Leukemia
is a malignant disease (cancer) of
the bone marrow and blood. It is characterized by
the uncontrolled accumulation of blood cells. Leukemia is
divided into four categories: myelogenous or lymphocytic,
each of which can be acute or chronic. The terms myelogenous
or lymphocytic denote the cell type involved. Thus, the
four major types of leukemia are:
• Acute Lymphocytic Leukemia
• Chronic Lymphocytic Leukemia
• Acute Myelogenous Leukemia
• Chronic Myelogenous Leukemia
Acute leukemia is a rapidly progressing disease that results
in the accumulation of immature, functionless cells in the
marrow and blood. The marrow often can no longer produce
enough normal red blood cells, white blood cells and platelets.
Anemia, a deficiency of red cells, develops in virtually
all leukemia patients. The lack of normal white cells impairs
the body's ability to fight infections. A shortage of platelets
results in bruising and easy bleeding. Chronic leukemia
progresses more slowly and allows greater numbers of more
mature, functional cells to be made.
New Cases
Among an estimated 30,600 new cases of leukemia in the United
States this year, about equal proportions are acute leukemia
and chronic types. Most cases occur in older adults; more
than half of all cases occur after age 64. Leukemia is
expected to strike 8 times as many adults as children
in 2003. (About 27,815 adults compared with 3,441 children,
ages 0-19). About 30 percent of cancers in children ages
0-14 years are leukemia. The most common form of leukemia
among children under 19 years of age is Acute Lymphocytic
Leukemia (ALL).
The most common types of leukemia in adults are acute myelogenous
leukemia (AML), with an estimated 10,500 new cases annually,
and chronic lymphocytic leukemia (CLL), with some 7,300
new cases each year. Chronic myelogenous leukemia (CML)
affects about 4,300 persons each year. Acute lymphocytic
leukemia (ALL) will account for about 3,600 cases this year.
Other unclassified forms of leukemia account for the 4,900
remaining cases.
Incidence by Gender
Incidence rates for all types of leukemia are higher among
males than among females. In 2003, males are expected to
account for more than 58 percent of the cases of leukemia.
(Note: Incidence rates are the number of new cases in a
given year not counting the pre-existing cases. The incidence
rates are usually presented as a specific number per 100,000
population.)
Ref: http://www.leukemia.org/all_page?item_id=9346
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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
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Note:
This is not an exhaustive list.
When time allows more information will be added.
Arsenic
trifluoride - Wood Preservative -
CAS No. 7784-35-2
HEMATOLOGIC. ACUTE EXPOSURE. Acute hemolysis and anemia may occur
after acute poisoning. Pancytopenia, aplastic anemia, or leukemia
may occur following chronic exposure. Bone marrow
depression can occur.
Ref: TOXNET profile from Hazardous Substances Data Bank for ARSENIC
TRIFLUORIDE
CASRN: 7784-35-2.
http://www.fluoridealert.org/pesticides/arsenic.trifluoride.toxnet.htm
Dichlorodifluoromethane
- Insecticide, Fungicide Propellant, EPA List 2 Inert
- CAS No. 75-71-8
-- Dichlorodifluoromethane
... /was/ tested by inhalation on Sprague-Dawley rats and Swiss
mice. The animals were exposed for 4 hr a day, 5 days a week;
rats were exposed for 104 weeks, and mice were exposed for 78
weeks. Animals were observed until spontaneous death. Exposure
of rats to dichlorodifluoromethane resulted in no noticeable differences
in the incidence of total benign and malignant tumors, and of
the most frequently expected or rate of tumors. Exposure of mice
to dichlorodifluoromethane resulted in a higher number of total
tumors in males and females which was dose related in males, pulmonary
adenomas in males and females at 5000 ppm, and leukemias
in males at 5000 and 1000 ppm and in
females at 1000 ppm. [Maltoni C et al; Annals of the New
York Academy of Sciences 534: 261-82 (1988)]
Ref: TOXNET profile from Hazardous Substances
Data Bank for Dichlorodifluoromethane.
