Clastogenic
= A clastogen is an agent that can cause one
of two types of structural changes. A clastogen can cause
breaks in chromosomes that result in the gain, loss, or
rearrangements of chromosomal segments. A clastogen can
also cause sister chromatid exchanges, which are "homologous
chromatid strand interchanges and reunions [that occur]
during DNA replication" (Thilly & Call, 1986, p. 181) -
Ref:. http://www.canoshweb.org/odp/html/rp6.htm
Cytotoxic
= of or relating to substances that are toxic to cells.
Cell-killing.
Embryotoxic
= This describes any chemical which is harmful to an embryo.
Fetotoxic
= Toxic to the fetus.
Genotoxic
= Describes a poisonous substance which harms an organism
by damaging its DNA.
Mitogenic
= Causing mitosis or transformation.
Mitosis = cell division in
which the nucleus divides into nuclei containing the same
number of chromosomes
Mutagenic
= capable of inducing mutation (used mainly of extracellular
factors such as X-rays or chemical pollution)
|
The
use of high doses increases the likelihood that potentially
significant toxic effects will be identified. Findings of
adverse effects in any one species do not necessarily indicate
such effects might be generated in humans. From a conservative
risk assessment perspective however, adverse findings in
animal species are assumed to represent potential effects
in humans, unless convincing evidence of species specificity
is available.
--
Food and Agricultural Organization of the United Nations
|
Note:
This is not an exhaustive list.
As time allows more information will be added.
Chlorodifluoromethane
-
Insecticide, Fungicide, Propellant - CAS No. 75-45-6
Chlorodifluoromethane
(FC-22) was evaluated for embyotoxicity and teratogenicity in
groups of 40 pregnant Charles River rats exposed to the test substance
by inhalation at concentrations of 0, 0.05, 0.10, and 2.00% on
days 6-15 of gestation. No clinical signs of toxicity were observed
in maternal animals. The number of implantations, early and late
resorptions, and number of live fetuses per litter were unaffected.
There was a sporadic appearance of major
malformations of the eye in all test groups. The increased
incidence of eye defects was not statistically significant. Authors
believe that the test substance may have interacted with the genetic
make-up of affected fetuses and caused the increased expressivity
of a mutant gene. The authors considered
the test substance to be a mutagen under the conditions of this
study.
Ref: 1992 - INITIAL SUBMISSION: EMBRYOTOXIC
AND TERATOGENIC STUDIES IN RATS WITH INHALED CHLORODIFLUOROMETHANE
WITH COVER LETTER DATED 06-15-92 AND ATTACHMENTS. HASKELL LABORATORY.
Report Nos. NTIS/OTS0540606 and EPA/OTS; Doc #88-920004258.
Teratogenicity
was evaluated in 4 groups of 19 pregnant CD female rats receiving
Arcton 22 via inhalation at concentration levels of 0, 100,
1,000 and 50,000 ppm for 6 hours per day on gestation days 6
through 15. There were no treatment-related effects in appearance,
behavior, mortality, or pregnancy rate. At 50,000 ppm maternal
weight gain was slightly lower than the control. There were
no effects on body weight at 100 or 1,000 ppm. In all test groups
litter size, post-implantation loss, litter wight, and mean
fetal weight were similar to the control. At
50,000, there was an increased incidence of anophthalmic•
fetuses.
Ref: 1989 - EFFECT
OF ACRTON 22 ON PREGNANT RATS: RELATIONSHIP TO ANOPHTHALMIA
AND MICROPHTHALMIA WITH ATTACHMENTS AND COVER LETTER DATED 07-05-89.
Report Nos. NTIS/OTS0520413 and EPA/OTS; Doc #87-890000011
•
Anophthalmic
definition:
Absence of an eye(s). It can be a congenital (born without)
or an acquired condition (surgically removed).
Clodinafop-propargyl
-
Herbicide
- CAS No. 105512-06-9
SUBCHRONIC AND CHRONIC
TOXICITY
-- 870.5315 Chromosome Studies; Human Lymphocytes in vitro. Owing
to the conflicting results from the cytotoxicity assessment and
the presence of rare complex chromosome
aberrations both with and without S9 activation, the study is
considered inconclusive.
Ref: US EPA Pesticide Fact Sheet. Reason
for Issuance: Conditional Registration. June 6, 2000.
http://www.epa.gov/opprd001/factsheets/clodinafop.pdf
Cyfluthrin
- Insecticide - CAS No. 68359-37-5
Abstract: ...
Our study describes the genotoxic effects
of PCP, lindane, transfluthrin,
cyfluthrin, and natural pyrethrum
on human mucosal cells of the inferior and
middle nasal conchae.
METHODS: Epithelial cells were isolated from nasal mucosa, which
was removed in the surgical treatment of chronic sinusitis and
nasal concha hyperplasia. After the cells had been tested for
vitality using the trypan blue exclusion test, the short-term
culture method was used. The material was incubated with PCP (0.3,
0.75, and 1.2 mmol), lindane (0.5, 0.75, and 1.0 mmol), transfluthrin
(0.05, 0.1, 0.5, 0.75, and 1.0 mmol), cyfluthrin (0.05, 0.1, 0.5,
0.75, and 1.0 mmol), natural pyrethrum (0.001, 0.005, 0.01, 0.05,
and 0.1 mmol), and N-methyl-N'-nitro-N-nitrosoguanidine for 60
minutes. Substance-induced DNA damage (single-strand and double-strand
breaks) were determined using single-cell microgel electrophoresis.
A fluorescence microscope was used together with an image processing
system to analyze the results obtained.
RESULTS: After exposure to all tested substances, a high percentage
of the cells of the middle nasal concha in particular were found
to have severely fragmented DNA as a result of strong genotoxic
effects. Although the reaction of the cells of the inferior nasal
concha was significantly less strong (p < 0.001), the tested
substances were nevertheless found to have a notable genotoxic
effect on these cells too.
