mice exposed to nickel sulfate ( 1.6 mg nickel/m ) and nickel subsulfide ( 1.8 mg nickel/m for rats and 3.6 mg nickelM for mice) 6 hours/day for 12 days over a 16-day period (Benson et al. 1987, 1988). The study authors indicated that testicular lesions were probably the result of emaciation rather than a direct effect of nickel (Benson et al. 1987). That testicular effects are secondary to generalized emaciation is supported by intermediate-duration studies. At doses that did not cause emaciation, no exposure-related effects were seen in sperm motility, or... 

Testicular degeneration (spermatogonial activity reduced, germ cells in testicular lobules degenerating, congested blood vessels) ovaries histologically different, oocytes resorbed... 

Following short-term inhalation exposure to 160 ppm [620 mg/m ] methyl bromide (6 h per day on five days per week for up to six weeks), B6C3F, mice were found to be more sensitive than Fischer 344/N rats 50% of male mice died after eight exposures and 50% of female mice after six exposures, while similar mortality was observed in male rats only after 14 exposures. Neuronal necrosis and testicular degeneration were observed in both species nephrosis was observed in nearly all mice, while necrosis of the olfactory epithelium was more marked in rats. Myocardial degeneration occurred in rats and to a lesser degree in male mice. In the adrenal cortex, there was cytoplasmic vacuolation in rats and inner zone atrophy in female mice (Eustis et al., 1988). 

Inhalation exposure of rats to 160 ppm [620 mg/m ] or 400 ppm [1550 mg/m ] methyl bromide for > 6 weeks caused testicular degeneration (Kato et al., 1986 Eustis et al., 1988). However, when male Fischer 344 rats were exposed to 200 ppm [780 mg/m ] methyl bromide for 6 h per day for five days and followed for two months, no effect was observed at any time during or after the exposure on testis weight, daily sperm production, cauda epididymal sperm count, sperm morphology, percentage motile sperm, linear sperm velocity, or epididymal or testicular histology (Hurtt Working, 1988). 

Endocrine and Reproductive Effects. Because the male and female reproductive organs are under complex neuroendocrine and hormonal control, any toxicant that alters any of these processes can affect the reproductive system (see Chapters 17 and 20). In addition metals can act directly on the sex organs. Cadmium is known to produce testicular injury after acute exposure, and lead accumulation in the testes is associated with testicular degeneration, inhibition of spermatogenesis, and Leydig-cell atrophy. 

There is a report of moderate testicular degeneration for rats exposed orally to high doses of stannous chloride (DeGroot et al. 1973). However, no reproductive effects were observed in animals after inhalation or dermal exposure to inorganic tin compounds. 

M (testicular degeneration and Gray et al. 2000 altered sexual differentiation in male offspring)... 

Wong, T-W., and Z. Hruban. Testicular degeneration and necrosis induced by chlorcyclizine. Lab. Invest. 26 278-289, 1972. 

Microwave radiation can damage tissues and organs, and also cause birth defects, testicular degeneration, partial or total sterility, cataracts, changes in immune and endocrine functions and behaviour abnormalities. Recommended limits are ... 

Vitamin E-deficiency diseases are well known among laboratory and farm animals and can be a considerable problem in animal husbandry. Thus, the vitamin was discovered because its absence from the diet causes pregnant female rats to resorb their foetuses [25], and male rats to suffer testicular degeneration [26]. In the rabbit muscular dystrophy occurs, and in sheep and cattle similar muscular degeneration also is the principle sign of vitamin E deficiency [27], In the chick given high levels of linoleic acid and no vitamin E an acute central nervous system lesion called encephalomalacia occurs... 

Vitamin A-deficient experimental animals fail to grow adults are blind and sterile, with testicular degeneration in males and keratinization of the uterine epithelium in females. Although deficient female animals wUl conceive, and the fetuses will implant, formation of the placenta is impaired and the fetuses are resorbed. Epithelia in general are hyperplastic and keratinized, and there is impaired cellular immunity with increased susceptibility to infection. Both retinol and retinoic acid are required for gestation in the rat in deficient animals, retinoic acid alone will not prevent fetal resorption after about day 10 of gestation (WeUik and DeLuca, 1995 WeUik et al., 1997). 

In chronic-duration studies, male rats given high oral doses (331 mg U/kg/day) of uranyl nitrate hexahydrate in the diet for 2 years developed testicular degeneration female rats given oral doses of 664 mg U/kg/day as uranyl nitrate hexahydrate for 2 years had reduced litter sizes (Maynard et al. 1953). Since incidence and dose-response data were not provided in this report, its significance is unclear. 

A small number of studies have reported that male rats fed aflatoxins developed testicular degeneration and impaired spermatogenesis, although no clear association with aflatoxins and clinical infertility was uncovered in one of these studies. 

High doses of fluorine gas and hydrogen fluoride in animal studies have resulted in testicular degeneration. The available animal and human data strongly suggest that the reproductive system is a target of fluoride toxicity at high exposure levels. 

Chapin RE, Morgan KT, Bus JS. 1983. The morphogenesis of testicular degeneration induced in rats by orally administered 2,5-hexanedione. Exp. Mol. Pathol. 38 149-69... 

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