IPCS INCHEM HomeAldrin
ALDRIN
International Programme on Chemical Safety
Poisons Information Monograph 573
Chemical
1. NAME
1.1 Substance
Aldrin
1.2 Group
Diene-organochlorine or chlorinated 'cyclodiene' insecticide
1.3 Synonyms
Common names:
Aldrin;
Aldrine;
HHDN;
Compound 118;
Octalene;
OMS 194.
Chemical names:
Hexachloro-hexahydro-endo-exo-dimethanonaphthalene;
1,2,3,4,10,10-hexachloro-1,4,4a,5,8,8a-hexahydro-1,4:5,8-
dimethanonapthalene
1.4 Identification numbers
1.4.1 CAS number
309-00-2
1.4.2 Other numbers
NIOSH RTECS: IO2100000
EPA hazardous waste: P004
OHM/TADS: 7215090
DOT/UN/NA/IMCO: IMO6.1NA2762
HSDB (1992): 199
NCI: C00044
1.5 Main brand names/main trade names
Aldrex; Altox; Drinox; Octalene; Toxadrin
1.6 Main manufacturers/main importers
1948-1974: J Hyman & Co., Denver, CO, USA
1954-1990: Shell Chemical Corporation, Pernis, The
Netherlands
2. SUMMARY
2.1 Main risks and target organs
The CNS seems to be the primary site with resultant
seizures. Toxic exposures produce tremors, giddiness,
hyperexcitability, seizures, and coma. Few case reports of
fatalities exist. Poisoning occurs mainly through absorption
through the skin. Epidemiological studies do not show any
carcinogenic risk.
2.2 Summary of clinical effects
Absorption can occur by inhalational, dermal, and
gastrointestinal routes. Clinical toxicity from aldrin
actually is due to its rapid metabolism in the body to
dieldrin. Symptoms reflect CNS toxicity due to GABA
neurotransmission inhibition: headache, tremors, giddiness,
hyperexcitability, seizures and coma. Most deaths are
intentional or accidental exposures to concentrated amounts.
Aldrin is used in various formulations which include
emulsifiable concentrates, wettable powders, granules, dusts
and solutions in hydrocarbon liquids (deJong, 1991).
2.3 Diagnosis
The diagnosis is based on the history of exposure
(dermal, inhalational or gastrointestinal) and signs of CNS
hyperexcitability including seizures.
Blood levels of dieldrin (as aldrin is rapidly metabolized to
dieldrin) help confirm the exposure (to aldrin or dieldrin)
where available, although treatment will be determined by
clinical status. Background levels of dieldrin in the
general population is in the order of 1 ng/mL.
2.4 First-aid measures and management principles
Skin decontamination should occur when dermal absorption
is suspected, along with protection of healthcare
workers.
Because of the potential for seizures, do not induce
vomiting. Gastric lavage can be performed after adequate
airway protection, in cases where large amounts (greater than
1 mg/kg) of concentrated product has been ingested and the
patient presents early.
Standard supportive care is recommended in severe
cases.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Manufactured by the Diels-Alder condensation of
hexachlorocyclopentadiene with
bicyclo[2.2.1]-2,5-heptadiene.
3.2 Chemical structure
C12H8Cl6
MW: 364.91
3.3 Physical properties
3.3.1 Colour
Pure aldrin is a white crystalline solid.
Technical grade aldrin is tan in colour.
3.3.2 State/from
Crystalline solid.
3.3.3 Description
Aldrin has a mild chemical odor, and is very
soluble in most organic solvents (aromatics, esters,
ketones, paraffins, halogenated solvents).
Density: 1.7 g/L at 20ーC
Conversion factor: 1 ppm = 14.96 mg/m3 at 25ーC, 1 atm
(ATSDR, 1993)
3.4 Hazardous characteristics
Melting point: 104ーC (pure), 40 to 60ーC
(technical grade)
Boiling point: 145ーC
Impurities of aldrin include octachlorocyclopentene (0.4%),
hexachloro-butadiene (0.5%), toluene (0.6%), a complex
mixture of compounds formed by polymerization during the
aldrin reaction (3.7%) and carbonyl compounds (2%) (FAO/WHO,
1968).
4. USES
4.1 Uses
4.1.1 Uses
4.1.2 Description
Aldrin is a very effective soil insecticide and
has been used to treat seed also. It has been used to
control termites, corn rootworms, seed corn beetle,
seed corn maggot, wireworms, rice water weevil,
grasshoppers, and Japanese beetles. It also is used,
in an emulsifiable concentrate or wettable powder, to
protect wooden structures from termite destruction
both pre- and post-construction in building exteriors.
It is also used to coat and protect rice. Additional
use includes soil treatment for non-food crops (de
Jong, 1991).
