INDUSTRIAL WASTE MANAGEMENT

SUBMITTED TO
Engr. Abaid Ullah

SUBMITTED BY

Zonaira Tariq 18-ENV-06

Aisha Babar 18-ENV-10
Shazray Uba 18-ENV-13
Syeda Lubaba Rehan 18-ENV-26
Asma Khan 18-ENV-31

DEPARTMENT OF ENVIRONMENTAL ENGINEERING

UNIVERSITY OF ENGINEERING AND TECHNOLOGY,

TAXILA.
IWM Project Report

Toxicity of Chemical Compounds in Pharmaceutical Industry Wastewater and

Its Reduction Strategy Quantification.
Zonaira Tariq (18-ENV-06)1, Aisha Babar (18-ENV-10)2, Shazray Uba (18-ENV-13)3, Syeda Lubaba Rehan,
(18-ENV-26)4, Asma Khan (18-ENV-31)5*
Department of Environmental Engineering

HIGHLIGHTS

 The toxicity of different pharmaceuticals in industrial wastewater

 T.E.S.T tool is used to describe the toxicity of different pharmaceuticals.
 Quantification and formation of range scale

ABSTRACT
This study evaluates the toxicity of various compounds present in the effluent of pharmaceutical industry. Increase in global
demand for drugs has made pharmaceutical industry one of the major 26 polluters of solid wastes and effluent into the
environment. According to estimates, about half of the global wastewater from pharmaceutical industries is released without
any recommended preprocessing. Pharmaceutical wastewater was characterized, and various compounds present were
identified. The toxicity of compounds is measured using Toxicity Estimation Software Tool of US EPA. Predicted values for
different medicines showing their toxicity were obtained. 96 hours’ fathead minnow LC50 toxicity endpoint value was used
that is concentration of the test chemical in water in mg/L that is lethal to 50% of exposed fathead minnows after 96 hours.
Based on a developed scale, the toxicity is quantified, and the compounds were ranged from very nontoxic to approaching
poisonous.

Keywords: global demand, toxic pharmaceutical industry, fathead minnow LC50 toxicity developed scale.

1. Introduction choice selections and resource allocation purposes

Water quality approach is a major risk management mainly in low-income and developing
approaches advocated by the World Health countries"(Nassiri Koopaei and Abdollahi 2017).
Organization (WHO) and Environmental Protection Increase in global demand for drugs has made
Agency (EPA) which implies that wastewater pharmaceutical industry one of the major 26
should be treated to the extent that meets certain polluters of solid wastes and effluent into the
water quality criteria to prevent any related risk environment. According to estimates, about half of
especially health concerns. This approach invites the global wastewater from pharmaceutical
countries to consider their specific cultural, industries is released without any recommended
socioeconomic and environmental conditions in the preprocessing"(Kumari and Tripathi 2019).
optimized development and implementation of In spite of the fact that the volume of untreated or
sustainable, economical and efficient risk entirely treated pharmaceutical industrial
management interventions. However, it has been wastewater is little, it contains a high level of
publicly accepted that the wastewater treatment pollutants because of the presence of non-
level should match the purpose of reuse. Therefore, biodegradable organic matter such as antibiotics,
cost-effectiveness studies are very important to other prescription drugs, non-prescription drugs,
evaluate different risk management options for animal and plant steroids, reproductive hormones,
evidence-based decision-making, intervention betalactamides, anti-inflammatories, analgesics,