CONCLUSION: Our study strongly suggests
that exposure to PCP, lindane, transfluthrin, cyfluthrin, and
natural pyrethrum has a genotoxic effect on the epithelial cells
of human nasal mucosa. In addition, we have shown that
nasal structures differ in susceptibility to the various pesticides
used in the tests. Thus, the study provides new evidence supporting
the biological plausibility of PCP- and lindane-induced effects,
thereby helping evaluate potential PCP- and lindane-induced mucous
membrane carcinomas of these parts of the nose. In addition, our
study shows that other substances that today are widely used for
controlling pests have a considerable genotoxic effect on human
target cells. The results obtained indicate the need for additional
studies on the genotoxicity of these substances and their adverse
effects on human health.
Ref: Genotoxic effects of pentachlorophenol,
lindane, transfluthrin, cyfluthrin, and natural pyrethrum on human
mucosal cells of the inferior and middle nasal conchae; by Tisch
M, Faulde MK, Maier H. Am J Rhinol. 2005 Mar-Apr;19(2):141-51.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15921213&query_hl=2
Cyhalothrin,
lambda - Insecticide - CAS No. 91465-98-6
Abstract
(2005): In this study, a synthetic pyrethroid insecticide, lambda-cyhalothrin
(LCT), was administered to adult female albino rats (Wistar
rats) by gavage dose of 6.12, 3.06, 0.8 mg/kg b.w. repeated
for 13 days at 48 h intervals. The cytotoxic and genotoxic
effects of LCT were investigated in bone marrow cells, using the
structural chromosomal aberration (SCA) and micronucleus (MN)
test systems. Mitomycin C (MMC) was also used as positive control
(2 mg/kg b.w.). All the doses of LCT
increased the number of SCAs and the frequency of micronucleated
erythrocytes, with respect to the control group.
Only the highest dose of LCT significantly increased the
MN frequency compared with control (P<0.01). It was also observed
that LCT caused a significant decrease in the number of polychromatic
erythrocytes compared with controls (p<0.001). These observations
indicate the in vivo suspectibility of mammals to the genetic
toxicity and cytotoxicity potential of LCT.
Ref:
Evaluation of cytogenetic effects of lambda-cyhalothrin on Wistar
rat bone marrow by gavage administration; by Ayla Çelika
(a), Birgül Mazmanci, Yusuf Çamlica, Ülkü
Çömelekogšlu, and Ali As¸kin
Ecotoxicology and Environmental Safety - Volume 61, Issue 1 ,
May 2005, Pages 128-133
Abstract
(2003). In
this study, the genotoxic and cytotoxic potential of
lambda-cyhalothrin (LCT), a synthetic pyrethroid insecticide,
was investigated in Wistar rat bone-marrow cells, using the structural
chromosomal aberration (SCA) and micronucleus (MN) test systems.
LCT was administrated to adult female albino rats as repeated
i.p. doses of 6.12, 3.06, 0.8 mg/kg BW for 13 days at 48 h intervals.
Mitomycin C (MMC) was used as a positive control (2 mg/kg BW).
All the doses of LCT increased the number of structural chromosomal
aberrations and the frequency of micronucleated erythrocytes,
compared with the control group. It was also observed that LCT
caused a significant decrease in the number of polychromatic erythrocytes.
Our results demonstrate that LCT has a clastogenic/genotoxic
potential as measured by the bone marrow SCA and MN tests in Wistar
rats.
Ref:
Cytogenetic effects of lambda-cyhalothrin on Wistar rat bone marrow;
by Celik
A, Mazmanci B, Camlica Y, Askin A, Comelekoglu U. Mutat Res. 2003
Aug 5;539(1-2):91-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12948817
Abstract
(2003). Micronucleus
formation in fish erythrocytes, as an indicator of chromosomal
damage, has been increasingly used to detect the genotoxic potential
of environmental contaminants. Nucleolar organizer regions (NORs)
stained with colloidal silver techniques indicate sites of active
RNA transcription. The number and size of NORs in interphase nuclei
reflect cellular activities such as proliferation and differentiation
of cells. In this study, nuclear (micronucleus frequency) and
nucelolar (changes in quantitative characteristics of nucleoli)
biomarkers were used to evaluate the functional and structural
genotoxic effects of the pyrethroid insecticide lambda-cyhalothrin
on Garra rufa (Pisces: Cyprinidae). The frequency of micronuclei
was examined in blood smears obtained from fishes exposed to three
different concentrations (0.005, 0.01, 0.05 microg/l) for a period
of 36 h. Nucleolar parameters (the average number of nucleoli
per cell; the volume of a single nucleolus; and the percentage
of cells with heteromorphic paired nucleoli) were examined in
epithelial cells obtained from the edge of caudal fins at the
90th and 180th minutes of exposure. Results
of both tests demonstrated the genotoxic potential of pyrethroid
lambda-cyhalothrin on G. rufa. The
frequency of micronucleated erythrocytes was significantly increased
while the nucleolar parameters were repressed by lambda-cyhalothrin
treatment. Our results confirmed that the use of nucleolar
biomarkers on fish fin cells, in addition to micronucleus test,
could provide valuable information in aquatic genotoxicity studies.
Ref:
Evaluation of the genotoxic potential of lambda-cyhalothrin using
nuclear and nucleolar biomarkers on fish cells; by Cavas T, Ergene-Gozukara
S. Mutat Res. 2003 Jan 10;534(1-2):93-9.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12504758
Abstract
(1999). In
order to develop experimental models able to detect genotoxic
effects of pollutants in aquatic organisms, the genotoxicity of
the pyrethroid lambda-cyhalothrin was studied using the micronucleus
test in erythrocytes of Cheirodon interruptus interruptus. The
frequency of micronuclei was examined in blood smears obtained
from fishes exposed in vivo to three different concentrations
(0.05; 0. 01; 0.001 ug/l) of the compound and sacrificed at nine
sampling times (24, 48, 72, 96 h and 8, 12, 15, 19 and 23 days).
As a positive control fishes were exposed to 5 mg/l of cyclophosphamide.
Results obtained demonstrated the genotoxic
effects of the pyrethroid in the experimental model employed.
The variation in the micronuclei frequencies in the different
sampling times could be related to the blood cell kinetics and
the erythrocyte replacement. The results could be considered as
a validation of the MN test in fishes for the assessment of genotoxic
pollutants.
Ref:
Genotoxic evaluation of the pyrethroid lambda-cyhalothrin using
the micronucleus test in erythrocytes of the fish Cheirodon interruptus
interruptus; by Campana MA, Panzeri AM, Moreno VJ, Dulout FN.
