See
FAN's summary of all the pesticides with Cancer effects.
Due
to length, the Cancer effects section is now presented in 4 parts.
The most recent United
States Cancer Statistics report was released in November
2003. This is the 2nd annual report prepared by the Centers
for Disease Control and Prevention and the National Cancer
Institute, in collaboration with the North American Association
of Central Cancer Registries.
In 1998 I published the Citizens' Guide
to 667 Chemicals Known to Cause Human Cancer in the newsletter
Waste Not. The four top uses of these chemicals were in
the manufacture of
Plastics
Pharmaceuticals
Pesticides
Dyes
Of the 667 known carcinogenic chemicals,
84 were identified by the US EPA in 1997 as "High Production
Volume Chemicals" - produced in quantities greater
than 1 million pounds a year.
If society wants to prevent cancer, the
first step would be to ban the use, production and release
of known and suspected carcinogens. - EC.
Towards
what ultimate point is society tending by its industrial
progress?
When the progress ceases, in what condition are we to expect
that it will leave mankind?
- John Stuart Mill, 1857 -
|
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.
When time allows more information will be added.
Acifluorfen
- Herbicide -
CAS No. 50594-66-6
PAN Bad Actor Pesticide: Carcinogen
Ref: Pesticide Action Network
http://www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC37357
Acifluorfen,
sodium -
Herbicide - CAS No. 62476-59-9
Likely
to be Carcinogenic to Humans at High Doses. Not Likely to be Carcinogenic
to Humans at Low Doses.
Liver; B6C3F1 & CD-1 mice (M & F).
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
Group B2--Probable
Human Carcinogen. Reviewed 3/ 17/
88.
Ref:
March 15, 2002. List of Chemicals
Evaluated for Carcinogenic Potential. Science Information Management
Branch, Health Effects Division, Office of Pesticide Programs,
U. S. Environmental Protection Agency.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm
-- Acifluorfen is classified
as a Group B2 compound, i.e., the chemical
is a probable human carcinogen. Acifluorfen produced an
increased incidence of combined malignant
and benign liver tumors in two different strains of mice.
The compound also displayed positive mutagenic activity in several
non-mammalian test systems, and is structurally similar to four
other diphenyl ether herbicide compounds which caused increased
incidences of liver tumors in two different strains of mice. EPA
believes that there is sufficient evidence for listing acifluorfen
sodium salt on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available carcinogenicity data.
Ref.
USEPA/OPP. Support Document for the Addition of Chemicals from
Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active
Ingredients to EPCRA Section 313. 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.
There are eight diphenyl ethers that are structurally similar
to diclofop-methyl. Of the chemicals, fomesafen
sodium, haloxyfop-methyl (Verdict), oxyfluorfen, acifluorfen
sodium, nitrofen, and lactofen were reviewed in the initial
CPRC report. All of these chemicals induced
liver adenomas and carcinomas in rats and/or mice. Except
for haloxyfop-methyl, all of the other chemicals
produced positive results in at least one of the mutagenicity
assays...
May
24, 2000 - Cancer
Assessment Document. Evaluation of the
Carcinogenic Potential of Diclofop-Methyl. (Second Review). Final
Report. Cancer Assessment Review Committee, Health Effects Division,
US EPA Office of Pesticide Programs.
Note:
Except for Nitrofen, all the pesticides cited above are fluorinated.
Benfluralin
- Herbicide -
CAS No. 1861-40-1
Suggestive
Evidence of Carcinogenicity, but Not Sufficient to Assess Human
Carcinogenic Potential. Liver tumors (hepatocellular adenomas
& carcinomas) in 2 genetically related strains of mice (CD-1
& Swiss SPF) (M & F).
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
Benthiavalicarb-isopropyl
- Fungicide - CAS No. 177406-68-7
Likely
to be Carcinogenic to Humans.
Malignant uterine tumors in female
Fisher 344 rats; Liver tumors in
both sexes of B6C3F1 mice with some supporting evidence of liver
tumors in male rats; Thyroid follicular
cell tumors in male B6C3F1 mice.
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
Bifenthrin
- Acaricide, Insecticide - CAS Numbers:
82657-04-3 (Cis); 83322-02-5 (Trans)
Group
C -- Possible Human Carcinogen. Hemangiopericytomas
in the urinary bladder; Hepatocellular
carcinomas & combined hepatocellular adenomas &
carcinomas; Swiss Webster mice (M)
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
Group
C--Possible Human Carcinogen.
Reviewed 4/ 29/ 92.
