1. DINAMIKA RACUN LINGKUNGAN DI DALAM EKOSISTEM Universitas Mulawarman
Oleh
Sudrajat
Dosen FMIPA, Fak.Kedokteran, Fak,Kesmas, Pasca Sarjana Ilmu Lingkungan dan
Staf Peneliti PPLH
Universitas Mulawarman
Samarinda
2005

2. Xenobiotik :
Merupakan bahan asing bagi tubuh makhluk hidup, antara lain adalah racun.
Di alam banyak sekali racun, termasuk polutan-polutan kimia dari pabrik, kendaraan dan lainnya.
Zat kimia / xenobiotik akan mengalami transportasi ke berbagai kompartemen lingkungan atau transformasi apabila terdapat zat yang dapat bereaksi dengannya membentuk senyawa lain.

3. PRINSIP-PRINSIP DASAR DI DALAM PEMAJANAN RACUN - ABSORPSI , - DISTRIBUSI, - METABOLISME & - ELIMINASI

4. TOXICOKINETICS - TOXICODYNAMIC

5. PEMAJANAN RACUN-RACUN YANG UMUM DI SEKITAR KITAUV
radiation PM
mercury
indoor
air
pesticides
& toxics
biologicals
lead
ozone
asbestos ?
Nearly 430,000 American children between the ages of one to five had elevated blood lead levels that can cause irreversible disabilities such as lower IQ and neurological damage. Today, children’s exposure to lead is mostly due to the ingestion of contaminated dust, paint, and soil.
According to the American Cancer Society, every year, about 130 new childhood cancers are diagnosed for every 1 million children. As such, cancer is the second leading cause of death in children under 14 years of age. The types of cancers that develop in children are different from the types that develop in adults.

6. Kasus Bhopal
December 3-4, 1984: 40 tonnes of methyl iso-cyanate (MIC) released from Union Carbide plant at Bhopal
Accidental release caused by leakage of water into MIC storage tank
None of the six safety systems worked
Safety standards and maintenance system ignored for months
Complete absence of community information and emergency procedures
Public alarm system operated after the gas had leaked for nearly four hours

7. Industrial disaster
“Industrial disasters are caused by chemical, chemical, mechanical, civil, electrical, or other process failures due to accident, negligence or incompetence, in an industrial plant which may spill over to the areas outside the plant causing damage to life and property.”

8. Chemical disaster
“Chemical disasters are occurrence of emission, fire or explosion involving one or more hazardous chemicals in the course of industrial activity or storage or transportation or due to natural events leading to serious effects inside or outside the installation likely to cause loss of life and property including adverse effects on the environment.”

9. Major industrial disasters that shaped public policy
Triangle Factory Fire New York (USA) 1911
100 garment workers died in fire
Minamata Mercury Disaster (Japan)
3,000 people suffered, severe mercury poisoning symptoms, deformities or death
Seveso Dioxin Disaster (Italy) 1976
3,000 animals died, 70,000 slaughtered to prevent dioxins entering food chain
Bhopal Gas Disaster (India) 1984
15,000 killed, over 500,000 affected
The fire led to legislation requiring improved factory safety standards and helped spur the growth of the International Ladies' Garment Workers' Union, which fought for better working conditions for sweatshop workers in that industry.
The Chisso Corporation, a fertilizer and later petrochemical company, was found responsible for polluting the bay during the years It is estimated that over 3,000 people suffered various deformities, severe mercury poisoning symptoms or death from what became known as Minamata disease.
The disaster lead to the Seveso Directive, which was issued by the European Community and imposed much harsher industrial regulations.

10. Bhopal Gas Tragedy Worst industrial disaster in history
2,000 people died on immediate aftermath
Another 13,000 died in next fifteen years
10-15 persons dying every month
520,000 diagnosed chemicals in blood causing different health complications
120,000 people still suffering from
Cancer
Tuberculosis
Partial or complete blindness,
Post traumatic stress disorders,
Menstrual irregularities
Rise in spontaneous abortion and stillbirth
India, the second most populated country of the world is one of the most disaster prone countries of Asia.

