Reproductive effects

Cadmium can act on the reproductive system by either directly affecting the gonads and accessory organs, or indirectly via interference with the hypothalamus-pituitary-gonadal axis. 

Cadmium produces testicular injury in experimental animals after acute exposure but not after chronic exposure (Kotsonis and Klaassen 1977, 

The testes of newborn rats are also resistant to damage by cadmium (Wong and Klaassen 1980). 

Osteomalacia and osteoporosis are reported primarily in patients (95% females) with itai-itai disease, and osteomalacia has been observed in cadmium industry workers, the majority of whom are male (Goyer 1991). While the mechanisms for these effects are not well known, cadmium disruption of calcium metabolism may be important. One of the manifestations of renal injury in cadmium-exposed populations is calcuria and negative calcium balance. It is not clear whether these effects on calcium metabolism occur secondary to renal injury, or whether there is a direct effect on calcium pathways (see discussion of calmodulin-calcium-cadmium interactions in Sect. B.I). 

The disease itai-itai became prevalent in Japan prior to and during the 1940s, and was associated with the ingestion of cadmium-contaminated rice. The rice became contaminated after growing in waste runoff water from a lead-zinc-cadmium mine. Clinical manifestations of the disease included kidney injury, osteomalacia, myalgia, and spontaneous fracture of long bones (Tsuchiya 1978). 

it seems evident that only B-Pb levels exceeding 400 pg are associated with a decrease in sperm count, volume, and morphological alterations. 

An evaluation by Skerfving (1993) indicated that a slight effect in the pregnant women, newborn (cord blood) and/or infant may be present at B-Pbs in the range of 100 to ISOpgL. However, the interpretation of these studies was complicated by several methodological problems. 

Lead exposure may impair the endocrine function of male animals, probably through disturbance of the hypothalamic-pituitary function (Erfurth et al. 2001). Furthermore, lead has been shown to induce testicular atrophy, and to reduce spermatogenesis, affect the spermatozoa and to reduce sperm motility (US EPA 1986, Skerfving 1993). 

In female animals, lead may disturb the hypothalamus-pituitary-ovarian-uterine function (Govoni et al. 1984), causing altered menstrual cycles. Implantation problems may then appear. Furthermore, lead exposure may decrease the blood flow throw the placenta and affect the heme metabolism of the fetus (US EPA 1986). 

The main toxic effect of lead in males and females is impairment of neurobehavioral test performance. Available evidence indicates that the LOAEL for long-term exposed subjects should be around 400 tg L (Scientific Committee 2000). 

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In laboratory tests, appHcation of DMAC to the skin of pregnant rats has caused fetal deaths when the dosages were close to the lethal dose level for the mother. Embryonal malformations have been observed at dose levels 20% of the lethal dose and higher. However, when male and female rats were exposed to mean DMAC concentrations of 31,101, and 291 ppm for 6 h per day over several weeks, no reproductive effects were observed (6). 

Formaldehyde is not considered a teratogen and has not been reported to cause adverse reproductive effects (138,139). vitro mutagenicity assays... 

In experimental animals and in vitro, DHBs show a variety of biological effects including binding of metaboHtes to various proteins. Clastogenic effects have been observed in vitro and in some in vivo studies with the three compounds. No reproductive effects have been shown by conventional studies with either hydroquinone, catechol, or resorcinol (122). Hydroquinone has been shown to induce nephrotoxicity and kidney tumors at very high doses in some strains of rat (123) catechol induces glandular stomach tumors at very high dose (124). Repeated dermal appHcation of resorcinol did not induce cancer formation (125). 

Exposure to excessive amounts of lead over a long period of time (chronic exposure) increases the risk of developing certain diseases. The parts of the body which may be affected include the blood, nervous system, digestive system, reproductive system, and kidneys. These effects include anemia, muscular weakness, kidney damage, and reproductive effects, such as reduced fertiHty in both men and women, and damage to the fetus of exposed pregnant women. 

Reproductive Effects. Phthalates have been shown to cause reproductive effects in rats and mice but primates are resistant to these effects. This may be due in part to pronounced differences in the way in which phthalates are metabolized by rodents and primates, including humans. 

Toluenediamine is classed as toxic. The oral LD q for animals is between 270—350 mg /kg body weight (45). TDA is readily absorbed through the skin and this is the major route of human exposure. Several studies have shown the 2,4 isomer of TDA to be carcinogenic for rats and mice, but tests on the 2,5 and 2,6 isomers were not positive. AH three of the isomers have been shown to be mutagenic (45). Results of limited studies on the reproductive ha2ards for male workers are equivocal, but animal experiments have shown TDA to cause adverse reproductive effects (45). 

