University Neurotoxicology Report: End Point Determination and Study

This report delves into the study of neurotoxicity, exploring the impact of chemical and physical agents on the nervous system, particularly during development. It highlights the increased vulnerability of the infant nervous system and the importance of neurotoxicity studies for identifying potential health risks. The report discusses the use of stem cell models, specifically examining the effects of silica nanoparticles on embryonic stem cell differentiation. It outlines the three-step process of neurotoxicity assessment, including identifying dangers, diagnosing neurotoxicities, and analyzing action pathways. Additionally, it references in vivo animal testing methodologies, as per OECD guidelines, and in vitro methods. The report emphasizes the need for alternative testing methods to meet regulatory demands and the importance of evaluating potentially damaging effects of new chemicals, including nanomaterials, to ensure public health risk management. The assignment brief focuses on organophosphorous pesticides, the chlorpyrifos, and their neurotoxic effects and the need for determining the developmental stages of neurotoxicity and end point determination.

Running head: END POINT DETERMINATION
End point Determination and study of Neurotoxic effect on Stem Cell Model
Name of the Student:
Name of the University:
Author Note:

1END POINT DETERMINATION
The understanding that chemical, biochemical and certain physical agents have a
negative influence on the organism during their development and progressive maturity is
termed as neurotoxicology. Neurotoxicology defines effect by certain chemical products
which are directly harmful to the nervous system, such as asbestos, mercury, toxins or
ethanol.
Similar to the adult nervous system, the infant nervous system is considered to be more
sensitive towards chemical exposure. For many regulatory bodies, roles are needed to be
measured as neurotoxicity is a significant health risk goal. Neurotoxicity studies are used to
identify possible neurotoxicants contributing to health risks.
Monitoring of Neurotoxicity is often seen as a locational toxicity aspect of the organ;
central nervous system (CNS) is one of the initial target body systems. Exposure of pesticide
and drug in utero can also have a deleterious effect of the nervous system by the impact of
neurotoxic development (Burke et al., 2017).
The higher vulnerability of the developing brain occurs due to the complex
developmental processes of neural progenitor cells, including their commitment and
distinction of the proliferation of neuronal and nerve cells; migration, differentiation into the
different neuronal and glial subtypes; synaptogenesis; pruneing; myelination; networking and
terminal functioning neuronal cells and glial maturation. One difficulty in assessing
developmental neurotoxicity (DNT) caused by an exogenous chemical is that it is not only
based on the type of exposure (dose, duration) but also on the stage of development of the
brain at the time of exposure that occurs during neurodevelopment. Moreover, at least six
months after birth, the immature's blood brain barrier (BBB) is not fully formed, thereby
enabling a chemical to enter a fetal/neonatal brain.

2END POINT DETERMINATION
While research is increasing on the potential toxic properties of nanomaterials, the
developmental toxicity field has remained uninvestigated. The embryonic stem cell analysis
is an in vitro diagnostic procedure used to examine chemicals ' embryotoxic potential by
evaluating their ability to prevent embryonic stem cell differentiation into spontaneously
contracting cardiomyocytes. To examine whether nanomaterials are effective enough to
inhibit differentiation in the embryonic stem cell process, four well known silica
nanoparticles of different sizes were used. Distributions of nanoparticles and dispersion
characteristics were determined in the stem cell culture medium, before and during
incubation by means of transmission electron microscopy (TEM) and dynamic light
scattering (Park et al., 2009).
The first-tier evaluation is designed to test the potential of chemicals in the first steps
of a risk-taking cycle for the identification of danger to generate certain neurotoxic effects.
The next step is the diagnosis of Neurotoxicities, such as structural or operational disturbance
and neuronal impairment degree and location. The study of the quantitative association
between the dosage (applied dose) and the target of the toxic behaviors (application) and the
dose-to-biological response was conducted during a risk assessment (second phase). The
analysis of chemically formed action pathways is the third and final step of neurotoxicity
chemistry (Legradi et al., 2018).
Discussion of evidence from studies on neurocognitive animal treatment from low to
moderate levels for the identification of prolonged or long-term exposure was noted.
Therefore, evaluation of the development of the brain, attention, impulse, motility, fatigue
and anxiety effects of the operation was done.
Neurotoxicity control is dependent on in vivo animal testing methodology. The
Organization for Economic Cooperation and Development (OECD) holds four test guidelines

3END POINT DETERMINATION
(TGs) that describe in vivo neurotoxicity studies. Compounds with acute exposure continue,
TG 418 requires a single oral administration for hens and is then followed for a period of 21
days. Delayed organophosphorus neurotoxicity is the key speculations which involve hen's
behavior, body weight, overall phenotype and microscope. Chemicals provide 28-day daily
dose analysis, TG 419, including a 28-day regular oral dosage of organophosphorous toxin
for hens of biochemical and histopathological trials. TG 424, a standard oral dosage of rats
for immediate, vital or harmful treatment (28 days, 90 days or one year or longer), involving
executive tests and histopathological evaluations of nervous tissue systems (Legradi et al.,
2018).
The research includes in-vitro methods. Neurotoxicology experiments and research
include in-vitro system tests for primary glial and neural tissues in specific areas of the brain;
cell line scans for cancers of glial cells or blood tumor, hippocampus monitoring and
organotyping of a variety of other cells (Wu et al., 2019).
Toxicity research is under- pressure to meet various alternative demands — the
regulation of a vast number of common chemicals, where most of them lack adequate toxicity
evidence. The analysis of every year's tremendous number of new chemicals and innovative
science include nanomaterial science, the evaluation of potentially damaging effects for all
critical endpoints and production stages. Therefore it can be concluded, the guidelines
by OECD DNT is the best accepted science for evaluating the ability for DNT in public
health risk management, and data generated with this protocol are valid and accurate for
evaluating these endpoints.

4END POINT DETERMINATION
References
Burke, R.D., Todd, S.W., Lumsden, E., Mullins, R.J., Mamczarz, J., Fawcett, W.P.,
Gullapalli, R.P., Randall, W.R., Pereira, E.F. and Albuquerque, E.X., 2017. Developmental
neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to
preclinical models and potential mechanisms. Journal of neurochemistry, 142, pp.162-177.
Legradi, J.B., Di Paolo, C., Kraak, M.H.S., Van Der Geest, H.G., Schymanski, E.L.,
Williams, A.J., Dingemans, M.M.L., Massei, R., Brack, W., Cousin, X. and Begout, M.L.,
2018. An ecotoxicological view on neurotoxicity assessment. Environmental Sciences
Europe, 30(1), p.46.
Park, M.V., Annema, W., Salvati, A., Lesniak, A., Elsaesser, A., Barnes, C., McKerr, G.,
Howard, C.V., Lynch, I., Dawson, K.A. and Piersma, A.H., 2009. In vitro developmental
toxicity test detects inhibition of stem cell differentiation by silica nanoparticles. Toxicology
and applied pharmacology, 240(1), pp.108-116.
Wu, L., Zhao, H., Weng, H. and Ma, D., 2019. Lasting effects of general anesthetics on the
brain in the young and elderly:“mixed picture” of neurotoxicity, neuroprotection and
cognitive impairment. Journal of anesthesia, 33(2), pp.321-335.