Document ID: EPA-HQ-OPP-2007-0833-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-10-10T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

SUBJECT:	Sodium Fluoride – Incident Report Summary

PC Code: 	075202

FROM:	Jonathan Chen, Ph.D.	

	Senior Toxicologist

	Risk Assessment and Science Support Branch (RASSB)

Antimicrobial Division (7510C)

THROUGH:	Norm Cook

Chief

RASSB / AD

TO:		Sanyvette Williams, Chemical Review Manager

		Regulatory Management Branch II

		Antimicrobials Division (7510P)     

Attached is RASSB’s incident reports summary associated with sodium
fluoride.



INCIDENT REPORTS ASSOCIATED WITH

Sodium Fluoride

 (PC CODE: 075202)

August 3, 2007

U.S. Environmental Protection Agency

Office of Pesticide Programs

Antimicrobials Division

TABLE OF CONTENTS

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc174769761"  0.0
INTRODUCTION	  PAGEREF _Toc174769761 \h  1  

  HYPERLINK \l "_Toc174769762"  1.0 	INCIDENT REPORT DATA ASSOCIATED
WITH HEALTH EFFECTS	  PAGEREF _Toc174769762 \h  1  

  HYPERLINK \l "_Toc174769763"  1.1	OPP’s Incident Data System (IDS)	 
PAGEREF _Toc174769763 \h  2  

  HYPERLINK \l "_Toc174769764"  1.2	Poison Control Center (1993 –
2003)	  PAGEREF _Toc174769764 \h  2  

  HYPERLINK \l "_Toc174769765"  1.4	National Pesticide
Telecommunications Network (NPTN)	  PAGEREF _Toc174769765 \h  3  

  HYPERLINK \l "_Toc174769766"  1.5	Incident Reports / Epidemiological
Studies Published in Scientific Literature	  PAGEREF _Toc174769766 \h  3
 

  HYPERLINK \l "_Toc174769767"  1.5.1 Acute Effects	  PAGEREF
_Toc174769767 \h  3  

  HYPERLINK \l "_Toc174769768"  1.5.2 Chronic Effects	  PAGEREF
_Toc174769768 \h  4  

  HYPERLINK \l "_Toc174769769"  2.0	CONCLUSIONS	  PAGEREF _Toc174769769
\h  5  

  HYPERLINK \l "_Toc174769770"  3.0	REFERENCES	  PAGEREF _Toc174769770
\h  6  

 

0.0	INTRODUCTION tc \l1 "0.0	INTRODUCTION 

The purpose of this chapter is to review the evidence of health effects
in humans resulting from exposure to sodium Fluoride.  

Two approaches are used in this section:

The potential health effects of sodium fluoride in humans, reported as
incident reports from different sources, are summarized. 

A literature search of chronic health effects associated with sodium
fluoride exposure, including results of epidemiological studies, is
summarized.

1.0 	INCIDENT REPORT DATA ASSOCIATED WITH HEALTH EFFECTS 

The following databases have been consulted for incident data:

OPP Incident Data System (IDS) - The Incident Data System of The Office
of Pesticide Programs (OPP) of the Environmental Protection Agency (EPA)
contains reports of incidents from various sources, including
registrants, other federal and state health and environmental agencies
and individual consumers, submitted to OPP since 1992.  Reports
submitted to the Incident Data System represent anecdotal reports or
allegations only, unless otherwise stated.  Typically no conclusions can
be drawn implicating the pesticide as a cause of any of the reported
health effects.  Nevertheless, sometimes with enough cases and/or enough
documentation risk mitigation measures may be suggested.

Poison Control Centers - as the result of a data purchase by EPA, OPP
received Poison Control Center data covering the years 1993 through 2003
for all pesticides.  Most of the national Poison Control Centers (PCCs)
participate in a national data collection system, the Toxic Exposure
Surveillance System, which obtains data from about 65-70 centers at
hospitals and universities.  PCCs provide telephone consultation for
individuals and health care providers on suspected poisonings involving
drugs, household products, pesticides, etc.