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IWM Project Report
lipid regulators, anti-depressants, cytostatic agents,
personal care products, detergent metabolites, flame
retardants, product of oil use and combustion, and
other broadly used chemicals, i.e., spent solvents,
reaction residues, used filter media, etc., heavy
metals (such as lead, mercury, cadmium, nickel, and
chromium), and other pollutants. Pharmaceutical
industrial wastewater contains toxic and hazardous
substances, the majority of which can be
unfavorable to human well-being"(Kumari and
Tripathi 2019).
The effects of pharmaceutical chemicals on public
health and environment are critical due to their acute
toxicity, including gene toxicity and mutagenic
potential. Drugs of various types, as active
metabolites or metabolized sometime, especially in
developing countries, are not well managed on
expiration and subsequently discarded in large
amount as environmental discharge in the
surrounding ecosystems. While in the environment
most of the pharmaceutical are discharge toxicants
present in wastewater accumulates in aquatic bodies,
soil, and other biological systems, and often exceeds
the critical threshold levels. A number of studies
have identified specific chemical components in
pharmaceutical effluents and demonstrated their
toxic effects on living organisms. Therefore, in
recent years, great concern is shown to study the
impacts of discharged pharmaceutical effluents on
the ecosystem and its services, and human wellness
tied to them"(Kumari and Tripathi 2019).
Most"of the manufacturing pharmaceutical plants
and academic/research institutes are located inside
the city where they work on the synthesis of new
nanomaterials, chemicals and pharmaceuticals. On
the other hand, the untreated or partially treated
wastewater that contains different chemicals and
heavy metals may find its way to some local
drinkable water wells. The issue gains more
importance when we get to know that a
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comprehensive wastewater treatment plan does not
exist for most of the cities and the untreated
wastewater may be used for the irrigation purposes
to grow vegetables for direct human use. The public
health risk could be managed through plans,
including wastewater pathogenic microorganisms
and chemical pollutant removal and minimizing
human exposure to wastewater"(Nassiri Koopaei
and Abdollahi 2017).
Pharmaceutical wastewater is highly polluted multi-
component mixture of various organic and inorganic
constituents, including hardly biodegradable, toxic
and bio-persistent xenobiotic and antimicrobial
agents that may inhibit the biological activity of the
activated sludge and cause treatment plant process
upsets. Activated sludge microorganisms react to the
presence of toxicants in wastewater. Responses
displayed include reduced rates of respiration,
biomass generation, and BOD degradation patterns.
These effects of toxicants can cause failure to reach
effluent standards, which also increase treatment
costs and cause other operational problems, such as
reduction of the efficiency of sludge settling and
compacting, because of filamentous bulking and
deflocculating. In extreme cases the bacteria are
killed by toxic wastewater, and there is a need for
cleanout and reseeding of plant, which is a costly
and time-consuming operation. Toxic inflow can
cause collapse of nitrification process and lead to
significantly exceeded total nitrogen concentration
in effluent. Wastewater streams from drug
manufacturing also contain residues of active
pharmaceutical ingredients (API) and their
intermediates, which are classified as micro
pollutant of emerging concern. They are biologically
active compounds that can potentially alter
physiology and behavior of non-target organism at
low doses. API negatively affect the performance of
secondary biological processes in wastewater
treatment plants (WWTP), cause shifts in the
IWM Project Report

structure of activated sludge bacterial communities The objectives of proposed project are:
and reduce bacterial diversity in the reactors.  To study the composition of pharmaceutical
Depending on manufacturing processes, the wastewater
composition and biological treatability as well as  To calculate LC 50 of various pharmaceutical
salinity of pharmaceutical wastewater fluctuate components using Toxicity Estimation
considerably within a short period of time, which Software Tool by US EPA"
make biological treatment of pharmaceutical  To quantify the toxicity values by development
wastewater even more troublesome. To avoid toxic of a scale
shock to activated sludge microorganisms and
LC 50 of various pharmaceutical components will
ensure the compliance of treated wastewater with
be calculated using Toxicity Estimation Software
regulatory requirements, characterization of
Tool by US EPA. LC stands for "Lethal
wastewater by their degree of biodegradation and
Concentration". LC values usually refer to the
potential toxicity to the biosensors of the specific
concentration of a chemical in air but in
treatment plant is essential. As toxic influent can
environmental studies it can also mean the
partially or completely damage treatment for long
concentration of a chemical in water. The Toxicity
periods, protective actions and alternative treatment
values obtained will be then quantified by the
solutions should be provided when increased
development of a scale.
toxicity is detected. For companies who treat their
According to the (Organization for Economic
own wastewater it is especially important to measure
Cooperation and Development) (OECD) Guidelines
the toxicity of the wastewater before a new process
for the Testing of Chemicals, a traditional
comes on-line to predict their impact on treatment
experiment involves groups of animals exposed to a
process performance. Mainly inhibitory effect of
concentration (or series of concentrations) for a set
toxic components depends on their concentration;
period of time (usually 4 hours). The animals are
therefore, potential impact of increased pollution
clinically observed for up to 14 days."
load on biological treatment system should be
The concentrations of the chemical in air that kills
evaluated in cases when production volumes
50% of the test animals during the observation
increase. Numerous bioassays (toxicity tests) are
period is the LC50 value. Other durations of
available for toxicity evaluation, but only few are
exposure (versus the traditional 4 hours) may apply
directly relevant to activated sludge
depending on specific laws. Since different
microorganisms. For example, the commonly used
chemicals cause different toxic effects, comparing
Microtome and Botox TM assays are based on
the toxicity of one with another is hard. We could
marine luminous bacteria Vibrio fischeri that are not
measure the amount of a chemical that causes
representative of activated sludge microbes and does
kidney damage, for example, but not all chemicals
not reflect the status of the microbial community
will damage the kidney. We could say that nerve
responsible"for treatment (Strade and Kalnina
damage is observed when 10 grams of chemical A is
2019).
administered, and kidney damage is observed when
The problem statement of the project is:
10 grams of chemical B is administered. However,
Characterization of Pharmaceutical Wastewater,
this information does not tell us if A or B is more
identification of toxicity of various pharmaceutical
toxic because we do not know which damage is
components and its Quantification."
more critical or harmful."

