Postnatal effects

KHERA AND RUDDicK Polychlowdibenzo-p-dioxins l -Dioxin Postnatal Effects on Progeny... 

The postnatal effects of maternal treatment with 2,7-dichlorodibenzo-p-dioxin are summarized in Table VII. No significant changes were found. The progeny on becoming adult were mated within the treatment groups. No effects on male or female fertility, embryonic viability, and total implantation/corpora lutea ratio were observed. 

Tetrachlorodibenzo-p-dioxin elicited no apparent prenatal or postnatal effects when doses of up to 800 /xg/kg/day were given orally for 10 days of gestation. Treatment with 250-2000 /xg/kg/day of 2,7-di-chlorodibenzo-p-dioxin (99% purity) had no significant effect on prenatal and postnatal measures of toxicity but caused a low incidence of cardiac lesions. 2,3-Dichlorodibenzo-p-dioxin and 2-chlorodibenzo-p-dioxin up to 2000 /xg/kg/day had no adverse effect on survival, average weight, and skeleton of term fetuses. 

Mushak P, Davis JM, Crocetti AF, et al. 1989. Prenatal and postnatal effects of low-level lead exposure Integrated summary of a report to the U.S. Congress on childhood lead poisoning. Environ Res 50 11-36. 

NT057 Singh, A., and S. P. Singh. Postnatal effect of smokeless tobacco on phytic acid or the butylated hydroxyanisole-... 

Postnatal effect of antidepressant drugs administered during gestation. Exp Neurol 3 542-555. 

Effect of Chemicals in Late Pregnancy and Lactation (Perinatal and Postnatal effects). These tests are usually carried out on rats, and 20 pregnant females per... 

The 1996 Food Quality Protection Act (FQPA) now requires that an additional safety factor of 10 be used in the risk assessment of pesticides to ensure the safety of infants and children, unless the EPA can show that an adequate margin of safety is assured with out it (Scheuplein, 2000). The rational behind this additional safety factor is that infants and children have different dietary consumption patterns than adults and infants, and children are more susceptible to toxicants than adults. We do know from pharmacokinetics studies with various human pharmaceuticals that drug elimination is slower in infants up to 6 months of age than in adults, and therefore the potential exists for greater tissue concentrations and vulnerability for neonatal and postnatal effects. Based on these observations, the US EPA supports a default safety factor greater or less than 10, which may be used on the basis of reliable data. However, there are few scientific data from humans or animals that permit comparisons of sensitivities of children and adults, but there are some examples, such as lead, where children are the more sensitive population. It some cases qualitative differences in age-related susceptibility are small beyond 6 months of age, and quantitative differences in toxicity between children and adults can sometimes be less than a factor of 2 or 3. 

Effect on reproductive performance Effects on animal mating behavior, reproduction, parturition, progeny, birth defects, postnatal development. Examines fertility, teratology, perinatal and postnatal effects, lactation. 

In case of prenatal treatment, care should be taken that pups are fostered appropriately (ref. 169). Otherwise, postnatal effects of changes of maternal behavior resulting from the treatment might be confounded with prenatal effects of fetal exposure to chemicals. Changes in pup-dam interactions, caused by effects of postnatal treatments on either the dam or the pup, may lead to indirect teratogenic effects. It is difficult to distinguish such effects from direct teratogenic effects. Furthermore, exposure of dam and fetus or pup to chemicals may cause indirect effects because of induction of... 

Moore JA, Gupta BN, Zinkl JG, et al. 1973. Postnatal effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Environ Health Perspect 5 81 -85. 

Joad JP, Jl C, Kott KS, Brie JM, Pinkerton KE (1995) In utero and postnatal effects of sidestream cigarette smoke exposure on lung function, hyperresponsiveness, and neuroendocrine cells in rats. Toxicol Appl Pharmacol, 132(1) 63-71. 