Ref:
List of Chemicals Evaluated for Carcinogenic Potential. Science
Information Management Branch, Health Effects Division, Office
of Pesticide Programs, U. S. Environmental Protection Agency.
March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm
Abstract: The tumor-promoting
activities of 5 commercial compounds used in termiticides were
measured by a cell-transformation assay employing Bhas 42 cells.
Their initiating activities were also measured by the microsuspension
assay employing S. typhimurium TA98 and TA100 strains. The
results of the transformation assay confirmed the tumor-promoting
activities of fenitrothion, silafluofen
[fluoridated] and bifenthrin.
Furthermore, the mutagenicity of S-421 and fenitrothion were also
confirmed. Consideration of 2-stage carcinogenesis
suggests that concurrent use of and long-term exposure to these
compounds that have tumor-promoting and initiator activity, and
compounds exhibiting either type of activity individually should
be avoided as much as possible.
Ref: Tumor-promoting
activity and mutagenicity of 5 termiticide compounds; by Goto
S, Asada S, Fushiwaki Y, Mori Y, Tanaka N, Umeda M, Nakajima D,
Takeda K. J UOEH. 2004 Dec 1;26(4):423-30.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15624354&query_hl=11
"Bifenthrin. Withdrawn.
Indication of carcinogenic effects.
1992."
Definition: "Withdrawn. A substance
which the manufacturer has either withdrawn from the market, or
for which he has withdrawn his application for registration, approval,
or renewed approval and when it is clear that these measures were
undertaken due to the health or environmental properties of the
substance."
Ref: Euopean Commission. Appendix 5. Substances
which may not be included as active ingredients in approved pesticide
products, Chapter 15, Section 2, subsection one.
http://www.kemi.se/lagar_eng/pdf/app5_8.pdf
A chronic/carcinogenicity
study in mice
fed at doses of 0, 50, 200, 500, or 600 ppm (0, 2.5, 10, 25, or
30 mg/kg/day) in the diet for 87 weeks (males) or 92 weeks (females).
Chronic LOEL is 10 mg/kg/day based on the incidence of tremors
in both sexes. Chronic NOEL is 2.5 mg/kg/day. Carcinogenic potential
was evidenced by a statistically significant increased trend for
hemangiopericytomas in the urinary bladders
of males, a significant dose-related trend for
combined hepatocellular adenomas and carcinomas in males, and
a significantly higher incidence of combined lung adenomas and
carcinomas in females.
Carcinogenicity. Using its Guidelines for Carcinogen Risk Assessment
published September 24, 1986 (51 FR 33992) the Carcinogenicity
Peer Review Committee (CPRC) has classified bifenthrin as a Group
C chemical, possible human carcinogen,
based on urinary bladder tumors in mice, but did not recommend
assignment of a cancer potency factor Q* (Q star) for a linear
quantitative cancer risk assessment, instead, the CPRC recommended
the RfD approach. Based on CPRC's recommendation that the RfD
approach be used to assess dietary cancer risk, a quantitative
linear dietary cancer risk assessment was not performed. Human
health risk concerns due to long term consumption of bifenthrin
residues are adequately addressed by the dietary risk evaluation
chronic exposure analysis using the RfD.
Ref: Federal Register: November 26, 1997.
Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/bifenthrin.fr.nov.1997.htm
Carcinogenic Effects:
There was no evidence of cancer in a 2-year study of rats who
ate as much as 10 mg/kg/day of bifenthrin. However, an 87 week
feeding study of mice with doses of 7, 29, 71, and 86 mg/kg showed
a significantly higher, dose related trend of increased tumor
incidence in the male urinary bladder
(63, 67). The incidence was significantly increased at 86 mg/kg/day.
Also, females had higher incidences
of lung cancer than the controls
at doses of 7 mg/kg and higher (67). The EPA has classified bifenthrin
as a class C carcinogen, a possible human
carcinogen (11, 63).
Ref: EXTOXNET Pesticide Information Profile.
1995.
http://ace.ace.orst.edu/info/extoxnet/pips/bifenthr.htm
Abstract: The tumor-promoting activities
of 5 commercial compounds used in termiticides were measured by
a cell-transformation assay employing Bhas 42 cells. Their initiating
activities were also measured by the microsuspension assay employing
S. typhimurium TA98 and TA100 strains. The results of the transformation
assay confirmed the tumor-promoting activities
of fenitrothion, silafluofen and bifenthrin.
Furthermore, the mutagenicity of S-421 and fenitrothion were also
confirmed. Consideration of 2-stage carcinogenesis
suggests that concurrent use of and long-term exposure to these
compounds that have tumor-promoting and initiator activity, and
compounds exhibiting either type of activity individually should
be avoided as much as possible.
