Exposure occurs from inhalation, absorption through the skin and/or
ingestion. A 9.3% dermal absorption rate has been established. The rate of
absorption is even higher through abraded skin. Fat and fat solvents also
enhance the rate of absorption, especially in the gastrointestinal tract.
Recognition and Management of Pesticide Poisonings
Absorption: Systemic absorption of up to 13% may occur.
www.healthgate.com/choice/med-emerg/dih_f/chapter/mono/mg076700.shtml
"Only one of the isomers shown has significant insecticidal properties,
the gamma isomer of lindane. This implies that the three dimensional structure
of the compound is important in toxicity." http://wcb.ucr.edu/wcb/schools/CNAS/entm/tmiller/1/modules/page27.html
"In view of possible human exposure situations and
the sensitivities of the two target tissues from both species, the data imply
that lindane will pose a health risk to humans by inhalation
but not by ingestion."
Detection of genotoxic effects in human gastric and nasal mucosa cells isolated
from biopsy samples.
Pool-Zobel BL; Lotzmann N; Knoll M; Kuchenmeister F; Lambertz R; Leucht U;
SchrÓoder HG; Schmezer P
Environ Mol Mutagen 1994;24(1):23-45 http://toxnet.nlm.nih.gov/
Behavioral Toxicology, Risk Assessment, and Chlorinated
Hydrocarbons
Lindane
This organochlorine pesticide is used in both human and veterinary medicine
to treat ectoparasites (93,94). In 1948, Wooldridge (95)
successfully treated human scabies (skin disease caused by mites) with 1%
lindane cream, and this treatment continues to be widely used. In addition,
lindane shampoo is used for pediculosis (infestation with lice). While dermal
absorption is generally low, there are exceptions. Lindane is also used as a
general insecticide, particularly in countries outside the United States, to
control structural pests such as termites although its environmental persistence
may not be sufficient to make it satisfactory in this capacity (94).
There have been numerous reports through the years of major toxicity and death
associated with accidental or deliberate exposure to lindane (96).
Lindane is a potent convulsant agent in humans and other mammals (96) as
a result of a direct action on the CNS (97). In the most severe incident
(98), epidemic poisoning occurred in India when lindane intended for
preservation of seed grains was instead mixed with food grains and was consumed.
The onset of signs of poisoning was sudden with seizures of the mixed type,
i.e., grand mal, petit mal, and myoclonus, predominating. Other effects included
intention tremors, memory impairment, irritability, and aggression.
Desi (99) found that repeated exposure to lindane increased the number
of errors made in a food-reinforced maze. One interpretation of these results is
that lindane may interfere directly with learning. Consistent with these data,
it was reported that lindane has effects on long-term potentiation in the
hippocampus, and it is possible that this effect may compete or interfere with
the utilization of new information. The post-training administration of lindane
did not affect retention. This suggests that the process of memory consolidation
is not altered (100). Data from Tilson et al. (101) suggest that
exposure to nonconvulsant doses of lindane can interfere with the ability to
acquire and use new information and that these effects may be associated with
alteration in GABA.
Although dieldrin and lindane have quite different chemical structures, the
signs of poisoning that they produce are similar in both insects and mammals.
Unlike the action of DDT, which is on the axonal membrane, the primary site of
action of lindane and dieldrin is the synapse where both increase release of
neurotransmitters (102). The action of lindane was first studied in insects and
shown to be on the ganglia rather than on the axon. In the cockroach, lindane
and dieldrin were both found to act on the cholinergic giant fiber system in the
abdominal ganglion and to increase evoked and spontaneous release of
acetylcholine (103,104). In addition, it has been shown that lindane interacts
with the rat brain GABA receptor-ionophore complex at the picrotoxinin binding
site (105); Matsumura and Ghiasuddin (106) demonstrated that dieldrin and
lindane mimicked the action of picrotoxinin in inhibiting GABA-stimulated
chloride uptake in cockroach muscle and competed directly with picrotoxinin for
binding in rat brain synaptosomes.
Lindane (and/or its metabolites) has been shown in the 2-year carcinogenicity
bioassay to increase the incidence of benign and malignant neoplasms in
endocrine organs (pituitary, adrenal, and thyroid) of both sexes; however, a
high incidence of ovarian carcinoma was also noted (38). Moreover, male rats
treated with lindane at 32 and 64 mg/kg bw for 2 years presented with severe
testicular atrophy. It is thus quite reasonable to assume that the testosterone
level in these rats, as a consequence of testicular atrophy, was low.