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IWM Project Report

Therefore, to compare the toxic potency or intensity

of different chemicals, researchers must measure the
same effect. One way is to carry out lethality testing
(the LD50 tests) by measuring how much of a
chemical is required to cause death. This type of test
is also referred to as a "quantal" test because it is
measures an effect that "occurs" or "does not occur".
(Canadian Centre for Occupational Health and
Safety n.d.)

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 IWM Project Report

2. LITERATURE REVIEW

Yr. AUTHOR TITLE OBJECTIVE METHODOLOGY CONCLUSION

Coagulation and sedimentation, Pharmaceutical wastewater has some

In this paper, the classification of flotation, activated carbon adsorption, characteristics, such as poor biodegradability
A Review on Advanced
the pharmaceutical technology membrane separation, advanced and high concentration. From these
Treatment of
was introduced, and the oxidation processes, membrane characteristics, advanced treatment of
2019 Y Guo Lie Pharmaceutical
characteristics of pharmaceutical separation and biological treatment. pharmaceutical wastewater is very necessary.
Wastewater
wastewater effluent quality were Meanwhile, the characteristics of each There are many kinds of advanced treatment,
summarized process were described. each method has its own features (Guo, Qi et al.
2017).
 Sample collection and
This study aimed to evaluate the wastewater treatment process
Toxicity evaluation of Compared with the DHA measurement, the
conventional pollution parameters
wastewater collected at  Analysis of conventional water Vibrio qinghaiensis test was faster and more
and toxicities of wastewaters
different treatment stages sensitive. Meanwhile, the toxicity indicators
Ke Ma, Zhe Qin, collected at different treatment quality parameters
from a pharmaceutical were significantly and positively correlated with
Zhongqing Zhao, stages from a pharmaceutical
2016
Chunxia Zhao, industrial park wastewater industrial park wastewater  Enzyme activity inhibition the TSS, TN, TP and COD concentrations.
treatment plant These results may aid the understanding of the
Shuxuan Liang treatment plant through assay using dehydrogenase in toxicity of pharmaceutical industrial park
dehydrogenase activity (DHA)
the activated sludge wastewaters
and bioluminescent bacteria tests
(Ma, Qin et al. 2016).  Statistical methods

The challenging part of the approach remains

Nassiri Koopaeind Health risks associated
Mohammad Abdollah with the pharmaceuticals in
wastewater (Nassiri
2020
Koopaei and Abdollahi
2017)
Vineeta Kumari Characterization
,A. K. Tripathi.
of pharmaceuticals
2019
industrial efuent using GC–
MS and FT-IR analyses
This paper reviews the evidence
on the health risks associated with
the wastewater use for irrigated
food production and the imposed
risk on the end consumers mainly
from pharmaceutical industry and
related research facilities.
Objective of the present study is to
identify physicochemical
parameters (viz. pH, electrical
conductivity (EC), total dissolved
we suggest an applied framework for
inefficient public and private sectors
planning and policy-making to
mobilization and enforcement of law and
mitigate the health risks and
regulations while scientific studies and
optimally employ reclaimed
technology availability play a critical role in the
wastewater for human purposes.
design and implementation of the policy
package.
The organic constituents were
The result suggests that the efuent contained
characterized using gas
toxic constituents, which imposed cytotoxic and
chromatography–mass
genotoxic hazard.
spectrophotometer (GC–MS) and

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 IWM Project Report

Yr. AUTHOR TITLE OBJECTIVE METHODOLOGY CONCLUSION

and defning its toxicity
(Kumari and Tripathi 2019)
solids (TDS), BOD, COD, and
heavy metals (Cu, Co, Cd, Ni, Pb,
Mn, Cr, Zn, Fe, As, and Hg) and
organic pollutants in
pharmaceutical efuent
Fourier-transform infrared
spectroscopy analyses (FT-IR). The
efuent toxicity was studied by
genotoxicity assays using Allium
cepa L. (onion) root tip cells.