California Department of Pesticide Regulation - California has
collected uniform data on suspected pesticide poisonings since 1982. 
Physicians are required, by statute, to report to their local health
officer all occurrences of illness suspected of being related to
exposure to pesticides.  The majority of the incidents involve workers. 
Information on exposure (worker activity), type of illness (systemic,
eye, skin, eye/skin and respiratory), likelihood of a causal
relationship, and number of days off work and in the hospital are
provided.

National Pesticide Telecommunications Network (NPTN) - NPTN is a
toll-free information service supported by OPP.  A ranking of the top
200 active ingredients for which telephone calls were received during
calendar years 1984-1991, inclusive, has been prepared.  The total
number of calls was tabulated for the categories of human incidents,
animal incidents, calls for information, and others.

1.1	OPP’s Incident Data System (IDS) tc \l2 "1.1 	OPPs Incident Data
System (IDS) 

There is no incident has been reported in the OPP incident data system
is specific associated with sodium fluoride exposure. 

1.2	Poison Control Center (1993 – 2003) tc \l2 "1.2 	 Poison Control
Center 

There are 5 incidents been reported in the American Association of
Poison Control Centers Toxic Exposure Surveillance System (TESS) between
1993-2003.  

Between 1993-1998, two cases involved oral exposure are reported.  The
patients exhibited symptoms as a result of the exposure which are
consider have moderate effects and were not life-threatening and the
patients have returned to a pre-exposure state of well-being with no
residual disability or disfigurement.  The reported symptoms including
blurred visions, and chest and abdominal pain.

Between 1999-2003, three cases (two involved oral exposure and one
involved aerosol inhalation exposure) are reported.  All the three cases
are classified as minor effects as the result of the exposure and the
symptoms resolve rapidly and returned to a pre-exposure state of well
being and have no residual disability or disfigurement.  For oral
exposure, vomiting is the primary reported symptom.  For inhalation
exposure, nausea and headache are the primary reported symptoms.

1.3	California Data - 1982 through 2003

There is one sodium fluoride involved incident reported.  A worker
applies a wood preservative to the base of a telephone pole and got some
on his cheek.  While wiping it off with his sleeve, he rubbed it into
his left eye.  He flushed the eye with a portable kit. The reported
symptoms include pain, burning sensation, and marked conjunctival
infection in the left eye. However, creosote and potassium dichromate
may also be involved in this incident.

1.4	National Pesticide Telecommunications Network (NPTN) tc \l2 "1.4 
National Pesticide Telecommunications Network (NPTN) 

There is no incident reported in the NPTN database related to sodium
fluoride exposure.

1.5	Incident Reports / Epidemiological Studies Published in Scientific
Literature

There are some concerns associated with sodium fluoride exposure
reported in the public literature.

1.5.1 Acute Effects

Direct contact with fluoride can result in tissue damage. At high
concentrations, fluoride can cause irritation and damage to the
respiratory tract, stomach, and skin following inhalation, oral, and
dermal exposure, respectively (ATSDR, 2003).  Dermal irritation and
contact urticaria have been reported from dermal contact of sodium
fluoride (Camarasa et al., 1993). 

There are incidences associated with sodium fluoride through acute oral
ingestion (Abukurah et al. 1972; Hayes, 1975; Eichler et al., 1982).  As
summarized by Dreisbach (1987), through oral exposure, soluble fluoride
salts may cause salivation, nausea and vomiting, diarrhea, and abdominal
pain. Later, weakness, tremors, shallow respiration, carpopedal spasm,
and convulsions occur. Death is by respiratory paralysis. If death does
not occur immediately, jaundice and oliguria may appear. Experience with
oral fluoride supplements used to prevent tooth decay has been
reassuring; no adverse effects occur unless enormous amounts are
ingested.  A variety of metabolic disorders may occur, including
hypocalcemia, hypomagnesemia, metabolic and/or respiratory acidosis and
sometimes hyperkalemia, may also occur in acute fluoride poisoning
(Gosselin, et al., 1984).  

 (Abukurah et al. 1972). Within 14 hours following exposure, the patient
experienced 63 episodes of ventricular fibrillation. For example, a
plasma fluoride level of 2,000 μg/L was reported in a case of severe
oral poisoning with 53 g fluoride as sodium fluoride (Abukurah et al.
1972).  The noticed cardiac symptoms may be associated with the
metabolic disorder resulted from acute fluoride exposure.

