Methodology of Toxicometric Evaluation

of Acute Poisonings

A.I. Iskandarov

and B. Eshmuratov

Ministry of Health of the Republic of Uzbekistan

Tashkent, Uzbekistan

Department of Forensic Medicine, Tashkent Medical Academy, Tashkent, Uzbekistan

Keywords: Toxicometry, Chemical Illness, Factor and Cluster Analysis, Concentration Thresholds, Toxicokinetics.

Abstract: This article introduces a novel methodological framework for evaluating acute chemical illness, facilitating

the identification of the primary impact of toxic agents on homeostasis. This approach enables tailored

detoxification strategies and supports a rigorously justified forensic medical evaluation of the severity of

chemical injuries and their postmortem diagnosis. By offering insights into the direction of toxic agent effects,

this methodology contributes to more effective management of chemical trauma cases. It enhances our ability

to provide targeted medical interventions and ensures a comprehensive understanding of the pathological

processes involved, thereby advancing forensic medicine practices in this domain.

1 INTRODUCTION

Chemical pollution poses a significant threat to

human life and the environment globally, including in

Uzbekistan, driven by extensive chemical production,

international trade, and widespread use in various

sectors. With over 7 million chemical substances

synthesized and approximately 70 thousand in daily

use, the potential consequences of this pollution are

vast and unpredictable. Public health protection from

chemical pollution receives insufficient attention in

environmental programs, despite humans being both

perpetrators and primary victims of environmental

disasters. Biomonitoring for acute human poisoning

could provide valuable insights into environmental

conditions, yet the country lacks adequate measures

and interdepartmental coordination for prevention.

Responsibility for chemical product safety falls on the

Ministry of Health's sanitary and epidemiological

service, primarily focused on setting maximum

allowable concentrations (MACs) and production

control. However, during emergencies, human

exposure often far exceeds MACs, necessitating the

development of acute toxicity passports. This study

aims to devise a new methodological approach for

assessing acute poisonings, leveraging real clinical

https://orcid.org/0009-0008-0110-1221

https://orcid.org/0009-0002-1787-4399

and morphological data from forensic medicine

centres.

2 MATERIALS & METHODS

The material for the research consisted of 252 cases

of acute poisonings with the most common industrial,

household toxins, and medications. The study

employed multidimensional statistical analysis

methods: factor, cluster, nonlinear regression

analyses, and a probit graph of the "poison

concentration-effect" relationship.

3 RESULTS & DISCUSSION

Below is the methodological rationale and examples

of toxicometric assessment of industrial, household,

and medicinal products. The use of toxicometric

(quantitative) assessment of chemical illness in

forensic medicine is proposed for the first time by the

author of this investigation.

In the first section, "Passports for the acute

toxicity of a chemical compound," an assessment of

the risk of death for victims is provided across the

1608

Iskandarov, A. and Eshmuratov, B.

Methodology of Toxicometric Evaluation of Acute Poisonings.

DOI: 10.5220/0012987800003882

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 2nd Pamir Transboundary Conference for Sustainable Societies (PAMIR-2 2023), pages 1608-1612

ISBN: 978-989-758-723-8

entire range of recorded concentrations of toxins in

the blood. For this purpose, the "probit analysis"

method is used (Fig. 1).

Figure 1. Probit graph of the "free hemoglobin

concentration-effect" relationship in acute poisonings with

acetic acid. On the abscissa axis - the logarithm of

intravascular hemolysis level, on the ordinate axis - the

percentage of the risk of death.

In a typical case, the probit plot of the "concentration

of poison-effect" relationship has an S-shaped form.

The lower flat portion of the graph (or its lower

asymptote) corresponds to poison concentrations

where the initial magnitude of chemical injury does

not exceed the limits of the physiological defense of

the organism, and the outcome of poisoning is always

favorable. This level is denoted as CL0 - the

maximum tolerable concentration of poison. It is

characterized by the onset of acute clinical symptoms

of poisoning and can be labeled as the threshold for

acute poisoning.

The next ascending portion of the graphical curve

corresponds to concentrations where the outcome of

poisoning is uncertain, and the risk of death

exponentially increases with the rise in poison content

in the blood. Within these concentrations, the

organism is in a critical state, and the treatment

outcome largely depends on the organization of

intensive detoxification therapy. When assessing the

critical condition of the organism, the mean lethal

concentration of poison in the blood (CL50) can be

used as an objective criterion. From a forensic

perspective, this level of poison in the blood is

considered life-threatening, and the data from

poisoning are regarded as severe bodily injuries

(harm to health) dangerous to life.