4.2 High risk circumstance of poisoning
In countries where aldrin is used for treating crops and
grain, severe acute poisoning (accidental or intentional) may
occur. Higher rates of exposure may occur in homes treated
with aldrin for termite control. Air concentrations of
dieldrin were elevated in home interior areas (Dobbs &
Williams, 1983). However, the concentration that was measured
(0.3 to 75 mg/m3 ) in crawl spaces and in slab houses during
application was less than most threshold limit values, time
weighted average (Marlow et al., 1982). This seems to imply
that workers may not be seriously exposed as long as they are
wearing appropriate equipment; household members may get low
level, long term exposure contributing to their overall body
burden. In public buildings contamination may occur, and in
one school building hard surfaces and carpets had the highest
concentrations of aldrin (Calder et al., 1993).
Persons living near hazardous waste sites may potentially be
exposed to dieldrin (as aldrin would be expected to decompose
to dieldrin) from contamination of water supplies. In one
community built over contaminated soil, Acceptable Dietary
Intake (ADI) limits were exceeded (Van Wijnen & Stijkel,
1988).
4.3 Occupationally exposed populations
Since aldrin is no longer manufactured, production
workers are currently not exposed. However, aldrin is still
used in certain countries and pest control operators and
field workers may have significant exposures. Hazardous
waste site clean-up workers potentially may be exposed
(ATSDR, 1993).
5. ROUTES OF ENTRY
5.1 Oral
Aldrin is readily absorbed after ingestion.
5.2 Inhalation
Aldrin vapor is absorbed by inhalation.
5.3 Dermal
Aldrin is readily absorbed after dermal contact, and is
variable depending on the type of solvent used.
5.4 Eye
No data available.
5.5 Parenteral
No data available.
5.6 Others
Not applicable.
6. KINETICS
6.1 Absorption by route of exposure
Skin absorption rate not available (ATSDR, 1993).
Gastrointestinal absorption rate not available. Respiratory
absorption occurs; expiratory aldrin concentrations are
decreased compared to inspired concentrations. However,
dieldrin blood concentrations remained below 1 ng/L (de Jong,
1991; Bragt et al., 1984; Beyermann & Eckrich, 1973).
6.2 Distribution by route of exposure
Oral
Aldrin is rapidly converted to dieldrin primarily in the
liver. Consequently little aldrin is found in the blood or
tissues. Dieldrin is found in a ratio of 156:1
(adipose:blood) in the body (Hunter & Robinson, 1967).
Autopsy cases show dieldrin levels in brain (0.0061 mg/kg
white matter, 0.0047 mg/kg grey matter), liver (0.03 mg/kg)
and adipose tissue (0.13 to 0.36 mg/kg) (Adeshina & Todd,
1990; Ahmad et al., 1988; Holt et al., 1986; DeVlieger et
al., 1968).
6.3 Biological half-life by route of exposure
After chronic, oral human exposure, blood dieldrin
concentration decreases exponentially following first order
kinetics with an estimated half-life of 369 days (Hunter et
al., 1969). No information is available for other routes of
exposure.
6.4 Metabolism
Aldrin is quickly metabolized to dieldrin, mediated by
the mixed-function mono-oxygenases. Liver tissue has the
largest activity but several other organs such as the lung
and skin also have this enzymatic process. Dieldrin is then
metabolized at a much slower rate to hydrophilic metabolites
(de Jong, 1991; ATSDR, 1993).
6.5 Elimination and excretion
Elimination occurs primarily through the feces via the
bile. 9-Hydroxydieldrin seems to be the major metabolite
excreted. Dieldrin is also excreted in breast milk (ATSDR,
1993; Richardson & Robinson, 1971). Small amounts (3 to 8%)
of dieldrin metabolites are excreted in the urine after
either topical or intravenous administration (Feldman &
Maibach, 1974). Dieldrin metabolites may also be found in the
urine after ingestion.
7. TOXICOLOGY
7.1 Mode of action
Aldrin and dieldrin may have several modes of action.
First, it may increase pre-synaptic neurotransmitter release.
In addition, aldrin and dieldrin may inhibit GABA (gamma
aminobutyric acid) mediated neuroinhibition (ATSDR, 1993;
Obata et al., 1988; Gant et al., 1987; Abalis et al., 1986;
Cole & Casida, 1986; Bloomquist et al., 1986; Bloomquist &
Soderlund, 1985; Lawrence & Casida, 1984).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
An acute convulsive episode may
occur without, or with minor, development of
warning symptoms when the dieldrin blood
concentration reaches 200 オg/L or higher.
Repetitive, small dose exposures to aldrin
may cause dieldrin to accumulate and cause
symptoms of intoxication (de Jong, 1991).
Concentrations of dieldrin in the blood
correlate with toxicity. Asymptomatic people
had concentrations in the blood ranging from
0.5 to 2 オg/L (IPCS, 1989a). Blood levels
greater than 105 オg/L are needed to develop
toxicity; this corresponds to a daily intake
of 0.02 mg dieldrin/kg/day (IPCS, 1989a).
Dieldrin concentrations in adipose tissue
range from 0.1 to 0.3 mg dieldrin per kg body
fat (IPCS, 1989a) Exposure may occur through
only one route or through a combination of
dermal, inhalational or gastrointestinal
absorption (de Jong, 1991). Acute ingestion
of 25.6 mg/kg with resulting severe toxicity
has been reported with survival (Smith,
1991).
