Heart
- Adverse Effects
Fluorinated and Fluoride Pesticides
The
use of high doses increases the likelihood that potentially
significant toxic effects will be identified. Findings of
adverse effects in any one species do not necessarily indicate
such effects might be generated in humans. From a conservative
risk assessment perspective however, adverse findings in
animal species are assumed to represent potential effects
in humans, unless convincing evidence of species specificity
is available.
--
Food and Agricultural Organization of the United Nations
Note:
This is not an exhaustive list.
As time allows more information will be added.
--
Potential Health Effects:If inhaled or swallowed, this compound can cause fluoride
poisoning. Early symptoms include nausea, vomiting, diarrhea,
and weakness. Later effects include central
nervous system effects, cardiovascular
effects and death.
-- Ingestion: May cause salivation,
nausea, vomiting, diarrhea, and abdominal pain, followed by symptoms
of weakness, tremors, shallow respiration,
carpopedal spasm, convulsions,
and coma. May cause brain and kidney damage. Affects
heart and circulatory system. Death
may be caused by respiratory paralysis. Lethal dose estimated
at between 1 teaspoonful and 1 oz.
Ref: Analytyka. Material Safety Data Sheet.
Online as of September 15, 2003. http://www.analytyka.com.mx/tabla%20periodica/MSDS/N/AMMONIUM%20BIFLUORIDE.htm
If inhaled or swallowed,
this compound can cause fluoride poisoning. Early symptoms include
nausea, vomiting, diarrhea, and weakness. Later effects include
central nervous system effects, cardiovascular
effects and death.
Ingestion: May cause salivation, nausea, vomiting, diarrhea, and
abdominal pain, followed by weakness, tremors, shallow respiration,
cardopedal spasm, convulsions, and
coma. May cause brain and kidney damage. Death may be caused by
respiratory paralysis. Affects heart and
circulatory system.
Chronic Exposure: Chronic exposure may cause mottling of teeth
and bone damage (osteosclerosis) and fluorosis. Symptoms of fluorisis
include brittle bones, weight loss, anemia, calcified ligaments,
general ill health and joint stiffness.
Ref: 1999 Material Safety Data Sheet prepared
by Mallinckrodt Baker, Inc. http://www.fluoridealert.org/pesticides/Ammonium.F.MSDS.htm
-- INHALATION - May
cause severe throat irritation, cough, dyspnea, cyanosis, lung
injury and noncardiogenic pulmonary edema.
-- RESPIRATORY. ACUTE EXPOSURE. Dyspnea, bronchospasm (with abnormal
PFTs and hypoxia), chemical pneumonitis, pulmonary edema (can
be hemorrhagic), tracheobronchitis, upper airway obstruction,
chemical burns (larynx, trachea, bronchi) and ARDS may occur following
inhalation.
Ref: TOXNET profile from Hazardous Substances
Data Bank for Ammonium fluoride. http://www.fluoridealert.org/pesticides/Ammonium.fluoride.TOXNET.htm
-- TARGET
ORGANS: Respiratory system, cardio-vascular system, central nervous
system.
-- ACUTE: The most significant hazard associated with Tetrafluoromethane
[carbon tetrafluoride] is inhalation of high concentrations of
Tetrafluoromethane. Such overexposure can cause oxygen deficiency.
Symptoms of such exposures include respiratory difficulty, ringing
in ears, headaches, dizziness, indigestion, nausea, and possible
death...
-- INHALATION: Exposures to high concentrations of this gas may
cause sensitization of the heart
to adrenaline and nor-adrenaline. Effects of such overexposure
can include light-headedness, giddiness, shortness of breath and
in extreme cases, irregular heartbeats, cardiac arrest, and death.
High concentrations of this gas can cause an oxygen-deficient
environment. Individuals breathing such an atmosphere may experience
symptoms which include headaches, ringing in ears, dizziness,
drowsiness, unconsciousness, nausea, vomiting, and depression
of all the senses. The skin of a victim of overexposure may have
a blue color. Under some circumstances of overexposure, death
may occur. The effects associated with various levels of oxygen
are as follows:
CONCENTRATION SYMPTOMS OF EXPOSURE
12-16% Oxygen: Breathing and pulse rate increased, muscular coordination
slightly disturbed.
10-14% Oxygen: Emotional upset, abnormal fatigue, disturbed respiration.
6-10% Oxygen: Nausea and vomiting, collapse or loss of consciousness.
Below 6%: Convulsive movements, possible respiratory collapse,
and death.
Ref: Material Safety Data Sheet: TETRAFLUOROMETHANE
- CF4 MSDS (Document # 001051). Airgas. http://www.airgas.com/documents/pdf/1051.pdf
HUMAN HEALTH
EFFECTS.
-- Overexposure by
inhalation may include temporary central nervous system
depression with such effects as dizziness,
headache, confusion, incoordination, and loss of consciousness;
or with gross overexposure (>20%), temporary alteration of the
heart's electrical activity with irregular pulse, palpitations
or inadequate circulation. Eye or skin contact with the liquid
may cause frostbite.
-- Individuals
with preexisting diseases of the central nervous or cardiovascular
systems may have increased susceptibility to the toxicity of excessive
exposures.
Ref:
UndatedDuPont's Material Safety Data Sheet. http://www.fluorideaction.org/pesticides/carbon.tetrafluoride.MSDS.pdf
The substance may cause
effects on the cardiovascular system
and central nervous system, resulting in cardiac
disorders and central nervous system depression.
Ref: ICSC: 0049. March 2002. International
Programme on Chemical Safety (IPCS).
http://www.inchem.org/documents/icsc/icsc/eics0049.htm
Potential Health Effects
- Inhalation of high concentrations of vapor is harmful and may
cause heart irregularities, unconsciousness or death. ..
Human Health Effects: Higher exposures may lead to temporary
alteration of the heartÕs electrical activity with irregular pulse,
palpitations, or inadequate circulation. Fatality may occur
from gross overexposure. Individuals with
preexisting diseases of the central nervous or cardiovascular
system may have increased susceptibility to the toxicity of excessive
exposures.
Ref: Material Safety Data Sheet for Freon
22. DuPont. 1996. http://www.fluoridealert.org/pesticides/Chlorodifluoromethane.MSDS.pdf
PubMed abstract: Case
report of a plumber's fatal work accident. Investigations on the
causes of death made at post mortem showed that the worker had
absorbed a large quantity of freon 22
(chlorodifluoromethane) which is known to
be a narcotic agent and capable of
inducing cardiac arrhythmia. It is believed freon inhalation
was the cause of loss of consciousness with consequent death from
drowning in the water issuing from the pipes. It is concluded
that preventive measures need to be reinforced by adequate information
to the workforce on the risks connected to this type of gas.
Ref: Med Lav 1992 Jul-Aug;83(4):361-4. [Sudden
death caused by freon 22?]. [Article in Italian]; by M Dal
Grande et al.
PubMed Abstract: After
exposure to decomposed chlorodifluoromethane (freon-22), a 65-year-old
man developed respiratory symptoms such
as cough, blood-stained sputum, and increasing dyspnea. Three
weeks later, his family doctor diagnosed infectious bronchitis.
Another week later he died due to myocardial
infarction. The discussion focuses on an inflammatory process
caused by the inhalation of decomposed freon and its possible
association with myocardial infarction.
Ref: Scand J Work Environ Health 2002 Jun;28(3):205-7,
Inhalation
of decomposed chlorodifluoromethane (freon-22) and myocardial
infarction; by Sjogren
B, Gunnare S, Sandler H.
Organophosphate
esters were studied in terms of their ability to affect neuropeptides
in the rat central nervous system. The in vivo biosynthesis of
enkephalin peptides in the basal ganglia and of vasopressin and
oxytocin in the hypothalamus were studied and the effect of subcutaneous
administration of diisopropylfluorophosphate (DFP) in the biosynthesis
of these neuropeptides was assessed. It
was found that DFP inhibited the biosynthesis of vasopressin and
oxytocin. These results suggest that organophosphates exert their
effects not only on cholinergic systems but also on neuropeptide
systems important in endocrine and cardiovascular function. Annual
rept. 1983-1984, {abstgract truncated]
Ref:
1986 - Effects of Organophosphate Esters on Neuropeptide Systems;
by McKelvy JF. Report No. NTIS/AD-A186 594/8 from The National
Technical Informatin Service.
Freon 152A ... causes
sensitization /of the heart/ to epinephrine in the dog. The mouse
exposed to FC 152A showed bronchoconstriction, respiratory depression,
and decreased compliance, but not cardiac arrhythmia. In the mouse
that developed bronchitis and in the rat with pulmonary emphysema,
the administration ... provoked abnormalities in the electrocardiogram.
These observations were noteworthy, indicating
that bronchopulmonary disease increases the cardiotoxicity to
FC 152A ... [Clayton, G. D. and F. E. Clayton (eds.). Patty's
Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology.
3rd ed. New York: John Wiley Sons, 1981-1982. 3095]
Ref:
1,1-DIFLUOROETHANE CASRN: 75-37-6. Hazardous Substance Data Bank
at Toxnet.
http://toxnet.nlm.nih.gov/
Dichlorodifluoromethane
- Insecticide, Fungicide, Propellant, US EPA List 2 Inert -
CAS No. 75-71-8
--
11 subjects (7 being maintenance technicians of large cooling
and refrigerating systems) were exposed for 130 min to CFC-12
(weighted exposure 0.46, 49.9, and 87.7 g/cu m. ... This led to
acute reduction of ventilatory lung capacity only at the two highest
CFC-12 concentrations, under which conditions a significant
decrease in the heart frequency was also observed. [WHO;
Environmental Health Criteria 113: Fully Halogenated Chlorofluorocarbons
p.90 (1990)]
-- Ten subjects /were exposed/ to CFC-11, CFC-12, CFC-114, two
mixtures of CFC-11 and CFC-12, and a mixture of CFC-12
and CFC-114 (breathing concentrations between 16 and 150
g/cu m) for 15, 45, or 60 seconds, and found significant acute
reduction of ventilatory lung capacity (FEV50, FEF25) on exposure
to each chlorofluorocarbon, as well as bradycardia and increased
variability in heart rate in seven subjects, negative T-waves
in two subjects (one was exposed to CFC-11 and CFC-12), and atrioventricular
block in 1 subject (CFC-114). Mixtures exerted stronger respiratory
effects than individual chlorofluorocarbon at the same
level of exposure. [WHO; Environmental Health Criteria 113: Fully
Halogenated Chlorofluorocarbons p.90 (1990)]
-- Deaths resulting from cardiovascular
collapse after arrhythmias have been reported after inhalation
of Freons 11 and 12.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis
and Treatment of Human Poisoning. New York, NY: Elsevier Science
Publishing Co., Inc. 1988. 528]
Ref:
TOXNET profile from Hazardous Substances Data Bank for Dichlorodifluoromethane.
http://www.fluoridealert.org/pesticides/Dichlorodifluorometh.TOXNET.htm
-- Health
Hazards - General ... Inhalation of high concentrations
may also result in temporary alteration
of the heart's electrical activity by increasing the sensitivity
of the heart to the arrhythmogenic action of epinephrine, causing
irregular pulse, palpitations, or inadequate circulation
(Dupont, 1996A; Dupont, 1996F; OSHA, 1998; Reprotext, 2003). Deliberate
inhalation (ÒsniffingÓ) may cause death without warning (Dupont,
1996A; Dupont, 1996F; OSHA, 1998).
-- Acute Effects ... Inhalation of
high concentrations (~5,000 ppm) is associated with the development
of arrhythmias and sudden death due to myocardial
sensitization to endogenous catecholamines (e.g., epinephrine).
-- Predisposing Conditions. Individuals
with pre-existing diseases of the central nervous or cardiovascular
system may have increased susceptibility to the effects
of Freons (Dupont, 1996A; OSHA, 1998; Dupont, 1996B; Dupont, 1996D).