Having reached a certain limit, and regardless of

further increases in the concentration of the toxic

agent, the probit plot curve returns to a horizontal

position. This segment (upper asymptote)

corresponds to CL100 - the absolutely lethal

concentration of poison or a life-incompatible

chemical injury.

Thus, the analysis of the "concentration of poison-

effect" relationship is a valuable tool in studying the

quantitative aspects of the relationship between the

absorbed dose of a chemical substance and the nature

of the overall response of the organism. From the

perspective of this relationship, the crisis of

homeostasis should be characterized as an unstable,

transitional state between the two only possible polar

outcomes of poisoning - recovery and death.

Using such normative graphs, an objective

prognosis of the outcome can be provided even at the

very beginning of a chemical injury. In accordance

with the risk of death, priority service can be ensured

for the most severely affected contingent in mass

chemical disasters. The results of the toxicometric

assessment of the risk of death in acute poisonings

with industrial, household poisons, and

pharmaceuticals are presented in Table 1.

Table 1. Results of toxicometric assessment of mortality

risk in acute poisonings with industrial, household toxins,

and medicinal preparations.

Name of

Poison

Toxicomet

ric

Parameters

Ch0 Ch2

Ch5

Ch75 Ch10

1 2 3 4 5 6

Dichloroetha

ne (

μg

)

2,76 8,31 14,6

19,20 26,44

Carbofos

(

μg

)

0,3 176 1,04 1,92 3,03

Chlorophos

(

μg

0,21 1,22 3,81 6,41 8,51

Acetic Acid

(free

hemoglobin

in blood

plasma,

μg

)

1,48 5,62 10,8

16,80 33,88

Phenobarbit

al (

μg

)

16,0 38,1

66,6

151,3

215,7

Critical condition is not only a specific form of

disturbances in the body's vital functions but also a

distinct phase in the course of a pathological process.

Unfortunately, in the majority of contemporary

studies, the dynamics of mortality risk in poisonings

are not considered. However, this indicator is no less

important as a criterion for the danger of a chemical

compound than the poison level in the blood. Figure

2 presents graphs of survival probabilities for patients

Methodology of Toxicometric Evaluation of Acute Poisonings

1609

at each moment in time during adverse outcomes of

various chemical diseases (Fig. 2).

Figure 2. Duration of life for victims in adverse outcomes

of acute poisonings. On the ordinate axis - the probability

of survival at time T; on the abscissa axis - time (hours).

This indicator is obtained using a computer when

determining the reliability function in a special

mathematical model by D.R. Cox.

Upon scrutinizing the graphs, it's evident that the

survival likelihood declines rapidly within the initial

hours of dichloroethane poisonings, whereas with

acetic acid or carbofos, homeostasis reliability

diminishes less drastically, allowing the dying

process to extend up to 120-200 hours.

Conversely, irreversible effects in phenobarbital

poisoning manifest relatively late, typically after

severe pulmonary complications set in, such as

pneumonia. Thus, based on mortality intensity,

dichloroethane merits classification as an extremely

hazardous substance, while carbofos and acetic acid

qualify as highly toxic, and phenobarbital as

moderately toxic poisons. This classification

becomes pivotal for patient triage during mass

poisonings.

In the study of acute poisonings, discerning

between the direct impact of the poison and the body's

response poses a crucial challenge. The specificity of

subsequent clinical symptoms and morphological

changes remains largely unexplored, impeding

informed pathogenetic treatment and expert

assessment of illness severity and postmortem

diagnosis.

To address this complexity, factor analysis

emerges as a methodologically sound approach,

enabling the identification of interdependent features

and their correlation with the overall reaction of the

organism.

By delineating the significance of each feature

within the studied process, factor analysis provides

invaluable insights into the pathological mechanisms

underlying acute poisonings, exemplified by the

clinical-morphological profile of organophosphorus

compound poisoning.Table 2. Factor structure of the

clinical and morphological picture of poisonings with

carbofos.

It is known that chemical substances affect the cells of

tissues and organs only when their concentration exceeds a

threshold. Thus, if clinical and morphological signs of

poisonings are arranged according to the magnitude of their

concentration thresholds (as depicted in Fig. 3, using acetic

acid poisoning as an example), they will be grouped based

on the resistance of each tissue to the specific toxic

substance.

Figure 3. Concentration thresholds for the main clinical and

morphological signs of poisonings with the mentioned toxic

substance.

As indicated in the presented table, the critical

phase of chemical poisoning is characterized by the

greatest clinical diversity. Its distinctive feature is the

involvement in the pathological process of tissues,

organs, and systems to which the selective action of

the poison does not directly extend. With the help of

this program, it is possible to establish a typical

clinical-morphological picture of poisonings for any

specific magnitude of chemical trauma based on the

degree of hemoglobinemia. Conversely, based on the

nature of clinical and morphological changes, one can

deduce the highest concentration of the toxic

substance.

