Chronic toxic effects reproductive

Absence of carcinogenity, genotoxicity, developmental and reproductive toxicity and of chronic toxicity effects at low exposure levels are indispensable prerequisites for food additive approvals. All substances approved in the European Union or the USA or deemed generally recognised as safe (GRAS) in the USA fulfil this requirement. 

The main chronic toxic effect in animals exposed to arsine for 28-90 days is in the hematopoietic system, including a decrease in packed erythrocyte volume and a peripheral erythrocyte regenerative response. The reproductive and developmental toxicity has not been completely studied. Rats exposed to 2.5 ppm arsine 6 h day on gestation days 6-15 exhibited an increase in fetal body weight. 

In May 1980, Notification 698 from the MHLW specified the type of data required for the evaluation of safety in animals and Guidelines for Toxicity Studies were subsequently established in 1984. It is necessary to generate data on acute, sub-acute and chronic toxicity, effect on reproduction, dependence, antigenicity, mutagenicity, carcinogenicity and local irritation. 

The assessment of adverse health effects such as acute and chronic toxicity, carcinogenicity, reproductive toxicity, but also skin sensitization require in depth scientific knowledge of the processes in the human body that absorb, distribute, biotransform (or metabolize), or excrete the foreign chemicals but also endogenous compounds and the events associated with the toxicities in... 

The hazards of the chemicals that may be transported are discussed in regulations, defined by the hazard class, and presented in Section 3.2.1 of this chapter. In addition, there are other published lists of chemicals of concern from a worker safety, public safety, environmental, and security perspective. For example, a material may not be a regulated toxic, but may have certain characteristics such as chronic toxicity or reproductive effects that may warrant a more detailed risk evaluation. This step is not limited to chemical hazards, and may also include ... 

Ecological Acute and chronic aquatic toxicity Adverse reproductive effects on wildlife Phytoxicity... 

Mirex has considerable potential for chronic toxicity because it is only partly metabolized, is eliminated very slowly, and is accumulated in the fat, liver, and brain. The most common effects observed in small laboratory mammals fed mirex included weight loss, enlarged livers, altered liver enzyme metabolism, and reproductive failure. Mirex reportedly crossed placental membranes and accumulated in fetal tissues. Among the progeny of mirex-treated mammals, developmental abnormalities included cataracts, heart defects, scoliosis, and cleft palates (NAS 1978 Blus 1995). 

The toxic effects of pesticides can be diverse and depend on the sensitivity of organisms to these toxicants, and the pesticide concentration or bioavailability. Typically, the short- and long-term effects of pesticides have been evaluated through acute or chronic toxicity bioassays, respectively, using lethality endpoints and sublethal endpoints (e.g., growth and reproduction), particularly these last in chronic bioassays. 

Episodic pollution events can adequately be addressed by acute toxicity bioassays, however these are not sufficient to investigate the water quality for delayed toxicity effects of chemicals present. Chronic effects of pesticides can include carcinogenicity, teratogenicity, mutagenicity, neurotoxicity, and reproductive effects (endocrine disruption). 

The acute toxicity of emorfazone was found to be equal to or less than that of aminopyrine depending on animal models used [45]. From chronic toxicity tests [46,47], safe doses of 30 mg/kg per day (rats) or 120 mg/kg per day (dogs) were deduced. In rats, no significant effects of (3) on the reproductive activity or newborn development were observed [48-50], nor were adverse effects on the embryos found when (3) was given to rabbits, rats or mice during the period... 

Humans are susceptible to the acute toxic effects of 1,2-dibromoethane from various routes of exposure. Except for adverse reproductive effects in men after occupational exposure, chronic effects of 1,2-dibromoethane exposure have not been documented in humans. Based on data derived from animal studies, mechanisms of action of 1,2-dibromoethane at a cellular level, toxicokinetics, and genotoxicity tests, there is a potential for certain adverse health effects in humans exposed chronically to low environmental levels of 1,2-dibromoethane that could exist near hazardous waste sites or areas of former agricultural use. 

UFm accounts for the quality and relevance of the database, i.e., accounts for the uncertainties in the establishment of a NOAEL for the critical effect. The UFm includes elements such as (1) the quality of the database, e.g., data on specific toxic endpoints are lacking or inadequate, default value of 1-10 (2) route-to-route extrapolation, e.g., no studies using the appropriate exposure route are available, no default value (3) LOAEL-to-NOAEL extrapolation, e.g., a NOAEL cannot be established for the critical effect, default value of 10 (4) subchronic-to-chronic extrapolation, e.g., no chronic studies on which to establish the NOAEL are available, default value of 10 and (5) nature and severity of toxicity, e.g., the critical effect is toxicity to reproduction, carcinogenicity or sensitization, default value of up to 10. A default value for UFm has not been recommended however, a value from 1 to 100 is generally used. The value is evaluated case-by-case based on expert judgment. 

A low order of systemic toxicity was found in chronic feeding studies with rats. Administered in the diet for 2 years 0.215% sodium metabisulfite caused no adverse effects. Reproductive parameters were not affected in three-generation feeding smdies in rats at concentrations up to 13mmol/kg /day. ... 

Table 7 Example application of process in Box B to evaluate the risk of dioxins in Dutch sediments. No observed effect (NOEC) concentrations for chronic toxicity of dioxins in vertebrates (immune, reproductive and developmental toxicity) expressed as internal concentration (ng TEQ/g Iw). The sediment to fish bioconcentration factor is set at 4 (ng TEQ/g Organic Carbon to ng/g lipid weight in fish) based on Traas et al. (2001). Based on a species-specific biomagnification factor (BMP) from fish to animal (ng TEQ/g Iw) the internal NOEC is extrapolated to a NOEC in sediment. These data are used to construct the SSDs in Figures 5 and 6.

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