Domingo, J.L., Ortega, A., Patemain, J.L., Corbella, J. (1989a). Evaluation of the perinatal and postnatal effects of uranium in mice upon oral administration. Arch. Environ. Health 44 395-8. 

Drugs given to the mother just prior to labour can cause postnatal effects CNS depressants may persist in and affect the baby for days after birth vasoconstrictors can cause fetal distress by reducing uterine blood supply 3-adrenoceptar blockers may impair fetal response to hypoxia sulphonamides displace bilirubin from plasma protein (risk of kernicterus) anticoagulants can cause haemorrhage. 

Fetal damage following intrauterine poisoning was especially pronounced. Affected infants were born with both physical malformations and profound mental retardation. Symptoms resembled cerebral palsy. Several infants were born completely blind. Pathology in these cases involved the cerebral hemispheres to a major extent and microcephaly was found in several instances. Cerebral cortices were not only underdeveloped but their convolutions were also narrowed. The corresponding maternal toxicity in these cases was minimal and rapidly reversible. The observable postnatal effects at the lowest levels of fetal exposure, was psychomotor retardation expressed as delayed behavioral... 

PCB-related effects were induced in the adult monkeys and their offspring (Arnold et al. 1995). Conception rate was significantly reduced at 0.02 mg/kg/day and higher doses. Because this effect occurred in the adult animals that were mated after 37 months of exposure, 0.02 mg/kg/day is a serious LOAEL for reproductive toxicity for chronic-duration exposure. Exposure during gestation and lactation resulted in both fetal toxicity and postnatal effects in the offspring. Fetal mortality was increased at... 

Tabacova S, Hinkova L, Balabaeva L. 1978. Carbon disulfide teratogenicity and postnatal effects in rat. Toxicol Lett 2 129-133. 

Schmahl W, Kollmer WE, Berg D, et al. 1979. Postnatal effects on Wistar rat pituitary morphology and function after application of strontium-90 on day 18 of pregnancy. Biological Implications of Radionuclides Released from Nuclear Industries. Proceeding of an International Symposium on Biological Implications 1 329-337. 

For most biotherapeutics that do not cross-react with rodents or rabbits, an embryofetal development study in macaques is generally conducted during clinical development to support the inclusion of women of childbearing potential in clinical trials. However, postnatal development studies in nonhuman primates have not routinely been conducted. Consequently, the protocols and the end points are less well established for evaluation of postnatal effects on the immune system. 

In a second experiment on postnatal effects of gestational exposure to maneb in the rat, Chernoff et al. 

Administration of 960 mg/kg maneb to pregnant mice on gestation days 6-15 also resulted in fetal mortality and minor structural malformations, such as head and neck shape and bent tails (Beck 1990). Postnatal effects of pups born to dams gavage dosed each day with 0, 190, or 380 mg maneb/kg on gestation days... 

Since speech and language acquisition develop relatively late in children, separating prenatal and postnatal effects on their development is often impossible. Known factors include the general social effects of poverty combined with fetal alcohol spectrum disorder, producing deficits in children in language performance.28 Other factors common in a poverty environment and known to affect language performance are prenatal exposure to cocaine and tobacco.29... 

Added to all this is an important postnatal effect fetuses less than 37 weeks gestational age of mothers who smoke throughout pregnancy have a delayed response to the maternal voice, and this may have implications for later language development.34... 

Davila-Garcia, M.I., Hlibczuk, V., Akbari, H.M., Alves, S.E. and Azmitia, E.C. (1988) Postnatal effects of prenatal administration of neuropeptides on H-5-HT uptake by serotonergic neurons. Soc. Neurosci. Abstr. 14 416. 

It was not stated whether neurotransmitter levels were measured in this low-dose group. In view of these results, suggesting some fetotoxicity in the mouse but not the rat at 300 ppm and postnatal effects in the rat at 900 ppm but not 100 ppm, there is a need for further studies at low levels between 900 and 100 ppm to establish a more accurate no-ef-fect-level. ... 

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