WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/DS/78.39
ORIGINAL: ENGLISH
DATA SHEETS ON PESTICIDES No. 39
June 1978
NALED
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
CLASSIFICATION:
Primary use: Insecticide
Secondary use: Acaricide and fungicide
Chemical group: Organophosphorus compound
Date issued: June 1978
1. GENERAL INFORMATION
1.1 COMMOM NAME:
Naled (ISO)
1.1.1 Identity:
1,2-dibromo-2,2-dichloroethyl dimethyl phosphate
1.1.2 Synonyms:
Dibrom
RE 4355
Local synonyms:
1.2 SYNOPSIS
Naled is an organophosphorus insecticide and acaricide of moderate
mammalian toxicity. It is not cumulative in body tissues.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
The technical product is a yellow liquid of about 93% purity with a
slightly pungent odour, b.p. 110°C at 0.5 mmHg. The pure compound
has a m.p. of 26°C.
1.3.2 Solubility
Naled is practically insoluble in water, slightly soluble in
aliphatic solvents and readily soluble in aromatic solvents.
1.3.3 Stability
Stable under anhydrous conditions, but is rapidly hydrolysed in
water: 90-100% in 48 hours at room temperature, and by alkali. It is
stable in glass containers but in the presence of metals and
reducing agents, rapidly loses bromine and reverts to dichlorvos.
1.3.4 Vapour pressure
266 x 10-6 kPa at 20°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
Emulsifiable concentrates 3.6 lb and 7.2 lb per US gal;
non-emulsifiable concentrates 12.6 lb per US gal; dusts 4%.
1.4.2 Pests controlled
Effective contact and stomach insecticide and acaricide with some
fumigant action. Brief residual activity. Recommended against adult
mosquitos and flies.
1.4.3 Use pattern
On many crop plants and under glass in mushroom houses at 3 g/1000
ft3.
1.4.4 Unintended effects
No data available.
1.5 PUBLIC HEALTH PROGRAMME
No data available.
1.6 HOUSEHOLD USE
No household use.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route
May be absorbed from the gastrointestinal tract, by inhalation and
through the intact skin.
2.1.2 Mode of action
Naled is a direct cholinesterase inhibitor.
2.1.3 Excretion products
Naled is rapidly hydrolysed to give a number of metabolites which
include dichlorvos, dichlorobromoacetaldehyde, dimethyl phosphate
and certain complex amino-acid conjugate of the degraded product.
When 25 mg/kg of 32p naled was given orally to a cow, 9% was
recovered in urine and 34% in faeces up to one week after dosing.
2.1.4 Toxicity, single dose
Oral: LD50 rat: 430 mg/kg
Dermal: LD50 rat: 800 mg/kg
LD50 rabbit: 1100 mg/kg
2.1.5 Toxicity, repeated doses:
Oral: Rats given 1/10 of the LD50 daily for 9 weeks showed
moderate inhibition of blood and brain cholinesterase.
Inhalation: No toxic effects were observed in rats and guinea-pigs
exposed to vapour at a concentration of 19 µg/l for 6 h per day, 5
days per week for 5 weeks.
Cumulation of compound: Naled is not cumulative in body tissues.
Cumulation of effect: Repeated exposure to na!ed may have a
cumulative effect on cholinesterase levels.
2.1.6 Dietary studies
Short-term: Groups of male and female rats were fed levels of 200,
400 and 800 mg technical naled kg diet respectively, for 28 days and
at levels of 800, 1600 and 3200 mg/kg diet for the balance of the
94-day test period. Growth patterns among all test animals were
comparable to the control group for the first 28 days. Significant
growth depressions and reduced food intake was observed among
animals fed 1600 and 3200 mg/kg throughout the 29-94 day feeding
period. No deaths and two isolated cases of tremor were observed
among two females in the 3200 mg/kg diet group. Blood and urine data
and clinical blood chemistry data were comparable to those of the
control animals. No gross or microscopic pathological changes could
be directly correlated to ingestion of technical naled. In another
experiment, groups of male and female dogs were administered 0.25,
0.75, 2.5 and 7.5 mg technical naled/kg diet per day for 89 days. No
mortalities or untoward signs of intoxication were observed at the
dose levels tested. Haematological studies, urine analysis, liver,
kidney function tests and microscopic examination did not reveal any
significant adverse effects. Plasma cholinesterase activity was
slightly inhibited at the 0.25 and 0.75 (mg/kg)/day levels; plasma
and erythrocyte cholinesterase activity was reduced in all animals
at dietary levels of 2.5 and 7.5 mg naled/kg per day.
Long-term: Technical naled was fed over a two-year period to a group
of male and female rats at dietary levels of 5, 25 and 100 mg/kg
diet and to groups of male and female dogs at graded dose levels of
0.25, 2.5 and 7.5 (mg/kg)/day. No adverse effects were observed in
either experiment in the following parameters: body weights and
weight gains; food consumption; mortality and intoxication
reactions; haematologic and urologic studies; gross and microscopic
pathological changes; organ weights and ratios; and rumour
incidence.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: See 2.1.6 Dietary studies, long-term.
