Cancer
Fluorinated and Fluoride Pesticides
Pesticides beginning with A-E F G-R S-Z
 
 

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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