Ref: J
UOEH. 2004 Dec 1;26(4):423-30. Tumor-promoting activity and mutagenicity
of 5 termiticide compounds.Goto S, Asada S, Fushiwaki Y, Mori
Y, Tanaka N, Umeda M, Nakajima D, Takeda K.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15624354
Chlorfenapyr
-
Acaricide, Insecticide - CAS No. 122453-73-0
-- Classification:
``Suggestive Evidence of Carcinogenicity,
but Not Sufficient to Assess Human Carcinogenic Potential''
based on significant trends in liver tumors
(adenomas and combined adenomas/ carcinomas), malignant histiocytic
sarcomas, and testicular cell tumors in male rats and uterine
polyps in female rats seen at the highest dose.
Ref:
Federal Register: September 26, 2003. Chlorfenapyr; Pesticide
Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/chlorfenapyr.fr.sept26.2003.htm
Suggestive
Evidence of Carcinogenicity, but Not Sufficient to Assess Human
Carcinogenic Potential. The
overall evidence in animals was Not persuasive, but could not
be dismissed. Increase in tumors in rats occurred with significant
positive trends only, and mainly at the highest dose.
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
page 3: ... BASF Corporation submitted a comprehensive weight-ofevidence
analysis to argue that the USEPA classification of chlorfenapyr
as “suggestive evidence of carcinogenicity, but not sufficient
to assess human carcinogenic potential” should be modified
to “not likely to be a human carcinogen.” When we
compared the registrant’s weight-of-evidence analysis with
the carcinogenicity study data reviewed by the USEPA’s Cancer
Peer Review Committee (Memorandum, January 9, 1997: Carcinogenicity
Peer Review of Chlorfenapyr), we found that
overall the registrant’s argument is not sufficiently persuasive
that chlorfenapyr should be classified as “not likely to
be a human carcinogen.” The main thrust of the registrant’s
argument is that overall there is no increase in liver adenomas/carcinomas,
malignant histiocytic sarcomas, testicular interstitial cell tumors
and uterine endometrial stromal polyps by pair-wise comparisons
between groups of rats fed different doses of chlorfenapyr. The
registrant further argues that the positive trends in tumor incidence
resulting from oral exposure to increasing doses of chlorfenapyr
are not significant when compared to the tumor incidence in historical
controls. To support their argument, the registrant cites only
maximum percent control tumor incidence values instead of the
mean values and ranges which would better illustrate background
tumor incidence. Furthermore, the registrant dismisses the experimental
control values obtained from the rat carcinogenicity study on
chlorfenapyr, by stating that these values are “...uniquely
and abnormally low.” While we acknowledge that the registrant
makes some valid points in their analysis, we believe that the
USEPA’s classification of the carcinogenic potential of
chlorfenapyr as “suggestive evidence of carcinogenicity,
but not sufficient to assess human carcinogenic potential”
is appropriate and should not be reclassified to “not likely
to be a human carcinogen.” In addition, the registrant’s
focus on specific carcinogenicity issues to the exclusion of the
other issues raised in our initial review (i.e., the comparative
risks posed by this product and the need for use on fruiting vegetables)
does not address the overall concerns for registering this product.
Ref: October 3, 2005, letter to BASF from
New York State Bureau of Pesticides Management.
http://www.fluorideaction.org/pesticides/chlorfenapyr.pylon.nys.reg.2005.pdf
1-Chloro-1,1-difluoroethane
-
Solvent, EPA List 2 Inert - CAS No. 75-68-3
Two short-term in vitro
tests for mutagenicity (Salmonella reverse mutation and BHK21
cell transformation) were conducted on a series of fluorocarbons.
Some of these materials (FC22, FC31, FC142b,
FC143 and FC143a) were found to be positive
in 1 or both of the tests and could therefore be considered as
being potentially carcinogenic to animals.
Ref: Longstaff E et al. (1984). Genotoxicity
and carcinogenicity of fluorocarbons: Assessment by short-term
in vitro tests and chronic exposure in rats. TOXICOL APPL PHARMACOL;
72 (1). 15-31.
From
Toxline at TOXNET: http://toxnet.nlm.nih.gov/
Chlorodifluoromethane
-
Insecticide, Fungicide, Propellant, EPA List 2 Inert
- CAS No. 75-45-6
Experimental data.
Chlorodifluoromethane was tested for carcinogenicity
in one experiment in rats by oral administration by gavage
and in experiments in rats and mice by inhalation exposure. No
increase in tumour incidence was observed in rats after oral administration.
