AVERAGE LETHAL DOSE (LD50) – EXPERIMENTALLY determined parameter (SOLIDS, LIQUIDS)

LD 50 = the dose that kills 50% of the lot of test animals

mg/kg
mM/kg
mg/m2
MLD (HUMAN MINIMAL LETHAL DOSE)

MERCURIC CHLORIDE 0.5 g ARSENIC 100 mg

METHANOL 70 ml
NICOTINE 50 mg ACONITINE 10 mg
PARALDEHYDE 100 ml BARBITURATES 1–5g
PARATHION 25 mg BORIC ACID 12 g
PHENOLS 10 ml CAMPHOR 2g
PHOSPHORUS (yellow) 0.1 g CHLORAL HYDRATE 7g
STRYCHNINE 50 mg K CHLORATE 8g
THALLIUM 0.8 g K FLUORIDE 1g
FORMALDEHYDE 30 ml

AVERAGE LETHAL CONCENTRATION (LC50) – EXPERIMENTALLY determined parameter (GASEOUS,

VOLATILE SUBSTANCES THAT ARE ABSORBED THROUGH INHALATION)
1 ppm = 1 g/m3 ppm (parts per milion)
LC 50
LCt 50 = average lethal concentration over a time unit
 Compound Species LD50 (mg/kg, Molecular mass LD 50 (mM/kg)
parenteral) (g/mol)
ETHANOL MOUSE 10000 46 0.2173

SODIUM CHLORIDE MOUSE 4000 58.443 0.068

FERROUS SULFATE RAT 1500 151.908 0.0098

MORPHINE SULFATE RAT 900 285.34 0.0031

PHENOBARBITAL RAT 150 232.235 0.00064

SULFATE
DDT RAT 100 354.49 0.00028

PICROTOXIN RAT 5 602.583 0.0000082

STRYCHNINE RAT 2 334.41 0.0000059

SULFATE
NICOTINE RAT 1 162.26 0.0000061

d-TUBOCURARINE RAT 0.5 624.765 0.0000008

HEMICHOLINIUM-3 RAT 0.2 414.538 0.0000004

TETRODOTOXIN RAT 0.1 319.27 0.0000003

DIOXIN GUINEA PIG 0.001 84.07

BOTULINUM TOXIN RAT 0.00001 149322.7
 CATEGORIES LD50

▪ SUPERTOXIC 5 mg/kg sau <

▪ EXTREMELY TOXIC 5 – 50 mg/kg
▪ VERY TOXIC 50 – 500 mg/kg
▪ MODERATELY TOXIC 0.5 – 5 g/kg
▪ REDUCED TOXICITY 5 – 15 g/kg
▪ PRACTICALLY NON TOXIC > 15 g/kg
 • BIOACTIVATION= INCREASE IN TOXICITY
• THE METABOLITES HAVE SUPERIOR TOXICITY

OXIDATION HYDROLYSIS
 MONOOXYGENASE (P450) • THE HIDROLYSIS OF ESTERS
 XANTHINE OXIDASE • CARBOXYLESTERASE
 PEROXIDASE • AMIDASE
 AMINE OXIDASE

 MAO

 DIOXYGENASE

THE REDUCTION OF
• MONOOXYGENASE (P450)
• KETOREDUCTASE
• GLUTATHION PEROXIDASE
• EPOXIDE HYDROLASE
• SOD
 THE CONJUGATION WITH OTHER CHEMICAL STRUCTURES LEADS TO THE
INACTIVATION OF THE HARMFUL METABOLITES

CONJUGATED COMPOUND FEATURES

 HYDROSOLUBLE
 URINARY EXCRETION
 TOXICODYNAMICLY INACTIVE

CONJUGATIONS
 GLUCURONYL TRANSFERASE (GLUCURONIDATION)

 SULFOTRANSFERASE (SULFURYLATION)

 GLUTATHIONE S-TRANSFERASE (GLUTATHIONE CONJUGATION)

 THIOLTRANSFERASE

 METHYLTRANSFERASE (METHYLATION)

 N-ACETYLTRANSFERASE (ACETYLATION)

 SULFURTRANSFERASE (RHODANESE)
 AFLATOXIN B1
BENZENE, BROMBENZENE
EPOXIDES FUROSEMIDE
OLEFINS
POLYCHLORINATED AND POLYBROMINATED BIPHENYLS
TRICHLOROETHYLENE
VINYL CHLORIDE

CARBON TETRACHLORIDE
FREE RADICALS HALOTHANE
BROMOTRICHLOROMETHANE
PARAQUAT
SOME FOODS
IONIZING RADIATION
INFLAMATION
PATHOLOGICAL PROCESSES
 ACETAMINOPHEN
N-HYDROXYLATED COMPOUNDS
URETHANE