A Review on Advanced In this paper, the classification of the

Y Guo, P S Qi and Y Z Due to the complexity of pharmaceutical
Treatment of The review aims to introduce the pharmaceutical technology was
Liu processes, pharmaceutical wastewater has some
2017 Pharmaceutical fundamental advanced treatment introduced, and the characteristics of
pharmaceutical wastewater effluent characteristics, such as poor biodegradability
Wastewater (Baasher, of pharmaceutical wastewater
quality were summarized. and high concentration.
Wang et al. 2022)
Fras Baasher, Tian-
Nyu Wang ,
Muhammad Zulhelmi
Bin Yusnan, Mohsen Characterizing the By means of solid phase extraction
Alkahtani , Yasir M. Chemical Contaminants The study aims to determine if and liquid chromatography with
Bashawri , Hamed Al Diversity and Toxic untreated hospital wastewater may tandem mass spectrometry (LC- Thus, wastewater streams from a specialty
Qarni and Pei-Ying Potential of Untreated impose a potentially detrimental MS/MS), chemical contaminants in hospital like Al Amal may be unlikely to
2022
Hong Wastewater from a Drug impact on the downstream these wastewater samples were significantly perturb the downstream
Rehabilitation Hospital: municipal biological wastewater determined in a non-targeted environment.
Understanding Impact on treatment process. manner.
Downstream Environment

The aim of this study was to Toxicity was assessed by direct

Cost Effective Method for evaluate the toxic effect of observing the effects of toxicants on
the BOD degradation activity of the The results indicated that wastewater
Toxicity Screening of pharmaceutical This Aim:
Elina STRADE, Daina Activated sludge microorganisms by containing multivalent Al3+ cations showed a
Pharmaceutical wastewater streams containing
KALNINA exposing test organisms to various strong toxic effect On activated sludge
Wastewater Containing harmful organic substances and
2019 doses of the pollutant. Experiments biocenosis irrespectively of dilutions, while
Inorganic Salts and inorganic salts on a mixed culture
were performed using chemically toxicity of phenol and formaldehyde containing
Harmful Organic from activated sludge, which was
polluted wastewater streams from wastewater decreased considerably with
Compounds (Strade and sampled from operating WWTP
JSC “Grindeks” pharmaceutical increasing dilution
Kalnina 2019) treating multiproduct
pharmaceutical wastewater production facility.

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IWM Project Report

 The composition of pharmaceutical improve the quality of pharmaceutical

wastewater is complex, which is high wastewater effluent, advanced treatment is
concentration of organic matter, microbial essential. In this paper, the classification of
toxicity, high salt, and difficult to the pharmaceutical technology was
biodegrade. After secondary treatment, introduced, and the characteristics of
there are still trace amounts of suspended pharmaceutical wastewater effluent quality
solids and dissolved organic matter. To were summarized"

Figure 1 Pharmaceutical wastewater effluent phases

indicated that the toxicities could be

 The toxicity of water-receiving bodies, the markedly reduced after treatment, with the
effluent and other treatment stages in toxicities of two out of the six effluent
wastewater treatment plants has recently samples at different treatment stages being
been of interest to the public due to the lack greater than the influent toxicity.
of a regulated toxicity-based index for  Wastewater use is a growing fact that could
wastewater discharge in China. The results cause significant levels of human health
of an analysis of conventional parameters risk for the human beings and
indicated that the total suspended solids environmental deterioration, especially if
(TSS), chemical oxygen demand (COD), inadequately treated. In this scope,
total nitrogen (TN), ammonia nitrogen pharmaceutical industries have an
(NH3N), and total phosphorus (TP) were important role in the efflux of biologically
largely removed after various treatments. and toxic agents. To address this concern,
However, the TN, NH3N and COD still country specific, locally adjusted and cost
exceeded the regulated standards. The effective wastewater treatment and
tested pharmaceutical park effluents were pathogen eradication measures should be
mainly polluted with organic pollutants and implemented that requires industry
nitrogenous. The toxicity test results cooperation in wastewater management