The inhalation study in mice was inconclusive for males, and negative
results were obtained for females. In the
inhalation study in rats, males receiving the high dose had increased
incidences of fibrosarcomas and Zymbal-gland tumours; negative
results were obtained for female rats...
Evaluation: There
is limited evidence for the carcinogenicity of chlorodifluoromethane
to experimental animals.
Ref: 5. Summary of Data Reported and Evaluation.
International Agency for Research on Cancer IARC. 1986
http://www.fluorideaction.org/pesticides/chlorodifluoromethane.iarc.htm
Note from FAN: The
Zymbal's gland is made up of several lobules
of modified sebaceous glands which are located at the base (anterioventral)
of the external ear. A section through the base of the skull
at the level of the external ear generally results in a section
plane through one or more lobules of Zymbal's gland tissue.
Ref: http://www.item.fraunhofer.de/reni/trimming/TR_034.HTM
-- Animal
bioassays - Rat long-term gavage study: Longstaff et al.,
1984. Squamous cell carcinoma and fibrosarcoma
of the stomach were reported in 92% of exposed males and 94% of
exposed females: Background incidence of these lesions
in both sexes was 1%. The study authors were unable to determine
whether the sites of origin of the tumors were in the forestomach
only or in both forestomach and glandular stomach.
-- Other
relevant data
- Chlorofluoromethane
was found to be a highly active mutagen in the Salmonella reverse
mutation assay, and to induce transformation of BHK21 cells in
vitro (Longstaff et al., 1984). A computerized analysis
of structure-activity relationships based on a set of rules generated
by US EPA experts (Oncologic, version 1.0) finds that chlorofluoromethane
is of high-to-moderate concern.
(This is the highest level of concern noted for chemicals which
are not included in the database of carcinogenicity bioassay results
from which the program rules are derived.)
Ref: PRIORITIZED
CANDIDATE CHEMICALS UNDER CONSIDERATION FOR CARCINOGENICITY EVALUATION:
BATCH #1. Office of Environmental Health Hazard Assessment, California
Environmental Protection Agency May 1997.
http://www.oehha.ca.gov/prop65/pdf/batch1.pdf
Chlorofluoromethane
- EPA List 3 Inert - CAS No. 593-70-4
-- Experimental data.
Chlorofluoromethane was tested for carcinogenicity in one study
in rats by oral administration by gavage at one dose level.
High incidences of squamous-cell carcinomas and of fibrosarcomas
of the forestomach and stomach were induced in animals
of each sex. No evaluation of the effects of chlorofluoromethane
on reproduction or on prenatal toxicity in experimental animals
could be made on the basis of the available data. Chlorofluoromethane
was mutagenic to Salmonella typhimurium and to cultured mammalian
cells in the presence and absence of an exogenous metabolic system.
-- Evaluation. There is limited evidence
for the carcinogenicity of chlorofluoromethane to experimental
animals.
Ref: International Agency for Research on
Cancer (IARC) Monographs. Chlorofluoromethane. VOL.: 41 (1986)
(p. 229).
http://www.fluoridealert.org/pesticides/chlorofluoromethane.iarc.86.htm
Abstract: Two short-term in vitro tests for mutagenicity (Salmonella
reverse mutation and BHK21 cell transformation) were conducted
on a series of fluorocarbons. Some of these
materials (FC22, FC31, FC142b, FC143 and FC143a) were found to
be positive in 1 or both of the tests and could therefore be considered
as being potentially carcinogenic to animals. Such activity
was not anticipated for what were previously considered inert
materials, and in consequence several examples of these fluorocarbons,
which represented different combinations of short-term test results,
were tested for carcinogenicity in limited in vivo bioassays.
Rats were dosed for 1 yr by gavage 5 days/wk with either FC22,
FC31, FC133a, FC134a, or FC143a dissolved in corn-oil at a single
dosage of 300 mg/kg body wt. The animals were then observed until
wk 125, with detailed necropsy at termination. FC31
was a potent carcinogen (to the rat stomach), a result
which reflected the short-term test predictions, but FC133a, which
gave a negative response in both the in vitro assays, induced
a high incidence of reproductive tract tumors. The weak bacterial
mutagens FC22 and FC143a did not induce tumors in this study,
and the nonmutagenic FC134a was without overt carcinogenic activity.
While recognizing the limitations of the in vivo component of
this study, the short-term tests were only partially successful
in identifying potential carcinogens for this series of chemicals.
