Note
that both bromine and fluorine are in this pesticide. |
Adverse Effects:
Ataxia
Brain
CNS
Lung
Tremor/Convulsions
Environmental
Date
active Ingredient registered in US: 1984
Bromethalin
is currently registered for the control of commensal rats
and mice in and around sewers, homes, industrial and agricultural
buildings, and similar man-made structures. It may also
be used in alleys located in urban areas, inside transport/cargo
vehicles such as ships, trains, and aircraft, and in and
around related port or terminal buildings. Baits may be
placed in rodent burrows. Placement of bromethalin formulated
as pellets or meal baits is prohibited in sewers. Baits
are not to be applied to water or areas where surface water
is present, or where there is the possibility of contaminating
food or surfaces that come in direct contact with food.
Applications may be made as frequently as necessary. At
this time the Agency is aware of only general-use bromethalin
products.
Ref: US
EPA Reregistration Eligibility Decision (RED) Rodenticide
Cluster. EPA738-R-98-007. July 1998.
Bromethalin
is used under FIFRA emergency exemptions to control introduced
rats on US islands in the Pacific Ocean.
Over
the past few years, the single dose anticoagulant brodifacoum
represented about 30 percent of total pounds of rodenticide
active ingredient. Bromadiolone ranked second with about
20 percent of the rodenticide market. Multiple-dose anticoagulants
chlorophacinone and diphacinone, and the acute poison
bromethalin accounted for another 20 percent
market share.
Ref:
US
EPA Reregistration Eligibility Decision (RED) Rodenticide
Cluster. EPA738-R-98-007. July 1998.
|
--
Bromethalin is currently registered for the control of commensal
rats and mice in and around sewers, homes, industrial and
agricultural buildings, and similar man-made structures.
It may also be used in alleys located in urban areas, inside
transport/cargo vehicles such as ships, trains, and aircraft,
and in and around related port or terminal buildings. Baits
may be placed in rodent burrows. Placement of bromethalin
formulated as pellets or meal baits is prohibited in sewers.
Baits are not to be applied to water or areas where surface
water is present, or where there is the possibility of contaminating
food or surfaces that come in direct contact with food.
Applications may be made as frequently as necessary. At
this time the Agency is aware of only general-use bromethalin
products.
-- Over
the past few years, the single dose anticoagulant brodifacoum
represented about 30 percent of total pounds of rodenticide
active ingredient. Bromadiolone ranked second with about
20 percent of the rodenticide market. Multiple-dose anticoagulants
chlorophacinone and diphacinone, and the acute poison
bromethalin accounted for another 20 percent market share.
Ref:
US
EPA Reregistration Eligibility Decision (RED) Rodenticide
Cluster. EPA738-R-98-007. July 1998.
--
Bromethalin is used under FIFRA emergency exemptions to
control introduced rats on US islands in the Pacific Ocean.
-- Bromethalin, a diphenylamine, is a neurotoxicant that
causes respiratory arrest from inadequate nerve impulse
transmission after fluid build-up and demyelination inside
the central nervous system (Spaulding and Spannring 1988,
Hyngstrom et al. 1994).
Ref:
Potential
Risks of Nine Rodenticides to Birds and Nontarget Mammals:
a Comparative Approach. December
19, 2002. US EPA Office of Prevention, Pesticices, and Toxic
Substances.
Excerpt:
Table 8 - Acute Toxicity Values of Technical Bromethalin
- page 14
|
Route |
Species |
Results |
Toxicity
Category |
MRID
(reference) |
Oral |
Rat |
LD50
(Males) = 10.7 mg/kg
LD50 (Females) = 9.1 mg/kg
|
1 |
00026524
|
Inhalation |
Rat |
LC50
= 0.024 mg/L |
1 |
00026524 |
LD50:
Median Lethal Dose. A statistically derived single
dose that can be expected to cause death in 50% of
the test animals when administered by the route indicated
(oral, dermal, inhalation). It is expressed as a weight
of substance per unit weight of animal, e.g., mg/kg.
LC50:
Median Lethal Concentration. A statistically derived
concentration of a substance that can be expected
to cause death in 50% of test animals. It is usually
expressed as the weight of substance per weight or
volume of water, air or feed, e.g., mg/l, mg/kg or
ppm.
Ref:
US
EPA Reregistration Eligibility Decision (RED) Rodenticide
Cluster. EPA738-R-98-007. July 1998. |
The
Agency [US EPA] has risk concerns for persons exposed to
bromethalin in both occupational and residential scenarios.