7.2.1.2 Children
There have been few cases of aldrin
toxicity (accidental) in children with
resulting signs of CNS stimulation similar to
adults. Death has occurred after acute
ingestion of 8.2 mg/kg (Smith,1991).
Theoretically the very young are at risk
because of their smaller rates of glucoronide
conjugation and subsequent excretion
(Calabrese, 1978). The fetus concentrates
dieldrin, and the possibility of contaminated
breast milk consumption increase the risk of
CNS effects in the very young (IPCS, 1989a;
Polishuk et al., 1977). However, based on
average breast milk dieldrin concentrations
(up to 6 オ/L) and a child drinking
approximately 150 mL milk/kg body weight, the
estimated daily intake would be 0.15 to 0.9
オg dieldrin/kg body weight (IPCS, 1989a).
Other estimates place this estimated daily
intake at 0.65 to 0.70 オg/day for the first
four months of breast feeding (Acker et al.,
1984). Because of these small levels, the
presence of dieldrin in the blood is
considered clinically
insignificant.
7.2.2 Relevant animal data
Oral LD50 (rats) is 39 to 64 mg/kg (Gaines,
1960; Treon et al., 1952). Chronic exposure for six
weeks showed an increase in rat mortality at doses of
8 mg/kg/day (NCI, 1978).
Inhalation exposure to aldrin in several species
resulted in death in at least some of each species at
levels greater than 108 mg/m3 (Treon et al., 1957).
Single dermal applications (in xylene) produce death
in 50% of animals given 98 mg/kg/day (Gaines, 1960).
Oral administration of aldrin to rats causes
convulsions like in humans, at doses of 10 mg/kg/day
(Mehrotra et al., 1989).
7.2.3 Relevant in vitro data
Aldrin (1 to 1000 オmol/L) induced unscheduled
DNA synthesis in SV-40 transformed human fibroblast
cells (VA-4) both in the presence and absence of rat
liver microsomes (Ahmed et al., 1977; Zelle & Lohman,
1977).
The DNA breakage rates in an Escherichia coli plasmid
after treatment with aldrin or dieldrin did not
differ from those in untreated plasmid DNA, suggesting
that, at least in these studies, the compounds did not
interact directly with DNA (Griffin & Hill, 1978).
The effects of aldrin and dieldrin (both at 100 オg/mL)
on the uptake of tritiated thymidine by cultured rat
thymocytes and human lymphocytes were tested under
different experimental conditions. Both compounds
appeared to have marginal effects on thymidine uptake,
suggesting inhibition of DNA synthesis (Rocchi et al.,
1980).
Aldrin (100 mmol/L) and dieldrin (500 mmol/L) did
not induce unscheduled DNA synthesis in primary
cultures of Fischer 344 rat hepatocytes (Probst et
al., 1981). Williams (1982) reported the results of
the hepatocyte primary culture/DNA repair test,
using freshly isolated hepatocytes of high
metabolic capability to monitor the production of
DNA damage by measuring DNA repair synthesis. Aldrin
and dieldrin gave equivocal results concerning DNA
repair, but there was no damage to DNA. Aldrin (0.3
to 3 mmol/L) induced DNA strand breaks in an alkaline
elution/rat hepatocyte assay (Sina et al., 1983).
Both aldrin and dieldrin inhibited gap junctional
intercellular communication between
6-thioguanine-sensitive and 6-thioguanine-resistant
human teratocarcinoma cells in culture (Zhong-Xiang et
al., 1986).
7.2.4 Workplace standards
Argentina
Max. permiss. conc. TWA 0.25 mg/m3
STEL 0.75 mg/m3
Australia
TLV-TWA 0.25 mg/m3
Belgium
TLV-TWA 0.25 mg/m3
Finland
Max. permis. conc. TWA 0.25 mg/m3
STEL 0.75 mg/m3
Germany
Max. work-site conc.(MAK) TWA 0.25 mg/m3
STEL (30 min) 2.5 mg/m3
Netherlands
Max. limit TWA 0.25 mg/m3
Poland
Max. permis. conc. CLV 0.01 mg/m3
Romania
Max. permis. conc. TWA 0.20 mg/m3
Ceiling value (CLV) 0.25 mg/m3
Switzerland
MAK-TWA 0.25 mg/m3
Thailand
Max. permiss. conc. 0.25 mg/m3
UK (recommended)
TWA 0.25 mg/m3
STEL (10 min) 0.75 mg/m3
USA
OSHA PEL-TWA (skin) 0.25 mg/m3(OSHA, 1989)
ACGIH TLV-TWA (skin) 0.25 mg/m3(ACGIH, 1993)
NIOSH REL-TWA (skin) 0.25 mg/m3(NIOSH, 1992)
USSR
MAC-CLV 0.01 mg/m3
Yugoslavia
MAC-TWA 0.25 mg/m3
(IPCS, 1989b)
7.2.5 Acceptable daily intake (ADI)
WHO (diet) 0.1 オg/kg (IPCS, 1989a)
WHO (water) 0.03 mg/L recommended
(IPCS, 1989b)
7.3 Carcinogenicity
No increased incidence of malignant neoplasms has been
found in several studies (de Jong, 1991; Ribbens, 1985; Van
Raalte, 1977). In animal assays however, an increased
incidence of hepatic tumors including hepatocellular adenomas
was found (Davis & Fitzhugh, 1962; NCI, 1978). The data does
not allow any conclusions to be made concerning an increased
risk of cancer development with aldrin or dieldrin (IARC,
1974a; IARC, 1974b).