Fluorocarbon 31 was a potent carcinogen
which was 1st identified by bacterial mutation and cell transformation,
whereas the equally potent carcinogen FC133a was not so identified.
The lack of genotoxic activity with this particular compound implies
that the carcinogenic activity may be due to mechanisms other
than those which involve direct DNA interactions.
Ref: Genotoxicity and carcinogenicity of
fluorocarbons: Assessment by short-term in vitro tests and chronic
exposure in rats. By E LONGSTAFF et al.
TOXICOL APPL PHARMACOL; 72 (1). 1984. 15-31.
Note
from FAN: |
Synonym |
Chemical |
CAS
No. |
FC 22 |
Chlorodifluoromethane |
75-45-6 |
FC
31 |
Chlorofluoromethane |
593-70-4
|
FC 133a
|
1,1,1-Trifluoro-2-chloroethane
|
75-88-7 |
FC142b
|
1-Chloro-1,1-difluoroethane
|
75-68-3
|
FC-143
|
Ammonium
perfluorooctanoate |
3825-26-1 |
Clodinafop-propargyl
-
Herbicide - CAS No. 105512-06-9
Suggestive
Evidence of Carcinogenic Potential.
Prostate gland adenomas in male Tif:RAIf(SPF)
rats at the high dose only cannot be discounted; Peroxisome Proliferator-Activated
Receptor Agonism MOA for liver tumors
in mice.
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
Likely
to be carcinogenic to humans.
Reviewed 12/ 7/ 99.
Ref:
List of Chemicals Evaluated for Carcinogenic Potential. Science
Information Management Branch, Health Effects Division, Office
of Pesticide Programs, U. S. Environmental Protection Agency.
March 15, 2002.
Carcinogenicity. In
accordance with the EPA Proposed EPA Weight-of-the-Evidence Categories,
August 1999, the Agency's Cancer Assessment Review Committee (CARC)
classified clodinafop-propargyl as "likely
to be carcinogenic to humans" by the oral route based on
the occurrence of prostate tumors in male
rats, ovarian tumors in female rats, and liver tumors in both
sexes of mice, as well as blood vessel tumors in female mice.
For the quantification of human cancer risk, the CARC recommended
a linear low-dose extrapolation approach based on the most potent
of these tumor types. This approach is supported by possible genotoxic
potential and the lack of confirmation of the mode of action of
clodinafop-propargyl. The most potent unit risk, Q1 * (mg/kg/day)
-1 , of those calculated for clodinafop-propargyl is that for
male mouse liver benign hepatoma and/or
carcinoma combined tumor rates at 0.129 (mg/kg/day) -1 in human
equivalents.
Ref: US EPA Pesticide Fact Sheet. Reason
for Issuance: Conditional Registration. June 6, 2000.
http://www.epa.gov/opprd001/factsheets/clodinafop.pdf
Cyhalofop-butyl
- Herbicide
- CAS No. 122008-85-9
-- Chronic dietary
all populations: Carcinogenicity in mice
based on kidney effects in females including tubular dilatation,
chronic glomerulonephritis, and hyaline casts. LOAEL =
10.06 mg/kg/day.
Ref: Federal Register. September 27, 2001.
Cyhalofop-butyl; Pesticide Tolerances for Emergency Exemptions.
Final Rule.
http://www.fluoridealert.org/pesticides/cyhalofop-butyl.fr.sep27.01.htm
Dichlofluanid
- Wood Preservative, Antifoulant, Fungicide, Acaricide -
CAS No. 1085-98-9
PubMed abstract: Seven
different endpoints for detection of genotoxicity
have been used to demonstrate the DNA-altering properties
of Dichlofluanid, a fungicide commonly used in viticulture pest
control. Each endpoint (DNA synthesis inhibition test, alkaline
viscosimetry, umu-test, alkaline filter elution, FADU-test, 32P-postlabeling,
and electron microscopy) shows clear evidence of genotoxicity.
These data indicate that application of
the fungicide dichlofluanid may be mutagenic and/or carcinogenic
for exposed humans.
Ref: Environ Mol Mutagen 1991;17(1):20-6.
Genotoxicity of the fungicide dichlofluanid in seven assays; by
Heil J, Reifferscheid G, Hellmich D, Hergenroder M, Zahn RK.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1991455&dopt=Abstract
Dichlorofluoromethane
- US EPA List 2 Inert, Propellant
- CAS No. 75-43-4
PAN Bad Actor: Carcinogen
Ref: Pesticide Action Network:
http://www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC33437
Dichlorotetrafluoroethane
- Propellant, Former EPA List
2 Inert -
CAS
No. 76-14-2
PAN
Bad Actor: Carcinogen.