These concerns are based on
(1) very high acute toxicity (category I for acute oral
toxicity);
(2) very low short-term and intermediate-term NOELs (0.1
mg/kg/day and 0.025 mg/kg/day respectively);
(3) the potential for acute, short-term, and intermediate-term
exposures for occupational handlers, and for acute and short-term
homeowner exposures;
(4) a relatively high number of incidents associated with
rodenticide baits in general; and
(5) an absence of exposure data for all exposure scenarios
considered.
Ref: US
EPA Reregistration Eligibility Decision (RED) Rodenticide
Cluster. EPA738-R-98-007. July 1998.
|
Ataxia
(click
on for all fluorinated pesticides)
Ten random source male
domestic shorthair cats, 2 to 6 years old and 3.0-4.4 kg body
weight, were each given a single oral dose (1.5 mg/kg) of bromethalin
(cat Nos. 1-5) or bait vehicle carrier (cat Nos. 6-10). Bromethalin-dosed
cats developed a toxic syndrome characterized by ataxia,
focal motor seizures, vocalization, decerebrate posture, decreased
conscious proprioception, recumbency, depression, and semicoma.
Ref: Neuropathologic
findings of bromethalin toxicosis in the cat, by Dorman DC,
Zachary JF, Buck WB. Vet Pathol 1992 Mar;29(2):139-44.
Brain
(click
on for all fluorinated pesticides)
-- Subchronic Toxicity.
Sprague Dawley rats (10/sex/group)
received daily gavage doses of 0 (25% polyethylene glycol in H
O), 5, 25, or 125 micrograms/kg/day (ug/kg/day) of bromethalin
technical for 13 2 weeks. Parameters evaluated included daily
observation, weekly body weight and food consumption, ophthalmoscopy,
clinical pathology, necropsy, organ weights, and histopathology.
The NOEL is 25 µg/kg/day. The LOEL is 125 µg/kg/day, based
on spongy degeneration (leukoencephalomyelopathy) observed in
most of the central white fiber tracts of the brain, cerebellum,
pons, brain stem, and thoracic spinal cord of both sexes and optic
nerves of males. There were no effects on mortality, clinical
chemistry, ophthalmoscopy, body weight, food consumption, clinical
pathology and histopathology of other tissues (MRID 43582102).
-- In a second 90-day study, groups of 4 male and 4 female beagle
dogs were orally dosed by gavage for 90 days at levels
of 0, 5, 25, 125, or 200 ug/kg/day with bromethalin technical.
Observations included daily clinical evaluations, ophthalmoscopy,
body weight, food consumption, clinical pathology evaluations
at weeks 6 and 13, necropsy, organ weights and histopathology.
The NOEL is 25 µg/kg/day. The LOEL is 125 µg/kg/day
based on spongy degeneration observed in nervous tissue components
(cervical, thoracic, and lumbar spinal cord, brain stem, right
and left optic nerves, frontal and median brain, pons, and cerebellum)
in both sexes of dogs. At the high dose, 3 male dogs displayed
the following neurotoxic signs before death or being sacrificed
moribund: salivation and hypoactivity, followed by trembling,
myoclonia, hyperesthesia, groaning, and decubitus... (MRID 43582101).
-- The following information is in the AgencyÕs [EPA] files and
are supportive of the endpoint of toxicological concern identified
in the above studies. Ph.D. Dissertation entitled "Bromethalin-Based
Rodenticides: Mode of Action, Toxicity, Clinical Effects, and
Treatment Efficacy in Rats, Dogs, and Cats", by D. Dorman, University
of Illinois, Dept. of Veterinary Biosciences (MRID 42759602).
This dissertation is a summary of information found in the literature.
According to the summary page of the dissertation, "The purpose
of these studies was to define the toxicity of bromethalin-based
rodenticides, develop treatments, and determine new modes of action
of bromethalin..... Sublethal doses of bromethalin to dogs and
cats resulted in delayed CNS depression, hind-limb ataxia, paresis,
and paralysis. Higher doses given to dogs resulted in rapid severe
muscle tremors and generalized seizures. Bromethalin toxicosis
was also associated with increased cerebrospinal fluid pressure
and cerebral edema. Bromethalin toxicosis
produced acute and chronic EEG changes.
Predominant abnormal EEG changes included spike and spike-and-wave
EEG patterns; high voltage slow wave activity; photoconvulsive
or photoparoxysmal irritative responses, and marked voltage depression.
Histologic lesions included diffuse white
matter spongiosis, mild microgliosis, and optic nerve vacuolization.
Ultramicroscopic examination of brainstem revealed occasional
swollen axons, intramyelenic vacuolization, and myelin splitting
at the intraperiod line."