7.4 Teratogenicity
No human studies were identified. In animals an
increase in fetal mortality, increased incidence of cleft
palate and webbed foot and a decreased postnatal survival
have been reported (Ottolenghi et al., 1974; Virgo &
Bellward, 1975; Treon et al., 1954).
7.5 Mutagenicity
Increased sister chromatid exchanges and exchange-type
chromosome aberrations were noted in floriculturists after
exposure to several pesticides including aldrin (Dulout et
al., 1985).
7.6 Interactions
Possible additive effects with other organochlorine
pesticides have been postulated (ATSDR, 1993).
8. TOXICOLOGICAL ANALYSIS AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple qualitative test(s)
8.2.1.2 Advanced qualitative confirmation test(s)
8.2.1.3 Simple quantitative method(s)
8.2.1.4 Advanced quantitative method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple qualitative test(s)
8.2.2.2 Advanced qualitative confirmation test(s)
8.2.2.3 Simple quantitative method(s)
8.2.2.4 Advanced quantitative method(s)
8.2.2.5 Other dedicated method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall interpretation of all toxicological analyses and
toxicological investigations
Sample collection
Blood collection for aldrin and dieldrin levels may be done.
However, aldrin may not be found as it is metabolized quickly
to dieldrin. Keep containers and any remaining product for
further identification. Typically collect 1 to 5 mL of serum
(preferred) or whole blood in an anticoagulant free evacuated
tube, which has an uncoated interior.
Biomedical analysis
Measurement of aldrin and dieldrin levels may be done.
However, aldrin may not be found as it is metabolized quickly
to dieldrin. Another problem is that few laboratories are
capable of determining dieldrin levels.
Remember that management is not dependent on levels and is
supportive and symptomatic.
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Case reports describe the onset of symptoms
within 15 minutes after oral exposure (Garrettson &
Curley, 1969; Spiotta, 1951; Black, 1974). Central
nervous system hyperirritability is the most common
manifestation attributable to aldrin. Symptoms may
include headache, dizziness, hyperirritability,
malaise, nausea and vomiting, anorexia, muscle
twitching, and myclonic jerking prior to the
development of seizures (Jager, 1970). Seizures may
be prolonged and signs of hyperirritability may last
several days (Spiotta, 1951; Black, 1974). Renal
dysfunction followed an acute ingestion of aldrin.
This resulted in an elevated blood urea nitrogen,
gross hematuria, and albuminuria (Spiotta,
1951).
9.1.2 Inhalation
This route of exposure usually occurs in
workers manufacturing or spraying the insecticide.
However, no acute poisoning cases were identified by
this exposure route. Most of these cases probably
represent multiple subacute and asymptomatic exposures
with a sudden unexpected seizure episode being the
first clinical effect (see chronic poisoning
below).
9.1.3 Skin exposure
This route of exposure is difficult to separate
from inhalation, and both may be occurring
simultaneously (ATSDR, 1993) Like inhalation
exposures, dermal absorption primarily occurs in
workers. If the exposure is severe one would expect a
progression of symptoms similar to oral exposure.
However, many exposures in workers involve multiple
subacute contacts which remain asymptomatic until a
seizure was the first observed clinical
effect.
9.1.4 Eye contact
No data available.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
No neurological, hepatic or hematological
effects are noted in humans at levels under 0.003
mg/kg/day (Hunter & Robinson, 1967).
9.2.2 Inhalation
Convulsions may appear suddenly and without
early signs and may be due to the accumulation of
aldrin (and its metabolite dieldrin) over several days
(Jager, 1970). Hemolytic anemia (dieldrin) and
aplastic anemia (aldrin) has been described after
prolonged exposure (Muirhead et al., 1959; Pick et
al., 1965; de Jong, 1991).
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
After an acute ingestion (or possibly through dermal or
inhalational methods) signs of CNS hyperirritability develop
as soon as 15 minutes after exposure. Seizures soon follow
and may last for several hours before being controlled with
medication. Motor hyperexcitabiltiy and restlessness may
persist for several days. The course may be mild or severe
depending on the amount ingested and any efforts to limit
absorption. The outcome may be fatal if complications from
seizures develop. Survivors recover completely; irreversible
effects have not been described in humans (IPCS,
1989a).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
No specific cardiovascular toxicity effect has
been described. Blood pressure fluctuations and
tachycardia have been described after overdose, but
these occurred in the presence of (and presumably due
to) CNS excitation and seizures (Spiotta, 1951; Black,
1974).
9.4.2 Respiratory
No data available.
9.4.3 Neurological
9.4.3.1 Central Nervous System (CNS)
Central nervous system excitation is
the primary adverse effect seen in humans.