The LD q for sodium bromide taken orally by rats is 3.5 g/kg body weight, and the TD q orally in rats is 720 mg/kg (8). RTECS Hsts data on reproductive effects in male and female rats. Sodium bromide is Hsted in the TSCA Inventory, the Canadian Domestic Substances Hst (DSL), the European Inventory of Existing Commercial Chemical Substances (EINECS), the Japanese Existing and New Chemical Substances (ENCS), and the Korean Existing Chemicals Hst (ECL). It is not regulated by the U.S. Department of Transportation. 

Value is toxic dose low. TD q, the lowest dose of a substance introduced by any route other than inhalation, over any given period of time to which humans or animals have been exposed and reported to produce any nonsignificant toxic effect in humans or to produce nonsignificant tiimorigenic or reproductive effects in animals or humans. 

Another section of the EPA, the Office of Prevention, Pesticides, and Toxic Substances (OPPT), has recently updated and harmonized its testing guidelines for evaluating the developmental and reproductive effects of pesticides and industrial chemicals to include an assessment of endocrine disrupting properties. These guidelines will be used in future testing of pesticides under both the Toxic Substances Control Act (TSCA) and the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). 

In addition to reproductive effects, fish exposed to endocrine disrupters may have a decreased response to stress or decreased growth and metabolism which can affect their ability to survive, or to defend themselves against predators. All of these factors can affect the ability of the species to survive and to reproduce itself in sufficient numbers to maintain the stocks on which our commercial and sport fisheries are based. Not all fish species will be equally susceptible to the effects of endocrine disrupters. Selective sensitivity to such effects, especially those affecting reproduction, may well lead to major changes in the flora and fauna of some of our major aquatic ecosystems as the balance between fish, mammals, invertebrates and plants, and between predators and prey, is destabilised... 

H. J. Drenth, M. van den Berg and C. Bouwman, Reproductive effects of PCBs, the role of... 

One of the earliest cattle problems involved widespread poisoning of cattle by arsenic at the turn of the century. Abnormal intake of arsenic results in severe colic (salivation, thirst, vomiting), diarrhea, bloody feces, and a garliclike odor on the breath cirrhosis of the liver and spleen as well as reproductive effects may be noted. Arsenic trioxide in the feed must be approximately 10 mg/kg body weight for these effects to occur. 

Eye, nose, and throat irritation headaches, nausea. Some VOCs are suspected or known carcinogens or causes of adverse reproductive effects. Some VOCs also have unpleasant odors or are irritants. VOCs are thought to be a cause of non-specific health symptoms. 

No studies were located regarding reproductive effects in humans or animals after inhalation exposure to methyl parathion. 

The highest NOAEL value in dogs for reproductive effects for the chronic-duration category is recorded in Table 3-3 and plotted in Figure 3-2. 

The highest NOAEL values and all reliable LOAEL values for reproductive effects in rats, mice, and dogs for each duration category are recorded in Table 2-2 and plotted in Figure 2-2. 

In terms of toxicity, NIOSH recommends that endosulfan be recognized as a Group 1 Pesticide (NIOSH 1992). Pesticides in Group 1 pose a significant risk of adverse acute health effects at low concentrations or carcinogenic, teratogenic, neurotoxic, or reproductive effects (NIOSH 1992). 

Gray LE, Ostby J, Wolf C, et al. 1998. The value of mechanistic studies in laboratory animals for the prediction of reproductive effects in wildlife Endocrine effects of mammalian sexual differentiation. Environ Toxicol Chem 17(1) 109-118. 

Toxic equivalency factors (TEFs) are estimated relative to 2,3,7,8-TCDD, which is assigned a value of 1. They are measures of the toxicity of individual compounds relative to that of 2,3,7,8-TCDD. A variety of toxic indices, measured in vivo or in vitro, have been used to estimate TEFs, including reproductive effects (e.g., embryo toxicity in birds), immunotoxicity, and effects on organ weights. The degree of induction of P450 lAl is another measure from which estimations of TEF values have been made. The usual approach is to compare a dose-response curve for a test compound with that of the reference compound, 2,3,7,8-TCDD, and thereby establish the concentrations (or doses) that are required to elicit a standard response. The ratio of concentration of 2,3,7,8-TCDD to concentration of test chemical when both compounds produce the same degree of response is the TEF. Once determined, a TEF can be used to convert a concentration of a dioxin-like chemical found in an environmental sample to a toxic equivalent (TEQ). 

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