End Point Determination and Study of Developmental Neurotoxicity

This report delves into the critical area of end point determination within developmental neurotoxicity, highlighting the adverse effects of neurotoxic agents on the nervous system. It explores various aspects, including the types of neurotoxicity such as developmental, reproductive, carcinogenicity, and mutagenicity, along with the first-tier evaluation for risk assessment. The report emphasizes the significance of in vivo animal testing and the role of OECD guidelines in evaluating neurotoxicity. It also discusses the research methods used, including in vitro models and the growing pressure to assess a large number of chemicals. The conclusion underscores the validity and accuracy of OECD DNT guidelines for evaluating developmental neurotoxicity, emphasizing the reproducibility and consistency of the approaches used. The report references several studies and research papers to support its findings, providing a comprehensive overview of the subject.

Running head: END POINT DETERMINATION
End point Determination and study of Developmental Neurotoxicity
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1END POINT DETERMINATION
Neurotoxicology is the knowledge of the detrimental factors on the nervous system
by actions of pesticides, biological, and certain physical agents throughout growth and
maturity. Several specific chemicals, like arsenic, mercury, contaminants, and ethanol, are
toxic to the nervous system [1].
Neurotoxicity is a significant hazard target for many regulatory body functions that
must be assessed. To identify potential neurotoxic agents, neurotoxicity testing is used.
Neurotoxicity monitoring is often considered as an element of location bound organ toxicity;
one of the prime target body systems is the central nervous system (CNS). Pesticide and
medication exposure in utero can also have harmful effects on the growth of the nervous
system, which is considered as developmental neurotoxicity [2].
The end points studies for various toxicity include the study of developmental toxicity
which is the toxicity in the fetus which are death, retardness of development, anatomical
changes, extreme external deformities, soft tissue / major organ abnormalities. Another
toxicity refers to the reproductive toxicity that is the toxicity by the parents which impacts the
deformities in the organs for reproduction which can lead to changes in sex ratio, the viability
of the offspring, development and characters.
Moreover, carcinogenicity neurotoxicity is one of the most impactful neurotoxicity,
which implements the formation of carcinogens in individual producing tumors in them. In
addition, mutagenicity is the last count among the effects of toxicity which impacts by
flowing from the generations and can even alter with the phenotypes of the offspring.
First-tier evaluation is designed to evaluate how well a chemical has the capacity to
produce any neurotoxic effects, i.e., the first phase of the risk management process to enable
risk detection. The next stage is dealing with neurotoxicity classification, such as the form of
structural or operational damage caused and the extent and position of synaptic failure. Tests

2END POINT DETERMINATION
were used during risk assessment (the second phase) to research the quantitative interaction
between dosage (applied dose) and dose at the target location of the toxic activity (delivered
dose) and dose-to-biological reaction. The third and final stage of research for neurotoxicity
is the analysis of chemical compound action pathways [3].
Review of the neurocognitive results of research aimed at recognising extended or
long term exposure to animal models from low to moderate rates of Organophosphorus (OP).
Thus, evaluating the effects of surgery on brain development, attention, impulsiveness,
motility, fatigue, and anxiety [4].
Regulatory monitoring of neurotoxicity is based on techniques of in vivo animal
testing. Four Test Guidelines (TGs) of the Organization for Economic Cooperation and
Development (OECD) identify reports of neurotoxicity in vivo. Delayed organophosphorus
neurotoxicity Substances proceed with acute exposure, TG 418 requires a single oral
administration to hens that are then followed for 21 days. The hen's actions, body mass, and
total phenotype and microscopic pathology are the primary speculations. Delayed
organophosphorus neurotoxicity Substances include 28-day Repeated Dose Review, TG 419,
includes 28 days of routine oral dosage of hens with an organophosphorous toxin
accompanied by biochemical and histopathological tests. Neurotoxicity Analysis in Rodents,
TG 424, includes a routine oral dosage of rats for acute, critical, or detrimental evaluations
(28 days, 90 days, or one year or more), including cognitive tests and histopathology
evaluations of the systems of the nerve tissue [3].
Studies of neurotoxicology and testing include in vitro models such as testing of
primary glial and neural tissues from various regions of the brain, testing of cell lines such as
tumors in glial cell testing or test of tumors in blood, testing of hippocampus and testing
through an organotypic method of culture of several other cells.

3END POINT DETERMINATION
Toxicity research is under growing pressure to achieve a number of alternative
requirements: Checking of large numbers of common substances, most of which lack
sufficient data on toxicity. Reviewing of the huge number of new chemicals and new
technologies launched into the market each year, such as nanomaterials, assessing possible
harmful effects for all vital endpoints and stages of development [5].
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. The
research methods used were entitled to a long tradition of global testing, statistical analysis,
and assessment found in the official record. The reproducibility, consistency and tolerance of
these approaches have been proven using a wide range of test substances in compliance with
OECD recommendations on validating and globally accepting new or modified hazard
classified optimisation techniques. Numerous independent, professional, scientific research
papers confirm such results.

4END POINT DETERMINATION
References
1. Burke RD, Todd SW, Lumsden E, Mullins RJ, Mamczarz J, Fawcett WP, Gullapalli
RP, Randall WR, Pereira EF, Albuquerque EX. Developmental neurotoxicity of the
organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical
models and potential mechanisms. Journal of neurochemistry. 2017 Aug;142:162-77.
2. Valciukas JA. Foundations of environmental and occupational neurotoxicology.
Routledge; 2019 Jul 9.
3. Legradi JB, Di Paolo C, Kraak MH, Van Der Geest HG, Schymanski EL, Williams
AJ, Dingemans MM, Massei R, Brack W, Cousin X, Begout ML. An ecotoxicological
view on neurotoxicity assessment. Environmental Sciences Europe. 2018 Dec
1;30(1):46.
4. Wu L, Zhao H, Weng H, Ma D. Lasting effects of general anesthetics on the brain in
the young and elderly:“mixed picture” of neurotoxicity, neuroprotection and cognitive
impairment. Journal of anesthesia. 2019 Apr 19;33(2):321-35.
5. Roundtable on Environmental Health Sciences R. Identifying and Reducing
Environmental Health Risks of Chemicals in Our Society: Workshop Summary.