AMINES
NITROSAMINES
(DIGESTIVE TRACT)
NITRITES
 Initial agent Toxic metabolite Mechanism of toxicity Organic and functional
consequences
Acetaminophen N-hidroxy derivative Covalent bond Hepatic necrosis

2-Acetylaminofluoren N acetoxy AAF, Covalent bond Cancer

AAF N sulphate
Aflatoxin B1 Aflatoxin-2,3-epoxide Covalent bond Hepatic cancer

Allyl formate Acrolein Covalent bond Hepatic necrosis

Alilizopropil acetamida Epoxide Unknown Cytochrome P450 distribution

Porphyria
Amygdalin Mandelonitrile Cyanide formation Cytotoxic hypoxia
(intestinal flora)
Benzene Benzene epoxide Covalent bond Bone marrow depression

Bromobenzene Bromobenzene Covalent bond Hepatic, bronchioles and renal

necrosis
Carbon tetrachloride Free radical Covalent bond, Lipid Hepatic necrosis,
trichloromethane peroxidation Hepatic cancer
Alkyl nitrosamines Alfa hidroxylation Alkylation Hepatic cancer
carcinogenic
Amino dyes N hidroxy derivatives Covalent bond Hepatic cancer
 Initial agent Toxic metabolite Mechanism of toxicity Organic and functional
consequences
Polycyclic aromatic Epoxides in some Covalent bond Cancer, cytotoxicity
hydrocarbons organs
carcinogen
Chloroform Phosgene Covalent bond Hepatic necrosis, renal necrosis

Cycasin Methylated methanol Alkylation Cancer, hepatic necrosis

Cyclamate Cyclohexylamine Unknown Urinary bladder cancer

Ethanol Acetaldehyde in some Complex Multiple

organs
Fluor acetate Fluor citrate Enzymatic inhibition Generalized toxicity

Furosemide Epoxide Covalent bond Hepatic and renal necrosis

Halothane Free radical Covalent bond Hepatic necrosis

Aromatic amine Metaboliti N-hidroxi Unknown Hemolysis

hemolyzing
Isoniazid Acetyl hydrazine Covalent bond Hepatic necrosis

Meclizine Norchlorcyclizine Unknown Teratogenesis

 Initial agent Toxic metabolite Mechanism of toxicity Organic and functional
consequences
Methanol Formaldehyde Complex Retinal and general toxicity

Nitro agents and aromatic N hidroxy metabolites Oxidation, cyclic Methemoglobinemia

amines reduction
Methemoglobin formation
Methoxyflurane Inorganic Fluor Enzymatic inhibition Renal failure

Naphtylamine N hidroxy Covalent bond Urinary bladder cancer

Naphtylamine
Secondary and tertiary Nitrosamine Alkylation Hepatic, pulmonary cancer
nitrites and amines
Olefins Epoxides Covalent bond Skin cancer

Parathion Paraoxon Cholinesterase Neuromuscular paralysis,

covalent bonds respiratory failure
Purine and pyrimidine Mononucleotide, Lethal synthesis, lethal Cytotoxicity
base analogues nucleotizi trifosfat absorption
Pyrrolizidine alkaloids Pyrolytic derivate Unknown Hepatic and cancerous necrosis

Thalidomide Phtaloyl L glutamic Unknown Teratogenesis

acid
Urethane N hydroxyl urethane Alkylation Cancer, cytotoxicity
 TOXICODYNAMIC TOXIC AGENT MECHANISM
RECEPTOR
CHOLINESTERASE ORGANOPHOSPHORIC ESTERASE CENTER BLOCKING
AGENTS
CYTOCHROME CYANIDE ELECTRON TRANSPORT
OXIDASE BLOCKING IN THE RESPIRATORY
CHAIN
THIOLIC ENZYME HEAVY METALS THIOLIC GROUP INACTIVATION
GROUPS
HEMOGLOBIN CARBON MONOXIDE, CARBOXYHEMOGLOBIN AND
NITRITES, NITRATES METHEMOGLOBIN
FORMATION
NUCLEIC ACIDS ALKYLATE NUCLEIC ACID SYNTHESIS
RADIOMIMETIC BLOCKING
STRUCTURAL LIPIDS CARBON TETRACHLORIDE FREE RADICALS
BROMOTRICHLOROMETHANE PEROXIDATION
NICOTINIC RECEPTOR NICOTINE DIRECT STIMULATION
CURARIZING BLOCKING, PARALYSIS
MUSCARINIC MUSCARINE INTENSE STIMULATION,
RECEPTOR (AMANITA MUSCARIA) MUSCARINIC SYNDROME