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IWM Project Report

policy supported by field research, compared with control which MI=64.1%.

feasibility study and the cost-effectiveness Further, the chromosomal aberration was
analysis. WHO promotes a stepwise investigated in root tip cell after treating
progressive approach to the efficient and with different concentration ranges of
safe wastewater use fed by methodical effluent exhibiting various CA, viz. c-
data. Such programs can be monitored by mitosis, chromosome loss, chromosome
improved health outcomes." break, micro nucleated cells, etc. The result
 The physicochemical analysis of suggests that the effluent contained toxic
collected effluent sample for different constituents, which imposed cytotoxic and
parameters shown results as pH (pH genotoxic hazard.
5.6±0.11) slightly acidic, high conductivity  The composition of pharmaceutical
(1563.34 ±176 μs cm−1), total dissolved wastewater is complex, which is high
solids (920.34 ±137 mg L−1), high BOD concentration of organic matter, microbial
(7253.34±1022 mg L−1), and COD toxicity, high salt, and difficult to
(756.67±1124 mg L−1) in the effluent biodegrade. After secondary treatment,
sample. The results of heavy metals there are still trace amounts of suspended
concentration are viz. as [Cu (1.98–2.56), solids and dissolved organic matter. To
Co (0.26–0.53), Cd (0.10–0.50), Ni (0.04– improve the quality of pharmaceutical
0.07), Pb (0.58–1.2), Mn (0.58–1.05), Cr wastewater effluent, advanced treatment is
(1.47–1.51), Zn (2.61–3.5), Fe (1.72–2.13), essential. In this paper, the classification of
As (0.05–0.09), and Hg (0.003–0.006)]. the pharmaceutical technology was
Results revealed the higher concentration introduced, and the characteristics of
of BOD, COD, TDS, and conductivity and pharmaceutical wastewater effluent quality
also the concentration of lead. Results of were summarized. The methods of
GC–MS also confirmed the high levels of advanced treatment of pharmaceutical
organic pollutants in effluent. Further the wastewater were reviewed afterwards,
effluent toxicity was evaluated by which included coagulation and
employing genotoxocity assays with the sedimentation, flotation, activated carbon
use of Allium cepa L. (onion) root tip cells. adsorption, membrane separation,
Geno toxicity measured mitotic index (MI) advanced oxidation processes, membrane
and chromosomal aberrations (CAs) in root separation and biological treatment.
tip cells obtained after treatment with Meanwhile, the characteristics of each
effluent of 6.25, 12.5, and 25% process were described."
concentration (v/v). The results of root  This study characterizes a total of 21
growth test showed that inhibition of root wastewater samples collected from Al
growth occurred at effluent Amal hospital, and aims to determine if
concentration≥50% (v/v). The lowest MI untreated hospital wastewater may impose
was recorded (MI=9.6%) in 25% of a potentially detrimental impact on the
effluent concentration, showing a downstream municipal biological
significant reduction in mitotic index wastewater treatment process. By means of