Mutat Res. 1999 Jan 13;438(2):155-61.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10036336&dopt=Abstract
Dichlorodifluoromethane
-
Insecticide, Fungicide Propellant, EPA List 2 Inert -
CAS No. 75-71-8
Significant mutagenic
activity of F 12 at 2.47x10+6 mg/cu
m (50%) in air in a Neurospora crassa test system. [USEPA; Ambient
Water Quality Criteria Doc: Halomethanes p.C-59 (1980) EPA 440/5-80-051]
---- Note from FAN: Dichlorodifluoromethane
is also called Freon 12 or F 12.
Ref: TOXNET profile from Hazardous Substances
Data Bank for Dichlorodifluoromethane.
http://www.fluoridealert.org/pesticides/dichlorodifluorometh.toxnet.htm
Dichlofluanid
- Wood Preservative, Antifoulant, Fungicide, Acaricide -
CAS No. 1085-98-9
Abstract:
The cytotoxicity
and lipid peroxidation of pesticides containing a halogen group
were examined in isolated rat hepatocytes. We examined 9 pesticides
of 3 different representative chemical families... The contents
of the hydroperoxides in phospholipid, phosphatidylcholine hydroperoxide
(PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) were
determined by the HPLC-chemiluminescence (CL-HPLC) method, which
is sensitive and specific for lipid hydroperoxide. Chlorothalonil,
dichlofluanid and captan were
the most potent cytotoxicants evaluated by lactate dehydrogenase
(LDH) leakage. PCP, NIP and CNP exhibited intermediate
cytotoxicity. PCNB, fthalide and chlomethoxynil showed low cytotoxicity.
The cellular phospholipid hydroperoxide
(PCOOH and PEOOH) levels were remarkably increased by chlorothalonil
(PCOOH, 23 times and PEOOH, 7 times), dichlofluanid
(PCOOH, 523 times and PEOOH, 22 times) and captan (PCOOH,
518 times and PEOOH, 16 times) as compared with the control group.
The PCOOH content was slightly increased by PCP (4.8 times) and
NIP (6.3 times), whereas the other 4 pesticides did not change
the phospholipid hydroperoxide level. Severe
cytotoxicity was observed with a remarkable increase of phospholipid
hydroperoxide by
chlorothalonil, dichlofluanid and
captan.
Ref: Biol Pharm Bull 1997 Mar;20(3):271-4.
Cytotoxicity
of organochlorine pesticides and lipid peroxidation in isolated
rat hepatocytes; by Suzuki T, Komatsu M, Isono H.
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.
1,1-Difluoroethane
(Freon 152A) - US EPA List 2 Inert -
CAS No. 75-37-6
Genetron 23, and Genetron-152A
[synonym] exposure increased the mutation
rate in progeny of Drosophila melanogaster. Genetron-23
appeared to be more mutagenic. Pronounced
phenotypic effects were observed among progeny of exposed males.
Part of the observed mutagenic effects of fluorinated hydrocarbon
gases may be due to anoxia.
[Foltz VC, Fuerst R; Environ Res 7: 275-85 (1974)]
Ref: Hazardous Substances Data Bank for
1,1-Difluoroethane at Toxnet
http://toxnet.nlm.nih.gov/
Dimefox
-
Acaricide, Insecticide - CAS
No. 115-26-4
PubMed abstract: ...
In addition, a series of pesticides structurally related to HMPA,
such as dimefox, hexamethylmelamine,
hexazinone, alachlor, CAM, pirimicarb, dimetilan, thiram and methabenzthiazuron
have been tested with the Oregon-K strain. Some of these pesticides
had already been shown to be genotoxic in other systems, whereas
others have either not been tested or gave negative results in
in vitro systems. Although genotoxicity was expressed only within
a narrow dose range, all pesticides were
genotoxic in the w/w+ system with the Oregon-K strain.
Thus, these compounds may be a genotoxic hazard to man...
Ref: Mutagenesis 1994 Jul;9(4):341-6. The
w/w+ SMART is a useful tool for the evaluation of pesticides
by Aguirrezabalaga I, Santamaria I, Comendador MA.
Ethalfluralin
- Herbicide - CAS No. 55283-68-6
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 e- 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
Etoxazole
- Miticide, Ovicide - CAS No.
153233-91-1
Abstract: Etoxazole is a member of the diphenyl oxazoline class
of insecticide, which was newly developed for use on pome fruits,
cotton and strawberries as an acaricide. In the present study,
genotoxic effects of acaricide etoxazole (ETX) (miticide/ovicide)
were investigated using chromosome aberration (CA) test, sister
chromatid exchange (SCE) test, and micronucleus test in human
lymphocytes. ETX induced the CAs at all
concentrations (5, 10, and 20 g/ml) for 24 h and also induced
the CA at the highest concentration (20 g/ml) for 48 h only. The
inducing the CAs for 48 h treatment period was dose-dependent.
In addition, it induced the SCE at all concentrations and treatment
periods in a dose-dependent manner as well. Although ETX
decreased the mitotic index (MI) at all concentrations and treatment
periods dose-dependently, it did not decrease the replication
index (RI) when compared to the negative and solvent controls.
In addition, ETX induced the micronucleus at all concentrations
except 5 g/ml for 48 h. This inducing was dose-dependent as well.
It can be concluded that ETX has a potential
genotoxic effects in cultured human peripheral lymphocytes.
Ref: The Genotoxic Effect of the New Acaricide
Etoxazole. E. Rencüzogullari; H. Basrila; A. Kayraldiz; M.
Arslan; S. Budak Diler; M. Topaktas. Russian Journal of Genetics,
November 2004, vol. 40, no. 11, pp. 1300-1304(5).
http://www.ingentaconnect.com/content/maik/ruge/2004/00000040/00000011/00500539
Gene mutation - in
vitro forward gene mutation assay in mouse lymphoma cells.
When tested up to cytotoxic levels, mutagenic in the presence
of S9 activation and equivocal for mutagenicity in the absence
of S9 activation.
Ref:
Federal Register: September 26, 2003. Etoxazole; Pesticide Tolerance.