Convulsions can occur suddenly after a
massive ingestion or after multiple, subacute
exposures. Typically a prodrome precedes
development of seizures and consists of
headache, dizziness, hyperirritability,
malaise, nausea and vomiting, and myoclonic
twitching (Patel & Rao, 1958; Jager
1970).
Persistent effects consisting of motor
hyperexcitability and restlessness for
several days have been reported (Spiotta,
1951).
9.4.3.2 Peripheral nervous system
An increased incidence of PNS
diseases was noted in pesticide workers.
However this increase was due to a higher
incidence of cervicobrachial and lumbosacral
syndromes; syndromes associated with manual
labor in a plant, not insecticide exposure
(de Jong, 1991).
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
Nausea, vomiting and anorexia may occur.
9.4.5 Hepatic
No data available with aldrin. Few case
reports with dieldrin which showed transient
transaminase elevation for several days, although the
effects of solvents (such as toluene) could not be
discounted (Garrettson & Curley, 1969; Black,
1974).
9.4.6 Urinary
9.4.6.1 Renal
Only one case report mentions an
elevation of blood urea nitrogen, gross
hematuria and albuminuria for several days
after an acute overdose although causality
was not established (Spiotta,
1951).
9.4.6.2 Other
None.
9.4.7 Endocrine and reproductive systems
Although aldrin levels in blood and placental
tissues were higher in women with premature labor or
spontaneous abortion than in women with normal
deliveries, other organochlorine pesticide levels were
also higher and therefore assigning causality to
aldrin is not possible. In addition other confounders
were not addressed in that study such as smoking or
alcohol consumption (Saxena et al., 1980).
9.4.8 Dermatological
No evidence of dermatitis was seen in pesticide
manufacturing workers (Jager, 1970).
9.4.9 Eye, ears, nose, throat: local effects
No data available.
9.4.10 Haematological
Normal haematological parameters were noted in
pesticide manufacturing workers during at least four
years of follow up (Jager, 1970). No increased
relative risk in pesticide workers has been noted (de
Jong, 1991). However a worker developed haemolytic
anaemia after working in an area sprayed with aldrin,
although it was not shown to be directly responsible
because other chemicals were in use also (Pick et al.,
1965).
9.4.11 Immunological
Although no data was found on aldrin, dieldrin
was associated with the development of
immunohaemolytic anaemia after eating contaminated
food (Hamilton et al., 1978).
9.4.12 Metabolic
9.4.12.1 Acid-base disturbance
May be observed in seizure states.
9.4.12.2 Fluid and electrolyte disturbance
No data available.
9.4.12.3 Others
No data available.
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
There was no increased incidence of malignant
neoplasm in pesticide workers (de Jong,
1991).
9.4.15 Special risks
Theoretically the very young are at risk
because of their smaller rates of glucuronide
conjugation and subsequent excretion (Calabrese,
1978). The fetus concentrates dieldrin, and the
possibility of contaminated breast milk consumption
increase the risk of CNS effects in the very young
(IPCS, 1989a; Polishuk et al., 1977). However, based
on average breast milk dieldrin concentrations (up to
6 オg/L) and a child drinking approximately 150 mL
milk/kg body weight, the estimated daily intake would
be 0.15 to 0.9 オg dieldrin/kg body weight (IPCS,
1989a). Other estimates place this estimated daily
intake at 0.65 to 0.70 オg/day for the first four
months of breast feeding (Acker et al., 1984). Because
of these small levels, the presence of dieldrin in the
blood is considered clinically insignificant.
9.5 Other
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
Clinical observation after appropriate decontamination,
and symptomatic treatment is usually sufficient.
10.2 Life support procedures and symptomatic/specific treatment
Make a proper assessment of airway, breathing,
circulation and neurological status of the patient. Maintain
a clear airway. Aspirate secretions from airway. Administer
oxygen. Perform endotracheal intubation and support
ventilation using appropriate mechanical device when
necessary. Control convulsions with benzodiazepines or
phenobarbital. Open and maintain at least one intravenous
route. Perform cardio-respiratory resuscitation when
necessary. Monitor vital signs. Correct hypotension as
required. Monitor blood pressure and ECG. Monitor fluid and
electrolyte balance. Monitor acid-base balance.(de Jong,
1991; Ellenhorn & Barceloux, 1988).
10.3 Decontamination
Remove and discard contaminated clothing. Irrigate
exposed eyes with copious amounts of water (or saline). Wash
skin with copious amounts of water. Emesis is
contraindicated. If the patient is obtunded, convulsing or
comatose, or since aldrin may induce these conditions
rapidly, insert an oro- or a naso-gastric tube and lavage
after endotracheal intubation. Administer activated charcoal.
If an oro- or naso-gastric tube is in place, administer after
lavage through the tube. Administer a cathartic unless
already given with activated charcoal.
10.4 Enhanced elimination
No data is available as to whether haemodialysis or
haemoperfusion are effective. However the large molecular
weight and lipophylic nature of aldrin would seem to indicate
that haemodialysis would not be effective. Forced diuresis,
alkalinization, acidifiction are not effective.
10.5 Antidote treatment
10.5.1 Adults
There is no antidote.
10.5.2 Children
There is no antidote.