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IWM Project Report

solid phase extraction and liquid treatment efficiency, accurate monitoring

chromatography with tandem
spectrometry (LC-MS/MS), chemical
contaminants in these wastewater samples
were determined in a non-targeted manner.
In-silico characterization for
mutagenicity and reactive oxygen species
(ROS) producing capabilities
performed by checking against database
and literature. However, majority of the
chemical contaminants have no prior
information available and
uncharacterized for both traits. Instead, in-
vitro mutagenicity tests by means of Ames
test showed that majority of the samples
were no mutagenic except for 5 samples
that imposed mutagenic effect at high
concentrations of >×10. In-vitro tests to
determine for intracellular ROS production
further showed that one of the mutagenic
samples collected on Jun-22 positively
induce ROS production and subsequently
increased horizontal gene transfer via
natural transformation. The findings in this
study suggest that a specialty hospital like
Al Amal does not frequently contribute
mutagenic compounds and ROS to the
wastewater streams, and in instances where
it contributed positively, would require a
high concentration to do so. Hence in
general, wastewater streams from a
specialty hospital like Al Amal may be
unlikely to significantly perturb
downstream environment."
 Pharmaceutical wastewater biological
mass of influent toxicity on activated sludge
microorganisms is essential. This paper
outlines how to predict highly toxic
streams, which should be avoided, using
the measurements of biochemical oxygen
demand (BOD), if they are made in a wide
was range of initial concentration. The results
indicated that wastewater containing
multivalent Al3+ cations showed a strong
toxic effect on activated sludge biosensors
remain irrespectively of dilutions, while toxicity of
phenol and formaldehyde containing
wastewater decreased considerably with
increasing dilution. Activated sludge
microorganisms were not sensitive to
wastewater containing halogenated sodium
salts (NaCl, NaF) and showed high
treatment capacity of saline wastewater.
Our findings confirm that combined
indicators of contamination, such as
chemical oxygen demand (COD), alone do
not allow evaluating potential toxic
influence of wastewater. Proposed method
is sensitive and cost effective and has
potential for practical implementation in
multiproduct pharmaceutical wastewater
biological treatment plants.
From the literature review, the identified research
gap is the quantification of toxicity of various
components present in pharmaceutical wastewater.
the 3. METHODOLOGY
3.1 Characterization of Pharmaceutical

treatment plants are stressed with multi- Wastewater

component wastewater and unexpected The Industrial effluents present higher average

variations in wastewater flow, composition percentages for analgesics (22–46%), antidiabetics

and toxicity. To avoid operational (12–31%), antiepileptic (7–15%), anti-

problems and reduced wastewater inflammatories (4–10%), diuretics (3–8%) and

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IWM Project Report
psych analeptics (10–28%). These
therapeutically categories comprise more than
90% of the total average concentration. Industry-1
and Industry-6 present similar average percentage
therapeutically category distributions with slight
percentage differences for disinfectants (2.20%–
0.30%), diuretics (3.59%–7.62%) and psych
analeptics (28.16%–21.21%). Industry-3 and
Industry-4 present similar average percentage
therapeutically category distributions with slight
percentage differences for antiepileptic (11.59%–
Figure 2. Total average percentage by therapeutically category for all Industries. Industry-5 therapeutically categories
additionally presented by sampling events (samples 1 and 2, and samples 3 and 4).
3.2 Highest Percentage of Compounds
Acetaminophen, caffeine, gabapentin, ibuprofen,
metformin, naproxen, theobromine
theophylline represent the highest percentages
measured for all Industrial effluents. The most
significant are acetaminophen (21–45%),
metformin (12–32%), and caffeine (7–27%)."
6 7.61%) and anti-inflammatories (6.89%–9.61%).
While the first sample pair (s1–s2) presents higher
percentages for 2 therapeutically categories (anti-
inflammatories and psych analeptics) the second
sample pair (s3–s4) presents a therapeutically
category pattern similar to the other Industries
investigated. The difference between the sample
pairs is most likely due to the fact that the
proportional composite sampling intervals did not
capture the Industrial activities in the first pair
for"Industry-5.
Antibacterial & Anti-infective — clarithromycin,
erythromycin, erythromycin-anhydrous,
lincomycin, norfloxacin and sulfamethoxazole;
and
Antiepileptic’s — carbamazepine; anti-
inflammatories — diclofenac, indomethacin and
mefenamic acid;
Lipid modifying agents — bezafibrate and
clofibric acid;
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IWM Project Report

Obstructive airway disease drugs — clenbuterol; medicine. This is the value which describes effective
Psycholeptics — lorazepam, lorazepam and dose over lethal dose. This is actually the amount
quetiapine;
Other receptor antagonists — ranitidine;
ß-blockers — propranolol and sotalol.

3.3 Finding Toxicity of identified compounds

from T.E.S.T Software (US EPA TOOL)
……..?

3.4 Quantification or Range Scale Development

of Pharmaceuticals from Literature
Source: (Gable, 2004)

Figure 2 Range Scale for Toxicity of Drugs through Literature.

