Utilization of juvenile animal studies to determine the human effects and risks of environmental toxicants during postnatal developmental stages

Brent, Robert L.

doi:10.1002/bdrb.20020

Cited by 59 publications

(50 citation statements)

References 117 publications

(123 reference statements)

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“…The parameters applied for environmental toxicants in animal studies such as threshold exposures, maximum permissible exposures and toxic effects that were estimated has to be interpreted with caution when accounted on human. Epidemiology studies that are well-performed are considered to be best suitable for determining human risk and effects of environmental toxicants [40]. Presently, measures are being taken to find effective alternatives to animal studies with the use of cell and tissue culture and computer simulation [41].…”

Section: Justification Of Unwarranted Resultsmentioning

confidence: 99%

Preclinical Research: A Rise or Dawn

Manjunath¹

2018

PPIJ

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IntroductionComplex processes are involved in developing a new drug along with its time and costs consumption. Prior to launching, it requires variety of evidences to show its potential activity [1]. Key step in drug discovery is considered to be the target discovery which ranges from molecular entities to biological phenomenon [2]. As there are urges in translating scientific discoveries into practical importance, preclinical studies using animal models play an important role in evaluating the efficacy and safety under clinical scenario [3]. After enormous debates, it is concluded that the benefits of animal research is worth to manage public health and medical research [4]. Subsequently, animal studies are justifiable if done in a way to minimize pain in animal models and wherever applicable alternative methods are explored and avoiding unnecessary cruel treatment to animals [5]. However, various reports have enforced on the failures of trails that has never capitalized after thorough observation of safety and efficacy in animal models which mainly portraits the requirement of robustness in preclinical studies [6][7][8][9][10]. For instance, reports say that, almost 95% of drugs that enter clinical trials related to stroke or septic shock do not get launched in the market though enormous expenditures have been dealt with the basic studies and drug discoveries [11] and similarly, the average success rate in clinical cancer trials is less than 8% after preclinical estimation [10].Still it is recommended to circumvent preclinical studies because of the scientific, practical and ethical reasons, to conduct studies in humans [6], and thus prior to this attempt, preclinical drug combination studies in vitro and/or in animals has to be carried out to obtain the base for studies in human [12]. Though the debate over use of the animals in medical experiments has a long and unpleasant history, eminent researches along with Nobel Prize winners have signed a declaration provided by the Research Defense Society has made claim that experiments on animals have made important contribution to advances in medicine and surgery [13]. Research focused on pain research has shown enormous rate of failures and increased costs of drug development this is because of phenotypic differences and complexity in behavioral alterations along with the changes in daily activities and psychological disturbances [14,15]. Moreover, the test and models of nociception has been questioned in the aspect of appropriateness between tests, models and procedures [16]. Thus in order to develop robustness in pain management and to effectively gather required evidences, it is better to evaluate pain states in higher order preclinical species where we can predict whether biological mechanisms and specific compounds have relevance for clinical pain better than rodent species. The pain models in non-rodent species may enhance the speed, and in addition reduce costs along with the increased probable results for a successful analgesic development [17]. Hiccups in...

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Section: Justification Of Unwarranted Resultsmentioning

confidence: 99%

Preclinical Research: A Rise or Dawn

Manjunath¹

2018

PPIJ

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“…Drugs like thalidomide, antiepileptics, warfarin, retinoic acid are teratogenic. 8 Maternal exposure to alcohol, smoking play a risk. Deficiency of folate leads to neural tube defects in the foetus.…”

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A two-year study of patterns and prevalence of congenital malformations