11. Second generation effect
ICMR, IMA, AMA studies show
Children born with genetic defects
Growth retardation in boys
Hormonal chaos among girls
Ground water contamination with high level of mercury, lead, nickel, VOCs and HCH
High prevalence of skin and gastro-intestinal diseases
Bioaccumulation of toxins found in vegetables and breast milk

13. Chisso Corporation Chisso = nitrogen Produced fertilizer
1907: Chisso Corp. builds a fertilizer plant in the Minamata.
Job openings
1925: plant begins dumping untreated wastewater into Minamata Bay
Kills fish
Fisherman Payoffs

14. Chisso Corporation
1932: Chisso plant begins to produce acetaldehyde to be used in the production of plastic, perfume and drugs.
Acetaldehyde is made from acetylene and water with a mercury catalyst.
After WWII plastic production boomed and Chisso Corp. grew.
By 1970: Chisso brought Japan 60% of its income and owned nearly 70% of the land in Minamata.
Affects from the wastewater began to be seen in the early 1950’s.

15. Bizarre Behavior in Animals
Early 1950’s:
Dead fish wash ashore
Crows fall out of sky
Suicidal dancing cats
Mercury moves up the food chain.

16. Mid 1950’s: Behavior Seen in Humans
Behaviors witnessed:
Loss of motor control in hands
Violent tremors
Swaggered walk
Insanity
“Cat-dancing” disease
Nobody knew the cause of the epidemic.
Many hid for fear of ridicule

17. Putting the Pieces Together
1956: Researchers at Chisso Corp. Hospital experiment on cats with wastewater from the Chisso plant.
They warn Chisso corp.
Chisso corp. redirects the flow of wastewater to avoid being caught.
A larger geographical area contaminated.
Children born with horrifying deformities.

18. Putting the Pieces Together
1968: Government ran Public Health service traces the contamination to the Minamata Chisso plant.
Government halts the production of acetaldehyde
1972: Government publically announces Chisso Corp’s part in the Minamata epidemic and orders Chisso Corp to pay compensation to the families that were affected.

19. The Aftermath 30-70 tons of methyl mercury was dumped into the Bay
10,000 people affected by Minamata disease.
3,000 died
Compensation has been given to families as recently as 1990.
Highest compensation for the disaster was just under $3,000.

20. Centers for Disease Control and Prevention

21. Methylmercury : In the Body
Methylmercury exposure in humans is from consumption of fish, marine mammals, and crustaceans
95% of fish-derived methylmercury is absorbed into the gastrointestinal tract and distributed throughout the body
Highest in concentration in hair

22. Minamata Disease in the Nervous System
Areas in red show areas typically affected by the presence of methylmercury in the system . The lesions show characteristic signs and symptoms in Minamata disease. 1. Gait disturbance, loss of balance (ataxia), speech disturbance (Dysarthria) 2. Sight disturbance of peripheral areas in the visual fields (constriction of visual fields) 3. Stereo anesthesia (Disturbance of sensation) 4. Muscle weakness, muscle cramp (disturbance of movement) 5. Hardness of hearing (hearing disturbance) 6. Disturbance of sense of pain, touch or temperature (Disturbance of sensation)
National institute of Minamata Disease Archives 22

23. Symptoms of the Disease
Mild
Ataxia
Muscle weakness
Narrowed field of vision
Hearing and speech damage
Severe cases cause
Insanity
Paralysis
Coma
Death
W. Eugene Smith Tomoko Uemura in Her Bath Minamata, 1972

24. More Symptoms
A significant effect of Minamata is the onset of symptoms similar to those of cerebral palsy
Fetal Minamata Disease
A pregnant mother ingests toxic fish and the methylmercury concetrates inside the placenta.
Harms the fetus while the mother is relatively unaffected

25. These are all children with congenital (fetal) Minamata Disease due to intrauterine methyl mercury poisoning (Harda 1986).