Ref: Pesticide Action Network
http://www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC35610
/UV-B Radiation is likely to incr by ozone depletion caused by
atmospheric concentrations of chlorofluorocarbons/. Indications
are increasing that UV-B radiation ... plays a role in the induction
and growth of cutaneous melanomas, a ... dangerous
type of skin cancer. ... There are indications that ...
suppression of the immune response by UV-B radiation may occur
in humans. The antigen presenting Langerhans cells in the skin
are damaged and allergic responses are depressed. ... There are
indications that UV-B radiation increases cataract formation,
an important cause of blindness especially in areas with limited
medical facilities. /Chlorofluorocarbons/
[WHO; Environmental Health Criteria 113: Fully Halogenated Chlorofluorocarbons
p.101 (1990)]
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
Diflubenzuron
- Insecticide, Acaricide - CAS
No. 35367-38-5
Chloroaniline,
p (or 4-chloraniline) is a metabolite of Diflubenzuron.
In 2006, USEPA classified chloroaniline, p as
a "Group B2 -- Probable Human Carcinogen." "Spleen
(fibrosarcomas,
hemangiosarcomas & osteosarcomas) (M); Adrenal
(pheochromocytomas (M & F); F344/N rats. Hepatocellular
adenomas/carcinomas (M); Hemangiosarcomas
in spleen and/or liver (M) in B6C3F1 mice."
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
EXCERPTS:... Diflubenzuron was found to induce murine CYP3A1/2
(activating, for example, aflatoxins and nitropyrenes) in lung
(both sexes) and kidney (for females only), as exemplified by
the increase 6B and 2B hydroxylations of testosterone. Inductions
were also recorded for CYP2B1/2 (activating olefins and halogenated
hydrocarbons) in lung (both sexes) and kidney (for female mice
only), as shown by the enhancement of testosterone 6a, 16a, 16B
and 2B hydroxylases. In the lung, induction in the 7a position
(linked to CYP2A, responsible for metabolizing nitrosamines, and
specific compounds such as esamethyl phospamide and butadiene)
was registered for both sexes. A generalized induction was seen
in the lung. Simultaneously, a marked reduction of testosterone
metabolism in the liver (both sexes), kidney (6? and 16? hydroxylations,
females) and lung (6a, 16a, 16B and 2B positions, males) was observed.
... In summary, our results demonstrated the induction and suppression
properties of diflubenzuron and acephate. With the increased bioactivating
potential toward ubiquitous environmental pollutants the induction
generates large amounts of oxygen free radicals acting at all
levels of multistep carcinogenesis (Paolini et al., 1999). Our
observations are in line with previous data on diflubenzuron or
acephate’s abilities to induce positive foci in Balb/c3T3
cells in an in vitro cell transformation model (medium-term test,
6–8 weeks) (Perocco et al., 1993 and Perocco et al.,
1996) as well as with the co-carcinogenicity potential of acephate
found in the rat (Paolini et al., 1997).
Notwithstanding diflubenzuron is negative in in vivo long-term
carcinogenicity studies, its co-mutagenic potential may be of
concern in the presence of ubiquitous premutagens (e.g. diet,
environmental pollutants). Furthermore, the ability of these insecticides
to act as homeostatic disruptors should not be underestimated.
Ref: CYP superfamily perturbation by diflubenzuron
or acephate in different tissues of CD1 mice. By A Sapone et al.
Food Chem Toxicol. 2005 Jan;43(1):173-83.
From
the report: Diflubenzuron.
TA:Environmental Health Criteria PG:153 p; 1996
IP: VI:184.
-- The minor
metabolite, 4-chloroaniline, was
shown to be positive in several in vitro mutagenicity assays using
various endpoints. It is carcinogenic in
rats and mice. The neoplastic lesions related to administration
of 4-chloroaniline were benign and malignant
mesenchymal tumours in the spleens of male rats and haemangiomas
and haemangiosarcomas, primarily in the
spleen and liver of male mice.
-- Effects on humans. The diflubenzuron metabolite, 4-chloroaniline,
has been reported to cause methaemoglobinaemia
in exposed workers and in neonates inadvertently exposed.
Some individuals who are deficient in NADH-methaemoglobin reductase
may be particularly sensitive to 4-chloroaniline and hence to
diflubenzuron exposure.