Persons exposed to epinephrine or other sympathomimetic amines,
e.g., bronchodilators and nasal decongestants (e.g., Sudafed ¥),
might be at increased risk for the cardiotoxic
effects of Freons (Reprotext, 2003).
-- Special Concerns for Children.
Children may inhale relatively larger doses of Freon because,
relative to their body weight, they have a greater lung surface
area and larger minute volume than adults. Since Freon has a high
vapor density, children could also receive high doses due to their
short stature and the higher levels of Freon vapor that may be
present near the ground when Freon is spilled.
Ref:
September
24, 2003 (Revised)
- FREON [11, 12, 113].
Technical Support Document: Toxicology.
Clandestine Drug Labs/ Methamphetamine. Volume 1, Number 11. California
EPA, Office of Environmental Health Hazard Assessment (OEHHA),
Department of Toxic Substances Control.
Other Long-Term Effects - Repeated exposure
can cause the heart to beat irregularly.
Ref: HAZARDOUS SUBSTANCE FACT SHEET. RIGHT
TO KNOW PROJECT.
Produced by: New Jersey Department of Health and Senior Services.
Provided by: Canadian Centre for Occupational Health and Safety. http://www.cchst.ca/products/databases/samples/njhsfs.html
--
When admin alone to anesthetized mice at concn of 100,000 ppm,
CFC-21 induced arrhythmia and sensitized
the heart to epinephrine. Tachycardia
with hypotension was observed in both monkeys and dogs that were
anesthetized and exposed at 50,000-100,000 ppm. Bronchoconstriction
was noted at 25,000 ppm. [American Conference
of Governmental Industrial Hygienists, Inc. Documentation of the
Threshold Limit Values and Biological Exposure Indices. 6th ed.
Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 434]**PEER REVIEWED**
-- /GUINEA PIGS/ ... EXPOSED /UP TO 2 HR/ @ CONCN OF 10.2% DIED
&, ON AUTOPSY, CONGESTED LUNGS, CONGESTED KIDNEYS, CONGESTED LIVER,
DISCOLORED SPLEEN, & HIGHLY CONTRACTED HEART
WERE FOUND. [American Conference of Governmental
Industrial Hygienists. Documentation of the Threshold Limit Values
for Substances in Workroom Air. Third Edition, 1971. Cincinnati,
Ohio: AmericanConference of Governmental Industrial Hygienists,
1971. (Plus supplements to 1979) 81]**PEER REVIEWED**
Ref: TOXNET profile from Hazardous
Substances Data Base for DICHLOROFLUOROMETHANE http://www.fluoridealert.org/pesticides/Dichlorofluoromethan.TOXNET.htm
-- The American Conference
of Governmental Industrial Hygienists (ACGIH) has assigned dichlorotetrafluoroethane
a threshold limit value (TLV) of 1000 ppm (6990 mg/m(3)) as a
TWA for a normal 8-hour workday and a 40-hour workweek [ACGIH
1994, p. 19].
-- Rationale for Limits: The NIOSH limit is based on the risk
of respiratory irritation, asphyxia at high concentrations [NIOSH
1992]. The ACGIH limit is based on the risk of systemic toxicity
and cardiac sensitization [ACGIH
1991, p. 444].
-- Effects on Animals: dichlorotetrafluoroethane is a cardiac
sensitizer, an asphyxiant, and a weak narcotic at extremely high
concentrations [ACGIH 1991]. Dogs exposed to 200,000 ppm of dichlorotetrafluoroethane
for 16 hours died, but exposures at this level for 8 hours caused
tremor and convulsions [Hathaway
et al. 1991]. Serious arrhythmia
occurred in one of 12 dogs exposed once to 25,000 ppm of dichlorotetrafluoroethane
and given intravenous epinephrine. Dichlorotetrafluoroethane is
reported to reduce pulmonary compliance and act as a bronchoconstrictor
[ACGIH 1991]. Guinea pigs exposed to a dichlorotetrafluoroethane
concentration of 47,000 ppm developed respiratory irritation [Hathaway
et al. 1991]. Repeated exposure to sprayed dichlorotetrafluoroethane
caused localized skin inflammation in rats and irritation of the
eyes of rabbits [ACGIH 1991].
Ref: US OSHA (Occupational Safety &
Health Administration, U.S. Department of Labor). http://www.osha-slc.gov/SLTC/healthguidelines/dichlorotetrafluoroethane/recognition.html
-- In persons with
impaired pulmonary function, especially those with obstructive
airway diseases, the breathing of Refrigerant
114 might cause exacerbation of symptoms due to its irritant
properties. ... In persons with impaired
cardiovascular function, especially those with history of cardiac
arrhythmias, the inhalation of Refrigerant 114 might cause exacerbation
of disorders of the conduction mechanism due to sensitizing effects
on the myocardium. [Mackison, F. W., R. S. Stricoff, and
L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health
Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123
(3 VOLS). Washington, DC: U.S. Government Printing Office, Jan.
1981. 1]
-- In one study, ten subjects were exposed to CFC-11, CFC-12,
and CFC-114; two mixtures of CFC-11
and CFC-12; & a mixture of CFC-12 and CFC-114 )breathing concn
between 16 & 150 g/cu m [2300 & 21,400 ppm]) for 15, 45, or 60
sec. Significant acute reduction of ventilatory lung capacity
was reported in each case, as well as bradycardia & increased
variability in heart rate & atrioventricular block. It was concluded
that the mixtures exerted stronger respiratory
effects than individual chlorofluorocarbons at the same level
of exposure. [American Conference of Governmental Industrial
Hygienists, Inc. Documentation of the Threshold Limit Values and
Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati,
OH: ACGIH, 1991. 444]
-- 10 PERSONS WERE EXPOSED TO FREON 114
FOR LENGTHS OF 15, 45, OR 60 SEC. IT INDUCED BIPHASIC REDN
OF VENTILATORY CAPACITY. MOST PERSONS DEVELOPED
VARIATIONS IN HEART RATE EXCEEDING THOSE NOTED BEFORE EXPOSURE.
IN A FEW THERE WERE INVERSION OF T-WAVE &
1 CASE OF HEART BLOCK. [VALIC ET AL; BR J IND MED 34 (2):
130-6 (1977)]
-- Fluorocarbon propellants are anesthetic and cardiotoxic.
... Aerosol propellants produce hallucinogenic effects, and, rarely,
contact dermatitis. /Fluorocarbon propellants/ [Ellenhorn, M.J.
and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment
of Human Poisoning. New York, NY: Elsevier Science Publishing
Co., Inc. 1988. 528]
-- Clinical pathologists exposed to fluorocarbons in the preparation
of frozen tissue sections have been seen to develop coronary
heart disease. /Fluorocarbons/ [Clayton, G.D., F.E. Clayton
(eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A,
2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley
& Sons Inc., 1993-1994. 1209]
Ref:
1,2-DICHLORO-1,1,2,2-TETRAFLUOROETHANE. CASRN: 76-14-2. TOXNET
profile from Hazardous Substances Data Base. http://www.fluorideaction.org/pesticides/dichlorotetrafluoroe.toxnet.htm
Abstract: The inhalation toxicity of a series of fluorinated
ethanes which are metabolized to fluoroacetate (144490) were studied
in the male CD-rat. When the rats were exposed
by inhalation to 1,2-difluoroethane (624-72-6), 1-chloro-2-fluoroethane
(762505), 1-bromo-2-fluoroethane (762492), or 1-chloro-1,2-difluoroethane
(338647) for 4 hours, the lethal concentrations for each compound
were less than 100 parts per million (ppm). Tests with
1,1-difluoroethane (75376) showed a 4 hour median lethal dose
of over 400,000ppm in rats. Clinical signs of fluoroacetate toxicity
were noted including lethargy, hunched posture, and convulsions.
Concentrations of citrate increased in serum and heart tissue
on exposure to 1,2-difluoroethane, 1-chloro-2-fluoroethane,
1-chloro-1,2-difluoroethane, and 1-bromo-2-fluoroethane. Fluoroacetate
was present in the urine of rats exposed to each of the toxic
compounds. Rats exposed to 1,2-difluoroethane showed fluorocitrate
in the kidneys. Rats exposed to 1,2-difluoroethane
showed a concentration related elevation of serum and heart citrate
up to 1000ppm of the compound. Serum citrate
was up five fold and heart citrate 11 fold over control
levels. The authors suggest that the metabolism of the
toxic fluoroethane was initiated at the carbon/hydrogen bond,
with metabolism to fluoroacetate via an aldehyde or an acyl fluoride.
The authors conclude that 1-(di)halo-2-fluoroethanes are highly
toxic to rats and should be viewed as a hazard to humans.
Ref: Fluoroacetate-Mediated Toxicity of
Fluorinated Ethanes; by Keller DA, Roe DC, Lieder PH. Fundamental
and Applied Toxicology, Vol. 30, No. 2, pages 213-219, 1996.
REPRODUCTIVE HAZARDS:
An increase in sternebral ossification defects,
hydronephrosis, runting (pup weight less than 2.7 g), variant
rib ossifications, extra vertebral ossification centers,
cardiac septal defects, and intrauterine
growth retardation were noted in rats.
Ref: TOXNET profile from Hazardous Substances
Data Base. http://www.fluoridealert.org/pesticides/Ethylene.fluorohydri.TOXNET.htm
Flucythrinate
- Acaricide, Insecticide
- CAS No. 70124-77-5
"Chronic Dietary Toxicity
Study in Dogs." (IRDC, 1/5/84.) Flucythrinate (85.4%) fed in the
diet at 0, 30, 100 and 300 ppm of 24 months; eye exam included;
6/sex/group; NOEL stated in report = 100 ppm (emesis); reviewerÕs
NOEL = 30 ppm (emesis, others); adverse
"pharmacological" effect on heart (arrythmia, slower rate);
ACCEPTABLE, Possible adverse effect.
JG, 7/14/86.
Ref: Summary
of Toxicological Data for Flucythrinate. California
EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
July 18, 1986 Revised August 12, 1987. Also available at
http://www.cdpr.ca.gov/docs/toxsums/pdfs/2168.pdf
-- In the rat chronic
feeding / carcinogenicity study the NOEL was less than 1.2 mg/kg/day
in males and less than 1.5 mg/kg/day in females and the LOEL was
1.2 mg/kg/day in males and 1.5 mg/kg/day in females based
on methemoglobinemia and multi-organ effects in blood, kidney,
spleen,
heart, and uterus.
Under experimental conditions the treatment did not alter the
spontaneous tumor profile. In the mouse carcinogenicity study
the NOEL was less than 7.4 mg/kg/day in males and was 9.4 mg/kg/day
for females and the LOEL was 7.4 mg/kg/day for males and was 38.4
mg/kg/day for females based on cataract incidence and severity.
There was no evidence of carcinogenicity for flufenacet in this
study.
-- A 55-day dog study subcutaneous via mini-pump with Thiadone
[flufenacet metabolite] supports the hypothesis that limitations
in glutathione interdependent pathways and antioxidant stress
result in metabolic lesions in the brain
and heart following flufenacet exposure. Non-guideline
studies provide evidence supporting the hypothesis of an extra
thyroidal mechanism to explain alterations in circulating thyroid
hormone concentrations.
-- Chronic Feeding/ Carcinogenicity (rat): NOEL < 25 ppm [1.2
mg/kg/day in males and 1.5 mg/kg/day in females]. LOEL = 25 ppm
[1.2 mg/kg/day in males and 1.5 mg/kg/day in females] based on
methemoglobinemia and multi-organ effects
in blood, kidney, spleen, heart,
and uterus.
Under experimental
conditions the treatment did not alter the spontaneous tumor profile.
-- Special Studies: In a 55-day dog study subcutaneous via mini-pump
with Thiadone [flufenacet metabolite] support the hypothesis that
limitations in glutathione interdependent pathways and antioxidant
stress result in metabolic lesions in the
brain and heart following flufenacet exposure. Non guideline
studies provide evidence supporting hypothesis of an extra thyroidal
mechanism to explain alterations in circulating thyroid hormone
concentrations.