26. Examples of chemicals in food, air, water linked to birth defects Cross placenta to embryo
Defects of brain, nerves, heart
Defects of skeleton (often limbs)
Blindness, deafness
Spasticity
Mental retardation
Defects of heart, brain
Decreased fetal growth
Defects of face (cleft palate/lip)
Emotional & learning problems

27. Mercury: The Basics
Mercury (Hg) is the only metal that is liquid at room temperature. It melts at oC and boils at 356.6oC.
Mercury conducts electricity, expands uniformly with temperature and easily forms alloys with other metals (called amalgams).
For these reasons, it is used in many products found in homes and schools.

28. Mercury Chemistry Mercury exists in three oxidation states:
Hg0 (elemental mercury).
Hg22+ (mercurous).
Hg2+ (mercuric).
Mercurous and mercuric form numerous inorganic and organic chemical compounds.
Organic forms of mercury, especially methyl mercury, CH3Hg(II)X, where “X” is a ligand (typically Cl- or OH-) are the most toxic forms.
Mercury is unusual among metals because it tends to form covalent rather than ionic bonds. Most of the mercury
encountered in water/soil/sediments/biota (all environmental media except the atmosphere) is in the form
of inorganic mercuric salts and organomercurics. Organomercurics are defined by the presence of a
covalent C-Hg bond. The presence of a covalent C-Hg bond differentiates organomercurics from
inorganic mercury compounds that merely associate with the organic material in the environment but do
not have the C-Hg bond. The compounds most likely to be found under environmental conditions are
these: the mercuric salts HgCl , Hg(OH) and HgS; the methylmercury compounds, methylmercuric 2 2
chloride (CH HgCl) and methylmercuric hydroxide (CH HgOH);

29. Uses of Mercury
We use its unique properties to conduct electricity, measure temperature and pressure, act as a biocide, preservative and disinfectant and catalyze reactions.
It is the use of mercury in catalysis that contributed to the events in Minamata.
Other uses include batteries, pesticides, fungicides, dyes and pigments, and the scientific apparati.

30. Mercury in the Environment
Upwards of 70% of the mercury in the environment comes from anthropogenic sources, including:
Metal processing, waste incineration, and coal-powered plants.
Natural sources include volcanoes, natural mercury deposits, and volatilization from the ocean.
Estimates are that human sources have nearly doubled or tripled the amount of mercury in the atmosphere.
Global anthropogenic emissions of mercury are estimated to range between 2000 and 6000 metric tons per year. Electric utilities, municipal waste combustors, commercial and industrial boilers, and medical waste incinerators account for approximately 80 percent of the total amount. Coal-fired utility boilers are the largest point source of unregulated mercury emissions in the United States.

31. 1. Mercury is emitted to the atmosphere as a gas or as particulate matter. Degassing of mercury from rock, soils, and surface waters,
or emissions from volcanoes and from human activities.
2. Movement in gaseous form through the atmosphere.
3. Deposition of mercury on land and surface waters. It can then return to the earth’s surface by wet deposition when it becomes incorporated into rain or snow, or by dry deposition when it settles out of the air. Erosion, rainfall, and leaching transport mercury from the land to waterbodies.
4. Conversion of the element into insoluble mercury sulfide
5. Precipitation or bioconversion into more volatile
or soluble forms such as methylmercury
6. Reentry to atmosphere or bioaccumulation in food-chain