Final Rule.
http://www.fluorideaction.org/pesticides/etoxazole.fr.sept.26.2003.htm
Fipronil
- Acaricide, Insecticide, Wood Preservative - CAS No. 120068-37-3
-- Chinese hamster lung cells were treated at different concentations
of fipronil (batch number 1747, 98.3%pure) in 1995 in duplicate
cultures to examine its potential to induce chromosomal aberrations
in the presence or absence of S9 rat liver metabolic activating
fracion (derived from Arochlor induced rats). The concentrations
tested (see Table 5.14, page 87) were chosen on the basis of preliminary
cytotoxicity tests ...There was a dose related increase in aberrations
at six hours in the absence of S9 (statistically
significant at the top two doses), and a possible increase
in the presence of S9 (although the increase at 60 ug fipronil/ml
was not statistically significant). The increases in aberrations
were due to increases in chromatid breaks and chromatid exchanges.
The mechanism is not considered to be due to cytotoxicity (i.
as outlined by Kirkland/1) as large proportion of the aberrations
seen were chromatid exchanges, whereas only breaks usually characterise
the mechanism relating to cytotoxicity ... To
conclude fipronil was clastogenic under the conditions of this
assay. (pages 86-87).
Summary of genotoxicity studies
... Although the in vitro cytogenetics assay in Chinese
hamster lung cells was positive, the mouse micronucleus test indicated
that the test material was not actually clastogenic in vivo.
It is considered unlikely that a second in vivo assay in a diferent
tissue is likely to produce anything other than a negative result.
The lack of any tumours that could be attributed to direct genotoxic
action in the rat and mouse chronic studies also support the lack
of in vivo genotoxicity by fipronil. (page 89)
Ref:
April 204. Evaluation
on : Fipronil (Horticultural Uses).
No. 212.
UK Dept. for Environment, Food and Rural Affairs, Pesticides Safety
Directory.
http://www.fluorideaction.org/pesticides/fipronil.uk.report.apr.2004.pdf
Flocoumafen
- Rodenticide - CAS No. 90035-08-8
Abstract: Embryotoxic
and teratogenic effects of flocoumafen (new anticoagulant rodenticide)
in chick embryos and white rats were studied. Flocoumafen was
injected (2 ug/egg) to the yolk sac of Fayuomi fertile eggs on
the 5th and 9th day of incubation. It was orally administered
to pregnant female rats (2.5 and 5 ug/kg B. Wt.) on the 8th, 10th
and 12th day of gestation. The study revealed
that flocoumafen was more embryotoxic than teratogenic in both
chick embryos and white rats.
Ref:
Khalifa BA et al. (1992). Embryotoxic and teratogenic effects
of flocoumafen in chick embryos and white rats. Journal of Applied
Animal Research;2(2):81-5
Fluazifop
butyl -
Herbicide - CAS No. 69806-50-4
Fetotoxicity
(delayed ossification and eye opacities) was also demonstrated
in New Zealand White rabbits (the LOEL was 30 mg/kg/day; the NOEL
was 10 mg/kg/day). EPA believes that there is sufficient evidence
for listing fluazifop butyl on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available hepatic and developmental
toxicity data for this chemical.
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.
--
Reproductive Effects: In a 3-generation reproductive study in
rats, effects included reductions in weight gain, fetal weight,
ossification, testicular weight, spleen weight, increased prostate
weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day.
Fetotoxic effects seen in the rabbit,
including reduced fetal weight and reduced ossification at higher
doses. No Effect Level (NEL)
was 30 mg/kg/day in rabbits. The NEL for teratogenic effects is
at least 10/mg/day in the rat, with diaphragmatic hernia at higher
doses. Not teratogenic at highest dose tested in rabbits (90 mg/kg/day).
While fluazifop-p-butyl is fetotoxic
when fed to
pregnant rats, human exposure data has concluded that female formulation
workers are not at increased risk of fetotoxic effects when skin
protection measures are applied.
Ref: Material Safety Data Sheet for Fusilade
DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21,
2002.
http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.msds.pdf
Fluazifop-P-butyl
- Herbicide - CAS No. 79241-46-6
--
Reproductive Effects: In a 3-generation reproductive study in
rats, effects included reductions in weight gain, fetal weight,
ossification, testicular weight, spleen weight, increased prostate
weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day.
Fetotoxic effects seen in the rabbit,
including reduced fetal weight and reduced ossification at higher
doses. No Effect Level (NEL)
was 30 mg/kg/day in rabbits. The NEL for teratogenic effects is
at least 10/mg/day in the rat, with diaphragmatic hernia at higher
doses. Not teratogenic at highest dose tested in rabbits (90 mg/kg/day).
While fluazifop-p-butyl is fetotoxic
when fed to
pregnant rats, human exposure data has concluded that female formulation
workers are not at increased risk of fetotoxic effects when skin
protection measures are applied.
-- Chronic/Subcrhonic Toxicity Studies: Chronic toxicity studies
in rodents have shown liver changes (cellular hypertrophy). The
No Effect Level (LEL) in rats is 10 ppm (0.5 mg/kg/day). Long
term feeding studies in dogs produced a range of potentially serious
effects at high dose rates (red cell, bone marrow and lymphadenopathy
changes and liver and spleen damage) with a No Effect Level
of 25 mg/kg/day.
Target Organs: Liver, skin, kidney, eye,
bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade
DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21,
2002.
http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.msds.pdf
Fluchloralin
- Herbicide
- CAS No. 33245-39-5
Pub Med Abstract: Fluchloralin
is cytotoxic and genotoxic and induces apoptosis in mammalian
cells.
The genotoxic and cytotoxic effects of a widely used herbicide,
fluchloralin, were assessed using cultured mammalian cells. Treatment
of cells for 8-12 hr with fluchloralin resulted in a significant
increase in the frequency of metaphase cells with chromosomal
damage. At higher concentrations, the herbicide also induced an
increase in the frequency of sister chromatid exchange. A 50%
loss in viability was observed when cells were exposed to the
herbicide for 72 hr. To understand the mechanism of cell death
caused by fluchloralin, its effect on DNA synthesis and its ability
to induce apoptosis were investigated. Even short (6 hr) treatment
of cells with fluchloralin resulted in a 30-50% inhibition of
DNA synthesis. Agarose gel electrophoresis of DNA from herbicide-treated
cells and cytochemical staining indicate the induction of apoptosis
by fluchloralin.