Ref: US EPA. Pesticide Fact Sheet. Flufenacet
Reason for Issuance: Conditional Registration Date Issued: April
1998.
http://www.epa.gov/opprd001/factsheets/flufenacet.pdf
-- "Teratology
Study of S-53482 Administered Dermally to Rats";
(S. Kawamura; Environmental Health Science Laboratory, Sumitomo
Chemical Co., Ltd., Osaka, Japan; Project ID 2018; 3/14/91); The
skin of twenty four mated Slc:SD¨ female rats was treated with 0,
30 or 100 mg/kg/day of S-53482 (lot no. PYG-89021-M, purity: 94.8%)
for 6 hours/day from day 6 through day 15 of gestation. An additional
group of 25 females were treated in the same manner with 300 mg/kg/day
of the test material... There was an increased incidence/litter
of cardiac malformations (0:1/23 vs.
300:9/17). The predominant cardiac malformation
was a ventricular septal defect... Among the visceral variations
noted for the 300 mg/kg group, there was an increased incidence/litter
of persistent right azygous vein (0:
1/23 vs. 300: 7/17) and supernumerary coronary
orifice in the heart (0:0/23 vs. 300: 3/17). Indicated adverse
effect: increased incidence of a ventricular
septal defect in the heart; Maternal NOEL: 100 mg/kg/day
(based upon decreased weight gain noted for the 300 mg/kg treatment
group); Developmental NOEL: 30 mg/kg/day (based upon the increased
incidence of cardiovascular variations
experienced by the 100 mg/kg treatment group); Study acceptable.
(Moore, 6/7/02)
Ref: January
32, 2003 (revised) -
Summary of Toxicological
Data. California EPA, Department of Pesticides
Regulation, Medical Toxicology Branch.
-- "Preliminary
Teratology Study of SB-1297, SB-1335 or SB-1855 Administered Orally
to Rats"; (S. Kawamura; Environmental
Health Science Laboratory, Sumitomo Chemical Co. Ltd, Osaka, Japan;
Project ID 599; 1/9/89); Six mated female SPF Slc:SD rats/group
were dosed by oral gavage with 0, 30, 100, 200, or 500 mg/kg of
SB-1855 (lot no. OK-86-01, purity: 98.2%, also identified as S-53482
in vol. 52894-082) from gestation day 6 through day 15... The
developing fetuses were adversely affected at all of the treatment
levels. There were no surviving fetuses in the 200 and 500 mg/kg
treatment groups. Excessive death was noted for both the 30 and
100 mg/kg groups. The mean fetal body weights of the 30 mg/kg
group were less than those of the control (p<0.05). Teratologic
abnormalities for the 30 mg/kg group included ventricular
septal defects in the heart (0:0/38 vs. 30:11/25, p<0.01)),
persistent left umbilical artery
(0:0/38 vs. 30:3/25), and wavy ribs (0:0/42
vs. 30:9/28). These data indicate that, even at the 30 mg/kg treatment
level, significant developmental defects occurred. Possible adverse
effect: ventricular septal defects in the
heart. Maternal NOEL: not determinable. Developmental NOEL:
< 30 mg/kg/day (based upon the incidence of developmental defects
in the 30 mg/kg treatment group). Study supplemental (non-guideline
study). (Moore, 7/29/02)
Ref:
January 32, 2003 (revised) -
Summary of Toxicological
Data. California EPA, Department of
Pesticides Regulation, Medical Toxicology Branch.
-- Prenatal developmental
- Maternal NOAEL = 30 mg/kg/day (HDT) LOAEL = rat (oral) >30 mg/kg/day
(HDT) Developmental NOAEL = 3 mg/kg/day LOAEL = 10 mg/kg/day based
on cardiovascular effects
(especially ventricular septal defects).
-- Prenatal developmental - Maternal NOAEL = 300 mg/kg/day (HDT)
LOAEL rat (dermal) = >300 mg/kg/day (HDT) Developmental NOAEL
= 30 mg/kg/day LOAEL = 100 mg/kg/day based on cardiovascular
effects (especially ventricular septal defects).
-- Special Study - Rat Developmental: Critical Time for Defects:
Pregnant females were administered 400 mg/ kg by gavage on gestation
day 11 or 12 or 13 or 14 or 15. Day 12 administration showed:
largest incidence of embryonic death, lowest fetal body weights
and greatest incidence of ventricular spetal
defects.
Ref: Federal Register: April 18, 2001. Flumioxazin;
Pesticide Tolerances. Final Rule. http://www.fluoridealert.org/pesticides/Flumioxazin.FR.Apr.18.2001.htm
-- Rats. A 90-day subchronic
toxicity study was conducted in rats, with dietary intake levels
of 0, 30, 300, 1,000 and 3,000 ppm flumioxazin technical (98.4%
purity). The NOAEL of 300 ppm was based on decreased bwts; anemia;
increases in absolute and/or relative liver, kidney, brain, heart,
and thyroid weights, and histological changes in the spleen, liver,
and bone marrow related to the anemia.
-- A second 90-day subchronic toxicity study was conducted with
a sample of flumioxazin technical of typical purity (94.8%) at
dietary concentrations of 0, 30, 300, 1,000, and 3,000 ppm. The
NOAEL was 30 ppm based on anemia and related hematological changes;
increases in liver, heart, kidney,
and thyroid weights; and histological changes in the spleen, liver,
and bone marrow related to the anemia.
Ref: Federal Register: February 14, 2001
[Notices] [Page 10292-10301]. Notice of Filing a Pesticide Petition
to Establish a Tolerance for a Certain Pesticide Chemical in or
on Food. http://www.fluoridealert.org/pesticides/Flumioxazin.FR.Feb.14.2001.htm
-- there is concern
for the severity of the effects observed in fetuses and young
animals when compared to those observed in the maternal and parental
animals (dose- and treatment-related increase in the incidence
of cardiovascular abnormalities, particularly
ventricular septal defect, in the developmental studies;
and decreases in the number of live born pups and
pup body weights in the absence of parental toxicity in
the reproduction study).
Ref: US EPA Pesticide Fact Sheet. April
12, 2001.
http://www.epa.gov/opprd001/factsheets/flumioxazin.pdf
Pregnant females were
admin 400 mg/kg by gavage on gestation day 11 or 12 or 13 or 14
or 15. Day 12 admin showed: largest incidence of embryonic death,
lowest fetal body weights
& greatest
incidence of ventricular spetal defects.
Ref: US EPA Pesticide Fact Sheet. April
12, 2001.
http://www.epa.gov/opprd001/factsheets/flumioxazin.pdf
Fluoroacetamine
-
Insecticide, Rodenticide - CAS No. 640-19-7
(also known as Fluoroacetamide
or Compound 1081)
-- Mechanism of action:...
THE HEART & CNS ARE THE MOST CRITICAL
TISSUES INVOLVED IN POISONING BY GENERAL INHIBITION OF
OXIDATIVE ENERGY METABOLISM. /FLUOROACETATE/ [Doull, J., C.D.Klassen, and M.D. Amdur (eds.).
Casarett and Doull's Toxicology. 3rd ed., New York: Macmillan
Co., Inc., 1986. 565]
-- Cardiac effects may include tachycardia,
ventricular fibrillation, and sudden onset of asystole. -- Moderately fast-acting rodenticide which is less likely
to lead to poison shyness because of sublethal dosing. It
acts chiefly on the heart, with secondary effects on CNS.
[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium.
10th ed. Surrey, UK: The British Crop Protection Council, 1994.
492]
Ref:
FLUOROACETAMIDE CASRN: 640-19-7. Hazardous Substances Data Bank. http://www.fluorideaction.org/pesticides/fluoroacetamide.hsdb.htm
Sodium fluoroacetate
and fluoroacetamide are readily absorbed by the gut, but only
to a limited extent across skin. The toxic mechanism is distinct
from that of fluoride salts. Three molecules of fluoroacetate
or fluoroacetamide are combined in the liver to form a molecule
of fluorocitrate, which poisons critical enzymes of the tricarboxylic
acid (Krebs) cycle, blocking cellular respiration. The heart,
brain, and kidneys are the organs
most prominently affected... Crimidine and sodium fluoroacetate
are no longer registered for use as pesticides.
Ref: US EPA. http://www.epa.gov/oppfead1/safety/healthcare/handbook/Chap17.pdf
--
Human Toxicity Excerpts: ... /MAJOR
EFFECTS/ INVOLVE CNS &
CARDIOVASCULAR
SYSTEM. SEVERE
EPILEPTIFORM CONVULSIONS ALTERNATE WITH COMA & DEPRESSION; DEATH
MAY RESULT FROM ASPHYXIA DURING CONVULSION OR FROM RESP FAILURE.
MOST PROMINENT FEATURES ... ARE CARDIAC IRREGULARITIES, NOTABLY
VENTRICULAR FIBRILLATION & SUDDEN CARDIAC
ARREST.
[International Labour Office. Encyclopedia of Occupational Health
and Safety. Vols. I&II. Geneva, Switzerland: International Labour
Office, 1983. 895]
-- Animal
Toxicity Studies:
Non-Human Toxicity Excerpts: VENTRICULAR
ARRHYTHMIAS, MARKED VENTRICULAR ALTERATION,
MYOCARDIAL DEPRESSION & VENTRICULAR FIBRILLATION ARE SEEN
IN HORSES, GOATS, RABBITS & MONKEYS; IN DOG & GUINEA PIG, CONVULSIONS
OCCUR WITHOUT PARALLEL CARDIAC ABNORMALITIES; CAT, PIG, RAT &
HAMSTER SHOW BOTH CARDIAC
& CNS RESPONSES.
/FLUOROACETATES/ [Clarke, E.G., and M. L. Clarke. Veterinary Toxicology.
Baltimore, Maryland: The Williams and Wilkins Company, 1975. 234]
Ref: TOXNET profile from Hazardous Substances
Data Bank. http://www.fluoridealert.org/pesticides/Fluoroacetic.Acid.TOXNET.htm
Fluorouracil
- Former
insect Chemosterilant; now used as a pharmaceutical -
CAS No. 51-21-8
POTENTIAL
ADVERSE EFFECTS ON FETUS: Exposure in first trimester resulted
in skeletal abnormalities; hypoplasia of
aorta, lungs, thymus, and gastrointestinal tract; and urinary
tract abnormalities. Fetus exposed in third trimester had cyanosis
and clonus.
Ref:
TOXNET profile from Hazardous Substances Data Base.
http://www.fluoridealert.org/pesticides/Fluorouracil.TOXNET.HSDB.htm
-- 7) 36-Week Feeding
- mouse: Dietary levels tested: 0, 0.02, and 2.0 mg/kg/day; B6C3F1
mice (10/sex/group) were administered haloxyfop-methyl in the
diet for 9 months. A significant increase in serum alkaline phosphatase
was reported for males at the 2.0 mg/kg/day level with a slight
increase in serum alkaline phosphatase for females. The liver
was slightly enlarged and darkened for both males and females
at 2.0 mg/kg/day. A significant increase
in the liver absolute weight and organ-to-body weight ratio of
both males and females fed 2.0 mg/kg/day was observed.