1.5.2 Chronic Effects

Fluoride intake has been shown to decrease the prevalence of dental
caries.  However, the primary concerns associated with chronic exposure
to high level of fluoride, especially through oral route, can cause
dental fluorosis and can result in an increased prevalence of bone
fractures in the elderly or skeletal fluorosis (ATSDR, 2003). 

Numerous epidemiological studies have examined the issue of a connection
between fluoridated water with heart disease. There are studies show
there were no significant differences between areas with different
fluoride levels in mortality due to coronary disease, angina, and other
heart disease (Leone et al. 1954; Heasman and Martin 1962).  Although
there is a study show a positive relationship between heart disease and
water fluoridation (Hagan et al. 1954), this study was criticized for
the sampling population was not properly age adjusted (Jansen and
Thomson, 1974).  There are other studies have suggested fluoridation can
decrease the incidence of cardiovascular disease (Bernstein et al. 1966;
Luoma 1980; and Taves, 1978).

Numerous epidemiological studies have examined the issue of a connection
between fluoridated water and cancer. Most studies have not found
significant increases in cancer mortality (Erickson 1978; Hoover et al.
1976; Rogot et al. 1978; Taves 1977) or site-specific cancer incidence
(Freni and Gaylor 1992; Gelberg et al. 1995; Hoover et al. 1976; Mahoney
et al. 1991; McGuire et al. 1991). However, a couple of studies have
reported significant fluoridation-related increases in cancer mortality.
 In order to address the cancer concern,  the National Toxicology
Program (NTP) conducted two chronic oral bioassays of fluoride
administered as sodium fluoride (0, 25, 100, or175 ppm) in drinking
water for 103 weeks, using F344/N rats and B6C3F1 mice (NTP, 1990). The
estimated total fluoride intake (including fluoride in both water and
diet) of control, low-, medium-, and high-dose male rats as 0.2, 0.8,
2.5, and 4.1 mg/kg/day, respectively. Similarly, the high doses for
female rats, male mice, and female mice were 4.5, 8.1, and 9.1
mg/kg/day, respectively. The study found osteosarcomas in the bone of
1/50 male rats in the mid-dose group and 3/80 of the high dose male
rats. An additional high-dose male had an extra skeletal osteosarcoma in
subcutaneous tissue. Osteosarcomas were observed in one low-dose male
mouse, one low-dose female mouse, and one control female mouse. There
was also one osteoma in a control female mouse. No osteosarcomas were
observed at mid- or high-dose levels in female rats or male or female
mice.

In 1996, the EPA’s Office of Prevention, Pesticides, and Toxic
Substances classified sodium aluminofluoride (cryolite) as a “Group
D” carcinogen (not classifiable as to carcinogenicity), citing the
National Toxicology Program’s carcinogenicity study of sodium fluoride
(NTP, 1990). More recently, the National Acedemy of Sciences (NAS, 2006)
at the request of the EPA, conducted a review of the toxicologic,
epidemiologic, and clinical data on fluoride since the 1993 NAS report.
With respect to carcinogenicity, the 2006 NAS report concluded that “
on the basis of the committee’s collective consideration of data from
humans, genotoxicity assays, and studies of mechanism of action in cell
systems…the evidence on the potential of fluoride to initiate or
promote cancers, particularly of the bone, is tentative and mixed.”
This recent conclusion is consistent with the past conclusion of OPPTS
regarding carcinogenic potential of fluoride.

2.0	CONCLUSIONS

There are only limited acute incidences associated with sodium fluoride
used in wood preservatives.  All the symptoms are classified as either
minor or moderate.  Historically, there are some fatal incidences
associated with oral exposure to sodium fluoride, it happened at much
higher concentration.  

For chronic exposure, fluoride intake has been shown to decrease the
prevalence of dental caries. At high level of fluoride, especially
through oral route, can cause dental fluorosis and can result in an
increased prevalence of bone fractures in the elderly or skeletal
fluorosis (ATSDR, 2003).  In 1996, the EPA’s Office of Prevention,
Pesticides, and Toxic Substances classified sodium aluminofluoride
(cryolite) as a “Group D” carcinogen (not classifiable as to
carcinogenicity).