Reproduction study and teratogenicity: Administration of 1, 5 and
25 mg technical naled/kg diet to three generations of albino rats
had no effect on mating and fertility indices, incidence of
pregnancy, parturition and gestation times, lactation indices,
offspring and their survival.
Mutagenicity: Intraperitoneal injection of male mice with single
doses of 15 and 30 mg technical naled/kg body weight, did not cause
a dominant lethal effect. No significant differences in mating
indices, early resorptions or mutation rates could be attributed to
naled administration.
Delayed neurotoxicity: No neurotoxicity was observed in hens on
high single and repeated doses.
2.1.8 Modification of toxicity:
No information available.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption
Naled may be absorbed from the gastrointestinal tracts by inhalation
and through the intact skin.
2.2.2 Dangerous doses
Single: Not known.
Repeated: Not known.
2.2.3 Observations of occupationally exposed workers
No information available.
2.2.4 Observations on exposure of the general population
No information available.
2.2.5 Observations of volunteers
No information available.
2.2.6 Reported mishaps
Entry into a chrysanthemum field previously sprayed with a
combination of naled, captan and dicofol and in which the spray had
not dried, has given rise to contact dermatitis. Three of the four
cases on subsequent patch testing, gave positive reactions to naled,
but not to other pesticides involved.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish
Toxic
2.3.2 Birds
Toxic (mallards, sharp tailed grouse, Canada geese, LD50
27-111 mg/kg).
2.3.3 Other species
Toxic (mule deer LD50 200 mg/kg). Bees unaffected.
3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(for definition of categories, see introduction)
All formulations above 5%, Category 3
All formulations 5% or less, Category 4
3.2 TRANSPORTATION AND STORAGE
All formulations - Should be transported or stored in clearly
labelled rigid and leakproof containers under lock and key safe from
access by unauthorized persons and children. No food or drink should
be stored in the same compartment.
3.3 HANDLING
All formulations in Category 3 - Full protective clothing (see
4.1.3 in part 4) should be used for all handling of the compound.
Adequate washing facilities should be available at all times during
handling and should be close to the site of handling. Eating,
drinking and smoking should be prohibited during handling and before
washing after handling.
All formulations in Category 4 - Protective clothing should be
used for those handling the concentrate. Adequate washing facilities
should be available at all times during handling and should be close
to the site of handling. Eating, drinking and smoking should be
prohibited during handling and before washing after handling.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER
All formulations - Container may be decontaminated (for method,
see paragraph 4.3 in part 4). Decontaminated containers should not
be used for food and drink. Containers that are not decontaminated
should be burned or should be crushed and buried below top-soil.
Care must be taken to avoid subsequent contamination of water
sources.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
Pre-employment medical examination including cholinesterase test for
workers desirable. Workers suffering from active hepatic or renal
disease should be excluded from contact. Special account should be
taken of the worker's mental ability to comprehend and follow
instructions. Training of workers in techniques to avoid contact
essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations - Pilot and loaders should have special training
in application methods and early symptoms of poisoning and must wear
a suitable respirator. Flagmen, if used, should wear overalls and be
located well away from the dropping zone.
3.7 LABELLING
All formulations - Minimum cautionary statement - Naled is an
organophosphorus compound which inhibits cholinesterase. It is
poisonous if swallowed. If may be absorbed through the skin and by
inhalation. Avoid skin contact; wear protective gloves, clean
protective clothing and a respirator when handling the material.
Wash thoroughly with soap and water after using. Keep the material
out of reach of children and well away from foodstuffs, animal feed
and their containers. If poisoning occurs call a physician. Atropine
and pralidoxime are specific antidotes and artificial respiration
may be needed.
3.8 RESIDUES IN FOOD
Maximum residue levels have not yet been recommended by the joint
FAO/WHO Meeting on Pesticide Residues.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General
Naled is an organophosphorus compound of moderate mammalian
toxicity. It is readily absorbed by inhalation, through the intact
skin and from the gastrointestinal tract.
4.1.2 Manufacture and formulation
T.L.V.: 3 mg/m3 (ACGIH). Closed systems and forced ventilation may
be required to reduce as much as possible the exposure of workers to
the chemical.
4.1.3 Mixers and applicators
When opening the container and when mixing, protective impermeable
boots, clean overalls, gloves and respirator should be worn. Mixing,
if not mechanical, should always be carried out with a paddle of
appropriate length. When spraying tall crops or during aerial
application, a face mask should be worn as well as an impermeable
hood, clothing, boots and gloves. The applicator should avoid
working in spray mist and avoid contact with the mouth or skin.
Particular care is needed when equipment is being washed after use.
All protective clothing should be washing immediately after use,
including the insides of gloves. Splashes must be washed immediately
from the skin or eyes with large quantities of water. Before eating,
drinking or smoking, hands or other exposed skin should be washed.
4.1.4 Other associated workers (including flagmen in aerial
operations)
Persons exposed to naled and associated with its application, should
wear protective clothing and observe the precautions described above
in 4.1.3 under "mixers and applicators".
