Teratogenicity developmental toxicity

In order to fully assess the hazardous properties of a substance with respect to reproductive toxicity, the key data requirements are a two-generation study and a prenatal developmental toxicity (teratogenicity) smdy in two species (EC 2003). 

Developmental toxicity is shown by the disubstituted methyl-, butyl-, and octyltins, but not by the corresponding monosubstituted compounds. The major reported effect is teratogenicity, with effects on fetuses shown at doses close to maternally toxic ones in most cases. NOAELs for dimethyltin, dibutyltin, and dioctyltin are 10 (10), 2.5 (1.0), and 45 (30) mg/kg body weight per day for teratogenicity (maternal toxicity NOAELs in parentheses). 

Developmental Effects. Evidence from human studies on congenital anomalies as an end point (Emhart et al. 1985, 1986 McMichael et al. 1986 Needleman et al. 1984) indicate no association between prenatal exposure to low levels of lead and the occurrence of major congenital anomalies. This conclusion is further supported by developmental toxicity studies conducted in rats and mice these studies provide no evidence that lead compounds (acetate or nitrate) are teratogenic when exposure is by natural routes (i.e., inhalation, oral, dermal). Intravenous or intraperitoneal injection of lead compounds (acetate, chloride, or nitrate) into pregnant rats, mice, or hamsters, however, has produced malformations in several studies reviewed by EPA (1986a). 

Developmental Toxicity. No information is available on developmental effects of acrylonitrile in humans by any route of exposure. Acrylonitrile is teratogenic and embryotoxic in rats both by the oral and inhalation routes of exposure. Developmental studies on other animal species have not been conducted. Because species differences for acute acrylonitrile toxicity and metabolism have been demonstrated, additional developmental studies in other species using various dose levels would be valuable in evaluating the potential for acrylonitrile to cause developmental effects in humans. Because the available oral study was conducted by gavage, additional studies are needed to determine if these effects will occur following ingestion of drinking water or food. 

When applied dermally to rats and rabbits, PGDN was not teratogenic and showed no evidence as a reproductive and developmental toxicant at doses that were less than maternally toxic (Cooper et al. 1993). In rats, lower fetal weights reflected the lower body weights of surviving dams. 

In addition, various treatments that simulate effects that can result from pharmaceutical treatment have been shown to cause developmental toxicity. Food deprivation can cause embryo-fetal toxicity and teratogenicity in mice (Szabo and... 

Currently, only the Hydra system incorporates a measurement of toxicity to the adult to provide a comparison of the sensitivity of the embryo with that of the adult (Johnson et al., 1988). However, the Hydra screen has not been fully validated as being predictive of results in mammals, and has fallen from favor. Thus, a major goal of research directed toward developing an in vitro teratogen screen should be to find a simple yet appropriate measure of toxicity unrelated to development. This would allow the comparison of the dose for a 50% effect (ED50) on developmental toxicity as measured in vitro to an ED50 for adult toxicity in vitro. The validation... 

Fabro, S., Shull, G. and Brown, N.A. (1982). The relative teratogenic index and teratogenic potency Proposed components of developmental toxicity risk assessment. Teratog. Carci-... 

Common Study Protocols. The dog is the most commonly used nonrodent species in safety assessment testing (i.e., acute, subchronic, and chronic studies). The exception to this is its use in developmental toxicity and reproductive studies. For developmental toxicity studies, the dog does not appear to be as sensitive an indicator of teratogens as other nonrodent species such as the monkey (Earl et al., 1973) or the ferret (Gulamhusein et al., 1980), and, for reproductive studies, the dog is not the species of choice because fertility testing is difficult to conduct (due to prolonged anestrus and the unpredictability of the onset of proestrus) and there is no reliable procedure for induction of estrus or ovulation. 

Developmental Toxicity. There is no information on developmental effects in humans exposed to bromomethane, but two inhalation exposure studies in animals (rats and rabbits) indicate that developmental or teratogenic effects do not occur even at doses that are toxic to the dam (Hardin et al. 1981 Sikov et al. 1980). No information is available on developmental effects after oral exposure of animals to bromomethane, but the inhalation data suggest that is not likely to be of concern. 

The three targets that are the first point of contact between environmental chemicals and the body will be discussed first the gastrointestinal tract, the respiratory system, and the skin. Recall from Chapter 2 that chemicals enter the blood after absorption, so this fluid is the next target (see Figure 2.1). Then come the liver, the kidneys, and the nervous system. The chapter concludes with a discussion of some chemicals that can damage the reproductive system and some that can cause birth defects, the so-called teratogens, and other forms of developmental toxicity. Brief discussions of immune system, cardiovascular system, muscle, and endocrine system toxicities are also offered. 

A particularly important type of developmental toxicity is called teratogenicity. After fertilization the ovum - a single cell - begins to proliferate, making more of its own kind by a series of divisions. In humans, at about the ninth day the remarkable process of cell... 

Developmental Toxicity. It is not known whether 1,2-diphenylhydrazine crosses the placenta, but there is no reason to assume that it (or its metabolites) would not do so. Developmental studies in mammals would provide information on possible fetotoxic and teratogenic effects of... 

No teratogenic effects have been reported in limited developmental toxicity studies in rodents. Decreased fetal body weight and crown-rump length were noted in rats and mice after parenteral administration. ... 

A number of developmental toxicity studies have been conducted on EEA. In rabbits, inhalation exposure to 100-3 00 ppm resulted in maternal toxicity, including clinical signs and alterations in hematology (reduced hemoglobin). Developmental toxicity was seen as an increased incidence of totally resorbed litters above 2 00 ppm and an increase in non-viable fetuses at 3 00 ppm fetal ossification was observed above 100 ppm, and the incidence of total malformations was 100% at 300ppm. Similar effects were observed in rats, with maternal and developmental toxicity at 100-300 ppm and teratogenic effects at 200-300 ppm. 

Developmental or teratogenic effects were not observed in rats, even at doses that were severely maternally toxic. ... 

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