10.6 Management discussion
Additional data is needed to identify differences in
toxicity from different routes of exposure. Also information
on less subtle forms of CNS effects is lacking (ATSDR, 1993).
The metabolism of aldrin may include some element of
enterohepatic recirculation, although this has not been
demonstrated.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
No cases of poisoning with aldrin were identified. The
following two cases reflect poisoning with dieldrin which
would be expected to be similar to aldrin poisoning.
Two siblings aged 2 and 4 years apparently ingested dieldrin
(5% solution) and within 15 minutes were noticed to be
salivating heavily when generalized convulsions started. By
the time a physician arrived the younger child was dead, and
the four year old male was treated with mechanical
respirator, anticonvulsants (phenobarbital, paraladehyde and
phenytoin) and general supportive care. He recovered
completely and was discharged (Garettson and Curley,
1969).
A 21-year-old male ingested 9 g (120 mg/kg) of dieldrin in a
15% solution with toluene. Within 20 minutes he was frothing
at the mouth, cyanotic and semi-conscious. En route to the
hospital he lost consciousness and had a grand mal seizure.
He was treated with an endotracheal tube, gastric lavage,
catharsis (with mannitol), anticonvulsants (diazepam,
phenobarbital, phenytoin and muscular paralysis), beta
blockers for tachycardia and hypertension and general
supportive treatment (Black, 1974).
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
The substance is not produced in most countries to our
knowledge, and is banned in many countries.Caution in using
this product with appropriate protective gear to prevent
absorption (dermal, inhalational, or gastrointestinal) is
imperative. Workers should be educated as to the proper
handling and use (IPCS, 1989a).
Use in the treatment of termite control for buildings as long
as it is used appropriately appears safe for the
occupants.
12.2 Other
Infants and toddlers appear to have higher dietary
intake of aldrin (and dieldrin) compared to adults. However,
the rates of intake have been decreasing over time as use of
aldrin and dieldrin have decreased (Gartell et al., 1986a,
1986b).
13. REFERENCES
Abalis IM, Eldefrawi ME, Eldefrawi AT (1986). Effects of
insecticides on GABA-induced chloride influx into rat brain
microsacs. J Toxicol Environ Health, 18: 13-23.
ACGIH (1993). Threshold limit values and biological exposure
indices for 1993-1994. American Conference of Governmental
Industrial Hygenists, Cincinnati, Ohio.
Acker L, Barke E, Hapke HJ, et al. (1984). [Residues and
impurities in breast milk.] Milchwissenschaft, 39(9): 541-544 (in
German).
Adeshina F & Todd EL (1990). Organochlorine compounds in human
adipose tissue from north Texas. J Toxicol Environ Health, 29:
147-156.
Ahmed FE, Hart RW & Lewis NJ (1977) Pesticide induced DNA damage
and its repair in cultured human cells. Mutat Res, 42:
161-174.
Ahmad N, Harsas W, Marolt RS, et al. (1988). Total DDT and
dieldrin content of human adipose tissue. Bull Environ Contam
Toxicol, 41: 802-808.
ATSDR (1993). Toxicological profile for aldrin/dieldrin. Atlatnta,
US Public Health Service, Agency for Toxic Substances and Disease
Registry, ATSDR/TP-92/01.
Black AMS (1974). Self-poisoning with dieldrin: a case report and
pharmacokinetic discussion. Anesth Intensive Care, 2:
369-374.
Bloomquist JR, Adams PM, Soderlund DM (1986). Inhibition of
g-aminobutyric acid-stimulated chloride flux in mouse brain
vesicles by polychlorocycloalkane and pyrethroid insecticides.
Neurotoxicology, 7: 11-20.
Bloomquist JR & Soderlund DM (1985). Neurotoxic insecticides
inhibit GABA-dependent chloride uptake by mouse brain vesicles.
Biochem Biophys Res Commun, 133: 37-43.
Bragt PC, Schuurbiers CJ, Hollander JCT, et al. (1984). Retention
of inhaled aldrin in man. Rijswijk, The Netherlands, Medical
Biological Laboratory TNO.
Calabrese E (1978). Pollutants and high risk groups: the
biological basis of increased human susceptibility to
environmental and occupational pollutants. New York, NY; John
Wiley & Sons.
Calder IC, Maynard EJ, Turczynowicz L (1993). Aldrin
contamination at a school in South Australia. Bull Environ Contam
Toxicol, 51: 185-192.
Cole LM & Casida JE (1986). Polychlorocycloalkane
insecticide-induced convulsions in mice in relation to disruption
of the GABA-regulated chloride ionophore. Life Sci, 39:
1855-1862.
Davis KJ & Fitzhugh OG (1962). Tumorigenic potential of aldrin
and dieldrin for mice. Toxicol Appl Pharmacol, 4: 187-189.
de Jong G (1991). Long-term health effects of aldrin and
dieldrin: a study of exposure, health effects and mortality of
workers engaged in the manufacture and formulation of the
insecticides aldrin and dieldrin. Amsterdam, Netherlands;
Elsevier Science Publishers B.V.
