CHLORINATED HYDROCARBON ORGANOCHLORINE

1
CHLORINATED HYDROCARBON (ORGANOCHLORINE)
BIOACCUMULATION UPWARD IN FOOD CHAINS FROM
ENVIRONMENT TO ANIMAL AND HUMAN HEAVILY
USED IN PEST CONTROL (1950-1970s) LEADS TO
RESIDUES, ENVIRONMENTAL PERSISTENCE
2
TOXICOKINETICS
HIGHLY LIPID-SOLUBLE ABSORPTION - THRU
SKIN AND MUCUS MEMBRANE DISTRIBUTION -
RAPIDLY ACCUMULATE IN ADIPOSE
TISSUES METABOLISM - METABOLITES MORE TOXIC gt
PARENT EXCRETION - SLOWLY RELEASED FROM
LIPID DEPOTS EXCRETE FROM BILE
DIGESTIVE TRACT
H H Cl O
C O Cl Cl
O C O Cl
C CCl2 Cl Cl Cl
DDT (LD50 14 ppm)
DDE (MORE PERSISTENT)
3
DICHLORODIPHENYL- ETHANE
DDT C14H9Cl5 METHOXYCHLOR C16H15Cl3O2
ALDRIN C12H8Cl6 CHLORDANE C10H6Cl8 DIELDRIN
C12H8Cl6O ENDRIN C12H8Cl7 LINDANE C6H6Cl6 TOX
APHENE
I
II
CYCLODIENES
BENZENE CYCLO- HEXANES
III
- CHLORINATED HYDROCARBON - ORGANOCHLORINE
4
CLASSIFICATION OF ORGANOCHLORINE
INSECTICIDE BY STRUCTURE
I DICHLORODIPHENYL-ETHANES DDT, DDD,
METHOXYCHLOR, KELTHANE II CYCLODIENES ALDRIN,
DIELDRIN, HEPTACHLOR, CHLORDANE III CHLORINATED
BENZENES CYCLOHEXANES LINDANE, BHC (BENZENE
HEXACHLORIDE) HCB, MIREX, KEPONE
5
??????????????????????????? ??? WHO
?????????????????????????????????????????
??? (PERSISTENT ORGANIC POLLUTANTS, POPs)
????????????????? ?????????????????????????????
???????????????? 12 ??? ALDRIN DIELDRIN
ENDRIN DDT TOXAPHENE CHLORDANE HETACHLOR
MIREX PCBs HEXACHLOROBENZENE
DIOXINS FURANS PCBs ???????????????
ELECTRONICS DIOXINS, FURANS ?????????????????????
???? DIOXINS FURANS ??????????????????????
6
MECHANISM OF ACTION OF DDT
??????????? SENSORY NERVE ??? INSECT Na
Na Na
DDT ??????????????????????? Na
MEMBRANE PORES K K
INHIBIT ION TRANSPORT K K
K INSIDE ON MEMBRANE Na
??????? MEMBRANE INHIBIT NERVE
ATPase gt ???? K ??????????????? ????????
MEMB. POTENTIAL HYPERSENSITIVITY
THRESHOLD HYPERACTIVITY ???, ???
DEPOLARIZATION MAMMAL ???????????
CNS - NEURON ???? EXCITATION - STIMULATE
SPINAL REFLEX, NERVE FIBER
7
CYCLODIENE BENZENE CYCLOHEXANE (DIELDRIN)
INHIBIT Ca/Mg ATPase INHIBIT TRANSPORT OF Ca
ACROSS MEMBRANE INTRACELLULAR FREE Ca
DEPOLARIZATION
8
CYCLODIENE (DIELDRIN) PYRETHRUM
Cl-
GABA
PRESYNAPTIC MEMBRANE
Ca
Ca
Ca/Mg ATPase
K
Na
CYCLODIENE
ANTAGONIZE GABA IN CNS (IN MAMMAL) (INHIBITOR
Y TRANSMITTER) Cl- UPTAKE BY
NEURONS PARTIAL REPOLARIZATION
9
CLINICAL SIGNS
STIMULATE DEPRESSION
NERVOUS SYSTEM NERVOUSNESS,
APPREHENSIVE, TREMORS HYPEREXCITABILITY,
INCOORDINATION (48-72 hr) HYPERTHERMIA
(106-108 F) DEPRESSION, ABNORMAL
POSTURES, WALK BACKWARDS
10
DIAGNOSIS
CLINICAL CHEMISTRY NOT HELPFUL TISSUE
CONC. (HPLC) ACUTE
LESIONS
UNRELIABLE FOR DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
MENINGITIS RABIES LEAD, STRYCHNINE, POISONING
11
TREATMENT
1. SPECIFIC ANTIDOTES NOT AVAILABLE 2.
DETOXIFICATION ACTIVATED CHARCOAL 1-2
gm/kg MINERAL OIL (4 hr INSECTICIDE INGEST) 3.
SUPPORTIVE TREATMENT PHENOBARBITAL,
PENTOBARBITAL FLUID THERAPY
12
ENVIRONMENTAL CONCERN
PERSISTENCE IN SOILS, SEDIMENTS ACCUMULATION
BY ORGANISMS OF FOOD CHAIN a. 1x CONC. IN
SEDIMENT b. 500x CONC. IN PLANKTON c. 50,000x
CONC. IN SMALL FISH (100 ????) d. 100,000x
CONC. IN LARGE FISH (20 ????)