Males also exhibited a significant decrease in kidney and heart
weights compared with the control organ
weight. Livers of males and
females at the 2.0 mg/kg/day dose exhibited an enlargement of
centrilobular hepatocytes cells with an increase cytoplasmic homogenity
and increased eosinophilia. Kidneys of males fed 2.0 mg/kg/day
showed a decrease of cytoplasmic vacuolation of the proximal convoluted
tubular cells. Based on the above effects, the LEL for
systemic toxicity is 2.0 mg/kg/day. The NOEL for systemic toxicity
is 0.02 mg/kg/day; core supplementary (Dow Chemical U.S.A., 1982d)
Ref:
Health Assessment. US EPA Integrated Risk Information System (IRIS). http://www.fluoridealert.org/pesticides/Haloxyfop.Methyl.IRIS.htm
**52425-040 162205
"Oncogenicity Study with DPX-JW062-106 (50% DPX-KN128, 50%
DPX-KN127) Eighteen-Month Feeding Study in Mice" (Frame,
S. 832-E. I. du Pont de Nemours and Company, Haskell Laboratory,
Elkton Road, Newark, Delaware, Study HLR 799-96, 3/24/97). DPX-JW062-106
technical (Batch DPX-JW062-106, approximately 48% DPX-KN128) was
given in the diet daily to 70 Crl:CD ¨ -1(ICR)BR mice/sex/dose
at 0, 20, 100, or 125/150/200 ppm for 18 months (200 ppm level
reduced to 150 ppm on day 126 and to 125 ppm on day 287 due to
excessive mortality). The cause of death
was either central nervous system disorder (determined
from clinical signs of abnormal gait/mobility and head tilt) or
heart inflammation/ necrosis (males only)...
Red fluid in plural cavity noted after gross
necropsy corresponded with heart lesions
in high-dose males (e.g., necrosis, hemorrhage and inflammation)...
Non-neoplastic changes were noted in the brain of both sexes and
in the heart of males only of mice
that died or were sacrificed in extremis... NOEL(M/F)=20 ppm (M:
2.63 mg/kg/day based on neurotoxicity, heart
lesions at 125 ppm and decreased body weight gain at 100
ppm; F: 3.99 mg/kg/day based on neurotoxicity at 100 and 125 ppm).
Ref:
March
11, 1999: Summary
of Toxicology Data - Indoxycarb.
California EPA Department of Pesticide Regulation, Medical Toxicology
Branch. http://www.fluorideaction.org/pesticides/indoxacarb.ca.epa.1999.pdf
Abstract. The selective toxicity of N-methyl-N- ( 1-naphthyl
) monofluoroacetamide ( MNFA ) in various species of animals and
the effects of the compound on the central action, the peripheral
action and the fluctuations in the cardiovascular and respiratory
systems were investigated. Tabulated data present the physiological
function or activity investigated, the test animal, the dosage
of MNFA administered and the route of administration. Results
showed that below the toxic level, MNFA had little or no general
pharmacologic effect and only a minute effect on the central and
peripheral nervous systems and various peripheral organs of the
differenct animals tested. When a toxic dose of MNFA was administered,
respiratory depression, a fall of blood pressure and body temperature
and a decrease in heart rate were generally observed.
Both the rat and cat developed convulsions.
Just prior to death, a flat wave was observed in the electrical
activity of the brain which was indicative of a serious impediment.
A drop in blood pressure
of about 30% was observed at 24 hr in rats that received 50 mg/kg
of MNFA orally. Cardiac response revealed
the characteristic feature of this compound to be cardiac depression
in every species tested. In addition,
among animals that have a high sensitivity to MNFA, such as the
guinea pig, dog and cat, bigeminal or trigeminal ventricular premature
beats were observed. An enhancement of epinephrine activity
by MNFA was also noted. MNFA had a slight effect on the red cell
count, but the white cell count in rabbits
decreased markedly accompanied by a decrease of pseudoeosinophils
and an increase of lymphocytes. The blood sugar level in mice
showed an initial increase prior to a final decrease, while in
rats and guinea pigs there was a decrease and the value remained
unchanged in rabbits and dogs. Ketone bodies were only detected
in the mouse.
Ref. Some pharmacologic properties
of a new fluorine pesticide, N-methyl- N- ( 1-Naphthyl ) monofluoroacetamide;
by Hasimoto Y, Noguchi T, Mori T, Kitagawa H. Toxicol. Appl. Pharmacol.;
13(2), 174-88, 1968.
Abstract. General aspects of pesticide intoxication and therapy
have been reported previously. Since most pesticides act on the
nervous system, appreciable pathological alterations can be produced
there, especially in the CNS. Four cases of pesticide intoxication
are described: one with endrin, two with ceresin(!) (O-methyl
O-cyclohexyl S(p-chlorophenyl)thiophosphate), and one
with Nissol (MNFA)... In the MNFA intoxication case the patient's
condition was serious with unconsiousness and a very low blood
sugar value (50 mg/dl). The EEGs recorded on the first and seventh
days of hospitalization showed flat, low-voltage waves without
any slow waves or spikes. Intravenous administration of 40 ml
of 40% glucose solution restored the alpha-waves, although at
low-voltage, and the EEG returned to normal after one month. ...
Ref. Electroencephalograms in pesticide
poisoning cases; by Hiraki K, Iwasaki, Namba M. Rinsho Noha (Clin.
Electroencephalog.) ; 14(6): 333-340; 1972. [Abstract from Toxnet.].
Abstract. A brief discussion of the use of fluoroacetic acid
as a pesticide, and a brief history of studies on this acid are
given. More detailed discussions include those of MNFA, comparative
toxicity of MNFA, pre-clinical test of antidotes, fluoroacetic
poisoning of men and antidote treatment, the mechanism of detoxication,
and various experiments of fluoroacetic acid effects on the brains
of mice. The effects that have been detected
on men include: mild nausea, vomiting, headache, dizziness; medium
ataxia, clouding of consciousness, epileptic convulsion, repetition
of tonic and clonic convulsion, decrease
in heart rate; and serious coma, cyanosis,
lack of abdominal reflex, arrhythmia, increase of tracheal secretion,
and hypotension. Clinical findings include: sudden decrease or
increase of blood sugar, increase of hemogram leucocyte, increase
of pseudo acidophils, lymphocytes, and decrease of electrolyte
K. The blood pressure gradually decreases, and various
types of premature beats, myocardial infarction, and coronary
insufficiency are found on electrocardiogram, as the heart rate
increases and respiration decreases, In
hepatic function, GOT and GPT gradually or slightly increase.
Electroencephalogram shows a slow malfunction, or irregular
slow wave; when serious, a flat pattern appears. The
body temperature increases temporarily and then gradually decreases.
The article is a review
of previously published material by other researchers.
Ref. Pre-clinical evaluation of detoxication
of organic fluoride toxins; by Hashimoto Y. Eisei Kagaku (Journal
of Hygienic Chemistr; 17(6): 363-379; 1971. [Abstract from Toxnet.].
Abstract. The effects of N-methyl-N-(1-naphthyl)-monofluoroacetamide
(MNFA) on cardiac function were studied in rabbits. Rabbits received
5 milligrams per kilogram (mg/kg) MNFA orally, or 2mg/kg MNFA
subcutaneously (sc). Electrocardiographic (ECG) recordings were
made from subcutaneously implanted electrodes before and up to
2 hours after oral MNFA, and for up to 10 hours after sc MNFA.
Serum electrolytes and enzymes were determined 30 minutes before
and after, and 3 and 6 hours after MNFA. One hour after oral MNFA,
and ECG showed small deflections and almost discernible P-waves
and T-waves in lead 1, with tall peaked T-waves in leads 2, 3,
and aVF; after 2 hours, the QRS complex was widened and the ST
junction was lowered. Leads 1 and aVL had ST depression consisting
of wide S-waves and inverted T-waves. One hour after sc MNFA,
the ECG revealed tachycardia; after 3 hours the ST junction was
lowered. Leads 1 and aVL had ST depression consisting of wide
S-waves and inverted T-waves. One hour after sc MNFA, ECG revealed
tachycardia; after 3 hours the ST junction was lowered and T-waves
were flattened or inverted. After 6 hours, there were wide S-waves
and QRS was prolonged in leads 1, 2, and aVF. At 10 hours R-deflections
were decreased in most leads, and tachycardia and ST junction
depression were improved. Serum calcium was decreased slightly
6 hours after MNFA, but serum levels of sodium, potassium, chlorine,
transaminases, and lactic-dehydrogenase were not affected. The
authors conclude that the ECG changes of the QRS, ST, and T-waves
are probably caused mainly by metabolic disturbances during MNFA
intoxication.
Ref. Agricultural Organofluoride
Poisoning: II. Cardiac Damage; by Iwasaki I, Nawa H, Hara A, Takagi
S, Hyodo KFluoride, Vol. 3, No. 3, pages 127-130, 1970.
Abstract. Patients suffering from severe organofluoride intoxication
(MNFA, Oxylan) were treated with glucose.
Prior to treatment the electroencephalograms (EEG) demonstrated
flat curves. Dysrhythmic patterns were observed in less severely
affected patients which suggest the presence of impaired cerebral
function associated with abnormal carbohydrate metabolism. The
appearance of paroxysmal waves is also indicative
of organofluoride poisoning. It is
evident that EEG findings are valuable in the prognostic evaluation
and diagnosis of organofluoride poisoning.
Ref: Studies on organofluoride poisoning
IV. Electroencephalographic (EEG) observations; by Iwasaki I,
Namba, Nawa H, Hara, Tagaki S, Hyodo K. Fluoride; 3(3): 133-136;
1970.
Abstract. The accumulation of citrate was studied in spider-mites,
house-flies and mice after treatment with the acaricide Nissol
(5903139). Male Swiss-Webster-mice were injected with various
concentrations of Nissol. House-flies were treated topically with
Nissol at various concentrations or received thoracic injections.
A slide/dip technique was used to dose two-spotted-spider mites
with Nissol. Mortality was recorded at 24 hours after treatment
and the median lethal dose (LD50) was calculated for each species.
The citric-acid (77929) content was determined in homogenates
of whole mice in brains, hearts, livers, and kidneys photospectrometrically.
Citric-acid content was also determined in homogenates of flies
and mites. The LD50 for intraperitoneal administration in mice
was 200 milligrams per kilogram (mg/kg). The topical LD50 in house-flies
was 525mg/kg and the injected LD50 was 14mg/kg. The LD50 for contact
administration to spider mites was 250 parts per million. Citric-acid
increased substantially in each species even by 3 hours after
dosing. The maximum accumulation in mice occurred at 6 hours.
Flies and mites continued to show increased accumulation through
12 hours. In the mouse citric-acid was accumulated
in decreasing order in the heart, kidney, brain, and liver. The
authors conclude that mites, flies and mice accumulate citrate
when treated with Nissol. The toxicity of
this acaricide may be related to inhibition of aconitase which
catalyzes transformation of citric-acid.
Ref. Citrate Accumulation In Twospotted
Spider Mites, House Flies, And Mice Following Treatment With The
Acaricide 2-Fluoro-N-methyl-N-(1-naphthyl) Acetamide; by Johannsen
FR. Knowles CO. Journal of Economic Entomology, Vol. 65, No. 6,
pages 1754-1756, 14 references, 1972.
Abstract. The effects of a single dose and repeated doses of
N-methyl-N- ( 1- naphthyl ) monofluoroacetamide (MNFA) on the
fluctuation of citrate in animals and the replationship between
the activity of MNFA hydrolysis and the acute toxicity of MNFA
in various species were investigated. MNFA
was administered intraperitoneally at 25 mg/kg to male Wistar
strain rats, 2.0 mg/kg to guinea pigs and 300 mg/kg to monkeys.
At specified periods after dosing, the animals were sacrificed
and the citrate content of heart, kidneys, liver and brain was
determined. For the multiple dose study, MNFA was administered
orally to male rats at doses of 0.625, 1.25, 2.5, 5.0 and 10.0
mg/kg/ day for 180 days and the citrate content was determined
in the brain, heart, liver, kidney, testis and blood.
In the rat, after a single dose of MNFA, the citrate level increased
to 27, 10, 10 and negligible times
the normal value in heart, kidneys, brain
and liver, respectively. In
the chronic toxicity experiment, the only increase
(3 times the control value) was in the testes of rats receiving
10 mg/ kg/day of MNFA. In
all other groups, the level in liver and kidney decreased significantly
in comparison with the levels in animals receiving a single dose.