ORGANOCHLORINE
INSECTICIDES IN SUBSTANTIA NIGRA IN PARKINSON'S DISEASE
Title: ORGANOCHLORINE
INSECTICIDES IN SUBSTANTIA NIGRA IN PARKINSON'S DISEASE
Author(s): F.M. Corrigan; C.L.
Wienburg; R.F. Shore; S.E. Daniel; D. Mann
Source: Journal
of Toxicology and Environmental Health Part A Volume:
59 Number: 4 Page: 229 -- 234
DOI: 10.1080/009841000156907
Publisher: Taylor and Francis
Ltd
Abstract: The concentrations
of organochlorine (OC) compounds in the substantia nigra (SN) were compared in
Parkinson's disease (PD) with concentrations in brain from cortical Lewy body
dementia (CLBD), Alzheimer's disease (AD), and nondemented nonparkinsonian
controls (CON). The levels of the gamma isomer of hexachlorocyclohexane (g HCH,
lindane) were significantly higher in PD tissues (mean +/- SD: 0.56 +/- 0.434
mug/g lipid) than in the other three groups (CLBD 0.052 +/- 0.101 mug/g lipid;
AD none detected; CON 0.125 +/- 0.195; all differences from PD significant at p
< .05, Mann-Whitney U-test). Dieldrin (HEOD) was higher in PD brain than in
AD or control brain, while 1,1'-(2,2-dichloroethenyl diene)-bis(4-chlorobenzene)
(p,p-DDE) and total Aroclor-matched polychlorinated biphenyls (matched PCBs)
were only higher in PD substantia nigra when these concentrations were compared
with those of CLBD. These findings are not inconsistent with the hypothesis
derived from epidemiological work and animal studies that organochlorine
insecticides produce a direct toxic action on the dopaminergic tracts of the
substantia nigra and may contribute to the development of PD in those rendered
susceptible by virtue of cytochrome P-450 polymorphism, excessive exposure, or
other factors.
Long-term psychological and neurological complications of lindane poisoning.
Hall RC, Hall RC
Department of Psychiatry, University of Florida, Gainesville, USA.
A thin, healthy, partial-vegetarian, white female, who was exposed to three
doses of lindane (through the application of Kwell), developed a severe case of
long-term lindane poisoning. Review of the literature suggests that her toxicity
was so severe because of the repetitive nature of her exposure and the fact that
she was partly protein restricted when first exposed. She developed profound
central nervous system toxicity, as well as skin and gastrointestinal changes,
that persisted for 20 months. She was treated with high doses of Valium. It was
noted that every time her Valium was diminished below a critical level, her
symptoms tended to recur until she had adequately cleared the lindane from her
system. We believe this is the longest term of poisoning reported following
exposure to an organochloride insecticide. Her symptoms are well explained by
the physiology of these compounds as described in the literature. The case is
important, for it represents the longest persistence of symptoms clearly
associated with poisoning by the potent gamma isomer of BHC-lindane.
... A CENTRAL NERVOUS STIMULANT ... LINDANE HAS HIGHEST ACUTE TOXICITY /OF
BHC ISOMERS/; ITS LETHAL DOSE IS PERHAPS 125 MG/KG. ... FEW HUMAN FATALITIES
HAVE BEEN ASCRIBED TO ... LINDANE, BUT MANY NONFATAL POISONINGS HAVE BEEN
REPORTED. IN U.S. MANY OF THESE ... OCCURRED IN CHILDREN WHO SWALLOWED LINDANE
PELLETS INTENDED FOR USE IN VAPORIZERS. ... WITHIN 30 MIN AFTER INGESTING AN EST
1.5 G LINDANE, A 2.5 YR OLD GIRL EXHIBITED IRRITABILITY & GRAND MAL
CONVULSIONS. WITH SUPPORTIVE CARE SHE RECOVERED WITHIN 24 HR. SERUM LEVELS OF
LINDANE WERE HIGH INITIALLY BUT FELL RAPIDLY. CONSIDERABLE AMT WERE RECOVERED IN
1ST STOOL SAMPLES.
... REFRESHMENT STAND OPERATORS SUFFERED SEVERE HEADACHE, NAUSEA, &
IRRITATION OF EYES, NOSE, & THROAT SHORTLY AFTER EXPOSURE TO VAPORS FROM A
DISPENSER IN WHICH LINDANE ... BECAME OVERHEATED. SYMPTOMS ABATED 2 HR AFTER
DEVICE WAS REMOVED. ... WOMAN ... DEVELOPED URTICARIA SOON AFTER VAPORIZER WAS
INSTALLED IN HER PLACE OF EMPLOYMENT. DERMATITIS IMPROVED DURING WEEKENDS BUT
RECURRED WHEN SHE RETURNED TO WORK. ... COMPLETE RECOVERY FOLLOWED REMOVAL OF
VAPORIZER.