DeVlieger M, Robinson J, Baldwin MK, et al. (1968). The
organochlorine insecticide content of human tissue. Arch Environ
Health, 17: 759-767.
Dobbs AJ & Williams N (1983). Indoor air pollution from
pesticides used in wood remedial treatments. Environ Pollution
(series B), 6: 271-296.
Dulout FN, Pastori MC, Olivero OA, et al. (1985). Sister-chromatid
exchanges and chromosomal aberrations in a population exposed to
pesticides. Mutat Res, 143: 237-244.
Ellenhorn MJ & Barceloux DG eds. (1988). Medical Toxicology
- diagnosis and treatment of human poisoning. New York, NY:
Elsevier.
FAO/WHO (1968) 1967 Evaluation of some pesticide residues in food,
Geneva, World Health Organization (FAO PL: 1967/M/11/1; WHO Food
Add./68.30).
Feldman RJ & Maibach HI (1974). Percutaneous penetration of some
pesticides and herbicides in man. Toxicol Appl Pharmacol, 28:
126-132.
Gaines TB (1960). The acute toxicity of pesticides to rats.
Toxicol Appl Pharmacol, 2: 88-99.
Gant DB, Eldefrawi ME, Eldefrawi AT (1987). Cyclodiene
insecticides inhibit GABAA receptor-regulated chloride transport.
Toxicol Appl Pharmacol, 88: 313-321.
Garrettson LK & Curley A (1969). Dieldrin: studies in a poisoned
child. Arch Environ Health, 19: 814-822.
Griffin DE & Hill WE (1978) In vitro breakage of plasmid DNA by
mutagens and pesticides. Mutat Res, 52: 161-169.
Hamilton HE, Morgan DP, Simmons A (1978). A pesticide
(dieldrin)-induced immunohemolytic anemia. Environ Res, 17:
155-164.
Holt RL, Cruse S, Greer ES (1986). Pesticide and polyclorinated
biphenyl residues in human adipose tissue from northeast
Louisiana. Bull Environ Toxicol, 36: 651-655.
HSDB (1992). Hazardous substance data bank. Bethesda, MD:
National Library of Medicine, National Toxicology Information
System.
Hunter CG, Robinson J, Roberts M (1969). Pharmacodynamics of
dieldrin (HEOD): ingestion by human subjects for 18 to 24 months,
and postexposure for 8 months. Arch Environ Health, 18:
12-21.
Hunter CG & Robinson J (1967). Pharmacodynamics of dieldrin
(HEOD). I. Ingestion by human subjects for 18 months. Arch
Environ Health, 15: 614-626.
IARC (1974a). Evaluation of the carcinogenic risk of chemicals to
humans. Aldrin. Lyon, France: World Health Organization,
International Agency for Research on Cancer. IARC Monograph, 5:
25-38.
IARC (1974b). Evaluation of the carcinogenic risk of chemicals to
humans. Dieldrin. Lyon, France: World Health Organization,
International Agency for Research on Cancer. IARC Monograph, 5:
125-156.
IPCS (1989a). Environmental Health Criteria 91: aldrin and
dieldrin. International Programme on Chemical Safety. Geneva,
Switzerland; World Health Organization.
IPCS (1989b). Health and Safety Guide No. 21: aldrin and dieldrin
Health and Safety Guide. International Programme on Chemical
Safety. Geneva, Switzerland; World Health Organization.
Jager KW (1970). Aldrin, dieldrin, endrin and telodrin: an
epidemiological and toxicological study of long-term occupational
exposure. New York: Elsevier.
Lawrence LJ & Casida JE (1984). Interactions of lindane,
toxaphene and cyclodiene with brain-specific
t-butylbiscyclophosphorothionate receptor. Life Sci, 35:
171-178.
Marlow RG, Wallace BG, Moore JP (1982). Assessment of exposure
following the use of aldrin as a termiticide in homes.
Sittingbourne, Shell Research (SBGR.82.370).
Mehrotra BD, Moorthy KS, Reddy SR, et al. (1989). Effects of
cyclodiene compounds on calcium pump activity in rat brain and
heart. Toxicology, 54: 17-29.
Muirhead EE, Groves M, Guy R, et al. (1959). Acquired hemolytic
anemia, exposure to insecticides and positive Coombs test
dependent on insecticide preparations. Vox Sang, 4: 277-292.
NCI (1978). Bioassays of aldrin and dieldrin for possible
carcinogenicity. Bethesda, MD: National Institutes of Health,
National Cancer Institute, Division of Cancer Cause and
Prevention, Carcinogenesis Program. U.S. Department of Health,
Education and Welfare, Publication No. 78-822.
NIOSH (1992). Occupational safety and health guidelines for
aldrin, potential human carcinogen. Cincinnati, OH: U.S.
Department of Health and Human Services, National Institute for
Occupational Safety and Health, Division of Standards Development
and Technology Transfer.
Obata T, Yamamura HI, Malatynska E, et al. (1988). Modulation of
g-aminobutyric acid stimulated chloride influx by
bicycloorthocarboxylates, bicyclophosphorus esters,
polychlorcycloalkanes and other cage convulsants. J Pharmacol Exp
Ther, 244: 802-806.
