Juvenile Toxicology

Remick, Amera K.; Catlin, Natasha; Quist, Erin M.; Steinbach, Thomas; Dixon, Darlene

doi:10.1177/0192623315595883

Cited by 11 publications

(5 citation statements)

References 70 publications

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“…The interest and increased numbers of juvenile animal toxicity tests reflect a growing need to predict chemical hazards in pediatric populations 12 . Juvenile kidney studies are emphasized because of the kidney’s ongoing postnatal periods of development and maturation 13 .…”

Section: Introductionmentioning

confidence: 99%

A brief review of kidney development, maturation, developmental abnormalities, and drug toxicity: juvenile animal relevancy

Seely

2017

J Toxicol Pathol

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Nonclinical juvenile animal tests perform a valuable role in determining adverse drug effects during periods of organogenesis and/or functional maturation. Developmental anatomic and functional maturation time points are important to consider between juveniles and adults when regarding different organ toxicities in response to drug administration. The kidney is an example of a major organ that has differences in these time points in comparing juveniles to adults and in contrasting humans to laboratory animal species. Toxicologic pathologists, involved in juvenile studies, need to be aware of these time points which are age-related exposure periods of sensitivity to drug toxicity. Age-related developmental anatomic and functional maturation are factors which can affect the way that a drug is absorbed, distributed, metabolized, and excreted (ADME). Changes to any component of ADME may alter drug toxicity resulting in kidney abnormalities, nephrotoxicity, or maturational disorders. Juvenile animal kidneys may either be less resistant or more resistant to known adult nephrotoxic drug effects. Furthermore, drug toxicity observed in juvenile animal kidneys may not always correspond to similar toxicities in humans. Juvenile animal nonclinical toxicology studies targeting the kidneys have to be carefully planned to attain the maximum knowledge from each study.

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Section: Introductionmentioning

confidence: 99%

A brief review of kidney development, maturation, developmental abnormalities, and drug toxicity: juvenile animal relevancy

Seely

2017

J Toxicol Pathol

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“…Pathologists and toxicologists are increasingly confronted with the challenging task of distinguishing potential exposure related histologic lesions from normal maturation changes associated with puberty in juvenile animals (Remick et al, 2015). There has been an increased need for toxicity safety assessments in juvenile animals, as a result of new requirements for the safe use of pharmaceuticals in pediatric patients, stemming from the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) passed by the United States Federal Drug Administration (USFDA) in 2002 and 2003, respectively.…”

Section: Introductionmentioning

confidence: 99%

Differentiating between Testicular Toxicity and Sexual Immaturity in Ortho-phthalaldehyde Inhalation Toxicity Studies in Rats and Mice

Catlin

Willson

Creasy³

et al. 2018

Toxicol Pathol

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Early deaths of young or juvenile animals (before sexual maturation is achieved) in routine regulatory safety studies present pathologists and toxicologists with the challenge of interpreting findings in the male reproductive tract. Additionally, the advent of toxicity testing regulations have resulted in a growing need for the use of juvenile animals in toxicology studies. Here we present the reproductive toxicity findings from a 13-week inhalation toxicity study with ortho- phthalaldehyde (OPA) in male rats and mice as a case example for working through this challenging task. In this study with OPA, survival was significantly reduced in the two highest exposure concentrations of OPA tested. Early deaths and histopathological lesions in the testes and epididymides were generally also limited to these two highest exposure groups. Therefore, there was concern that peripubertal morphological features could be a confounding factor for the histopathological evaluation of exposure-related testicular and epididymal findings. Although it can be difficult to differentiate exposure-related effects from the normal morphological features defining peripubertal changes in the testes and epididymides in animals that die early in a toxicity study, the use of age-matched controls in this case study with OPA provided a reference and aided in the differentiation of these effects.

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“…Recently, juvenile toxicity testing has become a topic of interest for pathologists, and the challenges in evaluating juvenile toxicity studies have been discussed 1 . These challenges include how to assess and interpret histopathological changes in tissues from juvenile animals.…”

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confidence: 99%

Histopathological evaluation of crypt fission during intestinal development in neonatal mice

Yamazaki¹,

Fujii

Watanabe³

et al. 2020

J Toxicol Pathol

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Pathological evaluation of juvenile toxicity studies requires the understanding of normal tissue development at different ages. Here, we report the morphological features of the neonatal mouse intestine, focusing on crypt fission. Postnatal day (PND) 7 and 14 mice showed fewer crypts and less mature epithelial morphology compared to PND 21 and 28. Crypt fission occurred in three stages: 1) flattening of the crypt base into a skirt shape, 2) penetration of myofibroblasts into the crypt base center, and 3) complete separation of a single crypt into two daughter crypts. The ratio of crypt fission to total number of crypts was the highest at PND 14 and 7 in the jejunum and colon, respectively. Crypt fission, a key phenomenon for balance or imbalance in epithelial cell hierarchy, including stem and differentiated cells, is related to tissue injury repair and tumorigenesis. Therefore, examining crypt fission can provide valuable insights into current conditions of intestine.

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Juvenile Toxicology

Cited by 11 publications

References 70 publications

A brief review of kidney development, maturation, developmental abnormalities, and drug toxicity: juvenile animal relevancy

A brief review of kidney development, maturation, developmental abnormalities, and drug toxicity: juvenile animal relevancy

Differentiating between Testicular Toxicity and Sexual Immaturity in Ortho-phthalaldehyde Inhalation Toxicity Studies in Rats and Mice

Histopathological evaluation of crypt fission during intestinal development in neonatal mice

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