additives, radiations, smoking, and atmospheric fine particles are continuously
produced in surrounding environment and adversely affects human health (Yao
et al. 2016). Most of these pollutants are either slow degrading or stable in nature
as a result of which they tend to accumulate in the environment. The harmful effects
of these toxic chemicals on health of humans have raised a growing concern about
the urgency and necessity to implement rapid, sensitive, cost-effective, novel, and
high-throughput screening tests which can assess toxicity of these toxic pollutants.
(Yao et al. 2016). Earlier most of the toxicity screening test for pollutants or drugs
were dependent on the animal models. In 1959 Russell and Burch postulated the
theory of “high fidelity fallacy,” which states that experimental animals based
toxicity assays are not always translatable to human health (Russell and Burch
1959) due to inter-specific variations. For example, numerous drugs which passed
the animal testing during the development process failed during the clinical trials.
The principles of alternative toxicology are mainly based on in vitro studies, i.e. 3Rs
(Replacement, Reduction, and Refinement) may be more important today than ever
before (Gibb 2008; Krewski et al. 2008; Russell and Burch 1959).
Though animal models and in vitro cell culture systems pose several limitations
including time consumption, intensive resourcing, and ethical concerns (Krewski
et al. 2008), most of the toxicity screenings and research in industries and research
institutes are still relying on it. Although toxicological screening systems based on
in vitro human models of fast growing immortalized or cancer cell lines present a
solution to this problem, these are not true representatives of the native tissue due to
accumulation of mutations or altered cell functions during expansion. Toxicity
screening system based on primary human cell cultures present a better option but
has limitations as these cells have limited growth and proliferative potential in
culture (Yao et al. 2016). Together these issues can significantly restrict the reproducibility of the tests, generation of data and its interpretation (McNeish 2004).
Generally, these in vitro assays rely on the response of a single cell type and are
unable to indicate correct information about the toxicological responses at the level
of tissues or even whole organism where there is a heterogenous population of cells
(Krewski et al. 2008).
Recently, Faiola et al. (2015) demonstrated that toxicology studies based on stem
cells could be a quick, powerful, and cost-effective screening system in detecting the
developmental toxicity of environmental pollutants (Jennings 2015). Human stem
cell-based toxicology studies present an efficient, quick, and specific toxicity screening, establishing it as an effective model to animal experimental testing or conventional toxicity assays because it utilizes the potential of stem cells to differentiate into
various cell types and tissues present in body relating it more closely to humans (Yao
et al. 2016). Other advantages include less time consumption, low cost, and higher
accuracy than tests using animals.
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A. Kumar et al.
produced in surrounding environment and adversely affects human health (Yao
et al. 2016). Most of these pollutants are either slow degrading or stable in nature
as a result of which they tend to accumulate in the environment. The harmful effects
of these toxic chemicals on health of humans have raised a growing concern about
the urgency and necessity to implement rapid, sensitive, cost-effective, novel, and
high-throughput screening tests which can assess toxicity of these toxic pollutants.
(Yao et al. 2016). Earlier most of the toxicity screening test for pollutants or drugs
were dependent on the animal models. In 1959 Russell and Burch postulated the
theory of “high fidelity fallacy,” which states that experimental animals based
toxicity assays are not always translatable to human health (Russell and Burch
1959) due to inter-specific variations. For example, numerous drugs which passed
the animal testing during the development process failed during the clinical trials.
The principles of alternative toxicology are mainly based on in vitro studies, i.e. 3Rs
(Replacement, Reduction, and Refinement) may be more important today than ever
before (Gibb 2008; Krewski et al. 2008; Russell and Burch 1959).
Though animal models and in vitro cell culture systems pose several limitations
including time consumption, intensive resourcing, and ethical concerns (Krewski
et al. 2008), most of the toxicity screenings and research in industries and research
institutes are still relying on it. Although toxicological screening systems based on
in vitro human models of fast growing immortalized or cancer cell lines present a
solution to this problem, these are not true representatives of the native tissue due to
accumulation of mutations or altered cell functions during expansion. Toxicity
screening system based on primary human cell cultures present a better option but
has limitations as these cells have limited growth and proliferative potential in
culture (Yao et al. 2016). Together these issues can significantly restrict the reproducibility of the tests, generation of data and its interpretation (McNeish 2004).
Generally, these in vitro assays rely on the response of a single cell type and are
unable to indicate correct information about the toxicological responses at the level
of tissues or even whole organism where there is a heterogenous population of cells
(Krewski et al. 2008).
Recently, Faiola et al. (2015) demonstrated that toxicology studies based on stem
cells could be a quick, powerful, and cost-effective screening system in detecting the
developmental toxicity of environmental pollutants (Jennings 2015). Human stem
cell-based toxicology studies present an efficient, quick, and specific toxicity screening, establishing it as an effective model to animal experimental testing or conventional toxicity assays because it utilizes the potential of stem cells to differentiate into
various cell types and tissues present in body relating it more closely to humans (Yao
et al. 2016). Other advantages include less time consumption, low cost, and higher
accuracy than tests using animals.
256
A. Kumar et al.