Ref: Environ Mol Mutagen 1998;31(3):257-62.
Fluchloralin
is cytotoxic and genotoxic and induces apoptosis in mammalian
cells. Sinha S, Panneerselvam N, Shanmugam G.
Abstract:
The genotoxic effect of fluchloralin (33245-39-5) in cultured
human blood lymphocytes was investigated. Venous blood samples
were obtained from healthy donors and lymphocyte cultures were
established. Cell cultures were treated with 2.5, 5.0, or 10 micrograms/milliliter
(microg/ml) fluchloralin for 24 or 48 hours. Following treatment,
slides were prepared and cells were scored for chromatid aberrations.
In a micronuclei (MN) test, cell were exposed up to 50microg/ml
fluchloralin for up to 48 hours. Cell microslides were prepared
and scored for MN frequency. Treatment of the lymphocytes for
24 to 48 hours resulted in a significant dose dependent increase
in the total number of chromatid type aberrations. The frequency
of chromatid aberrations was high compared to isochromatid breaks
at all dose levels. The increase in the frequency of isochromatid
breaks was notable after 48 hours of treatment. Gap formation
was high at all concentrations. Multiple aberrated cells showed
a dose dependent increase at both time points. The frequency of
occurrence of MN in cultured human blood lymphocytes following
fluchloralin treatment was noted. The induction of MN formation
was similar and significant at 24 and 48 hours of treatment at
2.5 to 10microg/ml. At the higher concentrations
there was a statistically dose related increase in the frequency
of micronucleated binucleate cells. The
authors conclude that fluchloralin at higher concentrations have
the ability to damage the human genome.
Ref: Genotoxicity
of the herbicide fluchloralin on human lymphocytes in vitro: chromosomal
aberration and micronucleus tests; by Panneerselvam N, Sinha S,
Shanmugam G. Mutat Res
1995 Aug;344(1-2):69-72
Fludioxonil
- Fungicide - CAS No. 131341-86-1
-- Gene mutation and
other genotoxic effects were studied
using fludioxonil technical: ... iii. Chromosome
aberrations assay (in vitro) in Chinese hamster ovary (CHO) cells
with and without S9 activation provided convincing evidence that
fludioxonil is a clastogen and polyploidy
inducer.
Ref: Federal Register. October 7, 1998.
Fludioxonil; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/fludioxonil.fr.oct.1998.htm
Flumequine
- Microbiocide - CAS No. 42835-25-6
PubMed Abstract:
The influence of flumequine on mitogen
induced lymphoid cell proliferation in European eels (Anguilla anguilla
L., 1758) was studied. For this purpose an in vivo test, using peroral
drug administration followed by successive intraperitoneal injections
with concanavalin A (ConA) or bacterial lipopolysaccharides (LPS)
and 5-bromo-2'-deoxyuridine, was applied. Direct counting of proliferated
cells in blood smears revealed that flumequine
possesses mitogenic properties. A synergistic and an antagonistic
effect of the drug was observed after LPS and ConA stimulation,
respectively. Flow cytometric analysis of peripheral blood lymphoid
cells showed a significant reduction of the mean proportion surface
immunoglobulin positive cells in the flumequine-treated
animals. It is concluded that flumequine enhances
proliferation of lymphoid cells (probably surface immunoglobulin
negative cells) in eel under the present experimental conditions.
Ref: Vet Immunol Immunopathol
1995 Jul;47(1-2):143-52. Influence
of flumequine on in vivo mitogen responses of European eel (Anguilla
anguilla L., 1758) lymphoid cells. van der Heijden MH et al.
Flumethrin
- Acaricide - CAS No. 69770-45-2
Abstract: The genotoxic
potential of the pyrethroid flumethrin was evaluated by using
the combined protocol of metaphase analysis and micronucleus test
in vivo in mouse bone marrow. The
dermal route was tested in a single treatment and the intraperitoneal
(i.p.) route in a single and a multiple treatment. Flumethrin
showed a cytotoxic effect on both myelopoiesis
and erythropoiesis, as evidenced by a reduction in the
mitotic index and in polychromatic erythrocyte values. An increase
in the frequency of gaps after the dermal exposure and of breaks
only at the highest dose tested in the i.p. treatment indicates
a weak clastogenic potential of the compound.
A significant increase in the frequency of micronucleated polychromatic
erythrocytes was observed after single and multiple i.p. treatments.
In the latter, the induction of micronuclei was highly significant
but not accompanied by an increase in breaks. This may indicate
that the clastogenic effect might
not account by itself for the induction of micronuclei, which
could also have arisen from an aneugenic potential of flumethrin.
Ref: Nakano E et al. (1996).
Evaluation of the Genotoxic Potential of Flumethrin in Mouse
Bone Marrow by Chromosomal Analysis
and Micronucleus Test. Teratogenesis, Carcinogenesis, and Mutagenesis,
Vol. 16, No. 1, pages 37-48.
The
above paper was abstracted in Food and Chemical Toxicology,
Volume 34, Issue 10, October 1996, Page 1021 :
Flumethrin
genotoxicity. Flumethrin,
asynthetic pyrethroid insecticide, tested as the technical
product Bayticol 60%, induced chromosomal damage in the
bone marrow cells when administered to mice by intraperitoneal
injection (Nakano
et al., Teratogenesis, Carcinogenesis and Mutagenesis
1996, 16, 37). |
Flumioxazin
- Herbicide - CAS No. 103361-09-7
Study # 870.4300. Combined
chronic carcinogenicity - rat. NOAEL = mg/kg/day: males = 1.8,
females = 2.2 LOAEL = mg/kg/day: males = 18.0, females = 21.8
based on increased chronic nephropathy in
males and decreased hematological
parameters in females (Hgb, MCV, MCH and MCHC) No evidence of
carcinogenicity 870.5100 Gene mutation in S. typhimurium
and E. coli Neither cytotoxic nor mutagenic up to 2000 g/plate.
There were reproducible increases in revertant
colonies of S. typhimurium strains TA1538 and TA98 in S9 activated
phases of the preliminary cytotoxicity and both mutation assays.