32. The Aquatic Mercury Cycle
In soil, mercury is relatively harmless in
its elemental, divalent or particulate
forms. It is only when Hg2+ is converted
to methylmercury (CH3Hg+) that
it becomes a hazard.
• Methylmercury is produced as a byproduct
of the metabolic processes of
sulfate reducing bacteria in anaerobic
environments.
• In the environment, sulfate-reducing bacteria take up mercury in its inorganic form and through metabolic processes convert it to methylmercury. Sulfate-reducing bacteria are found in anaerobic conditions, typical of the well-buried muddy sediments of rivers, lakes, and oceans where methylmercury concentrations tend to be highest. Sulfate-reducing bacteria use sulfur rather than oxygen as their cellular energy-driving system. One hypothesis is that the uptake of inorganic mercury by sulfate-reducing bacteria occurs via passive diffusion of the dissolved complex HgS. Once the bacterium has taken up this complex, it utilizes detoxification enzymes to strip the sulfur group from the complex and replaces it with a methyl group:HgS → CH3Hg(II)X + H

33. 1. Methylmercury is first taken up by bacteria and tiny plants and animals known as plankton.
2. Then the plankton and bacteria are eaten by small fish.
3. These small fish are eaten by larger predatory fish which accumulate large amounts of methylmercury in their tissues.
4. The large fish are caught and eaten by humans and animals, exposing them to large amounts of methylmercury which will accumulate in their bodies as well.
Mercury is found in all tissues and body parts of a contaminated fish. There is no way to clean or cook the fish that will remove or even reduce the amount of mercury present. When mercury levels are very high, states will release fish advisories. One of the main sources of mercury poisoning is eating methylmercury-contaminated fish.
The major source of methylmercury exposure in humans is consumption of fish, marine mammals, and crustaceans. Once inside the human body, roughly 95% of the fish-derived methylmercury is absorbed from the gastrointestinal tract and distributed throughout the body. Uptake and accumulation of methylmercury is rapid due to the formation of methylmercury-cysteine complexes. Methylmercury is believed to cause toxicity by binding the sulfhydryl groups at the active centers of critical enzymes and structural proteins. Binding of methylmercury to these moieties constitutively alters the structure of the protein, inactivating or significantly lowering its functional capabilities.

34. Methylmercury concentrations
Reference dose 0.1g/kg bw/day
135-lb. woman: 1.5oz. Swordfish or 7 oz. tuna/week
50-lb. child: oz. Swordfish or 2.6 oz. tuna/week
Methylmercury concentrations
Freshwater fish ppm
Ocean fish ppm
Predator fish > 1.0ppm
Fish in “polluted” water > 10ppm
Fish from Minamata Bay ~ 50ppm
Whale meat ~4ppm
Whale liver >1000ppm

35. Methylmercury poisoning
Minamata Japan, 1930s-1950s

36. Four Major Pollution di Jepang
Case
Accused
Ruling
Minamata Disease (organic mercury in sea water)
Chisso Corp.
Plaintiff wins in 1973
Itai-itai Disease (cadmium in river water)
Mitsui Kinzoku
Plaintiff wins in 1972
Niigata Minamata Disease (organic mercury in river water)
Showa Denko
Plaintiff wins in 1971
Yokkaichi Asthma (air pollution by petrochemicals)
Mitsubishi Petrochemicals etc
Award winning photo of Minamata Disease victim
Yokkaichi 1961
Yokkaichi today

37. Congenital Minamata disease; Mercury toxicity, Japan 1955
Microcephaly
Cerebral palsy / spastic
Mental deficits
Malformation of ears, heart, skeleton, eyes
Minamata Bay

38. Bhopal, India
In Dec. 3, 1984, an explosion at the Union Carbide plant released a deadly cocktail of poison gas made up of methyl isocyanante, hydrogen cyanide, monomethyl amine, carbon monoxide and up to 20 other chemicals.
4 months later report on 1,430 deaths.
By 1999, the toxic gas killed at least 16,000 according to local estimates; tens of thousands continue to suffer.
This presentation is based on the text articles, Bhopal, pp , and Chemical Safety in Developing Countries, the lessons of Bhopal, pp