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Ultimately, the outcome of acute poisonings depends on

whether the body can eliminate the absorbed dose of the

poison. Therefore, in our comprehensive problem, special

attention is paid to studying the kinetics of poisons in the

blood. For each type of chemical substance, we have

developed normative toxicokinetic graphs using a computer

program we created. Leading parameters of this process

have been determined: the elimination rate constant and the

half-life period of the poison in the blood. These parameters

should be considered fundamental in monitoring the

resuscitation period of acute poisonings, allowing forensic

experts to assess the correctness of the treatments

administered (Table 3).

Table 3 Comparative Characteristics of the Toxicokinetics

of Organophosphorus Insecticides

Name of

the Poison

n Initial

level of

poison in

the blood

(μg/kg)

Eliminatio

n rate

constant of

the poison

(Ke)

Half-life

of the

poison in

the blood

(T1/2)

Maximum

duration of

the

toxicogeni

c phase

(hours)

Carbofos 150 0,15±0,0

35 19,8

Chloropho

100 1,70±0,2

39 17,7

Foxim 107 0,87±0,0

37 18,7

THM-3 69 1,02±0,1

23 30,1

Metafos 50 0,96±0,1

43 16,1

It is always advisable to study the course of chemical illness

from two perspectives: what the poison does to the

organism and how the organism itself affects the

biotransformation of the poison. Our research results have

shown that toxic coma, exotic shock, and several other

critical states of the organism can significantly prolong the

duration of poison circulation in the blood. This

circumstance needs be taken into account by forensic

experts when organs are removed from corpses for forensic-

chemical examinations.

The body's response to its damage is not an instantaneous

reaction but a process unfolding over time through specific

phases of interacting factors. In chemical illness, where the

sequence of toxic effects is, to a certain extent, a

consequence of the distribution and biotransformation of

poisons in the organism, the analysis of this process is

particularly relevant. Figure 4 presents the toxicodynamics

of the clinical and morphological manifestations of acute

poisonings with сhlorophos and сarbofos.

The pathogenetic connection that effectively exists between

different types of toxic effects is expressed in their

sequence. From the perspective of the dynamics of

poisoning, each preceding stage of chemical illness

prepares and shapes the subsequent one. Therefore, as a risk

factor for bronchopneumonia in this poisoning, all

preceding toxic effects and syndromes, especially

bronchorrhea, chest rigidity, and artificial ventilation of the

lungs (AVL), should be considered.

Figure 4. Toxicodynamics of the clinical and morphological

picture of poisonings with сarbofos and сhlorophos.

Before our research in clinical and forensic toxicology, the

study of critical conditions in poisonings was typically

fragmented. For the first time, we proposed the use of

multidimensional statistical analysis in synthesizing the

entire complex of chemical illness (Fig. 5).

Methodology of Toxicometric Evaluation of Acute Poisonings

1611

Figure 5. Structural portrait of acute phenobarbital

poisoning.

This figure demonstrates the structural portrait of acute

poisonings with phenobarbital obtained through the cluster

analysis method. This picture is presented as a graph, where

the vertices represent clinical-morphological and

laboratory-functional features of chemical illness, and the

connecting edges reflect the direction and inter-system

connections. In addition, the arrangement of features is

ranked according to their influence (level of proximity) on

the outcome of the illness. In other words, the upper part of

the graph contains features that dominate in the mechanism

of thanatogenesis (respiratory paralysis, pneumonia, etc.),

while the lower part of the graph concentrates indicators

that do not have a significant impact on the outcome of

poisoning.

4 CONCLUSION

The implementation of toxicometric assessment in

acute chemical illness offers valuable insights into the

primary effects of toxic substances on homeostasis,

facilitating tailored resuscitation interventions and

scientifically informed expert evaluations of illness

severity and post-mortem diagnoses. However,

addressing the complexities of medical care in acute

poisonings, particularly during mass disasters,

necessitates innovative solutions such as intelligent

computer systems. The sheer volume and diversity of

chemical illnesses make comprehensive physician

training in pathogenesis, clinical manifestations, and

treatment virtually unattainable. Consequently, the

development and deployment of such computer-

based programs are imperative for enhancing medical

response capabilities. Moving forward, collaboration

with institutions like the Research Institute of Clinical

and Experimental Lethal would be vital for advancing

research and implementing practical solutions to

improve outcomes in cases of acute chemical

poisoning.

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