[Results considered to be equivocal.]
Ref: US EPA Pesticide Fact Sheet. April
12, 2001.
http://www.epa.gov/opprd001/factsheets/flumioxazin.pdf
Fluoroacetamine
-
Insecticide, Rodenticide - CAS No. 640-19-7
(also known as Fluoroacetamide
or Compound 1081)
GENOTOXICITY A. Cytogenetic
analysis detected chromosome aberrations in the rat in vivo and
in mammal lung cells. In Red Muntjac in vitro, fluoroacetamide
caused chromosomal breakage, increased rate of sister chromatid
exchanges, and a lag in the cell cycle.
Ref:
FLUOROACETAMIDE CASRN: 640-19-7. Hazardous Substances Data Bank.
http://www.fluorideaction.org/pesticides/fluoroacetamide.hsdb.htm
Abstract: HAPAB The
effects of single sublethal oral doses of fluoroacetamide (15
mg/kg in 0.03% aqueous
solution), administered to female white mice 2 days before or
10 days after fertilization, were studied on the embryonal and
postnatal development. The fluoroacetamide influenced the ovulation
and the viability of the ovi (later the embryonic and the postnatal
development) which led to increased prenatal
mortality, to prolongation of the pregnancy, and reduced viability
of the neonates. Females treated 10 days after fertilization
showed the greatest increase (by up to 30 days) in the duration
of pregnancy while embryonic mortality was highest in the group
treated two days before fertilization (11.7% against a control
value of 4.6%). Reduced body weight, cyanosis, respiratory distress,
and decreased motility were among the anomalies observed in neonates
in the test groups. 1971
Ref:
The action of fluoroacetamide on albino mouse fecunidty (preliminary
report). Authors: Tokareva TG Turov I Alekseyev AN Source: Zh.
Mikrobiol. Epidemiol. Immunobiol.; 48: 24-26; 1971.
Fluorodifen
- Herbicide
- CAS No.
15457-05-3
Abstract: Twenty-two
herbicides were studied in 67 tests for induction of DNA damage,
gene mutation and chromosomal changes in vitro and in vivo. Triazine
and urea-type herbicides were found to be inactive in all but
one test. Of 4 thiocarbamates, molinate and vernolate caused chromosomal
changes, namely increased incidence of sister chromatid exchanges
and chromosomal aberrations in vitro and increased frequency of
micronucleated polychromatic erythrocytes in mouse bone marrow.
These compounds, however, did not cause gene mutation and only
molinate gave equivocal positive result in bacterial repair test.
Out of 11 miscellaneous herbicides, ethofumesate, alachlor, dichlorprop
and fluorodifen proved to be positive only
in one or two tests. In the light of clastogenicity of
some thiocarbamates, serious consideration should be given to
start animal carcinogenicity studies with these chemicals.
Ref: Pinter A et al. (1989). Genotoxicity
of selected herbicides. Ann
Ist Super Sanita; 25(4):577-82.
Fluoroglycofen-ethyl
- Herbicide
-
CAS No.
77501-90-7
The teratogenic potential
and maternal toxicity of fluoroglycofen-ethyl was investigated
in rats and rabbits. In rats, fluoroglycofen-ethyl was not embryotoxic,
fetotoxic or teratogenic at doses of up to 200 mg/kg bw/day. It
was maternally toxic at doses of 60 mg/kg bw/day upwards, as seen
by overt signs and decreased body weight gain. In
rabbits, it was abortifacient (increased abortions) feto- and
embyotoxic (increased resorptions, decreased fetal size
and viability) and maternally toxic (maternal deaths and decreased
maternal weights) at 90 mg/kg bw/day. There was no evidence of
teratogenicity in rabbits. The NOEL for embryo/fetotoxicity was
30 mg/kg bw/day in rabbits and >200 mg/kg bw/day in rats. The
NOEL for maternal toxicity was 30 mg/kg bw/day in rabbits and
18 mg/kg bw/day in rats.
Ref:
Evaluation on: Fluoroglycofen-ethyl. May 1992. Issue No. 50. Department
for Environment, Food and Rural Affairs, Pesticides Safety Directorate,
UK.
http://www.pesticides.gov.uk/citizen/evaluations/050_confirm-box.htm
Fluorouracil
- Former
insect chemosterilant; now used as a chemotherapeutic drug
- CAS No. 51-21-8
Ref:
Gene-Tox from Toxnet.
GENE-TOX Evaluation B (post-1980):
Species/Cell
Type: |
Human
lymphocytes |
Assay
Type: |
Sister-chromatid
exchange (SCE) in vivo |
Assay
Code: |
SCY+ |
Results: |
Positive |
Panel
Report: |
EMIC/91392;
Mutat Res 1993 Sep;297(2):101-80 |
Reference: |
EMICBACK/31689;
MUTAT RES 67:289-294,1979 |
GENE-TOX
Evaluation A (pre-1980):
Species/Cell
Type: |
Mouse
(C3H/10T1/2) cells |
Assay
Type: |
Cell
transformation |
Assay
Code: |
CTH+ |
Results: |
Positive |
Panel
Report: |
EMICBACK/50076;
MUTAT RES 114:283-385,1983 |
Species/Cell
Type: |
Mammalian
polychromatic erythrocytes |
Assay
Type: |
Micronucleus
test, chromosome aberrations |
Assay
Code: |
MNT+ |
Results: |
Positive |
Panel
Report: |
EMICBACK/50890;
MUTAT RES 123:61-118,1983 |
Species/Cell
Type: |
Tradescantia
species |
Assay
Type: |
Chromosome
aberrations |
Assay
Code: |
TRC+D |
Results: |
Positive |
Dose
Response: |
With
dose response |
Panel
Report: |
EMICBACK/48094;
MUTAT RES 99:293-302,1982 |
Fluorouracil
Abstract: The chemotherapeutic agent 5-fluorouracil (5-FU) is
a known developmental toxicant in the rat both in vivo and in
vitro. The mechanism of the drug's embryotoxic effect is unclear,
but it has been postulated that 5-FU inhibits thymidylate synthase
activity, leading to a deficiency of thymidine and a decrease
in DNA synthesis. If this is the case, addition of excess exogenous
thymidine should reverse the drug's embryotoxicity.