39. Arsenic toxicity from well waters in Bangladesh and CCA
BMJ March 25; 320(7238): 826.
Half of Bangladesh population at risk of arsenic poisoning
Bangladesh may be heading for an epidemic of arsenic poisoning with an estimated 60 million regularly ingesting arsenic through drinking contaminated groundwater
Surveys of groundwater used for drinking and cooking have identified unacceptably high concentrations of arsenic in several thousand deep tube wells, Dr Karim said. Some wells contain 0.4 mg/l of arsenic, 40 times the acceptable concen

40. Dioxin and Chloracne
VIENNA, Austria (CNN) -- Dioxin poisoning caused the disfiguring illness afflicting Ukrainian opposition presidential candidate Viktor Yushchenko, doctors at an Austrian hospital said Saturday.
Doctors said at a news conference that they suspect a "third party" administered the poison in September, possibly by putting it in Yushchenko's soup.

41. External to Internal environment
..a hint of integration?

42. PESTICIDE EXPOSURE ISSUES
OCCUPATIONAL
ENVIRONMENTAL
Production
Farmers
Child labor
Women in reproductive age
Exterminators
Domestic use
Pesticides in: food
water
soil
Spillage (su do ra)
Waste

43. II. DINAMIKA POLUTAN DI DALAM EKOSISTEM
Mekanisme kerja suatu polutan/ zat terhadap suatu organ sasaran pada umumnya melewati suatu rantai reaksi yang dapat dibedakan menjadi 3 fase utama :
a) Fase Eksposisi
b) Fase Toksokinetik
c) Fase Toksodinamik
( Lihat gambar 2.1.).

44. Skema dampak pencemaran polutan terhadap makhluk hidup
( dimodifikasi dari : Holdgate, 1979)

45. 2.1). Fase Eksposisi :
Merupakan ketersediaan biologis suatu polutan di lingkungan dan hal ini erat kaitannya dengan introduksi oleh manusia. Selama fase eksposisi, zat beracun dapat diubah melalui berbagai reaksi kimia/fisika menjadi senyawa yang lebih toksis atau lebih kurang toksis. Jalur intoksikasinya lewat Oral, Saluran Pernafasan dan Kulit.

46. Faktor-faktor yang mempengaruhi sifat polutan tersebut adalah atmosfer, air dan biota. Transportasi dan transformasi zat/polutan di lingkungan berhubungan erat dengan sifat-sifat fisikokimia polutan; proses transportasi polutan di lingkungan dan transformasi polutan yang terjadi di lingkungan. Pemaparan bahan polutan ke lingkungan akan mengalami berbagai proses transformasi tergantung atas media transportasinya antara lain air, udara, tanah dan biota ( Connel Des. W . and Gregory J. Miller, 1984).

47. Gb. Interaksi xenobiotik dengan berbagai faktor di lingkungan ( Sumber : McKinney, 1981).

48. 2.1.2.Media Transpor
Media transpor dapat berupa :
Udara
Air
Tanah
Makanan
Organisme
Rantai Makanan
Dll

50. 2.1.3. PERILAKU POLUTAN DI LINGKUNGAN
Dipengaruhi oleh kompartemen penyusun bumi yakni :
Udara
Air
Tanah
Biota
Sifat-sifat kimiawi dan mekanisme yang mengatur bentuk penyebaran polutan di dalam kompartemen dan di antara kompartemen penyusun lingkungan tersebut merupakan hal yang penting untuk dikaji.
Aspek-aspek tersebut antara lain : LAJU PERPINDAHAN ZAT KIMIA DAN ENERGI DI DALAM ALAM DAN PROSES PENYEBERANGAN POLUTAN TSB ANTAR KOMPARTEMEN

56. 2.1.4. PROSES PERUBAHAN BENTUK
Proses perubahan bentuk polutan di perairan meliputi
hidrolisis,
fotolisis,
degradasi secara mikroorganisme dan
oksidasi.

