Testicular effects

Tandon R, Saxena DK, Chandra SV, et al. 1988. Testicular effects of acrylonitrile in mice. Toxicol Lett 42 55-63. 

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],... 

Foster PM, Thomas LV, Cook MW, et al. 1980. Study of the testicular effects and changes in zinc excretion produced by some n-alkyl phthalates in the rat. Toxicol Appl Pharmacol 54 392-398. 

Gangolli SD. 1982. Testicular effects of phthalate esters. Environ Health Perspect 45 77-84. 

The intermediate oral MRL was based on a LOAEL for splenic hemosiderosis in male rats administered 0.75 mg/kg/day 1,3-DNB by gavage in acetone/corn oil solution 5 days/week for 12 weeks (Linder et al. 1986). This dose-related response was minimal in controls and moderate to moderately severe at the highest dose level tested, 6 mg/kg/day. Splenic enlargement was also reported at 1.5 mg/kg/day. Adverse testicular effects were observed with doses of 1,3-DNB >1.5 mg/kg/day. Altered spermatogenesis was noted at >3 mg 1,3- DNB/kg/day. The observed splenic effects are considered secondary to the hematoxicity of 1,3-DNB and are supported by increased erythropoietic activity in rats in a study by Blackburn et al. (1988) and hemosiderosis in rats in a study by Cody et al. (1981), and are consistent with hemolytic anemia. The hematological effects of... 

In rat developmental studies, fetal effects including delayed ossification and decreased locomotor activity occurred at doses that also caused maternal toxicity. Cadmium sulfate injected into the lingual vein of female hamsters on day 8 of pregnancy caused a high incidence of resorption and malformed offspring. Acute necrosis of rat testes followed large doses orally or parenterally, but testicular effects have not been reported thus far in humans." ... 

A variety of reproductive effects including testicular effects, alterations in sexual behavior, and impaired fertility in females have been reported after high doses of chromium(VI) compounds." These effects, reproductive toxicity and testicular damage, were not replicated in a recent series of NTP studies in which mice and rats were exposed to 400 ppm in the diet." "... 

Limited data indicate that DMHP may have testicular effects calcification and atrophy of the testes were observed in mice in the course of chronic and subchronic oral studies at 200mg/kg for 103 weeks and 375 and 750mg/l for 13 weeks, respectively ... 

Reproductive and testicular effects have also been reported in humans with exposure to EE, but the significance of these studies cannot be evaluated because of concomitant exposures. 

No studies were located regarding the rate and extent of absorption of thorium following dermal exposure of humans or animals. Absorption of thorium through the skin of animals can be inferred, however, because testicular effects were seen in rats following application of thorium nitrate directly to the lateroabdominal and scrotal skin (Tandon et al. 1975). 

Reproductive Toxicity. No studies were located regarding the reproductive effects of thorium in humans following exposure by any route. Neither inhalation nor oral reproduction studies in animals were located. Pharmacokinetic data following inhalation or oral exposure were not located to allow the prediction of possible reproductive effects. One dermal rat study found testicular effects after administration directly onto the scrotal skin. Additional inhalation, oral, and dermal reproduction studies and multigenerational studies would be helpful in assessing the potential risk to humans. 

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 effects were also investigated after oral administration of 2000 mg/kg bw di(2-ethylhexyl) phthalate for seven consecutive days to 13-week-old male Wistar rats (Saxena et al., 1985). Degeneration was observed in about 40% of the seminiferous tubules. Loss of succinic dehydrogenase, NADH-diaphorase and acid phosphatase activity and increases in adenosine triphosphatase, glucose-6-phosphate dehydrogenase and alkaline phosphatase activity were observed in treated rats. 

Oral exposure of adult rats and mice caused effects on fertility in males and females and serious effects on the testicles. Young animals were much more sensitive to gonadal effects than adults and in some cases, the onset of occurrence of the testicular effects was earlier in young animals. Dose-dependent testicular effects were seen in young rats exposed to di(2-ethylhexyl) phthalate in the diet. 

In one study using small groups of adult marmosets, oral exposure did not cause testicular toxicity at doses higher than those producing testicular effects in adult rats. 

Testicular effects have been found after exposure of rats to diethanolamine in the drinking water. 

Responsible Metabolite. Since DEHP is metabolized to a variety of compounds following oral exposure, the question has been raised as to which of DEHP metabolites is responsible for the testicular effects of DEHP. Evidence suggests that mono(2-ethylhexyl) phthalate (MEHP) might be the toxic metabolite in the testes. In one study, 1,055 mg/kg/day of DEHP administered for 5 days to rats did not affect testicular weight or structure, but an equimolar dose of MEHP had a significant effect (Sjoberg et al. 1986a). 

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