It is suggested that this difference was due to metabolism and
to the detoxification mechanism of the liver
and kidney which may have been accelerated by the chronic administration
of MNFA. The citrate level in the monkeys after a single dose
was much lower than in the rat. In guinea pigs it
increased to the maximum at 9 hr when it reached 30 times the
control value in the kidney, 10 times in
the heart, 6 times in the brain while no appreciable increase
was found in the liver. The hydrolysis of MNFA by liver homogenates
was closely related to the acute toxicity and the product of the
hydrolysis was determined as N-methyl-1-naphthylamine. The enzyme
activity in the guinea pig was about 35 times that of the rat
or mouse. The LD50 of MNFA was 3.1 times that of N- ( 1-naphthyl
) monofluoroacetamide ( NFA ) and the amount hydrolyzed after
30 min incubation was about one- fifth.
Ref: Studies of the biochemical lesions
caused by a new fluorine pesticide, N-methyl-N- ( 1-naphthyl )
monofluoroacetamide; by Noguchi T, Hashimoto Y, Miyata H. Toxicol.
Appl. Pharmacol.; 13(2), 189-98, 1968.
The maternal and developmental
toxicities of perfluorooctane sulfonate (PFOS) were evaluated
in the rat and mouse. PFOS is an environmentally persistent compound
used as a surfactant and occurs as a degradation product of both
perfluorooctane sulfonyl fluoride and substituted perfluorooctane
sulfonamido components found in many commercial and consumer applications.
Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg
PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1
mice were similarly treated with 1, 5, 10, 15 and 20 mg/kg PFOS
from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1
ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food
and water consumption, and serum chemistry were monitored. Rats
were killed on GD 21, and mice on GD 18. PFOS levels in maternal
serum, maternal and fetal livers were determined. Maternal weight
gains in both species were suppressed by PFOS in a dose-dependent
manner, likely attributed to reduced food and water intake. Serum
PFOS levels increased with dosage, and liver
levels were approximately 4-fold higher than serum. Serum thyroxine
(T4) and triiodothyronine (T3) in the PFOS-treated rat dams were
significantly reduced as early as one week after chemical exposure,
although no feedback response of thyroid-stimulating hormone (TSH)
was observed. A similar pattern of reduction in T4 was also seen
in the pregnant mice. Maternal serum triglycerides were significantly
reduced, particularly in the high dose groups, although cholesterol
levels were not affected. In the mouse dams, PFOS produced a marked
enlargement of the liver at 10 mg/kg and higher dosages. In the
rat fetuses, PFOS was detected in the liver, but at levels
nearly half of those in the maternal counterparts, regardless
of administered doses. In both rodent species, PFOS did not alter
the numbers of implantations or live fetuses at term, although
small deficits in fetal weight were noted in the rat. A
host of birth defects including cleft
palate, anasarca, ventricular septal defect,
and enlargement of the right atrium were seen in both rats and
mice, primarily in the 10 and 20 mg/kg dosage groups, respectively.
Our results demonstrate both maternal and developmental toxicity
of PFOS in the rat and mouse.
Ref: Toxicol Sci 2003 May 28; Exposure
to Perfluorooctane Sulfonate During Pregnancy in Rat and Mouse.
I. Maternal and Prenatal Evaluations; by Thibodeaux JR, Hanson
RG, Rogers JM, Grey BE, Barbee BD, Richards JH, Butenhoff JL,
Stevenson LA, Lau C. Reproductive Toxicology
Division, National Health and Environmental Effects Research Laboratory,
Office of Research and Development, U.S. Environmental Protection
Agency, Research Triangle Park, North Carolina 27711, USA.
-- Inhalation of the
decomposition products of Poly TFE may cause polymer fume fever;
a lung irritation requiring medical treatment for fluorine compounds
which can cause delayed pulmonary edema. A polymer fume fever
is a flu-like condition which occurs several hours after exposure
and subsides within 24 hours even in the absence of treatment.
Polymer fume fever does not cause permanent injury and the effects
are not cumulative.
-- Human health
effects of overexposure by inhalation to very high concentrations
may cause temporary alteration of the heart's
electrical activity with irregular pulse, palpitations, or inadequate
circulation. Individuals with preexisting diseases of the
central nervous or cardiovascular system
may have increased susceptibility to the toxicity of excessive
exposures.
Ref:
Material
Safety Data Sheet for: VDX Dry Lubricant
Prepared: Sat Apr
05 2003. Also available at: http://www.microcare.com/MSDS/MSDS-VDX.US.phtml
Manufacturer: Micro Care Corporation, 595
John Downey Drive, New Britain, CT. 06051 USA
Title: [Potassium
hexafluorosilicate]
Source: English/French versions: Internet documents, 1999. Spanish
version: Instituto Nacional de Seguridad e Higiene en el Trabajo,
Ediciones y Publicaciones, c/Torrelaguna 73, 28027 Madrid, Spain,
1991. 2p. Illus.
Abstract: International Chemical Safety Card. Exposure routes:
inhalation and ingestion. Short term exposure effects: irritation
of the skin, eyes and respiratory tract; effects on the calcium
metabolism, resulting in cardiac disorders
and impaired function. Long-term exposure
effects: effects on the bone, resulting in fluorosis.
Threshold limit value: 2.5mg/m3 (TWA) as fluorine (ACGIH
1997-1998).
Ref: Toxline at Toxnet.
-- Short term toxicity
Target / critical effect: Liver (hepatocyte
hypertrophy), heart (myocardial degeneration),
hematopoietic system (red blood cells decreased) Lowest relevant
oral NOAEL / NOEL: NOAEL = 6 mg/kg b.w./day (90-day, dog)
Ref: July 2, 2002 - Review report for the
active substance prosulfuron. Finalised in the Standing Committee
on the Food Chain and Animal Health at its meeting on 26 February
2002 in view of the inclusion of prosulfuron in Annex I of Directive
91/414/EEC.European Commission Health & Consumer Protection
Directorate-General. http://www.fluoridealert.org/pesticides/Prosulfuron.EU.July.2002.pdf
Sodium
fluoride - Insecticide,
Wood preservative, US EPA List 4B Inert -
CAS No.
7681-49-4
Abstract: SUMMARY: Young albino rabbits were administered 5,
10, 20, and 50 mg of sodium fluoride/kg body weight/day subcutaneously
for 3.5 months. The control animals were given 1 mL of double
distilled water/kg body weight/day. In the
fluoridated rabbits, the myocardium showed cloudy swellings, sarcoplasmic
vacuolization, and small hemorrhages followed by fibrous necrosis.
The degenerative changes were most pronounced in animals treated
with 50 mg of sodium fluoride/kg body weight/day. The
myocardium exhibited fibrous necrosis, dissolution of nuclei,
fibrillolysis, extensive vacuole formation and interstitial cells
in the connective tissue. The degree of myocardial damage seemed
to be directly proportional to the dosage of fluoride administered.
In the control animals, the myocardium showed normal structure
without any of the changes mentioned above.
Ref: Fluoride 2001; 34(1):43-50. Histopathology
of myocardial damage in experimental fluorosis in rabbits; by
A Shashi and SP Thapar. Full
report available at
http://www.fluoride-journal.com/01-34-1/341-43.pdf
Abstract: The purpose of this study was to determine the mechanism
responsible for alterations in NaF-induced contractions of blood
vessels from streptozotocin-induced diabetic rats. In
the presence of AlCl3, NaF (¥7.5 mM) produced significantly
greater contractions in diabetic aorta and mesenteric artery compared
with age-matched controls. Pretreatment with 1 microM nifedipine
eliminated the enhanced contractile responses of diabetic vessels
to NaF, resulting in no difference in the magnitude of NaF-induced
contractions between control and diabetic vessels. In the presence
of 100 microM deferoxamine, an Al 3+ chela-tor, NaF-induced contractions
of diabetic vessels were markedly attenuated, whereas only the
responses to lower concentrations of NaF were reduced in control
vessels. No significant difference was found in the peak amplitude
of transient contractions induced by 10 microM cyclopiazonic acid
between control and diabetic vessels. The addition of 10 microM
okadaic acid produced attenuated contractions in diabetic vessels.
These findings indicate no involvement of the inhibitory effects
of NaF on endoplasmic reticular Ca 2+ -pump ATPase and protein
phosphatases in the genesis of the enhanced responsive-ness of
diabetic vessels to NaF. Western blot analysis showed a 2.5-fold
in-crease in the expression of G(qalpha) in diabetic aortic membranes.
In contrast, the G(ialpha) level was modestly decreased and the
G(salpha) and G(betagamma) levels were unchanged in diabetes.
The present results suggest that enhanced vascular contractions
to NaF in diabetes is attributed predominantly to a G protein-mediated
Ca 2+ channel acti-vation that results from markedly increased
G(qalpha) expression in vascular tissues under this pathological
state.
Ref: Predominant contribution of the G protein-mediated
mechanism to NaF-induced vascular contractions in diabetic rats:
association with an increased level of G(qalpha) expression
Hattori Y, Matsuda N, Sato A, Watanuki S, Tomioka H, Kawasaki
H, Kanno M. J Pharmacol Exp Ther 2000 Feb;292(2):761-8 - As cited
and abstracted in Fluoride 2000; 33(2):97-98
• Mesenteric artery,
arteria mesenterica -- (one of two branches of the aorta that
pass between the two layers of the mesentery to the intestines)
Abstract:
1. Previous studies from this laboratory have demonstrated that
alpha 1-adrenoceptor-mediated increases in tension and phosphoinositide
metabolism are enhanced in the aorta and mesenteric
arteries from diabetic rats. The purpose of the present
investigation was to determine whether contractile responses to
sodium fluoride (NaF), which directly stimulates GTP-binding proteins
(G-proteins), are also enhanced in diabetic arteries.
2. NaF (1-20 mM) in the presence of 10 microM aluminium chloride
produced slowly developing, concentration-dependent contractions
in mesenteric arteries from three month streptozotocin-diabetic
(60 mg kg-1, i.v.) male Wistar rats and age-matched control rats.
The maximum contractile response but not the sensitivity to NaF
was significantly greater in mesenteric arteries from diabetic
than from control rats, as was the response to noradrenaline (NA).
Maximum contractile responses of aorta and caudal artery from
diabetic rats to NaF were also significantly enhanced.
3. Removal of the endothelium and denervation with 6-hydroxydopamine
did not significantly alter the maximum contractile response of
mesenteric arteries from either control or diabetic rats to NaF.
Similarly, NaF had no effect on cyclic AMP levels in aorta, and
no difference in cyclic AMP levels, either basally or in the presence
of NaF, was detected between control and diabetic rat aorta.
4. Contractile responses of mesenteric arteries from both control
and diabetic rats to NaF were diminished in calcium-free Krebs
solution, but the NaF response remained significantly elevated
in mesenteric arteries from diabetic rats compared to control.
5. Ryanodine (30 microM) which depletes intracellular calcium
stores, nifedipine (3 microM) which blocks dihydropyridine-sensitive
calcium channels and calphostin C (0.5 microM) which selectively
inhibits protein kinase C, all significantly inhibited maximum
contractile responses of mesenteric arteries from control and
diabetic rats to NaF. There were no significant differences between
control and diabetic arteries in the relative magnitude of the
inhibition produce by the three antagonist.
6. These data suggest that there may be
increased activation of the same signalling processes that mediate
NA-stimulated vasoconstriction, perhaps contraction-associated
G-proteins or the effectors coupled to these G-proteins, in response
to NaF in mesenteric arteries from diabetic rats. This
may also be responsible for the enhanced contractile responses
of these arteries to alpha 1-adrenoceptor stimulation.
Ref: Br J Pharmacol 1996 May;118(1):115-22.
Enhanced contractile responses of arteries from streptozotocin
diabetic rats to sodium fluoride. Weber LP, Chow WL, Abebe
W, MacLeod KM.
• Mesenteric artery,
arteria mesenterica -- (one of two branches of the aorta that
pass between the two layers of the mesentery to the intestines)
Effects of Short-Term Exposure: The substance
may cause effects on the cardiovascular system and central
nervous system, resulting in cardiac disorders
and respiratory failure. Exposure may result in death.