-- Evaluation of human health risks. The primary manifestation
of diflubenzuron toxicity is methaemoglobin induction. This toxicity
occurs in a range of test animal species. It is attributable to
the metabolite, 4-chloroaniline,
which is known to induce methaemoglobin formation in several animal
species and in humans. Diflubenzuron does not cause other toxicities
on chronic dietary administration. It is not mutagenic or carcinogenic
in mice or rats. However, its metabolite,
4-chloroaniline, is mutagenic in vitro and is carcinogenic in
mice and male rats. Although 4-chloroaniline is a minor
urinary metabolite of diflubenzuron in rats, the extent to which
it is formed in vivo in various animal species remains unknown.
Similarly, the comparative degree of absorption of its parent
compound in various species is unknown. The sensitivity of human
haemoglobin to methaemoglobin formation by 4-chloroaniline in
vivo is not known. However, since induction of methaemoglobinaemia
is consistently the most sensitive measure of diflubenzuron toxicity
in the various animal species tested, it may be used as the basis
to estimate the levels causing no toxicological effect. Evaluation
of effects on the environment.
•
Note:
Uses PCA is used as an intermediate in the production of several
urea herbicides and insecticides (e.g., monuron, diflubenzuron,
monolinuron), azo dyes and pigments (e.g., Acid Red 119:1, Pigment
Red 184, Pigment Orange 44), and pharmaceutical and cosmetic
products (e.g., chlorohexidine, triclocarban [3,4,4'-trichloro-
carbanilid], 4-chlorophenol) (Srour, 1989; BUA, 1995; Herbst
& Hunger, 1995; Hunger et al., 2000; IFOP, 2001). In 1988, about
65% of the global annual produc- tion was processed to pesticides
(Srour, 1989). In Germany, in 1990, about 7.5% was used as dye
precur- sors, 20% as intermediates in the cosmetics industry,
and 60% as pesticide intermediates. The use for the remain-
ing 12.5% of the production quantity was not specified (BUA,
1995). More recent data on the use pattern of PCA are not available.
Ref: Concise International Chemical Assessment
Document 48. 4-CHLOROANILINE. World Health Organization Geneva,
2003.
http://www.who.int/pcs/cicad/full_text/cicad48.pdf
Cancer risk from PCA
and related metabolites:
-- Estimations of the carcinogenic risk to humans resulting from
lifetime dietary exposure were performed for food commodities
containing PCA and/or CPU. For the purpose of calculating dietary
risk assessments, the Agency has developed the following procedure:
1) CPU (a diflubenzuron metabolite that is structurally related
to PCA and for which no adequate carcinogenicity data are available)
is considered as having the same carcinogenic potential (Q ) as
PCA; 1 *
2) The sum of PCA and CPU residues in ingested
food are used to estimate the dietary exposure of humans to the
carcinogenic metabolites of diflubenzuron; and
3) In addition to ingested residues of these two metabolites,
amounts of PCA and/or CPU formed in vivo following ingestion of
diflubenzuron are included when estimating the total exposure
of humans to the carcinogenic metabolites of diflubenzuron. The
in vivo conversion of ingested diflubenzuron to PCA and/or CPU
was estimated to be 2.0%, based on data in the rat metabolism
study. (MRIDs 41720901 and 41919001)
-- The Agency used results from mushroom metabolism studies to
determine the percent of total radioactive residue (TRR) present
as PCA or CPU in mushrooms. Then, using tolerance levels for diflubenzuron
in animal commodities, and adjusting for percent crop treated
of feed items, total levels of PCA and related compounds were
estimated for mushrooms (using 0.69 ppm / 100% crops treated)
as 0.000015 mg/kg/day (9.4 x 10 Carcinogenic Risk) and for milk/liver
(using anticipated residue -7 / percent crops treated) of 0.000004
mg/kg/day (2.7 x 10 Carcinogenic Risk) based -7 on the overall
U.S. population.
-- Based on the results of a rat metabolism study, an assumption
of a 2.0% conversion of diflubenzuron to PCA in humans is assumed
for the PCA risk assessment. The upper bound of the total cancer
risk estimate from PCA and related metabolites in the overall
U.S. population is 1 x 10 . The U.S. population and all of -6
the population subgroups have ARCs for chronic dietary risk from
diflubenzuron well below the RfD when all tolerances or anticipated
residues are considered. If additional uses are added to diflubenzuron
for commodities not covered by this assessment, the total cancer
risk estimate for diflubenzuron will increase.
Epoxiconazole
- Fungicide - CAS No. 135319-73-2 or 133855-98-8.
"Likely
to be Carcinogenic to Humans." Combined
hepatocellular tumors in male or female mice.
