Reproductive and Developmental Effects

Potential modes of action of lead reproductive toxicity include disraption of the hypothalamic-pituitaiy-gonadal axis through reduced luteinizing hormone secretion and reduction in the expression of the steroidogenic acute regulatory protein (Crain et al. 2008 EPA 2012). Lead may also interfere with cation-dependent secondary messenger systems that mediate pituitary hormone release 

459 men selected at random from Normative Aging Study of healthy veterans in greater Boston area 

Random sample of 965 men, 1,016 women in areas witii low or high environmental cadmium 

9 pg/dL in those with low, high chelatable lead burden, respectively, as assessed with CaNa2EDTA 

10-fold increase in BLL was associated with increase of 0.08 mg/dL in serum creatinine. Study of veterans with BLLs in range of interest. Kim et al. 1996 

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Sever EE, Arbuckle TE, Sweeney A. 1997. Reproductive and developmental effects of occupational pesticide exposure The epidemiologic evidence. Occup Med 12 305-325. 

The only available data regarding reproductive and developmental effects of monomethylhydrazine involved parenteral administration and, therefore, are of questionable relevance for AEGL derivation. Those data are discussed here to provide insight relative to monomethylhydrazine exposure. 

Hopenhayn-Rich, C., K.D. Johnson, and I. Hertz-Picciotto. 1998. Reproductive and developmental effects associated with chronic arsenic exposure. SEGH 3rd Inter. Conf. Arsenic Expos. Health Effects 21. 

Schreiner, C., et al., Toxicity evaluation of petroleum blending streams Reproductive and developmental effects of hydmdesulfuri/.cd kerosene,./. Toxicol. Environ. Health, 52,211, 1997. 

There has been no comprehensive evaluation of the reproductive and developmental effects of hexachloroethane. Limited data indicate that it is maternally toxic and retards fetal development. It does not appear to be a teratogen. 

The database for HFC-134a is extensive it contains studies with both human subjects and animal models. Potentially sensitive populations, including patients with COPD and adult and pediatric asthmatic patients, were tested with direct inhalation of HFC-134a from metered-dose inhalers. The response of these groups was no different than that of healthy adults. The animal studies covered acute, subchronic, and chronic exposure durations and addressed systemic toxicity as well as neurotoxicity, reproductive and developmental effects, cardiac sensitization, genotoxicity, and carcinogenicity. The metabolism of HFC-134a is well understood, and the relationship of exposure con... 

Some variations exist between the susceptibility of mammalian species to the teratogenic action of nickel salts. No detrimental reproductive and developmental effects have been documented in humans [422], Yet exposure to nickel salts must be assumed to constitute a teratogenic risk. 

Suppose there are several animal studies available for a chemical, including some which have involved long-term exposures, and some relating to possible reproductive and developmental effects. Assume data for both mice and rats are available, and that there are well-defined NOAELs for each of the identified toxicity endpoints. The lowest NOAEL from all those available derives from a chronic study, and is 10 mg/(kg day). Given such a data base, and the defaults listed above, a Dy for this chemical applicable to the general population, would be derived as follows... 

Target organs of chloroform toxicity are the central nervous system, liver, and kidneys (see Section 2.2). Respiratory, cardiovascular, and gastrointestinal toxic effects have also been reported. Studies in animals also indicated that chloroform exposure may induce reproductive and developmental effects and cause cancer. Several studies investigated the possible mechanism for chloroform-induced toxicity (see Section 2.5). Proposed mechanisms of chloroform toxicity and potential mitigations based on these mechanisms are discussed below. The potential mitigation techniques mentioned are all experimental. 

The disinfection of drinking water has been rightly hailed as a public health triumph of the twentieth century. Before its widespread use, millions of people died from waterborne diseases. Now, people in developed nations receive quality drinking water every day from their public water systems. However, chemical disinfection has also produced an unintended health hazard the potential for cancer and reproductive and developmental effects (including early-term miscarriages and birth defects) that are associated with chemical disinfection by-products (DBFs) [1-6]. Research is being conducted worldwide to solve these important human health issues. 