57. PROSES BIODEGRADASI
Biotransformasi ( perubahan bentuk biologis) dan biodegradasi polutan oleh mikroorganisme ( bakteri, jamur, protozoa dan ganggang) merupakan proses pembuangan dan perubahan yang penting dalam air, sedimen dan tanah. Reaksi mencakup oksidasi, reduksi, hidrolisis dan terkadang penataan ulang dan dipengaruhi oleh bangun molekul dan kepekatan zat polutan, sifat alamiah mikroorganisme, keadaan lingkungan dan suhu.

58. Dalam udara akan mengalami fotolisis, reaksi; dalam air akan mengalami hidrolisis, foto-lisis, degradasi oleh mikrobiota, oksidasi; dalam tanah akan mengalami proses fotolisis, degradasi dan pada biota akan mengalami proses metabolisme ( Lihat gambar 3 ).
Jika suatu polutan/zat kimia mengalami kontak dengan suatu organisme, maka terjadinya efek biologi atau efek toksis setelah proses absorbsi polutan tersebut ke dalam tubuh organisme.

59. Umumnya hanya bagian zat yang berada dalam bentuk terlarut, terdispersi secara molekul yang dapat diabsorbsi. Penyerapan ini sangat ditentukan oleh faktor kadar zat dan lamanya bersentuhan antara zat yang terdapat dalam bentuk yang dapat diabsorpsi dengan permukaan organisme yang berkemampuan mengabsorbsi zat tersebut. Pada pencemaran lingkungan, bagian dosis yang dapat diabsorbsi menentukan derajat eksposisi yang efektif terhadap organisme.

60. 2.2. Fase Toksokinetik :
Hanya sebagian dari jumlah zat yang diabsorpsi mencapai organ target suatu zat toksis di dalam tubuh organisme , yakni di lokasi jaringan/molekul yang sesuai. Dibedakan atas proses -proses :
- Absorbsi dan distribusi ( Invasi)
- Biotransformasi
- Akumulasi
- Ekskresi

62. ROUTES OF ENTRY INGESTION (MAINLY IN ACUTE EXPOSURES)
INHALATION (MAINLY IN CHRONIC)
DERMAL (MAINLY IN CHRONIC)
PARENTERAL

63. Routes of administration
Drug half-life varies as a function of route of administration Half-life = time for plasma drug conc. to fall to half of peak level

64. ROUTES OF
ADMINISTRATION

66. 2.3. Fase Toksodinamik :
Suatu kerja zat toksis pada umumnya adalah hasil interaksi dari sejumlah proses yang sangat rumit dan kompleks.

67. a) Lewat interaksi kimia antara suatu zat atau metabolitnya dengan substrat biologi akibat terbentuknya ikatan kimia kovalen yang tak bolak-balik atau terjadinya perubahan substrat biologi sebagai akibat dari suatu perubahan kimia zat.
b) Lewat interaksi yang bolak-balik ( reversible) antara zat asing dengan substrat biologi. Hal ini menyebabkan suatu perubahan fungsional, yang lazimnya hilang bila zat tersebut dieliminir dari plasma.

68. PENYEBARAN RACUN LINGK. DI DALAM TUBUH MANUSIA :
- Protein plasma mengikat senyawa asing HATI DAN GINJAL
- Bertugas untuk mengeluarkan senyawa asing. Hati berkapasitas merubah senyawa racun ( biotrans-formasi) menjadi tidak aktif).
- LEMAK
Tempat penyimpanan penting bagi senyawa yang larut dalam lemak ( mis. DDT, PCB, )
- TULANG
Berfungsi sebagai penyimpan senyawa Flour, Pb, Strontium.

