Transcript Mechanism of toxicity

呼吸功能障碍性毒物
Respiratory dysfunction
toxicant
Department of Forenxic
Toxicology
Shizhong Bian
氰化物中毒
Cyanide Poisoning
Cyanide
rapid acting toxin (used for suicide)
combined with sugar as cyanogenic
glycoside
localized in vacuoles in leaves and seeds
enzymes that separate CN from sugar
are in the cytosol
wilting or crushing plant releases CN
Cyanide
more than 1000 plant species
variety of CN glycosides – don’t learn
names or structures:
cherries
sorghum
flax
white clover
arrowgrass
prunasin and amygdalin
dhurrin
linamarin
lotaustralin
triglochinin
Potential CN glycoside toxicity
concentration in plant, N in soil
species of plant; breed crop for less CN
stage of growth (young plants)
hormone herbicides
dry weather followed by rain
low sunlight – glycosides may accumulate
over night so highest toxicity in morning
Potential CN glycoside toxicity
damage to plant – trampling, frosting
amount eaten, rate of ingestion
size and type of animal – ruminants most
susceptible (enzymes more active at
neutral pH, microbes release CN)
food ingested with it
Detoxification of cyanide
endogenous thiosulfate
catalyzed by rhodanese
thiocyanate forms
(thiocyanates from chronic low level
exposure produce goiter in adult or fetus)
excreted in urine
Other sources of cyanide
electroplating or cleaning metals
soil sterilant
rodenticides
Cyanide
CN combines with cytochrome oxidase
system
ties up ferric iron so can no longer
transport oxygen into cells
histotoxic anoxia
bright red blood with lots of oxygen
• Mechanism of toxicity
• Cyanide ions bind to the iron atom of the
enzyme cytochrome c oxidase (also known
as aa3) in the fourth complex in the
mitochondrial membrane in the
mitochondria of cells. This deactivates the
enzyme, and the final transport of
electrons from cytochrome c oxidase to
oxygen cannot be completed. As a result,
the electron transport chain is disrupted,
meaning that the cell can no longer
aerobically produce ATP for energy.
Mechanism of toxicity
• Tissues that mainly depend on aerobic
respiration, such as the central nervous
system and the heart, are particularly
affected.
• binds to sulfhydryl groups and sulphur ,
disrupts sulfhydryl or sulphur-containing
enzymes.
Clinical signs
found dead (15 min)
excited, generalized muscle tremors
rapid breathing, dyspnea
increased salivation and lachrymation
involuntary urination and defecation
Clinical signs
down, gasping for breath
clonic convulsions
dilated pupils
mucous membranes bright pink
blood very bright red
Rarely time to treat
Necropsy of acute case
bright red blood
blood slow to clot or does not clot
hemorrhage from terminal struggling
bitter almond odor to ingesta
Diagnosis
history of exposure, clinical signs
confirm by testing blood, rumen content,
liver, muscle for CN
test forage for CN
freeze sample, submit frozen
preserve in 1-3% mercuric chloride if can’t
freeze
Picric acid test
• It is the second drug that comes to mind
when one talks about homicidal poisoning
is cyanide. Cyanide has been discussed in
detail in another section of the book and
this discussion will not be repeated.
Carbon monoxide
Carbon Monoxide CO
• Colorless
The SILENT KILLER
• Odorless
• Tasteless
• Slightly lighter than air (drop in a fire!)
• Product of incomplete combustion
– 1. Time
– 2. Temperature
– 3. Turbulence (oxygen)
Carbon monoxide
• Carbon monoxide Odorless and colorless.
Non-irritating. Found in car exhausts. It is
cumulative - repeated small doses can build up
over time. It kills by preventing the blood from
carrying oxygen. Symptoms: Initially, dizziness
and headaches when exerting yourself, then
when at rest too. A higher dose affects
coordination and makes the heart throb. Then
comes collapse and death. Often the victim is
unaware and just drifts slowly to sleep.
 Post-mortem appearance: Pinky skin.
Cherry-red blood. Blood is fluid and
doesn't want to clot. Lungs congested and
the upper air passages contain a frothy
fliud. Carbon monoxide remains in the
blood for up to six months after death.
COHB
• Carboxyhemoglobin
• Oxygen carried by hemoglobin on red
blood cell (rbc)
• Hemoglobin likes CO better than it likes
oxygen
• Tissues (brain) don’t get enough oxygen
Chloroform
• Chloroform Heavy colorless liquid. Nice smell.
Used as anaesthetic, and to render a victim
unconsious. However, it's not easy to cholorform
a sleeping victim without waking them, and it
can take up to 15 minutes to knock the victim
out. Victim often convulses as the drug takes
effect. Skin blisters on face, where choloroform
is in contact with the skin. Prolonged inhalation
leads to death by heart failure, and ingestion by
heart and liver failure.
• Chloral Hydrate is related. It is usually
ingested and, in small doses, can knock
someone out very quickly if, for example,
placed in their drink. Larger doses cause
death by heart and lung failure