Chronic exposure to vapors of ... /lindane/ has resulted in fatal aplastic
anemia & other hematologic disorders. These adverse effects have not been
reported following use of 1% lindane lotion, cream, or shampoo.
DERMAL APPLICATION OF 1% LOTIONS OF LINDANE (KWELLADA), FOR TREATMENT OF
SCABIES RESULTED IN SEVERE INTOXICATIONS IN SOME CHILDREN & INFANTS. MARKED
MENTAL & MOTOR RETARDATION ... NOTED 2 DAYS AFTER TREATMENT IN 4 MO OLD
CHILD. LOCAL APPLICATION OF 1% ... PROVED PARTICULARLY DANGEROUS FOLLOWING HOT
SOAPY BATH, SINCE THIS INCREASED PERCUTANEOUS ABSORPTION OF THE CMPD. ACCIDENTAL
INGESTION BY 1 YR OLD BOY OF 1 TEASPOON OF 1% LINDANE SOLN, IN ADDN TO LOCAL
APPLICATION OF THIS SOLN ... RESULTED IN IRRITABILITY, HYPERACTIVITY, &
VOMITING, FOLLOWED BY RECOVERY. ...
A 2 MONTH OLD, 4.5 KG, MALE INFANT WAS FOUND DEAD IN HIS CRIB AFTER EXCESSIVE
APPLICATION OF 1% LINDANE LOTION. IT WAS IDENTIFIED IN BRAIN AT CONCN OF 110 PPB
WHICH WAS 3 TIMES GREATER THAN LEVELS FOUND IN BLOOD.
SIXTY MALE WORKERS BETWEEN 24 & 62 YR OLD EMPLOYED 1 TO 30 YR IN LINDANE
PRODUCING FACTORY WERE EXAMINED WITH REGARDS TO FUNCTIONS OF NERVOUS SYSTEM IN
COMPARISON WITH 2 EXTERNAL CONTROL GROUPS (20 CLERKS & 20 DAIRY WORKERS OF
SAME AGE DISTRIBUTION) HAVING NO CONTACT WITH HAZARDOUS SUBSTANCES. NO SIGNS OF
NEUROLOGICAL IMPAIRMENT OR PERTUBATION OF "NEUROMUSCULAR FUNCTION"
COULD BE ASCERTAINED.
... Therapeutic doses used in treatment of scabies have been found to have
neurotoxic & other effects (ie, nausea, convulsions, cyanosis). Ingestion of
large (unspecified) doses has led to muscle & kidney necrosis &, in 1
case, to pancreatitis. Digestive tract inflammation, hemorrhage, coma, &
death have been reported after lindane poisoning.
CONCN OF 5-10 UG/ML LINDANE INHIBITED CELL DIVISION IN HUMAN PERIPHERAL BLOOD
LYMPHOCYTES IN VITRO & CAUSED CONCENTRATION-RELATED INCR IN FREQUENCY OF
CHROMATID BREAKS. IN SV40-TRANSFORMED HUMAN FIBROBLASTS (VA-4), 1 OR 1000 UMOLAR
LINDANE FAILED TO INDUCE UNSCHEDULED DNA SYNTHESIS ... IN PRESENCE OR ABSENCE OF
RAT LIVER MICROSOMAL ACTIVATION SYSTEM.
Toxic concn of lindane found in human blood: 0.050 mg % or 0.50 ug/ml.
Kwell, a pediculicide for external use, contains a solid organochlorine, 1%
lindane (BHC). In six months, ... five cases of accidental ingestions of Kwell
/have been treated/. Case #1 occurred in a mental institution, #2 and #3
involved misunderstanding by a Spanish speaking mother and #4 and #5 were a
mother and child who mistook Kwell for a bottle of cough syrup. The first case
was given ipecac but seized while vomiting and aspirated, seized several more
times and arrested. He suffered anoxic brain damage when resuscitated, developed
rhabdomyolysis and died in one week. Treated with cholestyramine, his BHC blood
level fell from 1.3 mg/l to 0.11 mg/l on the fifth day. BHC tissue levels were
measured at autopsy. /Cases/ #2, #3, ingested 30 to 60 ml each, #3 seizing
initially was not given ipecac. Their BHC levels were 0.22 and 0.48 mg/l,
respectively. Cases #4 and #5 took a teaspoon each and were managed at home with
poison center /consultation/.