http://www.fluoridealert.org/pesticides/Dichlorodifluorometh.TOXNET.htm
Dichlorofluoromethane
(CFC-21)
- Propellant, EPA List 2 Inert - CAS
No. 75-43-4
TSCA Test Submissions:
A subchronic inhalation toxicity study was conducted with groups
of male (35) and female (35) albino rats (strain not reported)
receiving whole body exposure to dichloromonofluoromethane at
a nominal concentration of 0, 50, 150 or 500ppm in a dynamic air
flow chamber for 6 hours per day, five days per week for approximately
90 days. On day 45 and day 90, 5 animals per sex and 20 animals
per sex, respectively were sacrificed. The remaining animals were
observed for an additional 30 days and then sacrificed. Four high
dose males were found dead during the exposure period and one
female and six males from the high dose group were found dead
during the recovery period. High dose rats were observed to have
statistically significant (p < 0.01) lower body weights than controls
during the exposure period, but were comparable after the 30 day
recovery period. Hematology, clinical chemistry and urine analysis
values were similar between all dosed animals and control animals,
with the exception of a slightly higher total blood leukocytes
counts and elevated
mean SAP and SGPT values for high dose animals at approximately
45, 90 and 120 days. A dose related increase in urine fluoride
levels was also observed. Histopathology evaluation of treated
animals revealed portal cirrhosis of the
liver,
interstitial edema of the pancreas and degeneration
of the seminiferous epithelium. Three cases of leukemia
were observed in high dose male rats. [Industrial Bio-Test
Laboratories; Subacute Inhalation Toxicity Study with Genetron
21 in Albino Rats, (1979), EPA Document No. FYI-OTS-0779-0045,
Fiche No. OTS0000045-0 ]
[Note from FAN: seminiferous epithelium
= the epithelium lining the convoluted tubules of the testis where
spermatogenesis and spermiogenesis occur.]
Ref: TOXNET profile from Hazardous Substances
Data Base for DICHLOROFLUOROMETHANE.
http://www.fluoridealert.org/pesticides/Dichlorofluoromethan.TOXNET.htm
Fluometuron
- Herbicide - CAS No. 2164-17-2
EPA
has determined that there is not enough evidence that fluometuron
causes cancer in animals to justify its classification as a carcinogen.
Fluometuron is not classified as a carcinogen by the EPA (20).
An increased incidence of liver-cell tumors in male mice was noted
in a study of rats and mice. In the same study, no carcinogenic
effects were observed in female mice or in rats of either sex
(18). Mice that were given oral doses of 87 mg/kg for two years
had evidence of liver tumors and leukemia,
a condition characterized by uncontrolled growth in the number
of white blood cells in the blood stream (National Institute
for Occupational Safety and Health (NIOSH). 1986. Registry of
toxic effects of chemical substances (RTECS). Cincinnati, OH:
NIOSH.)
Ref:
1994 Pesticide Information Profile. EXTOXNET.
http://www.fluoridealert.org/pesticides/fluometuron.extoxnet.1994.htm
Penoxsulam
- Herbicide - CAS No. 219714-96-2
Suggestive
Evidence of Carcinogenicity, but
Not Sufficient to Assess Human Carcinogenic Potential. Mononuclear
cell leukemia
in Male Fischer 344 rats. Although dosing in male mice was not
considered to be adequate, an additional mouse carcinogenicity
study was not required.
Ref: April
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf
--
Carcinogenicity: Evidence of carcinogenicity
in male rats based on possibly treatment related increase incidence
of Large Granular Lymphocyte (LGL) Leukemia at 5, 50, & 250
mg/kg/day. Also
increase severity at 250 mg/kg/day. Female rats - negative for
carcinogenicity, but dosing was only marginally adequate.
-- Carcinogenicity-mice: In males, negative for carcinogenicity
at doses tested. Dosing inadequate.
-- The Agency (US EPA) has
classified penoxsulam as Suggestive Evidence of Carcinogenicity,
But not sufficient to assess human carcinogenic
potential and, therefore, quantification of human cancer risk
is not required. The weight-of-the-evidence for this classification
is as follows: a. Evidence of carcinogenicity (mononuclear cell
leukemia (MNCL)) was seen in one sex (males) of one species (rat).b.