4.1.5 Other populations likely to be affected
With good agricultural and manufacturing practice subject to 4.2
below, other persons should not be exposed to hazardous amounts of
naled.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Unprotected persons should be kept out of treated areas for at least
one day.
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS
Residues in containers should be emptied in a diluted form into a
deep pit, taking care to avoid ground waters. The empty container
may be decontaminated by rinsing two or three times with water and
scrubbing the sides. An additional rinse should be carried out with
5% sodium hydroxide solution, which should remain in the container
overnight. Impermeable gauntlets should be worn during this work and
a soakage pit should be provided for the rinsings. Decontaminated
containers should not be used for food and drink. Spillage of naled
and its formulations should be removed by washing with 5% sodium
hydroxide solution and then rinsing with large quantities of water.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning
Early symptoms of poisoning may include, excessive sweating,
headache, weakness, nausea, vomiting, stomach pains, blurred vision,
slurred speech, salivation and muscle twitching. Later there may be
convulsions, coma, loss of reflexes and loss of sphincter control.
4.4.2 Treatment before person is seen by a physician; if these
symptoms appear following exposure
The person should stop work immediately, remove contaiminated
clothing and wash the affected skin with water and soap, if
available, and flush the area with large quantities of water. If
swallowed, vomiting should be induced if the person is conscious. In
the event of collapse, artificial respiration should be given,
bearing in mind that if mouth to mouth respiration is used, vomit
may contain toxic amounts of haled.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information
Naled is an organophosphorus insecticide of moderate mammalian
toxicity, which also has some fumigant properties. It is readily
absorbed through the intact skin, by inhalation and from the
gastrointestinal tract.
5.1.2 Symptoms and signs
Initial symptoms of poisoning may include excessive sweating,
headache, weakness, giddiness, nausea, vomiting, stomach pains,
blurred vision, slurred speech, salivation, and muscle twitching.
More advanced symptoms of poisoning may be convulsions, coma, loss
of reflexes and loss of sphincter control.
5.1.3 Laboratory
The most important laboratory finding is reduction in activity of
blood cholinesterases.
5.1.4 Treatment
If the pesticide has been ingested, unless the patient is vomiting,
rapid gastric lavage should be performed using 5% sodium
bicarbonate, if available. For skin contact, the skin should be
washed with soap and water. If the compound has entered the eyes,
they should be washed with isotonic saline or water.
Persons without signs of respiratory insufficiency but with manifest
peripheral symptoms should be treated with 2-4 mg of atropine
sulfate and 1000-2000 g of pralidoxime chloride or 250 mg of
Toxogonin (adult dose) by slow intravenous injection. More atropine
may be given as needed.
Persons with severe intoxication with respiratory difficulties,
convulsions, and unconsciousness, should immediately be given
atropine and an oxime. In such severe cases, 4-6 mg of atropine
sulfate should be given initially followed by repeated doses of 2 mg
at 5-10 minute intervals. The patient's condition including
respiration, blood pressure, pulse frequency, and salivation should
also be carefully observed as a guide to further administration of
atropine. If the patient is cyanotic, artificial respiration should
be given simultaneously with atropine sulfate. Contraindicated are
morphine, barbiturates, phenothiazine tranquillizers and central
stimulants of all kinds.
5.1.5 Prognosis
Although there have been no reported cases, if may be assumed that
if the acute toxic effect is survived, the chances of complete
recovery are good. In very severe cases it is possible that without
adequate artificial respiration, prolonged anoxia could give rise to
permanent brain damage.
5.1.6 Reference of previous reported cases
Edmundson, W. F. (1967) Dermatitis from naled, Arch. Envir. Health,
15, 89-91.
5.2 SURVEILLANCE TESTS
Test Normal level* Action level* Symptomatic level*
Plasma cholinesterase 100% 50% variable
Erythrocyte cholinesterase 100% 70% 40%
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compounds
References are given only.
Most methods for the estimation of residues of naled require the
conversion of naled to dichlorvos by reaction with a sulfydryl
compound and estimation by microcolouri-metric gas chromatography,
see: Pack, D. E. et al. (1964) Dibrom, 11, 125 Analytical methods
for pesticides plant growth regulators and food additives, Vol. II
insecticides edited by G. Zweig, Academic Press.
Analytical methods for pesticides and plant growth regulators, Vol.
VI Gas chromatographic analysis, edited by G. Zweig & J. Sherma,
Academic Press, 1972.
A method involving flame photometric determination of bromine may
also be useful, see: Gutsche, B. et al. (1969) Ueber eine
Angwendungsmaeglichkeit der glammen photometrischen Bromanlysen [The
suitability of flame photometric bromine analysis] Deut
Lebansm-Rundscha, 65(11), 352-355.
*Expressed as percentage of pre-exposure activity.
5.3.2 Other tests in cases of poisoning
Levels of cholinesterase activity in the blood provide the most
useful data in diagnosi of poisoning. Michel, N. O. (1949) J. Lab.
Clin. Med., 34, 1564-1568. Ellman, G. L. et al. (1961) Biochem.
Pharmacol., 7, 88-95.