The rapidity with which symptoms develop after the ingestion of BHC varies
with the isomer: the gamma isomer is fastest (within 1 hr) and the alpha isomer
/is the slowest/ (within 24 hours), and the technical or commercial mixture is
intermediate (usually within 2 hours but sometimes as late as 12 hours). Death
from the pure gamma isomer is usually prompt (24 hr), whereas from the others it
may be several days.
QUANTITATIVELY, THE ACUTE TOXICITY ... IS SOMEWHAT GREATER THAN THAT OF
TECHNICAL BENZENE HEXACHLORIDE. CHRONICALLY, HOWEVER, THE TECHNICAL BENZENE
HEXACHLORIDE IS SOMEWHAT MORE TOXIC THAN LINDANE.
Target organs /include/: Eyes, CNS, blood, liver, kidneys, and skin.
Lindane is a convulsant.
The use of thermal vaporizers with lindane has caused acute poisoning by
inhalation.
The gamma (lindane) and alpha isomers are central nervous system stimulants.
Lindane levels in human blood and placental and fetal tissues are higher in
cases of spontaneous abortion and prematurity than in normal-term pregnancies.
Tissues from stillborn babies show the same range of lindane values as adult
tissues.
... lindane crosses the placenta, is excreted in human breast milk, and may
be fetotoxic.
Lindane used in malaria control in India in 1975-77 caused no skin and
coordination problems in 464 sprayers, nor did it cause higher SGPT and serum
alkaline phosphatase activities or serum whole cell counts relative to 201
controls. ... Serum protein concentration was affected, as was serum glucose.
In the biopsy report of one man who had eaten lindane-contaminated foods and
who had experienced grand mal seizures for 2 hr, /observers/ described
widespread muscle necrosis that followed acidemia, hypertension, myoglobinuria,
anemia, and acute renal failure.
These pesticides are chlorine containing compounds
including DDT, aldrin, dieldrin and lindane. The organochlorines act through
disruption of neurotransmission. PCB's, which are not used as pesticides, are
also organochlorines with similar human action and thus have the potential for
an additive effect.
•The greatest concern with the organochlorines are the long
term effects. The U.S. EPA has concluded that DDT, DDE and DDD are probable
human carcinogens. On this basis both Canada and the U.S. banned the
organochlorines however, they continue to be very prevalent posing long term
health risks.
•The organochlorines are still widely used in developing
countries including Central and South America, India, China and many other
countries. Products imported from these countries are obvious sources of DDT and
other organochlorines. They are also transported in air, oceans and
bioaccumulate in organisms.15
•Food is the primary route of exposure. Foods which may
contain DDT include: meat, fish and poultry, dairy products and root and leafy
vegetables. Fish from the Great Lakes Basin and inland waters are a large food
source of organochlorine exposure.
•A study of the concentrations and dietary intake of
selected organochlorines in fresh food composites grown in Ontario demonstrated
that organochlorine residues were detected in all of the food composites. This
included all types of fresh food grown in Ontario including beef, poultry,
fruits and vegetables (it did not include fish). The Findings suggest that
consumption of eggs and meat is also a significant source of exposure to the
majority of organochlorine chemicals studied.16
•The provincial and federal health departments report that
there are instances where maximum allowable levels of DDT intake may be exceeded
in breast-fed infants.16
•Similarly, they report that people living near hazardous
waste sites have been found to have an increased exposure to organochlorines in
large part because of leaching into the soil.16
•In Fish and wildlife, there is evidence of reproductive
and developmental effects as a consequence of chronic exposure. There is
increasing concern that exposure of humans to these chemicals may be causing
adverse effects on reproductive function. A number of chemicals in the
environment possess estrogenic activity and these compounds include pesticides
as well as plasticizers, estrogenic agents administered to livestock and a
variety of other chemicals.
•Dr. W. Foster, Head of the Reproductive Toxicology Section
at Health Canada concludes, "on the topic of environmental exposures and
human reproduction in women, that the consequences of exposure to environmental
contaminants over the course of a lifetime are difficult to assess and the
available literature does not support a clear conclusion that reproductive
health of women has been adversely affected. Nevertheless, the absence of sound
epidemiological data to support a causal association between various adverse
reproductive outcomes and exposure to chemicals present in the environment
cannot be viewed as evidence that such an association does not exist – it is
possible that trace contaminant levels may exert clinically subtle effects on
female reproductive function such as altered steroid hormone levels. There is a
need for well designed studies that need to incorporate sensitive outcome
measures such as time to pregnancy, spontaneous abortion rates and breast cancer
as well as better defined means of determining body burdens of suspected
reproductive toxins."17