Figure"shown above is taken from literature (Gable that works over the amount kills. For example, in
2004), which shows the therapeutic ratio of different case of Tobacco, this ratio is 1/21, which means
lethal toxicity will be caused if value reaches 21

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IWM Project Report

which shows that it is nontoxic and it cannot
overdose. For heroine, the ratio is 1/6 which means
it is highly toxic and over dosage will cause sudden
death. In this range scale, the red color shows highly
toxic, orange as prescribable but dangerous, yellow
as low danger and green as nontoxic."
 Relation Between Toxicity and Lethal
Concentration
There"is an inverse relation between toxicity and
lethal concentration. Higher is the value of lethal
concentration less will be the toxicity value and
vice versa."
A chemical or medicine having high value of LC 50
will show less toxic effects and is not much harmful
(Wheeler, Park et al. 2006). A distinction is made
between less vulnerable and more vulnerable
populations and between different levels of physical
activity, with a standard level defined which is
applicable to most daytime activity. Mortality is
expressed in terms of a lethal toxic load which is a
function of concentration and time (Wheeler, 2016).

Source: (Gable, 2004)

Figure 3 Drug Safety

using 96 hours’ fathead minnow LC50 toxicity

4. RESULTS
Predicted values of different medicines in the below
table shows the toxicity value of medicines. We are
endpoint value that is concentration of the test
chemical in water in mg/L that is lethal to 50% of
exposed fathead minnows after 96 hours.
The test tool results for LC50 are given below:

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 IWM Project Report

4.1 PPCPs
Pred_
Exp_V
Value:
alue: Exp_Value
Inde - Pred_Value:
ID Query SmilesRan - :
x Log10 mg/L
Log10( mg/L
(mol/L
mol/L)
)
O=C(NC1=CC=C(O)C=C
1 103-90-2 Acetaminophen 2.27 3.09 813.76 123.08
1)C
O=C1C2=C(N=CN2C)N(
2 58-08-2 Caffeine N/A 2.22 N/A 1161.78
C(=O)N1C)C
60142-96- O=C(O)CC1(CN)CCCCC
3 Gabapentin N/A 2.94 N/A 196.00
3 1
15687-27- O=C(O)C(C1=CC=C(C=C
4 Ibuprofen N/A 4.34 N/A 9.52
1 1)CC(C)C)C
5 657-24-9 Metformin N=C(N)NC(=N)N(C)C N/A 3.05 N/A 115.21
22204-53- O=C(O)C(C1=CC=C2C=
6 Naproxen N/A 4.93 N/A 2.73
1 C(OC)C=CC2=C1)C
O=C1NC(=O)N(C=2N=C
7 83-67-0 Theobromine N/A 2.36 N/A 789.02
N(C12)C)C
O=C1C=2NC=NC2N(C(=
8 58-55-9 Theophylline N/A 1.98 N/A 1885.67
O)N1C)C

4.2 Anti-bacterial & Anti-infective

4.3 Psycho-leptics

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4.4 Obstructive airway disease drugs

Clenbuterol

The three major chemical composition that has been found in excess amount was analyzed separately and TEST
software interface is shown below showing the results.

Metformin

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Acetaminophe
n

Caffeine

4.5 Quantification or Range Scale Development of Pharmaceuticals in Industrial Wastewater

(An Implementation of Researcher’ Work)

Adopting"the quantification of different pharmaceuticals from this range scale, a scale for the pharmaceuticals is
developed which are analyzed using T.E.S.T. Tool as a part of this research in pharmaceutical waste
management."

