Reproductive toxicity in males

There is [sufficient, insufficient] evidence in [humans and/or animalsl that [chemical/aaent] [does or does not] cause [reproductive toxicity in males/females. developmental toxicity] when exposure is [route, dose range, timing, duration]. Relationship to adult toxicity stated. The data are [relevant, assumed relevant, irrelevant] to consideration of human risk. 

The RACB studies were designed by NTP to test chemicals for potential reproductive toxicity in males and females. In addition, this two-generation study design can be used to characterize the toxicity and to define the dose-response relationship for each chemical. 

Ethanol has been investigated for reproductive toxicity in male mice and rats, and while producing effects upon testes and other reproductive tissues, has generally not been shown to affect reproductive outcome or performance. 

The acute oral toxicity of this compound is low. It is, however, more toxic, than the phthalic acid diaUcyl esters discussed in the preceding sections. The toxic symptoms include nausea, dizziness, somnolence, and hallucination. The oral LD50 value in mice is within the range of 4200 mg/kg. Oral administration produced reproductive toxicity in male mice (paternal effects). At a dose of 2% in diet, it caused maternal and developmental toxicity and an increased incidence... 

In summary, although the available reproductive studies indicate that endosulfan has no adverse effects on reproductive performance in animals, severe adverse effects on male reproductive organs have been seen in rats and mice. This apparent discrepancy needs to be resolved with further research. Endosulfan may potentially cause reproductive toxicity in humans. 

One-generation reproduction exposure To assess the potential reproductive and developmental toxicity in males and females hy the intended route of exposure... 

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. 

It is not known if HDI affects reproductive tissues in males or females however, given its short half-life in biological fluid, this seems unlikely. HDI has been reported to bind to biological tissues (protein) (Ted and Pesce 1979) however, the relevance of this observation to reproductive toxicity is not known. The toxicity of the HDI metabolite (HDA) is not known. Toxicological studies should be designed to answer questions about the potential reproductive toxicity of HDI or its prepolymers in both male and female himians and laboratory animals. 

Zenick H, Blackburn K, Hope E, Baldwin DJ (1984) Evaluating male reproductive toxicity in rodents A new animal model. Teratog Carcinog Mutagen, 4 109-128. 

Chlorodifluoromethane causes malformations of the eyes of fetal rats, but has no reproductive effect in male rats and does not cause prenatal toxicity in rabbits following exposure by inhalation (lARC, 1986). 

Subchronic studies49 in rabbits treated dermally with 35 resulted in testicular atrophy and spermatogenic depression. The material is also active, when applied by the oral route. Toxicity and reproductive studies in male rats and monkeys showed that 35 is likewise active p.o. in rats and monkeys but inactive in monkeys when administered dermally at daily doses over an extended period of time. Further studies50 showed that 35 interrupts the normal oestrous cycle in mature female rats. 

White Phosphorus Smoke. No reproductive performance effects or histological lesions on reproductive tissues were observed in male and female rats exposed to white phosphorus smoke for intermediate durations (Brown et al. 1981). A limitation of this study is that the rats were exposed for a very short daily duration (15 minutes/day). Studies that involved longer daily inhalation exposures or dermal exposures would be useful to determine the potential for reproductive toxicity in humans exposed to white phosphorus smoke. 

Thejowest dose, 14 mg/kg/day, is a NOAEL for reproductive toxicity in the male and female mice. 

Chronic exposures to lead by inhalation or the oral route cause adverse effects that include damage to the peripheral and central nervous system, anemia, and chronic kidney damage. Lead accumulates in the soft tissues and bones, with the highest accumulation in the liver and kidneys, and elimination is slow. Lead has shown developmental and reproductive toxicity in both male and female... 

A standard reproductive study in rats showing no effect on the ability of males to impregnate females should not be considered to support a conclusion that there is no male reproductive toxicity in all species. Unlike humans, rodents produce sperm in numbers that greatly exceed the minimum requirements for fertility. A substantial reduction in sperm production in rodents may not compromise fertility in rodents while a less severe reduction in human males could cause reduced fertility. 

Depending on dose, external irradiation may lead to different types of reproductive toxicity in the male companion animal (Scialli et al, 1995, cited in Ellington and Wilker, 2006 De Celis et al, 1996, cited in Ellington and Wilker, 2006). At very high doses, it may lead to permanent aspermia. At intermediate doses it may lead to reduction in sperm numbers. Finally, at lower doses external irradiation may lead to DNA alterations in sperm cells (Scialli et al, 1995, cited in Ellington and Wilker, 2006 De Celis et al, 1996, cited in Ellington and Wilker, 2006). 

Synthetic dyes are extensively used in many up-to-date industrial processes and research, mainly in the preparation of textile, food, and leather products, as well as in cosmetics and medicine. The widespread application of synthetic dyes has resulted in serious environmental pollution Their occurrence in ground water and waste-water and the accumulation in sediment, soil, and various biological tissues has often been observed and reported. Dyes and intermediates can cause abnormal reproductive function in males and show marked toxic effects toward bacteria. The rate of biodegradation of the majority of synthetic dyes is very low, enhancing the toxicological hazard and environmental impact. 

Azamethiphos has not been found to be carcinogenic, teratogenic, or to result in reproductive toxicity in rodent studies. The no-observed-adverse-effect level established in a 52 week study with beagles fed azamethiphos was 2.7-2.9mgkg day in males and females, respectively. Azamethiphos did not cause delayed neuropathy in hens given two LD50 dosages 21 days apart. 

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