Ref: US EPA Reregistration Eligibility Decision
(RED) Rodenticide Cluster. EPA738-R-98-007. July 1998.
http://www.fluoridealert.org/pesticides/Bromethalin.RED.EPA..1998.pdf
Abstract: Ten random
source male domestic shorthair cats, 2 to 6 years old and 3.0-4.4
kg body weight, were each given a single oral dose (1.5 mg/kg)
of bromethalin (cat Nos. 1-5) or bait vehicle carrier (cat Nos.
6-10). Bromethalin-dosed cats developed a toxic syndrome characterized
by ataxia, focal motor seizures, vocalization,
decerebrate* posture, decreased
conscious proprioception, recumbency, depression, and semicoma.
Bromethalin-dosed cats were euthanatized if seizure activity or
hindlimb paralysis developed. Survival times were 48 hours (cat
No. 1), 89 hours (cat No. 2), 90 hours (cat No. 3), and 97 hours
(cat No. 4). Control cats (cat Nos. 6-10) and one bromethalin-dosed
cat (cat No. 5) were euthanatized on day 20 after dosing. Spongy
change (edema--characterized by the formation of vacuoles
in extracellular spaces and myelin
lamellae), hypertrophied fibrous
astrocytes,
and hypertrophied oligodendrocytes
were observed in the white matter of the
cerebrum, cerebellum, brain stem,
spinal cord, and optic nerve of all bromethalin-dosed cats.
Spongy change occasionally extended
into contiguous cerebellar Purkinje
cell layer and cerebral cortical gray matter.
The severity of lesions varied among cats but was most pronounced
in cat No. 5 (480 hours after dosing). A leukocytic inflammatory
response, gitter cell (macrophage) response, or
axonal degeneration was not observed in the vacuolated areas.
Ultrastructural findings included separation
of myelin lamellae at the interperiod lines with
the formation of intramyelinic vacuoles (intramyelinic edema),
rupture and coalescence of intramyelinic vacuoles into larger
extracellular spaces (spongy change),
and pronounced cytosolic edema of astrocytes
and oligodendroglial cells.
PMID: 1632057 [PubMed - indexed for MEDLINE]
Ref: Vet Pathol 1992 Mar;29(2):139-44.
Neuropathologic findings of bromethalin toxicosis in the cat.
Dorman DC, Zachary JF, Buck WB.
Abstract: Dogs given
a single oral dose of bromethalin at 6.25 mg/kg developed a toxic
syndrome characterized by hyperexcitability, tremors, seizures,
depression, and death within 15-63 hours after bromethalin administration.
Gross lesions included mild cerebral edema
(2/5) and mild pulmonary congestion (2/5). Histologic lesions
included diffuse white matter spongiosis
(5/5), mild microgliosis (3/5), optic nerve vacuolization
(3/5), mild thickening of Bowman's capsule (2/5), and occasional
splenic megakaryocytes (2/5). Ultramicroscopic examination of
midbrain stem revealed occasional swollen
axons, intramyelinic vacuolization,
and myelin splitting at the intraperiod line. Bromethalin was
detected in kidney, liver, fat, and brain
tissues, using gas chromatography with electron capture
detection. Photodegradation of extracted bromethalin may limit
accurate quantification of tissue residues.
Ref:
J Vet Diagn Invest 1990 Apr;2(2):123-8. Diagnosis
of bromethalin toxicosis in the dog; by Dorman DC, Simon J,
Harlin KA, Buck WB.
Abstract: Bromethalin
is a new rodenticide for the control of commensal rodents. Doses
in excess of the LD50 (2 mg/kg in rats) will cause death within
8-12 hr and it is preceded by one to three episodes of clonic
convulsions with death usually due to respiratory arrest. Multiple
low doses or sublethal intoxication yields hind leg weakness and
loss of tactile sensation in rodents. Histopathology of the brain
and spinal cord of these animals revealed a spongy
degeneration of the white matter which was shown upon ultramicroscopic
examination to be intramyelenic edema.
No inflammation or cellular destruction of neuronal tissue was
noted. LD50 values ranged from 1.8 mg/kg in the cat to approximately
13 mg/kg in rabbits. The only apparent nonsusceptible species
was the guinea pig which could tolerate doses in excess of 1000
mg/kg without effect. Identification of the desmethyl metabolite
was demonstrated in the blood and liver of treated animals by
comparison of chromatographic retention times to that of a reference
standard, but direct mass spectral identification was unsuccessful
in part due to the low dose which could be administered. Therefore,
the metabolism of bromethalin was studied by indirect means. Animals
were pretreated with three inducers of microsomal drug metabolism:
phenobarbital, 3-methylcholanthrene (3MC), and Aroclor 1254 (Aroclor)
and one inhibitor, SKF-525A. Pretreated mice or rats were given
an LD50 dose of bromethalin or the desmethyl analog and the percentage
of surviving animals was determined. (ABSTRACT TRUNCATED AT 250
WORDS) PMID: 3229590
Ref:
Fundam Appl Toxicol 1988 Nov;11(4):664-72 The
toxicity and mechanism of action of bromethalin: a new single-feeding
rodenticide; van Lier RB, Cherry LD. Toxicology Division,
Lilly Research Laboratories, Greenfield, Indiana 46140.