Rat embryos were cultured beginning on day 10 of gestation (for
48 hours) in a whole embryo culture system. For the initial three
hours of the culture period, 5-FU was present at a final concentration
of 3 ug/mL. Following removal of 5-FU, various concentrations
of thymidine were added for the remainder of the culture period.
Treatment with 5-FU decreased the morphological score, number
of somite pairs, crown-rump and head lengths, as well as DNA and
protein contents; the incidence of malformations, particularly
those affecting the tail, hindlimb bud, and brain, was increased.
With addition of thymidine, there was attenuation of all parameters
examined and fewer malformations. Exogenous thymidine was not
able to reverse the effects of 5-FU completely, even if it was
present for the entire 48 hour culture period, including the three
hour 5-FU treatment phase. These results suggest that 5-FU may
induce a thymidine deficiency in treated rat embryos, but some
other effect(s) also appear to be involved in the embryotoxicity
induced by the drug.
Ref: Hansen DK et al. (1988-89). Attenuation
of 5-fluorouracil-induced embryotoxicity by exogenous thymidine
in vitro. Attenuation of 5-fluorouracil-induced embryotoxicity
by exogenous thymidine in vitro. As cited on Toxnet.
Fluorouracil Abstract:
5-Fluorouracil (5-FU) is a widely used antitumor agent that is
embryotoxic in rats at maternal therapeutic levels. A biologically
based dose-response model (BBDR) was developed that relates a
single dose of 5-FU on gestation day 14 in rats to cell cycle
effects in developing fetuses, specifically the inhibition of
thymidylate synthetase (TS; due to formation of a FdUMP/TS/folate
complex) with subsequent reduction in thymidylate (dTMP) levels,
thymidine-5'-triphosphate (dTTP; a DNA precursor) and, ultimately,
disruption of DNA synthesis. The initial modeling of the pharmacokinetic
component of the BBDR model was based upon a two-compartment PBPK
model (Collins et al., 1980) for the maternal kinetics with an
added compartment for the fetal kinetics of 5-FU. This BBDR model
described well the 5-FU concentration data from gestation day
19, but fetal compartment concentrations on day 14 and the time
course of the inhibition were modeled empirically rather than
mechanistically. To incorporate more physiological information,
a pregnant rat PBPK model developed by O'Flaherty et al. (TAP
112:245-256, 1992) for the weak acid dimethyloxazolidine-2,4-dione
(DM0) was adapted for use in the 5-FU BBDR model. The O'Flaherty
model adjusts for changes in the dam and fetal body weights, blood
flows, and organ volumes as the gestation progresses. Metabolism
of 5-FU and tissue partitioning was also added to the model. Sensitivity
analysis and use of different data sets as the basis for parameter
estimates in this more detailed PBPK component provided insights
into the importance of 5-FU pharmacokinetics to the resulting
changes in thymidylate synthesis compared with other potential
pharmacodynamic interactions.
Ref: Setzer RW et al. (2000). Incorporating
a validated PBPK pregnant rat model into a BBDR model for the
embryotoxicity of 5-fluorouracil. Toxicologist 2000 Mar;54(1):93.
As cited on Toxnet.
Fluquinconazole
- Fungicide
- CAS No.
136426-54-5
-- Developmental toxicity
studies. (a) Oral teratology study in rats.
In a study (1992), groups of 30 mated outbred albino Sprague-Dawley
CRL:COBS CD(SD)BR rats were administered by gavage fluqinconazole
(96% purity) in a 1% w/v aqueous methylcellulose solution at concentrations
of 0, 0.4, 2 and 20 mg/kg bw/day (based on a range-finding study)
from day 6 to 15 of presumed gestation... An increase
in abnormal sternebrae was seen in the low dose group (27%)
and the high dose group (31%, p<0.05) but not at the mid dose
group (15%) when compared to controls (13%) - as the incidence,
of this relatively common anomaly, in the low dose group is not
statistically significant and not party of a dose response it
is considered to be of no biological significance.
Fluquinconazole was clearly maternally toxic, producing abortion
and mortality at 8 mg/kg bw/day. There
was evidence of mild fetotoxicity (abnormal sternebrae)
but not teratogenicity at 9 mg/kg bw/day. The
NOAEL for maternal and fetotoxicity was 2 mg/kg bw/day based on
increased incidence of abortions in dams and increased mortality.
-- In the rabbit the NOEL for maternal
and fetal toxicity was 2 mg/kg bw/day. Fluquinconazole was not
teratogenic in the rabbit in the presence of maternal toxicity.
Fluquinconazole was clearly maternally toxic, producing abortion
and mortality at 8 mg/kg bw/day. There was
evidence of mild fetotoxicity (abnormal sternebrae) but not teratogenicity
at 8 mg/kg bw/day.
Ref: Evaluation on: Fluquinconazole. May
1999. No. 184. Evaluation of Fully Approved or Provisionally Approved
Products. Department for Environment, Food and Rural Affairs,
Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme
Green, York YO1 7 PX, UK. Available online: http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm
Fluthiacet-methyl
- Herbicide - CAS No. 117337-19-6
-- Cytogenetics. In
vitro cytogenetic assays performed with two different mammalian
cell lines demonstrated that fluthiacet-methyl
is clastogenic both in the presence and absence of S9 activation.
Ref: Federal Register: December 21, 2001.
Fluthiacet-methyl; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/fluthiacet.m.fr.dec.21.2001.htm
Haloxyfop-etotyl
- Herbicide - CAS No. 87237-48-7
Abstract: The developmental
toxicity of haloxyfop-ethoxyethyl-ester (87237487) (HEE) was studied
in rats. Pregnant Wistar-rats were gavaged with 5, 10, or 50mg/kg
HEE on days six to 16 of gestation. They were observed for clinical
signs of toxicity and sacrificed on gestational day 21. The uteri
were removed, examined, and the number of implantations, live
and dead fetuses, and resorption sites recorded. The live fetuses
were weighed and examined for malformations.