There was an increased incidence of MNCL at all dose levels with
all incidences exceeding the laboratory historical control, however,
the dose-response was flat over a wide range of doses. c. Although
MNCL is recognized as a common neoplasm in Fischer rats, the mechanism
of producing MNCL is not completely understood. Therefore, the
significance of MNCL and its biological relevance for human cancer
risk remains uncertain and cannot be discounted ...
Ref: September 24, 2004. Penoxsulam Pesticide
tolerance. Final Rule. Federal Register.
http://www.fluorideaction.org/pesticides/penoxsulam.fr.sept.24.04.htm
-- Chronic toxicity.
Chronic exposure in the dog indicated that the renal effects were
not exacerbated with long-term exposure. Following long-term exposure
in rats, the kidneys and urinary bladder
were the primary target organs. Histologic changes seen at the
end of 2 years of exposure consisted of inflammation and hyperplasia
of the renal pelvic transitional epithelium, crystal deposition
in the kidneys and urinary bladder, and hyperplasia of the mucosa
of the urinary bladder. In
the mouse, the liver was the primary target organ, and histologic
changes consisted of hepatocellular hypertrophy. There were no
treatment-related increases in tumors in either rats or mice.
The
incidence of mononuclear cell leukemia (Fischer rat leukemia)
was increased in all groups of treated male
rats compared to the concurrent controls. However, the
incidences in the treated groups were identical across a 50-fold
increase in dosage, and well within the range of control values
reported in the literature.
Ref: August 6, 2003. Federal Register: August
6, 2003 (Volume 68, Number 151)] [Notices] [Page 46609-46613].
Penoxsulam; Notice of Filing a Pesticide Petition To Establish
a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/penoxsulam.fr.aug.6.2003.htm
In a carcinogenicity study in rats, male and female rats were
given penoxsulam in the diet for two years at dose levels of 0,
5, 50 or 250 mg/kg/day. In this study, there
was a statistically significant increased incidence of malignant
large granular lymphocyte (LGL) leukemia in each of the male treatment
groups. The incidence was 24%, 60%, 58% and 60% in the
control, low, mid and high dose level groups respectively. There
was no dose response with all treated male groups having an approximately
2.5 fold increase over control animals. The
incidence in the male treatment groups exceeded the conducting
laboratory‘s historical control mean (28.5%) and range (16-40%),
but fell within the National Toxicology Program (NTP) historical
control data base of mean (50.5%) and range (32-74 %). There
was also an increased severity (Stage 3) of LGL leukemia in all
the treated male groups compared to the control group.
There was no increase in incidence or severity of LGL leukemia
for the treated female rats in this study. The dose levels in
this study were considered to be adequate in male rats and marginally
adequate in female rats to assess the carcinogenicity of penoxsulam.
Reference: September 2004. US EPA Fact Sheet
on Penoxsulam. Page 4.
http://www.fluorideaction.org/pesticides/penoxsulam.epa.fact.sheet.2004.pdf
Trichlorofluoromethane
-Insecticide, Fungicide, Propellant, EPA List 2 Inert - CAS
No. 75-69-4
-- Trichlorofluoromethane
... /was/ tested by inhalation on Sprague-Dawley rats and Swiss
mice. The animals were exposed for 4 hr a day, 5 days a week; rats
were exposed for 104 weeks, and mice were exposed for 78 weeks.
Animals were observed until spontaneous death. Trichlorofluoromethane
exposure to rats caused no carcinogenic effects. Trichlorofluoromethane
exposure to mice caused increased numbers
of total tumors in females which was dose related, mammary tumors
in females at 5000 ppm, lung adenomas and leukemias
in females, both dose related. [Maltoni C et al; Annals of
the New York Academy of Sciences 534: 261-82 (1988)]
Ref: Hazardous Substances Data Base for TRICHLOROFLUOROMETHANE.
http://www.fluoridealert.org/pesticides/Trichlorofluorometha.TOXNET.htm
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