Prenatal development studies

OECD (2001) Test Guideline 414. OECD Guideline for Testing of Chemicals. Prenatal developmental toxicity study, http / / www.oecd-ilibrary.org/environ-ment/test-no-414-prenatal-development-toxicity-stud y 9789264070820-en. Accessed 12 Feb 2012... 

Organisation for Economic Cooperation and Development (2001). Guideline 414, prenatal development toxicity study, see http //www. oecd-ilibrary.org/environment/oecd -guide -lines-for-the-testing-of-chemicals-section-4-health- effects 20745788... 

Effects on prenatal development (such as increased pre- and postimplantation losses, embryonic resorption, reduced fetal weights, and external fetal alterations) will also be assessed in this preliminary study and will allow a better preparation of the main study design. 

Repeat-dose neurotoxicity studies may identify behavioral effects or impaired nerve functions that can interfere with mating or maternal care. Developmental neurotoxicity studies have been conducted for specific pesticide classes, following requirements of US-EPA. If such a study is available it can be examined not only for the study-specific endpoints on the developing brain but also compared to the prenatal toxicity study and the two-generation smdy with respect to general endpoints of pre- and postnatal development, respectively. 

The placenta, although of vital importance for the viability and the development of the conceptus, is a neglected organ in most prenatal toxicity studies for pesticides. Older studies often give no information at all, while newer investigations contain at least placental... 

Hoder et al. (1984) studied clonidine in seven newborn infants with neonatal narcotic abstinence syndrome and found no significant changes in blood pressure, pulse, or electrocardiograms (EKG) in any of the seven infants. One infant had a transient abnormal eye exam and two infants developed a transient mild metabolic acidosis. On follow up 4-9 months later, four infants were found to be developmentally age appropriate. However, Huisjes et al. (1986) reported that 22 children exposed in utero to clonidine as result of treatment for maternal hypertension had increased sleep disturbances and hyperactivity, compared to a control group at a mean age of 6 years. It is unclear whether these differences were a direct effect of clonidine on prenatal development. More sophisticated preclinical studies need to be done in this area. At best the level of short-term and long-term safety regarding clonidine is level C. 

Myers, G.J., P.W. Davidson, C. Cox, C.F. Shamlaye, D. Palumbo, E. Cernichiari, J. Sloane-Reeves, G.E. Wilding, J. Kost, L.S. Huang, and T.W. Clarkson. 2003. Prenatal methyl mercury exposure from ocean fish consumption in the Seychelle child development study. Lancet 361(9370) 1686-1692. 

The prenatal developmental toxicity study was originally designed to investigate malformations, and the pregnant animals are sacrificed on the day prior to the expected birth. The background for this is that the dams may eat malformed offspring. As such, the prenatal developmental toxicity study covers only effects induced during prenatal development and visible at term. 

As noted above, the lowest effective doses in adults and young are often similar. However, the type and severity of effects from an exposure may be very different. This becomes an important consideration, especially in evaluating prenatal animal studies. Because the developing embryo/fetus is exposed in the maternal animal, it has been argued that if maternal toxicity is observed, any developmental toxicity could be due to the compromised maternal system. However, several issues should be considered. The difference between the lowest maternally toxic dose and the developmentally toxic dose may at times be related to the relative thoroughness with which endpoints are evaluated in dams and offspring, as well as to the sensitivity of the end-points. Moreover, the severity of the effects must be considered the developmental effects may be permanent, while the maternal effects may be reversible. From a risk assessment perspective, developmental toxicity in the presence of maternal toxicity cannot be simply considered secondary to maternal toxicity and discounted (USEP A, 1991). 

Myers GJ, Davidson PW, Cox C, Shamlaye CF, Palumbo D, Cernichiari E, Sloane-Reeves J, Wilding GE, Kost J, Huang LS, Clarkson TW (2003) Prenatal methylmercury exposure from ocean fish consumption in the Seychelles child development study. Lancet, 361(9370) 1686-1692. 

The science of teratology (a word coined in 1832 by Geoffrey Saint-Hilares as literally the study of monsters ) has a history predating that of medicine as we know it today. The contemporary definition of teratology is the science dealing with the causes, mechanisms, and manifestations of a structural or functional nature of abnormal prenatal development . Teratology can be considered a subdivision of... 

Davidson PW, Myers GJ, Cox C, et al. 1998. Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment Outcomes at 66 months of age in the Seychelles child development study. JAMA 280(8) 701-707. 

Polluted air is a postnatal developmental problem as well as a prenatal one. Studies in California have demonstrated that exposure to polluted air impairs lung development and lung function in children and young adults. I35-37 ... 

Davidson, P.W., G.J. Myers, C. Cox, C. Axtell, C. Shamlaye, J. Sloane-Reeves, E. Cemichiari, L. Needham, A. Choi, Y. Wang, M. Berlin, and T.W. Clarkson. 1998. Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment Outcomes at 66 months of age in the Seychelles Child Development Study. JAMA 280 (8) 701-707. 

Shamlaye, and T.W. Clarkson. 1998. Semiparametric modeling of age at achieving developmental milestones after prenatal exposure to methylmercury in the Seychelles child development study. Environ. Health Perspect. 106(9) 559-564. 

MTBE has been tested by inhalation and ETBE has been tested by gavage for effects upon reproduction and prenatal development. The experiments with MTBE were a one-generation study at concentrations up to 2900 ppm, 6 h/day for 12 and 3 weeks before mating of male and female Sprague-Dawley (CD) rats, respectively [125] and a two-generation study in Sprague-Dawley... 

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