Ref: IPSCS INCHEM. ICSC: 0484. Date of Peer
Review: April 1997. Prepared in the context of cooperation between
the International Programme on Chemical Safety (IPCS) and the
Commission of the European Communities. http://www.inchem.org/documents/icsc/icsc/eics0484.htm
Abstract: Groups
of Sprague-Dawley rats received sodium monofluoroacetate (Compound
1080) at 0.025, 0.075, and 0.25 mg/kg by oral gavage once daily
for 90 days and were then euthanized. The control and 0.25 mg/kg/day
groups included additional rats of each sex that were treated
for 90 days, then maintained without treatment for a further 56-day
recovery period. Microscopic changes were
restricted to the testes and the heart, and
were seen only in males dosed with 1080 at 0.25 mg/kg/day and
included severe hypospermia in the epididymides, severe degeneration
of the seminiferous tubules of the testes, and cardiomyopathy.
Sperm evaluation indicated severe decreases
in all three sperm parameters evaluated (concentration, % motile,
and % abnormal) at 0.25 mg/kg/day. There
were no microscopic changes or 1080-related effects on
sperm parameters at 0.025 and 0.075 mg/kg/day. The no observable
effects level (NOEL) for rats administered 1080 via oral gavage
for 90 days was 0.075 mg/kg/day. The lowest observable effects
level (LOEL) dose was 0.25 mg/kg/day. After dosing with the LOEL
dose of 0.25 mg/kg/day, mean concentrations of 1080 in rat plasma
were 0.26 micro g/ml at 1 h and 0.076 microg/ml at 12 h. Rat urine
collected from the same animals contained 0.059 microg/ml.
Ref: A 90-day toxicological evaluation of
Compound 1080 (sodium monofluoroacetate) in Sprague-Dawley rats;
by Eason CT, Turck P.Toxicol Sci. 2002 Oct;69(2):439-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12377993
Abstract: A TLV-TWA
of 0.05 mg/m3 is recommended for occupational exposure to highly
toxic sodium fluoroacetate. This value is intended to minimize
the potential for progressive central nervous
system and
cardiovascular system effects.
These may include nausea, womiting, apprehension, nystagmus,
facial twitching, and convulsions that are usually followed or
accompanied by tachycardia, ventricular fibrillation, and death
due to cardiac failure or respiratory arrest. Rapid absorption
through intact and abraded or cut skin warrants a Skin notation.
Sublethal sodium fluoroacetate is reported to cause changes in
testicular morphology in exposed rodents. Sufficient data were
not available to recommend SEN or carcinogenicity notations or
a TLV-STEL.
Ref: Anon (2001). Sodium Fluoroacetate.
TA:ACGIH. Documentation of the threshold limit values and biological
exposure indices PG:4 p YR:2001 IP: VI:7th Ed
In a 13-week oral study
in rats, gavage administration of sodium fluoroacetate (0.02 mg/kg/day)
resulted in decreased testis weight and altered spermatogenesis
in males (the NOAEL was 0.05 mg/kg/day). In addition, increased
heart weight was noted in females and males administered
0.20 mg/kg/day of sodium fluoroacetate. The increase
in heart weight, however, was only accompanied by subacute,
minimal inflammation (not dose-related). Also, fluorocitrate levels
were significantly increased after 4 weeks in males administered
0.50 mg/kg/day and after 13 weeks in both male and female rats
administered 0.20 or 0.50 mg/kg/day. The testicular and cardiac
effects were reported to be consistent with those noted
in the literature. EPA believes that there is sufficient evidence
for listing sodium fluoroacetate on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the neurologic, reproductive,
and myocardial toxicity data for
this chemical.
Ref:
USEPA/OPPT. Support Document for the Health and Ecological Toxicity
Review of TRI Expansion Chemicals. U. S. Environmental Protection
Agency, Washington, DC (1993). As cited by US EPA in: Federal
Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition
of Certain Chemicals; Toxic Chemical Release Reporting; Community
Right-to-Know; Proposed Rule.
Subchronic Toxicity:
... Technical sodium fluoroacetate was administered by gavage
for 13 weeks to Crl:CD(SD)Br rats. The doses were 0, 0.05, 0.20,
or 0.50 mg/kg/day. The NOEL was 0.05 mg/kg/day. The LOEL was 0.20
mg/kg/day, based on dose-related findings in histopathology
(hypospermatogenesis, fusion bodies, and immature or abnormal
sperm) and decreased size and weight of testes and epididymides
in males. Females had dose-related increases in absolute
and relative heart weights at the
mid and high doses (Wolfe, 1988).
Ref: US EPA Reregistration Eligibility Decision
(RED) for Sodium fluoroacetate. September 1995. http://www.fluoridealert.org/PESTICIDES/Sodium_fluoroacetate.RED.95.pdf
Sodium
fluorosilicate
(Sodium Hexafluorosilicate) - Insecticiide,
Wood Preservative, EPA List 3 Inert - CAS No. 16893-85-9
-- Toxicological Data.
Human Data. Chronic exposure to sodium
hexafluorosilicate dust at levels above the eight-hour TWA can
result in severe calcification
of the ribs, pelvis, and spinal column ligaments;
effects on the enzyme system; pulmonary
fibrosis; stiffness; irritation of the eyes, skin, and mucous
membranes; weight loss; anorexia; anemia; cachexia; wasting;
and dental effects. Long-term or repeated exposure to the skin
can result in skin rash. A probable oral lethal dose of 50-500
mg/kg, classified as very toxic, has been reported for a 150-pound
(70-kg) person receiving between 1 teaspoon and 1 ounce of sodium
hexafluorosilicate. Cases of sodium hexafluorosilicate ingestion
reported symptoms such as acute respiratory
failure, ventricular
tachycardia and fibrillation,
hypocalcemia, facial numbness, diarrhea, tachycardia,
enlarged liver, and cramps of the palms, feet, and legs.
-- -- Guinea pigs, 13- 55 mg/ m 3 (1.2- 7.2 ppm) in air for ¥
6 h; Pulmonary irritation was observed. The lowest concentration
that caused death when inhaled for 6 h was 33 mg/ m 3 . Patty
(1963; cited by HSDB, 2000b)
-- -- Mice orally given sodium hexafluorosilicate (70 mg/kg; 0.37
mmol/kg) exhibited toxic effects in the peripheral nerves, sensation,
and in behavior. In rats, an oral dose (248 mg/kg; 1.32 mmol/kg)
administered intermittently for one month produced toxic effects
in the kidney, ureter, and/or bladder, as well as musculoskeletal
and biochemical effects (RTECS, 1997). Using guinea pigs, inhalation
experiments (13-55 mg/m 3 [1.7-7.2 ppm] sodium hexafluorosilicate
in air for ¥6 hours) resulted in pulmonary irritation; the lowest
concentration that caused death was 33 mg/m 3 (4.3 ppm) (Patty,
1963; cited by HSDB, 2000b).
Ref: Sodium Hexafluorosilicate [CASRN
16893-85-9] and Fluorosilicic Acid [CASRN 16961-83-4]. Review
of Toxicological Literature. October 2001. Prepared for Scott
Masten, Ph.D. National Institute of Environmental Health Sciences
P.O. Box 12233 Research Triangle Park, North Carolina 27709 Contract
No. N01-ES-65402. Submitted by Karen E. Haneke, M.S. (Principal
Investigator) Bonnie L. Carson, M.S. (Co-Principal Investigator)
Integrated Laboratory Systems P.O. Box 13501 Research Triangle
Park, North Carolina 27709. http://www.fluoridealert.org/pesticides/Fluorosilicates.NIH.2001.pdf
Poisonings and fatalities
have been reported in humans following inhalation exposure to
sulfuryl fluoride... A second person died of cardiac
arrest after sleeping in the house overnight following
fumigation. A plasma fluoride level of 0.5
mg/L (10 times normal) was found in this person following exposure.
Prolonged chronic inhalation exposure to concentrations of sulfuryl
fluoride gas significantly above the TLV of 5 ppm have caused
fluorosis in humans because sulfuryl fluoride is converted to
fluoride anion in the body. Fluorosis is characterized by
binding of fluoride anion to teeth (causing mottling of the teeth)
and to bone.
Ref:
Federal Register: September 5, 2001 (Volume 66, Number 172). Sulfuryl
Fluoride; Proposed Pesticide Temporary Tolerances. http://www.fluorideaction.org/pesticides/sulfuryl.flu.fr.sept.5.2001.htm
-- Two fatalities occurred when the owners of a home re-entered
after the dwelling had been fumigated with 250 pounds of sulfuryl
fluoride. The concentration to which the occupants were exposed
was not determined. The man died within 24 hr, and the woman expired
6 days after exposure. Signs of intoxication included severe dyspnea
[abnormal breathing], cough, generalized seizure, cardiopulmonary
arrest (in the male), and weakness, anorexia, nausea, repeated
vomiting, and hypoxemia [subnormal oxygenation of arterial blood,
short of anoxia]; ventricular fibrillation and diffuse pulmonary
infiltration were also reported in the female. [American Conference
of Governmental Industrial Hygienists, Inc. Documentation
of the Threshold Limit Values and Biological Exposure Indices.
6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991.1471]
Ref:
Hazardous Substances Data Bank for SULFURYL FLUORIDE CASRN: 2699-79-8.
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB •
Note:
Ventricular fibrillation (VF) is a severely abnormal heart rhythm
(arrhythmia) that, unless treated immediately, causes death. VF
is responsible for 75% to 85% of sudden deaths in persons with
heart problems. http://www.1uphealth.com/health/ventricular_fibrillation_info.html
Abstract. This report
describes for the first time a novel anionic background current
(I(AB)) identified in guinea-pig isolated ventricular myocytes.
It also shows that I(AB) has both novel and differential pharmacology
from other (cardiac) chloride currents. Using the whole-cell patch-clamp
technique and external anion substitution, I(AB) was found to
be outwardly rectifying and highly permeable to NO(-)(3), with
a relative permeability sequence of NO(-)(3) > I(-) > Cl(-). I(AB)
was not blocked by 50 microM DIDS, by hypertonic external solution,
or by the nonselective protein kinase inhibitor H7-DHC. Exposure
to the pyrethroid agent tefluthrin (10 microM) increased the current
density of I(AB) significantly at positive voltages (P < 0.05),
but had no significant effect on other cardiac chloride currents.
We conclude that I(AB) possesses a distinct pharmacology and does
not fall into the three major classes of cardiac chloride conductance
commonly reported. (C)2002 Elsevier Science (USA).
Ref: Borg JJ et al. (2002). Tefluthrin
modulates a novel anionic background conductance (I(AB)) in guinea-pig
ventricular myocytes. Biochem
Biophys Res Commun. Mar 22;292(1):208-15.
Abstract: Pyrethroid
insecticides are known to modify neuronal sodium channels, inducing
persistent, steady-state sodium current at depolarized membrane
potentials. Cardiac myocytes are also rich in sodium channels
but comparatively little is known about the effect of pyrethroids
on the heart, or on the cardiac sodium channel isoform. In the
present study therefore, we determined the actions of type I and
type II pyrethroids against rat and guinea pig ventricular myocytes
under current and voltage clamp, and on isolated perfused rat
hearts. In myocytes, tefluthrin
(type I) and fenpropathrin and alpha-cypermethrin (type
II) prolonged action potentials and evoked
afterdepolarizations. The time course of sodium current
(I(Na)) was also prolonged by these compounds. Pyrethroids delayed
I(Na) inactivation, when measured under selective conditions as
current sensitive to 30 microM tetrodotoxin, by increasing the
proportion of slowly inactivating current at the expense of fast
inactivating current. Further experiments, focusing on fenpropathrin,
revealed that its effects on I(Na) inactivation time course were
dose-dependent, and the Na(+) "window-current" was increased in
its presence. In unstimulated, isolated hearts perfused with the
same pyrethroids, the variability in contraction amplitude increased
due to variations in the intervals between heartbeats. These potentially
arrhythmogenic changes are consistent with the effects observed
at the cellular level. The type I pyrethroid tetramethrin had
little effect in any of the preparations. These
findings suggest that some pyrethroids possess considerable mammalian
cardiac arrhythmogenic potential, the manifestation of
which in vivo may depend on the route of exposure.