CNS
(click on for all fluorinated
pesticides)
Bromethalin, a diphenylamine,
is a neurotoxicant that causes respiratory arrest from inadequate
nerve impulse transmission after fluid build-up and demyelination
inside the central nervous system
(Spaulding and Spannring 1988, Hyngstrom et al. 1994).
Ref:
Potential
Risks of Nine Rodenticides to Birds and Nontarget Mammals: a Comparative
Approach. December 19, 2002. US EPA Office of Prevention,
Pesticices, and Toxic Substances.
Lung
(click
on for all fluorinated pesticides)
Abstract: Bromethalin
is a new rodenticide for the control of commensal rodents. Doses
in excess of the LD50 (2 mg/kg in rats) will cause death within
8-12 hr and it is preceded by one to three episodes of clonic
convulsions with death usually due to respiratory
arrest.
Ref: Fundam Appl Toxicol 1988 Nov;11(4):664-72.
The
toxicity and mechanism of action of bromethalin: a new single-feeding
rodenticide by van Lier RB and Cherry LD.
Tremors/Convulsions
(click
on for all fluorinated pesticides)
PubMed Abstract: Dogs
given a single oral dose of bromethalin at 6.25 mg/kg developed
a toxic syndrome characterized by hyperexcitability, tremors,
seizures, depression, and death within 15-63 hours after bromethalin
administration. Gross lesions included mild cerebral edema (2/5)
and mild pulmonary congestion (2/5). Histologic lesions included
diffuse white matter spongiosis (5/5), mild microgliosis (3/5),
optic nerve vacuolization (3/5), mild thickening of Bowman's capsule
(2/5), and occasional splenic megakaryocytes (2/5). Ultramicroscopic
examination of midbrain stem revealed occasional swollen axons,
intramyelinic vacuolization, and myelin splitting at the intraperiod
line. Bromethalin was detected in kidney, liver, fat, and brain
tissues, using gas chromatography with electron capture detection.
Photodegradation of extracted bromethalin may limit accurate quantification
of tissue residues.
Ref: Diagnosis of bromethalin toxicosis
in the dog, by Dorman DC, Simon J, Harlin KA, Buck WB. J Vet Diagn
Invest 1990 Apr;2(2):123-8
http://www.fluoridealert.org/pesticides/Bromethalin-MEDLINE.htm
Abstract: Bromethalin
is a new rodenticide for the control of commensal rodents. Doses
in excess of the LD50 (2 mg/kg in rats) will cause death within
8-12 hr and it is preceded by one to three episodes of clonic
convulsions with death usually due to respiratory arrest.
Multiple low doses or sublethal intoxication yields hind leg weakness
and loss of tactile sensation in rodents. Histopathology of the
brain and spinal cord of these animals revealed a spongy degeneration
of the white matter which was shown upon ultramicroscopic examination
to be intramyelenic edema.
Ref: Fundam Appl Toxicol 1988 Nov;11(4):664-72
The toxicity and mechanism of action of bromethalin: a new single-feeding
rodenticide. by van Lier RB and Cherry LD.
http://www.fluoridealert.org/pesticides/Bromethalin-MEDLINE.htm
Environmental
(click on for all fluorinated
pesticides)
Ecological
Toxicity Data. Primary toxicity to
mammals is very high for all five of these rodenticides.
Primary toxicity to birds is high
to very high for the single-feeding compounds (brodifacoum,
bromadiolone, bromethalin)...
Toxicity to aquatic organisms ranges
from moderate to very high.
Ref:
US
EPA Reregistration Eligibility Decision (RED) Rodenticide
Cluster. EPA738-R-98-007. July 1998
Table
46 - Bromethalin Freshwater Fish Acute Toxicity (page
64)
Ref:
US
EPA Reregistration Eligibility Decision (RED) Rodenticide
Cluster. EPA738-R-98-007. July 1998
|
Fish |
%
of active ingredient (a.i.) |
LC50
ppm a.i. |
Toxicity
Category |
MRID,
Author, Year |
Bluegill
sunfish
(Lepomis macrochirus)
|
99 |
598 |
Very
highly toxic |
42733501
Conner, 1993 |
Rainbow
trout
(Oncorhynchus mykiss) |
99 |
38 |
Very
highly toxic |
42733502
Conner, 1993 |
|
|