Medicine Name Predicted Value of Toxicity/ Con. (mg/L) Toxicity Quantification

Acetaminophen 123.08

Caffeine 1161.78

Gabapentin 196

Ibuprofen 9.52

Metformin 115.21

Naproxen 2.73

Theobromine 789.02

Theophylline 1885.67

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LEGENDS

Very Non Toxic

Non Toxic

Getting Toxic

Getting More Toxic

Very Toxic

The pharmaceuticals having highest LC50 values in
mg/L are likely to cause less toxicity because they
are difficult to occur and cannot be overdosed. For
example, Theophylline having value 1885.67 mg/L
is the lethal concentration this pharmaceutical which
is very less toxic. Now, in Naproxen, the lethal
concentration is 2.73 mg/L so that’s why it is
declared a very highly toxic."
Scale"above is showing the range from very
nontoxic to very highly toxic denoted by the color
coding indicating green as very nontoxic, yellow as
nontoxic, light orange as moving towards toxicity,
orange as more toxic and redder as very highly
toxic."
5.CONCLUSION ANDRECOMMENDATIONS
After“quantification, the highly toxic compound
found in pharmaceutical industrial wastewater
comes out to be Naproxen having a toxicity value of
2.73mg/L and in opposite to that the compound
Theophylline having value of 1885.67 mg/L which
is very non-toxic. Similarly, Caffeine is very non-
toxic with a value of 1161.71 mg/L, Thermobrine is
non-toxic with a value of 789.02 mg/L, Gabapentin
is regarded as getting toxic having a value of 196
mg/L, Acetaminophen and Metformin are quantified
as getting more toxic having values of 123.08 and
115.21 respectively. Ibrufen and Naproxen are very
toxic having values of 9.52 and 2.73 mg/L
respectively.
In“wastewater treatment plants (WWTPs), true
mineralization or complete removal of
pharmaceutical compounds is hard to achieve. The
water treatment technologies which have been
investigated to remove pharmaceutical compounds
were either conventional or advanced systems. The
conventional techniques include physical–chemical
and biological systems, such as sedimentation,
coagulation, filtration, adsorption/bio-adsorption on
activated carbon, activated sludge process, and
chemical disinfection. Whereas, the advanced
techniques include membrane filtration and
advanced oxidation processes (AOPs) such as,
zonation, UV photolysis, photocatalysis, and Fenton
reaction. Huge disparities have been observed in
removal efficiencies of pharmaceutical compounds
due to the treatment applied at individual WWTPs.
Also contaminants physicochemical properties and
varying operating parameters such as pH, solids
retention time, hydraulic retention time and
microbial activity influence removal efficiency. ”
Recently, “environmental residues of
pharmaceutical compounds have been identified as
problematic, of which, their presence in aquatic
environment is crucially important. Evidence
suggests that physicochemical characteristics and
structural complexity of pharmaceutical compounds
hinder their complete removal in conventional
WWTPs which highlights their inadvertent
persistence in environmental mediums. This review
culminates that knowledge on the toxicity of

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IWM Project Report

pharmaceutical compounds is essential since it (Registration, Evaluation and

serves as the basis to reduce their use through legal Authorization of Chemicals)
enforcement. There is mounting evidence which (iv) Ensuring safe disposal of products in
suggests that aquatic life is more vulnerable to reverse distribution
involuntary and continuous exposure of (v) Defining legal limits for active
pharmaceutical compounds. As of yet, little pharmaceutical ingredients in the
evidence is found to suggest pharmaceuticals effluent.
detrimental impacts on humans at environmentally
The“various types of the raw materials which are
relevant concentrations. There is limited
used should be either modified or should be replaced
understanding of pharmaceutical compounds fate in
with other nontoxic substances, and the
natural habitats. They are transported unhindered
manufacturing design and source of toxic substances
through waterbody to reach subsurface which
should be reduced by employing various types of
complicates their attenuation. Among
technological methods.”
pharmaceuticals, antibiotics have also been given
The“new concepts of zero liquid waste discharged
consideration due to the growing threat of antibiotic
should be involved in the waste disposal methods. It
resistance. ”
is critical to develop an integrated multidisciplinary
Studying“toxicity mechanism across species and
treatment system which could efficiently degrade
taxa, particularly of amphibians, mammals, and
the pharmaceutical ingredients in the effluent before
birds, is important to better understand possible
their discharge in the surrounding environment. ”
toxic effects. Further, endpoints and species based
The“rules and regulations and norms of the
on highly conserved biological mechanisms must be
pharmaceuticals industries should be strict. The
evaluated to understand toxicity mechanisms in
monitoring of the pharmaceuticals industries should
humans. Moreover, human epigenome and the
be carried out by the regulatory authority to check
endocrine system have the prospective to be
the illegal discharge of unused waste materials and
explored in terms of pharmaceuticals toxicity to
wastewater in the environment, which pose health
humans. Due to accelerating progress on the
hazards for biotas when mixed with the water
occurrence of pharmaceuticals in the environment,
bodies.”
the pharmaceutical industry in part shares the
responsibility to manage their wastewater at point-
source. Implementing the following guidelines is
necessary to minimize pharmaceutical
contamination in the environment. ”
(i) Recovery of valuable products which
could considerably reduce raw materials
requirement and waste disposal cost
(ii) Investing in sustainable production by
introducing green chemistry initiatives
(iii) Phasing out chemicals used in the
manufacturing process listed under
critical substances of EU REACH

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IWM Project Report

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