Discussion from
full paper: The principal findings of the present study
at the cellular level are that the type I pyrethroid tefluthrin
and the type II pyrethroids fenpropathrin and -cypermethrin
1) prolonged ventricular action potentials
and evoked afterdepolarizations;
2) modified the time course of INa by altering
the relative proportions of fast and slowly inactivating current;
and
3) altered the voltage dependence of INa.
At the whole heart level, these effects corresponded with a pyrethroid-induced
increase in the variability of contractile force, suggestive of
proarrhythmic activity. Several aspects of these findings
merit detailed consideration.
Ref: Spencer CI et al. (2001). Actions
of pyrethroid insecticides on sodium currents, action potentials,
and contractile rhythm in isolated mammalian ventricular myocytes
and perfused hearts. J Pharmacol
Exp Ther. 2001 Sep;298(3):1067-82. Erratum
in: J Pharmacol Exp Ther 2001 Oct;299(1):399.
Full free report available at
http://jpet.aspetjournals.org/cgi/content/full/298/3/1067
4.2 Mechanism of Toxicity
(pages 143 - 144)
At high concentrations, HFC-134a has anesthetic and narcotic properties;
cardiac sensitization may also occur.
The biochemical mechanism(s) of action of these two efects is
not well understood. The anesthetic effect was fully reversible.
Inhalation of certain hydrocarbons, including some anesthetics,
can make the mammalian heart abnormally
sensitive to epinephrine, resulting in ventricular arrhythmias,
which is some cases can lead to sudden death (Reinhardt
et al. 1971). The mechanism of action of cardiac sensitization
is not completely understood but appears to involve a disturbance
in the normal conduction of the electrical impulse through the
heart, probably by producing a local disturbance in the electrical
potential across cell membranes. The hydrocarbons themselves do
not produce arrhythmia; the arrhythmia
is the result of the potentiation of endogenous epinephrine (adrenalin)
by the hydrocarbon ... In the study with human volunteers exposed
to HFC-134a (Emmen and Hoogendijk 1998),
the relationship between exposure concentration and blood level
was linear, and at all exposure concentrations (1,000, 2,000,
4,000, and 8,000 ppm), blood concentrations approached equilibrium
at 55 min. Cardiac sensitization is considered
a concentration threshold phenomenon (page 146).
-- Emmen
HH, Hoogendijk EMG. 1998. Report on an ascending dose safety study
comparing HFA-13a with CFC-12 and air, administered by whole-body
exposure to healthy volunteers. MA-250B-82-306, TNO Report V98.754,
The Netherlands Organization Nutrition and Food Research Institute,
Zeist, The Netherlands.
-- Reinhardt
CF, Azar A, Maxfield ME, Smith PE, Mullin LS. 1971. Cardiac arrhythmias
and aerosol "sniffing." Arch Environ Health 22:265-279.
Ref:
National
Research Council. 2002. Acute Exposure Guideline Levels for Selected
Airborne Chemicals. Volume 2. Subcommittee on Acute Exposure Guideline
Levels. Committee on Toxicology, Board of Environmental Studies
and Toxicology, Division of Earth and Life Studies. National Academy
Press, Washington DC. Available from: National Academy Press,
2101 Constitution Ave, NW, Box 285, Washington DC 20055. ISBN
0-309-08511-X.
Online
at:
http://books.nap.edu/books/030908511X/html/index.html
Subject
#3 was the first volunteer exposed to HFC-134a. The exposure
concentration was 4000 ppm (0.4% v/v) and was scheduled to last
for 30 minutes with a 5-minute postexposure evaluation period
as was accomplished in the Halon 1301 portion of the study. Approximately
4.5 minutes into the exposure, the subject lost consciousness
and both pulse and blood pressure dropped to zero. The
exposure was immediately aborted and the subject was removed from
the exposure apparatus. Medical personnel intervened and after
pulse and blood pressure were restored the subject was administered
100% oxygen. Blood pressure and pulse remained
low (approximately 1/2 of baseline) and the subject could not
maintain consciousness in a seated position. The subject
was reclined and moved to an operating room recovery area where
he rested for approximately 1 hour after which the subject's vital
signs had returned to pre-exposure values...
Subject #5 was also exposed
to 4000 ppm (0.4% v/v) HFC-134a. There was some difficulty with
blood collection and manipulation of the cannula was noted,
but exposure was uneventful through the first 10 minutes of exposure.
Breathing effort and rate appeared normal. At
approximately 10.5 minutes into the exposure the subject's blood
pressure and pulse began to rise
rapidly and the subject gave the hand signal for possible trouble.
His pulse rose rapidly until it was double the pre-exposure value,
at which time the subject gave the hand signal to terminate the
exposure. The exposure was aborted and the subject began
breathing room air, but the in-dwelling cannula was not removed
from the subject. After 30 seconds, the subject's blood pressure
and pulse were at pre-exposure levels.
The HFC-134a concentration in blood reached 0.70 mg/L at the point
where the exposure was terminated (Figure 3).
Subject #5 breathed room air for 1 hour
and was then re-exposed to 2000 ppm (0.2% v/v) HFC-134a. After
2.5 minutes of exposure, the subject's
blood pressure and pulse again rose rapidly, the subject signaled
trouble and the exposure was terminated.
The subject's vital signs returned to pre-exposure levels
within 30 seconds after the exposure was terminated... No further
human HFC-134a exposures were conducted. In addition to the monitored
effects, there were several subjective effects associated with
the inhalation exposures to HFC-134a. Subject
#3 reported problems with dizziness and balance following the
exposure. At the time of this report (6 weeks post exposure),
both the dizziness and balance problems still persisted. Subject
#5 reported chest tightness and a headache with associated dizziness
immediately following the exposure. The headache subsided by the
time the subject woke up the day following the exposure.
The day following the exposure, subject
#5 reported unusual feelings in the chest resembling "flutters".
The chest tightness was reported to subside within 3 days of the
exposure and the "flutters" within 2 weeks of the exposure.
As with subject #3, subject #5 was still experiencing dizziness
and balance problems at the time of this report (6 weeks post
exposure). Subject #5 also reported persistent ringing in the
ears which was still present at the time of this report. The
adverse events observed during the exposures to HFC-134a and HFC-227ea
were unexpected and inconsistent with the published data...
Based on published work, regulatory approval and commercial use
of Halon 1301, HFC-134a and HFC-227ea, the exposure levels selected
for the 30-minute inhalation exposures were expected to be without
adverse effects in humans.
Ref: 1997.
Human Inhalation of Halon 1301, HFC-134a and HFC-227ea for Collection
of Pharmacokinetic Data.
http://www.fluoridealert.org/pesticides/1.1.1.2.3.3.3-Hep.97.REPORT.htm
- also available at http://www.autofrost.com/r134atox.txt
Trichlorofluoromethane
-Insecticide, Fungicide, Propellant, EPA List 2 Inert - CAS
No. 75-69-4
-- Health
Hazards - General ... Inhalation of high concentrations
may also result in temporary alteration
of the heartÕs electrical activity by increasing the sensitivity
of the heart to the arrhythmogenic action of epinephrine, causing
irregular pulse, palpitations, or inadequate circulation
(Dupont, 1996A; Dupont, 1996F; OSHA, 1998; Reprotext, 2003). Deliberate
inhalation (ÒsniffingÓ) may cause death without warning (Dupont,
1996A; Dupont, 1996F; OSHA, 1998).
-- Acute Effects ... Inhalation of
high concentrations (~5,000 ppm) is associated with the development
of arrhythmias and sudden death due to myocardial
sensitization to endogenous catecholamines (e.g., epinephrine).
-- Predisposing Conditions. Individuals
with pre-existing diseases of the central nervous or cardiovascular
system may have increased susceptibility to the effects
of Freons (Dupont, 1996A; OSHA, 1998; Dupont, 1996B; Dupont, 1996D).
Persons exposed to epinephrine or other sympathomimetic amines,
e.g., bronchodilators and nasal decongestants (e.g., Sudafed ¥),
might be at increased risk for the cardiotoxic
effects of Freons (Reprotext, 2003).
-- Special Concerns for Children.
Children may inhale relatively larger doses of Freon because,
relative to their body weight, they have a greater lung surface
area and larger minute volume than adults. Since Freon has a high
vapor density, children could also receive high doses due to their
short stature and the higher levels of Freon vapor that may be
present near the ground when Freon is spilled.
Ref:
September
24, 2003 (Revised)
- FREON [11, 12, 113].
Technical Support Document: Toxicology.
Clandestine Drug Labs/ Methamphetamine. Volume 1, Number 11. California
EPA, Office of Environmental Health Hazard Assessment (OEHHA),
Department of Toxic Substances Control.
-- Populations
at Special Risk: Employees /with cardiovascular disease
are/ at increased risk. [Mackison, F. W., R. S. Stricoff, and
L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health
Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123
(3 VOLS). Washington, DC: U.S. Government Printing Office, Jan.
1981.]
-- There are isolated reports of poisoning from exposure to refrigerants
and solvents, and some studies showing a higher incidence of coronary
heart disease among hospital personnel are required to
establish causal relationship between fluorine containing organic
compounds, and cardiovascular and bronchopulmonary diseases among
exposed workers. The high incidence of cancer among hospital personnel
repeatedly exposed to fluorine-containing general anesthetics
raises a fundamental need to examine other chlorofluorocarbon-exposed
workers for similar effects. /Fluorocarbons/ [Clayton, G.D., F.E.
Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes
2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John
Wiley & Sons Inc., 1993-1994. 1209]
-- Clinical pathologists exposed to fluorocarbons in the preparation
of frozen tissue sections have been seen to develop coronary
heart disease. /Fluorocarbons/ [Clayton, G.D., F.E. Clayton
(eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A,
2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley
& Sons Inc., 1993-1994. 1209]
-- Fluorocarbon propellants are anesthetic and cardiotoxic.
... Aerosol propellants produce hallucinogenic effects, and, rarely,
contact dermatitis. /Fluorocarbon propellants/ [Ellenhorn, M.J.
and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment
of Human Poisoning. New York, NY: Elsevier Science Publishing
Co., Inc. 1988. 528]
-- Deaths resulting from cardiovascular
collapse after arrhythmias have been reported after inhalation
of Freons 11 and 12. [Ellenhorn,
M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment
of Human Poisoning. New York, NY: Elsevier Science Publishing
Co., Inc. 1988. 528]
-- The toxicity of Chlorofluorocarbons (CFCs) had been considered
to be low; it is absorbed via the lungs and undergoes little subsequent
biotransformation. In the United States when sudden unexplained
deaths of aerosol "sniffers" were reported they were considered
to be possibly due to cardiac arrhythmias
induced by the CFC propellants. /CFCs/ [Rom, W.N. (ed.).
Environmental and Occupational Medicine. 2nd ed. Boston, MA: Little,
Brown and Company, 1992. 1299]
-- Ten subjects /were exposed/ to CFC-11,
CFC-12, CFC-114, two mixtures of CFC-11 and CFC-12, and a mixture
of CFC-12 and CFC-114 (breathing concentrations between 16 and
150 g/cu m) for 15, 45, or 60 seconds, and found
significant acute reduction of ventilatory lung capacity (FEV50,
FEF25) on exposure to each chlorofluorocarbon, as well as bradycardia
and increased
variability in heart rate in
seven subjects, negative T-waves in two subjects (one was exposed
to CFC-11 and CFC-12), and atrioventricular block in 1 subject
(CFC-114). Mixtures exerted stronger respiratory
effects than individual chlorofluorocarbon at the same
level of exposure. [WHO; Environmental Health Criteria 113: Fully
Halogenated Chlorofluorocarbons p.90 (1990)]
-- Propellant /fluorocarbon/ gases were generated from commercial
aerosol units and applied to the from distance of 50 cm for periods
of 15 to 60 sec. At a measured concn of 95,000 mg/cu m (1700 ppm),
there was a biphasic change in ventilation capacity, the first
reduction occurring within a few minutes after exposure, and second
delayed until 13 to 30 min after exposure, and second delayed
until 13 to 30 min after exposure. Most
subjects developed bradycardia, and inversion of the T-wave.