Lavanya¹,

Seethalakshmi²

2017

Int J Reprod Contracept Obstet Gynecol

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Background: India is undergoing an epidemiological transition; communicable diseases are on the decline due to better living conditions and healthcare delivery. On the other hand, the relative increase in the prevalence of non-communicable, chronic and genetic diseases threatens to be a public health problem in India like congenital malformations. Congenital malformations remain one of the least focused areas of disease surveillance in India compared with communicable and some chronic diseases. Thus, data on the magnitude of birth defects are essential to plan preventive strategies and organize methods of supportive care for affected individuals and families. The aim of this study is to study the incidence and prevalence of the birth defects and the patterns of congenital malformations in our institute and the various risk factors influencing the occurrence.Methods: A cross sectional study was conducted on all Ant natal patients and deliveries conducted in the institution for a period of two years from June 2015 to May 2017. Mediscan Systems extended a big hand in further confirmation of diagnosis. A detailed history was taken regarding the patients and husband’s age, parity, occupation, previous obstetric outcome, family history of birth defects and exposure to teratogens and environmental factors and intake of periconceptional folate. Data analysis was done with respect to age, parity, consanguinity, sex, previous defects.Results: CNS defects were the most recognisable malformations at birth. Pick up rate for CVS anomalies were low requiring expertise. As against the wide prevalence of cardiac defects across total population the reported prevalence is less as similar to rest of the studies done in many centres across the country. Target scan has halved the burden of birth defects.Conclusions: Congenital malformations though cannot be prevented totally but can be minimised and if detected early will reduce the mental agony in the mother and family. Prenatal counselling, periconceptional folate, anomaly scan, Prenatal diagnosis reduce the incidence of birth defects.

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“…This is almost a perfect study for the following reasons 10,11 : bisphenol was placed in the diet ad libitum among 7 exposure groups with a range of exposures that were over a 500 000-fold range. Only at the highest dosages were any potential toxic effects of BPA observed.…”

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Urine Chemical Content May Be a False Measure of Environmental Exposure

Brent

2013

Pediatrics

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Dr Trasande and his group in the article on phthalates conclude that urine phthalate concentrations (represented by urine di-2-ethylhexylphthalate [DEHP] concentrations) were associated with increased insulin resistance in this cross-sectional study of adolescents. Dr Trasande refers to this as an association and indicated that this study cannot rule out the possibility that insulin-resistant children ingest food with higher phthalate content or that insulin-resistant children excrete more DEHP. Without knowing the tissue or serum concentration of DEHP or referring to primate studies, the authors' hypotheses are appropriate.The second article by Eng et al deals with bisphenol A (BPA). It is most important for authors to be familiar with the literature concerning the chemical that they are evaluating. Unfortunately, the BPA article fails to cite important publications dealing with the metabolism of BPA. For example, Daniel Doerge, a well-known authority on the metabolism of BPA, has co-written 5 publications that Eng et al have not cited. [3][4][5][6][7][8] In 2011, in a report entitled, "Twenty-Four Hour Human Urine and Serum Profiles of Bisphenol A during High-Dietary Exposure" 3 these investigators found that urinary BPA is not a surrogate of a serum or tissue exposure to BPA, but reflects the intake of BPA in the diet of the individual whose urine has been collected. This study, published in Toxicological Sciences, studied 20 adult volunteers who ingested 100% of 1 of 3 specified meals comprising of standard grocery store items for breakfast, lunch, and dinner. They studied the serum concentration of BPA, which was only measurable in the serum of the patients with exposure of 1.3 to 3.9 times higher than the 95th percentile of aggregate US exposure. "BPA serum concentrations were primarily less than or equal to the limit of detection…and were on average, 42 times lower than urine concentrations. During these high dietary exposures, BPA concentrations in serum were undetectable in 83% of the 320 samples collected and BPA concentrations were determined to be less than or equal to LOD [limit of detection] in all samples."Because there is little BPA in the serum even with large intakes of BPA and the metabolism of BPA in the serum destroys its endocrine receptor affinity, there is little justification to assume that BPA has toxic exposure in the human, even with very high exposure in the diet.Most BPA articles in humans use the urine content of BPA as a surrogate of exposure, when in reality it is a measure of the intake of BPA

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Utilization of juvenile animal studies to determine the human effects and risks of environmental toxicants during postnatal developmental stages

Cited by 59 publications

References 117 publications

Preclinical Research: A Rise or Dawn

Preclinical Research: A Rise or Dawn

A two-year study of patterns and prevalence of congenital malformations

Urine Chemical Content May Be a False Measure of Environmental Exposure

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