Species, Strain and Individual
Generally, animals of different species have different respond towards toxic substance. The distinction may be due to structure and function of their body. The study in this field is very useful in order to develop product such as pesticides which only more toxic and lethal to pests compared to other mammals as well as human. In addition, antibiotics are directly toxic to microorganisms while indirectly nontoxic to humans. Despite the fact that different species have different toxic effect, even among the several species of mammals have different toxic effect. For instance, rats cannot excrete toxicants by vomiting before they are absorbed and lead to severe inflammation, whereas humans and dogs are capable of vomiting to eliminate the toxic.
The difference trait of host also affects the level of toxicity. In toxicokinetic, there are four factors that influence the distinction of susceptibility of an organism towards the toxic substance including absorption and metabolism. The level of absorption of the toxicant via skin exhibit the species variation. Oral absorption however depends on the presence of food, pH of digestive tract as well as fasting. Absorption through inhalation also influence the toxicity effect which depends on the size of the organism and the rates of ventilation. As for the metabolism, small organisms metabolize substances at a faster rate compared to the large organisms.
Gender, Hormonal Status and Pregnancy
Gender have a huge responsibility in influencing toxicity. Commonly male and female animals have similar toxic response to the same compound. When differences existed, they are mostly in terms of quantitative. Male rats able to metabolize xenobiotics faster than females. As similar to human because men metabolize xenobiotics faster than woman. However, female mice can metabolize substances faster than male mice. When toxicity is related to gender, toxic response of males becomes similar to toxicity in females if the males undergo castration. This can be reversed if castrated animals undergo testosterone therapy.
For instance, the toxic that involve in gender-related is barbiturate which it can cause female to have longer sleep as compared to males. This is because the hydroxylation of hexobarbital need higher activity of liver microsomal enzymes of female. Other than that, chloroform is one of the first anaesthetic which is left behind because it can lead to lethal arrhythmias or respiratory arrest. The chloroform also hepatotoxic with more critical liver damage in male than in female mice. In male rats, testosterone can induce liver microsomal enzymes which will cause higher metabolism of chloroform and production of phosgene which is hepatotoxic compared to female rat’s.
In aged animals and humans, some toxic substances can cause more harm. This is caused by the reduced detoxification done by the liver and throughout the body, chances of impaired renal excretion, lower bad flow efficiency and also decreased level of total plasma protein. Based on ones’ body fat percentage and water retention, the toxicants or drugs distribution might also be altered.
Diet that are lacking of essential fatty acids and proteins or digestive diseases that might cause it can cause suppression of cytochrome activity. Thus, a chemical substance’s toxicity will end up being modified. In human, poor nutrition intake can affect toxicity of chemicals as it can deteriorate biotransformation capability. For example, in Africa, the causative agent of Kwashiorkor disease is the Aflatoxin B1, a mycotoxin that cannot be metabolised properly due to the poor nutritional intake.
Diseases such as acute and chronic liver damage such as cirrhosis, hepatitis, toxic hepatitis, porphyria, and liver tumours will affect the process of biotransformation in the body. For example, renal disease can cause difficulties in elimination of a chemical which can cause to increasing its toxicity. As for acute heart diseases, toxicity of chemicals may be increase by damaging the circulation of liver and kidney. Furthermore, respiratory tract diseases such as asthma induce the respiratory tract to be more vulnerable to air pollutants. (Peraica, 2018)
Environmental factors are the main factor which will affect disease development as health status may affect by the physical and social of environmental factors. This is significantly can be seen by their geographic area that are various and difference from one and to another country in the world. Diseases from each of country in the map would not be the same as differences may come from their social and physical of environmental factors.
The physical factors that include harmful substances such as air pollution detected in the area at which the exposure towards the air that polluted may harm and developed symptoms of specific disease. Researcher who had undergone research on this topic has identified that specific physiologic mechanisms of the exposure may lead to inflammatory, autonomic and vascular process (Brook et al., 2010; Tzivian, 2011).
In addition, the social factor is because of their social environment that had obtained from that specific social status of a community or country. The ethnicity, socioeconomic or racial also plays main role as their occupation differ from each other which that some may have involved with farming that need to conduct fertilisers for their crop which it is their job to make sure that their crop is well grown for the market needs. In considerations of their social status which the poor may need to work hard for their health than the one with stable income that can always rely to the hospital or even private hospital for treatment.
Type of Interaction
A chemical interaction require the process of changing one substance into another substances. The involved chemical substances is known as reactant and the substances formed a product.
The major type of chemical interaction are:
1. Combination or synthesis reaction
2. Decomposition reaction
3. Displacement or replacement reaction
4. Acid base reaction
5. Combustion reaction
6. Redox reaction
The combination or synthesis reaction is a new product formed by combination of two or three reactant to make complex substances. For example is water. Water is combination of oxygen and hydrogen.