70. MEKANISME KERJA POLUTAN THDP BAGIAN TUBUH ORGANISME
- Interaksi dengan sistem enzim :
Inhibisi enzim tak bolak balik
Inhibisi enzim secara reversible
Pemutusan Reaksi Biokimia
Sintesis Zat mematikan
Pengambilan ion logam yang penting untuk
kerja enzim Inhibisi penghantaran elektron
dalam rantai respirasi

71. MEKANISME KERJA POLUTAN THDP BAGIAN TUBUH ORGANISME
Inhibisi pada transpor oksigen karena
gangguan pada hemoglobin
Keracunan karbon monoksida
Pembentukan Metheglobin
dan Sulfahemoglobin
Proses Hemolitik

72. Pengaruh Penghantaran Rangsang Neurohumor
- Interaksi dengan Fungsi Umum Sel
Kerja Narkose
Pengaruh Penghantaran Rangsang
Neurohumor
- Gangguan pada sintesis DNA dan RNA
Kerja Sitostatika
Kerja Imunsupresiva
Kerja Mutagenik
Kerja Karsinogenik

73. - Kerja Teratogenik
- Reaksi Hipersensitif ( Reaksi alergi)
Reaksi fotoalergik
Sensibilisasi cahaya
Reaksi fototoksis

74. Kerusakan kulit akibat zat kimia Gas yang merangsang Gas air mata
Iritasi Kimia langsung pada Jaringan
Kerusakan kulit akibat zat kimia
Gas yang merangsang
Gas air mata
Zat yang berbau
- Toksisitas pada Jaaringan
- Penimbunan ( Sekuestrasi) Zat asing
Penimbunan dalam jaringan lemak
Penimbunan dalam Tulang
Pneumokoniosis

76. Gb Skematik Mekanisme metabolik zat racun di luar hati dan di dalam hati

77. Gb Skematik Mekanisme metabolik zat racun di luar hati dan di dalam hati

78. EFEK BIOLOGIS
MERUPAKAN RESULTANTE AKHIR DARI SEJUMLAH PROSES YANG SANGAT KOMPLEKS, YAKNI INTERAKSI ANTARA FUNGSI HOMEOSTASISNYA DENGAN XENOBIOTIK. Jika proses homeostasis gagal, karena berbagai hal misalnya dosis terlalu tinggi, paparan konsentrasi terlalu pekat dan kontinyu, keadaan gizi kurang, dstnya maka akan terjadi efek biologis yang diekspresikan bermacam-macam .

79. Sasaran Proses yang Terganggu
Tabel 1. Rangkuman beberapa pengaruh biokimia dan fisiologis penting dari
suatu zat beracun. No
Sasaran
Proses yang Terganggu 1.
Membran sel
Perubahan atau modifikasi permeabilitas
memberan
b. Pengacauan sistem transportasi membran sel 2.
Enzim
Inhibisi dapat balik atau tidak balik dari enzim (koenzim, subtrat atau pengaktif logam), oleh zat kimia 3.
Metabolisme
Lemak
Pengacauan metabolisme lemak dapat menyebabkan kegagalan fungsi hati, termasuk akumulasi lemak patologis dalam hati dan kapasitas lemak untuk mengsintesis kolesterol dapat digagalkan.

80. Tabel 1. Rangkuman beberapa pengaruh biokimia dan fisiologis penting dari
suatu zat beracun. No
Sasaran
Proses yang Terganggu 4.
Biositensis Protein
Sintesis zat protein dapat dipengaruhi oleh sejumlah besar zat eksogenus, terutama melalui penekanan kapasitas protein untuk mensintesis yang bertempat di dalam reticulkum kasar endoplasmik (r ER) di dalam sitoplasma. Dalam beberapa kasus, salah satu pengaruh dapat merangsang timbulnya pertambahan sintesis protein mikrosomal. 5.
Sistem enzim Mikrosomal
Pergantian dalam fungsi enzim mikrosomal-rangsangan atau inhibisi yang diinduksi oleh banyak zat kimia di lingkungan. 6.
Proses Pengaturan dan Pertumbuhan
Struktur atau kegiatan enzim pengatur dapat diubah dan sintesis, penyimpanan, pelepasan atau pengasingan hormon dapat digagalkan oleh zat beracun dalam berbagai cara, penurunan laju pertumbuhan dapat mengikuti gangguan kimiawi jalur dan laju metabolisme.