CERHR (2003) National Toxicology Program—Centre for the Evaluation of risks to human reproduction. Monograph on the Potential Human Reproductive and Developmental Effects of Di-Isodecyl Phthalate (DIDP). NIH Pub No. 03-4485. US Department of Health and Human Services, April 2003. http //ntp.niehs.nih.gov/ntp/ohat/phthalates/didp/DIDP Mono-graph Pinal.pdf... 

Dose-response characteristics and adverse reproductive and developmental effect... 

Toxicology. Dibutyl phthalate (DBP) is of low-order acute toxicity reproductive and developmental effects have been reported in animal studies. 

Humans may be exposed to 2-hexanone through contaminated air in the workplace and in the vicinity of hazardous waste sites and consumption of and dermal contact with contaminated water, especially in the vicinity of hazardous waste sites. Epidemiological studies that followed populations exposed to 2-hexanone, either in the vicinity of hazardous waste sites or in the workplace, would be useful in assessing adverse health effects in humans. In any such studies, emphasis should be placed on neurological, hematological, immunological, reproductive, and developmental effects. Similarly, human dosimetry studies of these populations would be useful in associating 2-hexanone levels with the reported effects. 

In animals, information exists on lethality, acute systemic effects (respiratory), reproductive and developmental effects, and cancer following inhalation exposure, but none was found on other systemic effects after acute, intermediate, or chronic exposure. Much of the information in animals focused on oral exposure. Lethality, systemic effects after acute, intermediate and chronic exposures, immunotoxicity, developmental effects, reproductive effects, genotoxicity, and cancer have been evaluated. Reports on dermal exposure after direct application to the skin involved lethality, acute systemic effects (kidney, liver, dermal/ocular), and cancer. 

There are an estimated 50,000 to 60,000 industrial chemicals in common use. We know very little about the reproductive and developmental effects of the majority of these chemicals. In addition, there are no safety testing requirements for natural products. In 1986, the voters of the State of California passed a law requiring the Governor of the state to publish, at least annually, a list of chemicals known to the state to cause cancer or reproductive toxicity . This effort is an excellent source of information on chemicals that can cause birth defects or reproductive harm. 

Reproductive and Developmental Effects of Contaminants in Oviparous Vertebrates. Fairmont, Montana, 13 to 18 Jul 1997. Published by SETAC, 1999. 

The principal effects of carbon tetrachloride in humans are on the liver, the kidneys and the central nervous system. These effects are apparent following either oral or inhalation exposure, and limited data indicate they can occur after dermal exposure as well. All of the effects seen in humans except renal injury are demonstrable at roughly comparable exposure levels in animals, although there are some variations in susceptibility between species that are likely to be related to differences in metabolism. No studies were located regarding reproductive and developmental effects in humans after exposure to carbon tetrachloride. In rats, carbon tetrachloride was not shown to adversely affect reproduction or development. Studies with both mice and rats suggest that sufficiently high doses of carbon tetrachloride may increase the risk of liver tumors in exposed humans. 

Several chronic inhalation and oral studies and acute dermal studies in animals are reported in the literature. These studies exposed several species of animals to both soluble and less-soluble nickel compounds. The target organs were found to be the respiratory system for inhalation exposure and the respiratory system, gastrointestinal tract, hematological system, and kidneys for oral exposure at high levels. Reproductive and developmental effects were observed in animals after inhalation exposure and after oral exposure to nickel. Nickel sensitivity and dermatitis were also observed. 

Fort, D J., T.L. Propst, E.L. Stover, P.L. Strong, and F.J. Murray. 1998. Adverse reproductive and developmental effects in Xenopus from insufficient boron. Biol. Trace Elem. Res. 66 237-259. 

For chemicals and complex mixtures of chemicals such as those in some occupational situations or involving cultural habits (e.g. tobacco smoking), the other data considered to be relevant are divided into those on absorption, distribution, metabolism and excretion toxic effects reproductive and developmental effects and genetic and related effects. 

No data on reproductive and developmental effects in humans were available. 

No data on reproductive and developmental effects in htunans were available. No signs of teratogenicity were observed in mice, rats, rabbits or miniature pigs. 

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