OSHA (1989). OSHA safety and health standards for general
industry. U.S. Department of Labor, Occupational Safety and
Heatlh Administration. Code of Federal Regulations 29 CFR
1910.1000 sub part Z.
Ottolenghi AD, Haseman JK, Suggs F (1974). Teratogenic effects of
aldrin, dieldrin, and endrin in hamsters and mice. Teratology, 9:
11-16.
Patel TB & Rao VN (1958). Dieldrin poisoning in man: a report of
20 cases observed in Bombay State. Br Med J, 1: 919-921.
Pick A, Joshua H, Leffkowitz M, et al. (1965). [Aplastic anemia
following exposure to aldrin.] Medicine, 68: 164-167. (in
Hebrew)
Polishuk ZW, Wasserman D, Wasserman M, et al. (1977).
Organochlorine compounds in mother and fetus during labor. Environ
Res, 13: 278-284.
Probst GS, Mcmahon RE, Hill LE, Thompson CZ, Epp JK & Neal SB
(1981) Chemically-induced unscheduled DNA synthesis in primary rat
hepatocyte cultures: a comparison with bacterial mutagenicity
using 218 compounds. Environ. Mutagenesis, 3: 11-32.
Ribbens PH (1985). Mortality study of industrial workers exposed
to aldrin, dieldrin and endrin. Int Arch Occup Environ Health,
56: 75-79.
Richardson A & Robinson J (1971). The identification of a major
metabolite of HEOD (dieldrin) in human feces. Xenobiotica, 12:
212-219.
Rocchi P, Perocco P, Alberghini W, FinI A & Prodi G (1980) Effect
of pesticides on scheduled and unscheduled DNA synthesis of rat
thymocytes and human lymphocytes. Arch Toxicol, 45: 101-108.
Saxena MC, Siddiqui MKJ, Bhargava AK, et al. (1980). Role of
chlorinated hydrocarbon pesticides in abortions and premature
labor. Toxicology, 17:323-331.
Sina JF, Bean CL, Dysart GR, Taylor VI & Bradley MO (1983)
Evaluation of the alkaline elution/rat hepatocyte assay as a
predictor of carcinogenic/ mutagenic potential. Mutat Res, 113:
357-391.
Spiotta EJ (1951). Aldrin poisoning in man. Arch Ind Hyg Occup
Med, 4: 560-566.
Treon JF, Gahegen T, Coomer J (1952). The immediate toxicity of
aldrin, dieldrin and compound 49-RL-5, a possible contaminant of
impure aldrin. The Kettering Laboratory in the Department of
Preventive Medicine and Industrial Health, College of Medicine,
University of Cincinnati. Cincinnati, Ohio.
Treon JF, Boyd J, Berryman G, et al (1954). Final report on the
effects on the reproductive capacity of three generations of rats
being fed on diets containing aldrin, dieldrin or DDT. The
Kettering Laboratory in the Department of Preventive Medicine and
Industrial Health, College of Medicine, University of Cincinnati,
Cincinnati, Ohio.
Treon JF, Larson EE, Cappel J (1957). The toxic effects sustained
by animals subjected to the inhalation of air containing products
of the sublimation of technical aldrin at various temperatures.
The Kettering Laboratory in the Department of Preventive Medicine
and Industrial Health, College of Medicine, University of
Cincinnati, Cincinnati, Ohio.
Van Raalte HGS (1977). Human experience with dieldrin in
perspective. Ecotoxicol Environ Safety, 1: 203-210.
Van Wijnen JH & Stijkel A (1988). Health risk assessment of
residents living on harbour sludge. Int Arch Occup Environ
Health, 61: 77-87.
Virgo BB & Bellward GD (1975). Effects of dietary dieldrin on
reproduction in the Swiss-Vancouver (SWV) mouse. Environ Physiol
Biochem, 5: 440-450.
Williams GM (1982) Organochlorine pesticides and inhibition of
intercellular communication as the mechanism for their liver tumor
production. In: Miyamoto, J. & Kearney, P.C., ed. Pesticide
chemistry: human welfare and the environment. Oxford, New York,
Pergamon Press, Vol. 3, pp. 475-478.
Zelle B & Lohman PHM (1977) Repair of DNA in cultured human cells
treated with dieldrin and 4-nitroquinoline-N-oxide, Rijswijk, The
Netherlands, Medical Biological Laboratory TNO.
Zhong-Xiang L, Kavanagh T, Trosko JE & Chang CC (1986) Inhibition
of gap junctional intercellular communication in human
teratocarcinoma cells by organochlorine pesticides. Toxicol Appl
Pharmacol, 83: 10-19.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: John G. Benitez, M.D.
Toxicology Treatment
University of Pittsburgh Medical Center
Room NE 583, MUH
200 Lothrop Street
Pittsburgh, PA 15213
U.S.A.
Tel: 412-257-2142
Fax: 412-648-6855
Date: September 1995
Peer
review: Berlin, Germany, October 1995
Finalized: IPCS, September 1996
Editor: Mrs J. Dum駭il
International Programme on Chemical Safety
Date: June 1999