The decomposition reaction is the substances that decomposed or split into two or more different product into simpler substances. For example is lead nitrate break into lead oxide, nitrogen dioxide and oxygen.
The displacement or replacement reaction have two types which are single displacement and double displacement. The single displacement is occur when one element replace another one in a compound. The double displacement is when different atom in two different compound exchange places.
The acid base reaction is a reaction that form salt and water. This reaction also called neutralization.
The combustion reaction are the reaction that require oxygen to burn organic compound and produce carbon dioxide as exchange gas. For example, butane will burn in the presence of oxygen then formed carbon dioxide and water.
The redox reaction is the reaction that require transfer of electron between two chemical species.
Mechanisms of Action
Basically, mechanisms of action mean how exposure of toxicant results in functional or anatomical change at cellular level. There are two types which are acute toxicity mechanism the other one is called as subchronic and chronic toxicity mechanism.
Acute toxicity mechanism is classified as follow:
1. Simple asphyxiants
2. Chemical asphyxiants
3. Central nervous system depressants
4. Skin effect
5. Chemical sensitization
6. Lung sensitization
7. Eye effects
Simple asphyxiants are chemicals like inert gases or other non-reactive substances which cause deprivation of oxygen to the central nervous system. For example, a space occupied with nitrogen and less oxygen will cause depletion of oxygen in brain and leads to unconsciousness in a few seconds. If rescue is delayed, irreversible brain damage can occur from the death of neurons.
Chemical asphyxiants are such like carbon monoxide and cyanide. Carbon monoxide causes toxicity competing with oxygen for binding with haemoglobin in red blood cells. It then makes tissue deprivation of oxygen for energy and finally leads to cellular death.
Central nervous system depressants are characterized by sedation or unconsciousness. They usually are used for anaesthetic purpose. Once drug is administered, it will interact with membrane of cells in CNS and thus impairs the ability to transmit electrical and chemical signals.
Next, skin effect can be presence of irritation or corrosion. Scarring, might due to chemical burns occurred by the death of the dermal, in which featured with deep skin cells responsible for regeneration.
Chemical sensitization like 2,4-dinitrochlorobenzene and poison ivy trigger immune system which recognizes foreign material on skin. In response of 2,4-dinitrochlorobenzene, special cells are activated to eliminate foreign substance by release of cytokines which cause dermatitis.
In lung sensitization, one example of toxicants is toluene diisocyanate. This chemical targets lungs which causes lung oedema, bronchial constriction and impaired breathing.
For eye effects, the symptoms are reddening of the outer layer to cataract formation of the cornea to damage to the iris. Materials like strong acids can corrode the eye and causes blindness as corrosion in skin. Positively charged surfactants can cause burns, permanent opacity of the cornea, and vascularisation. Dinitrophenol can also cause cataract formation.
Subchronic and chronic toxicity mechanism can be divided into:
1. Anticholinesterase inhibition
2. Metabolic activation
3. Cancer mechanism
4. Reproductive mechanism
Chronic toxicity is possible when someone is exposed for a long duration or high dose of toxicants.
Anticholinesterase inhibition like organophosphate pesticides can be metabolically activated in the liver. Upon prolonged exposure of the chemical, it can inhibit acetylcholinesterase in the brain and peripheral nervous system. As the effect of inability to terminate the stimulation of neurotransmitter acetylcholine, overstimulation of cholinergic nervous system would happen. It then can cause respiratory arrest or death if not treated.
Metabolic activation for chemical such as carbon tetrachloride, chloroform, acetylaminofluorence, nitrosamines and paraquat are metabolically activated to free radicals. If these are exposed at high levels, they can inhibit or interfere normal cellular function and results in cell death.
In cancer mechanism, alterations in DNA can cause increased susceptibility or cancerous lesions. For example, natural chemicals in cooked beef and fish, benzidine, ultraviolet from sun, radon from soil and gamma radiation from medical procedures or industrial activity.
Reproductive mechanism can be from exposure to virus like rubella, bacterial infections and drugs. They are able to cause adversely affect in the development of reproductive system.
Characteristic of Enzyme Induction
Enzyme induction is a procedure which a molecule which is drug induce the appearance of an enzyme. In other word, the enzyme induction are molecule that increase enzyme activity.
The characteristic of enzyme induction are:
• Enzyme quicken the process of reaction by decrease the activation of reaction.
• Enzyme increase rate of chemical reaction but does not affect the end product
• Enzyme does affect by temperature and pH
• Small amount of enzyme can speed up the chemical reaction
• All enzyme are protein, heat liable and water soluble
• Enzyme can recycle but the effect may decrease
Example of enzyme induction are rifampicin, smoking, carbamazepine, phenobarbital, phenytoin and some of the other drugs.
Peraica, M. (2018). Retrieved from http://htd.hr/wp-content/uploads/sites/414/2016/04/Lecture_Factors-affecting-toxicity_4.pdf