REFERENCES

Abukurah AR, Moser AM Jr, Baird CL, et al. 1972. Acute sodium fluoride
poisoning. JAMA 222:816- 817.

Agency for Toxic Substances and Disease Registry (ATSDR) , 2003.
Toxicological Profile for Fluoride, Hydrogen Fluoride, and Fluorine. 
U.S. Dept. of Health and Human Services.  Public Health Service

Bernstein DS, Sadowsky N, Hegsted DM, et al. 1966. Prevalence of
osteoporosis in high- and lowfluoride areas in North Dakota. JAMA
198(5):85-90. 

Camarasa JG, Serra-Baldrich E, Lluch M, et al. 1993. Contact urticaria
from sodium fluoride. Contact Dermatitis 28(5):294. 

Dreisbach, R.H. 1987.  Handbook of Poisoning. 12th ed. Norwalk, CT:
Appleton and Lange, , p. 217 Cited in Hazardous Substances Data Bank
(HSDB) 2007-06-04 Update

Erickson JD. 1978. Mortality in selected cities with fluoridated and
non-fluoridated water supplies. N. Eng J Med 298:1112-1116. 

Freni SC, Gaylor DW. 1992. International trends in the incidence of bone
cancer are not related to drinking water fluoridation. Cancer
70(3):611-618. 

Gelberg KH, Fitzgerald EF, Hwang S-A, et al. 1995. Fluoride exposure and
childhood osteosarcoma: A case-control study. Am J Pub Health
85(12):1678-1680. 

Gosselin RE, Smith RP, Hodge HC. 1984. Clinical toxicology of commercial
products. 5th ed. Baltimore, MD: Williams & Wilkens, 112, 185-193. 

Hagan TL, Pasternack M, Scholz GC. 1954. Waterborne fluorides and
mortality. Public Health Rep. 69:450-454. 

Hayes WJ Jr. 1975. Ingestion of sodium fluoride as roach powder caused
47 deaths in 260 cases in U.S.A. In: Toxicology of pesticides.
Baltimore, MD: Williams & Wilkins, 323.

Heasman MA, Martin AE. 1962. Mortality in areas containing natural
fluoride in their water supplies. Mon Bull Minist Health Public Health
Lab Serv 21:150-173. Hoover et al. 1976

Hoover RN, McKay FW, Fraumeni JF Jr. 1976. Fluoridated drinking water
and the occurrence of cancer. J Natl Cancer Inst 57(4):757-768. 

Jansen I, Thomson HM. 1974. Heart deaths and fluoridation. Fluoride
7:52-57. 

Leone NC, Leatherwood EC, Petrie IM, et al. 1964. Effect of fluoride on
thyroid gland: Clinical study. J Am Dental Assoc 69:179-180. 

Luoma H. 1980. Fluoride and magnesium, two ions in the prevention of
calcium salt imbalance, including caries prevention, in man and animals.
Proc Finn Dent Soc 76:73-81. 

Mahoney MC, Nasca PC, Burnett WS, et al. 1991. Bone cancer incidence
rates in New York State: Time trends and fluoridated drinking water. Am
J Public Health 81(4):475-479. 

McGuire SM, Vanable ED, McGuire JA, et al. 1991. Is there a link between
fluoridated water and osteosarcoma? J Am Dent Assoc 122:38-45. NAS, 2006

National Academy of Science (NAS).  2006. Fluoride in Drinking Water: A
Scientific Review of EPA's Standards. The National Academies Press.
United States.

NTP. 1990. NTP technical report on the toxicology and carcinogenesis
studies of sodium fluoride in
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Rogot E, Sherrett AR, Feinleib M, et al. 1978. Trends in urban mortality
in relation to fluoridation status. Am J Epidemiol 107:104-112. 

Taves DR. 1977. Fluoridation and cancer mortality. In: Origins of human
cancer: Book A: Incidence of cancer in humans. Cold Spring Harbor
Conferences on Cell Proliferation 4:357-366.

Taves DR. 1978. Fluoridation and mortality due to heart disease. Nature
272:361-362.

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