/Propellant gases/ [Clayton, G.D., F.E. Clayton (eds.) Patty's
Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E,
2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc.,
1993-1994. 1201]
-- Freon 11, inhaled at 5% concentration, sensitizes the myocardium
to epinephrine. A 6% concentration results in apnea and areflexia.
A 10% concentration produces cardiac arrhythmias. Deaths resulting
from cardiovascular collapse after arrhythmias
have been reported after inhalation of /Freon 11/ ... .
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis
and Treatment of Human Poisoning. New York, NY: Elsevier Science
Publishing Co., Inc. 1988. 528]
-- Non-occupational exposure and accidental or abusive inhalation
of aerosols /due to Fluorocarbon propellants/ have also been documented,
the main symptoms being CNS depression and cardiovascular
reactions. Cardiac arrhythmia, possibly aggravated by elevated
levels of catecholamines due to stress or by moderate hypercapnia,
is suggested as the cause of these adverse response, which may
lead to death. /Aerosols/ [WHO; Environmental Health Criteria
113: Fully Halogenated Chlorofluorocarbons p.20 (1990)]
-- A SPECIAL CLASS OF CHEMICALS SUBJECT TO ABUSE BY INHALATION
ARE THE FLUOROHYDROCARBONS ... THE "SNIFFING" OF SUCH AEROSOL
SPRAYS IS HAZARDOUS PRACTICE. ... 110 "SUDDEN SNIFFING DEATHS"
/HAVE BEEN IDENTIFIED/ ... IN EACH CASE THE VICTIM SPRAYED THE
AEROSOL INTO A PLASTIC BAG, INHALED THE CONTENTS, BECAME EXCITED,
RAN 90 M OR SO, COLLAPSED, & DIED. NECROPSY FINDINGS WERE LARGELY
NEGATIVE ... ALTHOUGH AMOUNT OF PROPELLANT ABSORBED INTO BLOOD
FROM USE OF HAIRSPRAY, COSMETIC, HOUSEHOLD, & MEDICATED AEROSOLS
MUST VARY WITH CIRCUMSTANCES, PHYSICIAN IS ADVISED TO COUNSEL
... PATIENT ON POTENTIAL DANGERS, PARTICULARLY FROM THEIR USE
IN POORLY VENTILATED CONFINED AREAS. IT
IS POSSIBLE THAT PATIENTS WITH CARDIAC OR RESPIRATORY DISORDERS
MAY PROVE ESPECIALLY SUSCEPTIBLE. /FLUOROHYDROCARBONS/
[Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis
of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc.,
1975. 910]
-- -- Freons are toxic to humans by several mechanisms. Inhaled
fluorocarbons sensitized the myocardium
to catecholamines, frequently resulting in lethal ventricular
arrhythmias. Because they are gases heavier than air, fluorocarbons
can displace atmospheric oxygen, thus resulting in asphyxiation.
These compounds also have a central nervous
system (CNS) anesthetic effect analogous to a structurally similar
general anesthetic, halothane. Pressurized refrigerant or liquid
fluorocarbons with a low boiling point have a cyrogenic
effect on exposed tissues, causing frostbite, laryngeal or pulmonary
edema, and gastrointestinal perforation. Certain fluorocarbons
degrade at high temperatures into toxic products of chlorine,
hydrofluoric acid, or phosgene gases. /Freons/ [Haddad, L.M.,
Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia,
PA: W.B. Saunders Co., 1990. 1281]
-- ... Workers who spilled a large volume of CFC-11 were exposed
to high concentrations & developed signs of narcosis. One of the
workers became unconscious, & another experienced tachycardia.
[American Conference of Governmental Industrial Hygienists, Inc.
Documentation of the Threshold Limit Values and Biological Exposure
Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991.
1621]
Ref:
Hazardous Substances Data Base for TRICHLOROFLUOROMETHANE. http://www.fluoridealert.org/pesticides/Trichlorofluorometha.TOXNET.htm
-- Interactions: The
interaction of Freon 113 and hypoxia
on the heart conduction system was investigated by using the isolated
perfused hearts from Wistar rats. The mean preexposure heart rate
was 214.8 beats per minute and the mean preexposure atrioventricular
conduction time (PQ interval was 42.9 milliseconds. Freon
113 alone elicited significant change
to control levels in heart rate which was enhanced by the
coadministration of hypoxia. An enhanced delayed PQ interval was
noted following coadministration of Freon 113 and hypoxia, although
significant PQ interval changes were noted with Freon
113 alone or with hypoxia alone.
In the coadministration group, a 2:1 atrioventricular
block was elicited in two of four hearts. It was suggested
that in occupational deaths among Freon
113 workers, there may be complex
interactions between hypoxia, enhanced cardiac sensitivity to
circulating epinephrine, and direct alterations of cardiac muscle
cell membrane potentials which result in arrhythmias following
Freon 113 exposures. [Kawakami T et al; Toxicol Indust
Health 6 (3/4): 493-8 (1990)]
-- .. CARDIOTOXIC EFFECTS, MANIFESTED IN
ARRHYTHMIAS ... ARE ASSOCIATED WITH PULMONARY EXPOSURE
TO FLUOROCARBONS, ESPECIALLY ... FLUOROCARBON
113 ... . [Hamilton, A., and H. L. Hardy. Industrial
Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc.,
1974. 293]
-- .. Working with high conc of CFC-113
or other chlorofluorocarbons in confined spaces has the potential
to cause death by cardiac arrhythmia, asphyxiation, or both. ...
4 reports of 12 fatalities resulting from occupational exposure
to CFC-113 under conditions typical
of situations in which CFC-113 can
cause death. In most of the reports, the conc of CFC-113
was not specified. However, in one of the deaths from cardiac
arrhythmia, the exposure was for 1 min & the CFC-113
concn measured 24 hr after exposure was 7600 ppm. In a death from
asphyxiation, the CFC-113 conc was
estimated to be 300,000 ppm, but the duration of exposure was
not stated; however from the description of the incident, the
exposure was relatively brief. [American Conference of Governmental
Industrial Hygienists, Inc. Documentation of the Threshold Limit
Values and Biological Exposure Indices. 6th ed. Volumes I, II,
III. Cincinnati, OH: ACGIH, 1991.1633]
-- IN EXPERIMENTAL ANIMALS VARIABLE DEGREES OF TACHYCARDIA,
MYOCARDIAL DEPRESSION, AND HYPOTENSION
HAVE BEEN DESCRIBED. [Hamilton, A., and H. L. Hardy. Industrial
Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc.,
1974. 293]
-- TRICHLOROTRIFLUOROETHANE CAUSED
TACHYCARDIA, HYPOTENSION IN ANESTHETIZED
RHESUS MONKEYS WHEN INHALED @ 2.5-5%. [AVIADO DM, SMITH DG; TOXICOL
3 (2): 241-52 (1975)]
-- TRICHLOROTRIFLUOROETHANE @ 2.5
& 5% DEPRESSED VENTRICULAR FUNCTION IN HEART-LUNG
PREPN FROM DOG. [AVIADO DM, BELEJ M; TOXICOLOGY 3 (1): 78-86 (1975)]
-- Various animal studies (non-human primates and dogs) have indicated
that acute exposure to high concn of CFC-113
(as low as 2,000
ppm or 15,400 mg/cu m in a 6 hr exposure period) followed by a
large injected dose of epinephrine resulted in cardiac
arrhythmias. [USEPA; Health Assessment Document for 1,1,2-Trichloro-1,2,2-Trifluoroethane
p.2 (1983) EPA-600/58-82-002F]
Ref:
Hazardous Substances Data Bank for 1,1,2-TRICHLORO-1,2,2-TRIFLUOROETHANE
CASRN: 76-13-1. http://www.fluorideaction.org/pesticides/trichlorotrifluorome.toxnet.htm
-- Health
Hazards - General ... Inhalation of high concentrations
may also result in temporary alteration
of the heartÕs electrical activity by increasing the sensitivity
of the heart to the arrhythmogenic action of epinephrine, causing
irregular pulse, palpitations, or inadequate circulation
(Dupont, 1996A; Dupont, 1996F; OSHA, 1998; Reprotext, 2003). Deliberate
inhalation (ÒsniffingÓ) may cause death without warning (Dupont,
1996A; Dupont, 1996F; OSHA, 1998).
-- Acute Effects ... Inhalation of
high concentrations (~5,000 ppm) is associated with the development
of arrhythmias and sudden death due to myocardial
sensitization to endogenous catecholamines (e.g., epinephrine).
-- Predisposing Conditions. Individuals
with pre-existing diseases of the central nervous or cardiovascular
system may have increased susceptibility to the effects
of Freons (Dupont, 1996A; OSHA, 1998; Dupont, 1996B; Dupont, 1996D).
Persons exposed to epinephrine or other sympathomimetic amines,
e.g., bronchodilators and nasal decongestants (e.g., Sudafed ¥),
might be at increased risk for the cardiotoxic
effects of Freons (Reprotext, 2003).
-- Special Concerns for Children.
Children may inhale relatively larger doses of Freon because,
relative to their body weight, they have a greater lung surface
area and larger minute volume than adults. Since Freon has a high
vapor density, children could also receive high doses due to their
short stature and the higher levels of Freon vapor that may be
present near the ground when Freon is spilled.
Ref:
September
24, 2003 (Revised)
- FREON [11, 12, 113].
Technical Support Document: Toxicology.
Clandestine Drug Labs/ Methamphetamine. Volume 1, Number 11. California
EPA, Office of Environmental Health Hazard Assessment (OEHHA),
Department of Toxic Substances Control.
Prenatal developmental
in nonrodents (rabbit). Maternal
NOAEL: 100 mg/kg/day Maternal LOAEL: 250 mg/kg/day based on increased
mortality, increased vaginal/ anal bleeding. Developmental NOAEL:
50 mg/kg/day Developmental LOAEL: 100 mg/kg/day based on abnormally
shaped heart (one fetus at 100 mg/kg/day and 3 fetuses
from 2 litters at 250 mg/kg/day)... In historical
control data provided by the registrant, there were no reported
instances of abnormally shaped hearts.
Ref:
Federal Register: September 17, 2003 (Volume 68, Number 180)]
Rules and Regulations. Trifloxysulfuron; Pesticide Tolerance.
Final Rule. http://www.fluorideaction.org/pesticides/trifloxysulfuron.fr.sept.03.htm
-- ** 089 036915 "A
Teratology Study (I) of Trifluralin (EL-152, Compound 36352) Administered
Orally to Dutch Belted Rabbits." (Lilly
Research Labs., 10/31/84, Study B02283 and Study BO1784) Trifluralin
(96.7% pure), lot 00554AP2; 0, 100, 225, 500, or 800; oral gavage,
days 6 - 18; 20/group; maternal NOEL = 225 mg/kg (maternal death
and abortions), developmental toxicity NOEL = 225 mg/kg (decreased
fetal weight); Complete and ACCEPTABLE WITH 036916. No adverse
developmental toxicity reported. JAP, 11/18/85. EPA one-liner:
Maternal NOEL = 225 mg/kg (abortions and anorexia), fetotoxic
NOEL = 225 mg/kg (decreased percentage of live fetuses - cardiomegally
and wavy ribs at 500 mg/kg/day);
Core grade =
Supplementary
Ref:
SUMMARY OF TOXICOLOGY DATA TRIFLURALIN. California EPA, Department
of Pesticides, Medical Toxicology Branch. Revised as of 11/29/95. http://www.cdpr.ca.gov/docs/toxsums/pdfs/597.pdf •
Note:
Definition
of "Cardiomegaly" - an abnormal enlargement of the heart.