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
Ethalfluralin
- Herbicide - CAS No. 55283-68-6
Group C --
Possible Human Carcinogen. Mammary tumors
(F); Suggestion of bladder tumors
(F) and kidney tumors (M & F);
Fischer 344 rats.
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
Group
C--Possible Human Carcinogen.
Reviewed 9/ 14/ 94.
Ref:
List of Chemicals Evaluated for Carcinogenic Potential. Science
Information Management Branch, Health Effects Division, Office
of Pesticide Programs, U. S. Environmental Protection Agency.
March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm
--
Combined chronic toxicity/ carcinogenicity in rats. NOAEL = 32.3
mg/kg/ day HDT. LOAEL = > 32.3 mg/ kg/day no systemic effects
were seen at the HDT. Mammary gland fibroadenomas
were found in dosed female rats at statistically
significant incidences in mid and high doses.
-- Cancer (oral, dermal, inhalation). Ethalfluralin has been classified
as a possible human carcinogen (Group C). Q1* = 8.9 x 10-2 (mg/kg/
day)-1. 2-year chronic carcinogenicity study in rats, showing
an increased incidence of mammary gland
fibroadenomas and combined adenomas/ fibroadenomas in female
rats.
-- In vitro mammalian chromosome aberration test: In Chinese hamster
ovary cells, ethalfluralin was negative without S9 activation,
but it was clastogenic with activation.
Ref: Federal Register: January 17, 2002.
Ethalfluralin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/ethalfluralin.fr.jan17.2002.htm
-- EPA's Office of
Pesticide Program's Carcinogenicity Peer Review Committee concluded
that ethalfluralin should be classified as Group C, a possible
human carcinogen, based on increased mammary
gland fibroadenomas and adenomas/fibroadenomas combined
in female rats. The tumor incidences were statistically significant
at both the mid and high dose, and exceeded of the upper range
of historical controls. Based on a low dose extrapolation,
the Q1* of 8.9 x 10-2 (mg/kg/day)-1 has been calculated.
-- -- Cancer risk was estimated based on percent crop treated
and anticipated residues as provided in EPA's Reregistration Eligibility
Decision (RED) for ethalfluralin. Exposure to ethalfluralin from
food is estimated to result in a lifetime cancer risk of 7.11
x 10-7. Cancer risks of less than 1 x 10-6 are generally considered
to be negligible.
-- -- Genotoxicty. Ethalfluralin was weakly
mutagenic in activated strains TA1535 and TA100 of Salmonella
typhimurium,but not in strains TA1537, TA1538, and TA98 in an
Ames assay. In a modified Ames assay with Salmonella typhimurium
and Escherichia coli, ethalfluralin was weakly
mutagenic in strains TA1535 and TA100, with and without
activation, and in strain TA98 without activation, at the highest
dose. No mutagenicity was found in the mouse lymphoma assay for
forward mutation. Ethalfluralin did not induce unscheduled DNA
synthesis in rat hepatocytes. In chinese hamster ovary
cells, ethalfluralin was negative without S9 activation, but it
was clastogenic with activation.
Ref: Federal Register. November 14, 2001.
[PF-1052; FRL-6808-9]
http://www.fluoridealert.org/pesticides/ethalfluralin.fr.nov14.2001.htm
• Chronic
toxicity. Ethalfluralin
was administered to Fisher 344 rats in the diet for 2 years in
combined chronic toxicity and carcinogenicity replicate studies.
The doses were equivalent to 0, 4.2, 10.7, or 32.3 mg/kg/day.
The NOAEL for systemic effects was 32.3 mg/kg/day.
Mammary gland fibroadenomas were found in dosed female rats at
statistically significant incidences in the mid and high doses.
EPA's Office of Pesticide Program's Carcinogenicity
Peer Review Committee concluded that, ethalfluralin should be
classified as Group C, a possible human carcinogen, based
on increased mammary gland fibroadenomas and adenomas/fibroadenomas
combined in female rats. The tumor incidences were statistically
significant at both the mid and high dose, and exceeded the upper
range of historical controls. Based on a
low dose extrapolation, the Q1* of 8.9 x 10-2 (mg/kg/day)-1 has
been calculated. Based on both registered and proposed product
uses, exposure to ethalfluralin from food is estimated to not
exceed a lifetime cancer risk of 8.47 x 10-7. Cancer risks of
less than 1 x 10-6 are generally considered to be negligible.
Ref: Federal Register. August 31, 2005.
Ethalfluralin; Notice of Filing a Pesticide Petition to Establish
a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/ethalfluralin.fr.aug.2005.html
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