HEE at 10 and 50mg/kg caused vaginal bleeding in 40 and 50% of
the dams, respectively. The 10 and 50mg/kg doses significantly
increased the number of resorptions per litter and decreased the
number of live fetuses per litter. The 50mg/kg dose caused a significant
decrease in fetal weight. HEE caused
a significant dose related increase in the number of cachectic
fetuses. The proportion of cachectic fetuses•
following exposure to 5, 10, and 50mg/kg was 2.0, 6.8, and 20.3%,
respectively. Ureterohydronephrosis was
the most frequently observed soft tissue malformation,
the prevalence of this defect following the 10
and 50mg/kg doses being 42.9 and 54.8%, respectively. The
10 and 50mg/kg doses caused skeletal malformations
such as retarded ossification of the sternum and absence of rib
13. The author concludes that haloxyfop-ethoxyethyl-ester is
embryotoxic and teratogenic.
The no observable effect level is expected to be below
5mg/kg.
Ref: Machera K (1993). Developmental Toxicity
of Haloxyfop Ethoxyethyl Ester in the Rat. Bulletin of Environmental
Contamination and Toxicology, Vol. 51, No. 4, pages 625-632. As
cited at Toxnet.
Definitions:
cachectic - relating
to or having the symptoms of cachexia
cachexia - A profound and marked
state of constitutional disorder, general ill health and malnutrition.
The loss of body weight and muscle mass frequently seen in patients
with advanced diseases. Synonyms: cachexy, wasting
Indoxacarb
- Insecticide - CAS No. 173584-44-6
--
DPX-MP062 No evidence of mutagenic activity at the following concentration
range: 1.56-200 [mu]g/mL; cytotoxicity was
seen at concentrations of >100 [mu]g/mL DPX-JW062 No evidence
of mutagenic activity at the following concentration range: 0.1-50
[mu]g/mL, cytotoxicity observed at >50 [mu]g/mL
Ref: Federal Register: July 18, 2002. Indoxacarb;
Pesticide Tolerance. Final Rule. Federal Register. http://www.fluoridealert.org/pesticides/indoxacarb.fr.july.18.2002.htm
Lithium
perfluorooctane sulfonate - Insecticide,
Adjuvant - CAS
No. 29457-72-5
Abstract (rat):
Lithium Perfluorooctane sulfonate (LPOS) was administered by gavage
at 3, 6, or 12 mg/kg to mated Crl:CD„BR VAF/Plus„ female rats
once daily on days 6 through 15 of gestation. Body weights and
clinical observations were on days 0, 6, 9, 12, 16, 20 of gestation.
Food consumption was also measured. Cesarean sections were done
on surviving animals on day 20 of gestation, and the fetuses were
removed for examination. The dams were necropsied following sacrifice.
Clear maternal toxicity was observed in both the 6 and 12 mg/kg
groups. Five out of 25 females in the 12 mg/kg group did not survive
to scheduled sacrifice. Both the 6 and 12 mg/kg groups had test
material-related changes including lower mean body weights, body
weight gains, and food consumption. Treatment
at 12 mg/kg resulted in embryolethality as evidenced by lower
uterine weights, fewer live fetuses per litter, reduced fetal
bodyweights and lower percent of live fetuses than the control
treated. There was also significant
increased incidences of cleft palate (79%), and edema (36%). Variations
at this dose included reduced ossification of bone and unossified
bone. The no-observable-effect level (NOEL) for LPOS for
teratogenicity in rats is 6 mg/kg, whereas the NOEL for maternal
toxicity in rats is 3 mg/kg.
Ref: Toxicologist
1994 Mar;14(1):162; Developmental
toxicity study with lithium perfluorooctane sulfonate in
rats; by Henwood
SM, Costello AC, Osimitz TG
Developmental Toxicity
In the developmental study in rabbits, maternal toxicity was observed
at 1 mg/kg/day and above, based on reduced body weight gains during
the dosing period, followed by a rebound in body weight gains
post-dosing. Developmental toxicity was observed at the highest
dose tested, 4 mg/kg/day. Effects included fetolethality,
skeletal variations (unossified skull bones, sternebrae, talus,
pubis and extra full rib) and decreased fetal body weights. A
maternal NOAEL was not established and the maternal LOAEL was
1 mg/kg/day, based on reduced body weight gains. The developmental
NOAEL was 2 mg/kg/day. In the rat developmental study, maternal
toxicity was observed at 6 mg/kg/day based on reductions in mean
body weights, mean body weight gains, food consumption and clinical
signs (hunched and few feces in one animal). The maternal NOAEL
is 3 mg/kg/day. The developmental NOAEL is 6 mg/kg/day and the
LOAEL is 12 mg/kg/day based on increased fetolethality, lower
fetal body weights, external and soft tissue malformations, and
skeletal variations.
Ref:
US EPA. New Pesticide Factsheet. Lithium
Perfluorooctane sulfonate (LPOS). August 1990. EPA-730-F-99-009.
http://www.fluoridealert.org/pesticides/lithium.per..epa.facts.1999.pdf
Metaflumizone
(BAS 320 I) - Insecticide
- CAS
No. 139968-49-3
Genotoxicty.
In a battery of three in vitro and two in vivo mutagenicity assays
consisting of all required end-points (point mutation, chromosomal
damage, and DNA damage and repair), the weight of the evidence
for BAS 320 I indicates a lack of potential genotoxicity.
Specifically, for the battery of three in vitro mutagenicity assays
with BAS 320 I, no positive responses were observed for increased
revertant frequencies with and without metabolic activation bacterial
reverse mutation assay or for increased mutant frequencies with
and without metabolic activation Hypoxanthine guanine phophoribosyl
transferase (HGPRT) locus assay. Although
there was a positive result for a statistically increased number
of structurally aberrant metaphases in the chromosomes, which
indicates clastogenic potential under in vitro conditions, this
result was only observed without metabolic activation cytogenicity
study with V79 cells.
Importantly, the potential biological significance of this
apparent chromosome damage observed in vitro only without metabolic
activation, was evaluated in vivo using the mouse micronucleus
assay. Testing in the in vivo micronucleus study with NMRI mice
was conducted at a high dose level (2,000 mg/kg b.w.) that demonstrated
clinical symptoms of toxicity, including piloerection and poor
general state, in 5 of 5 animals. No significant or dose-related
increases in chromosomal damage were observed in this in vivo
test, indicating that BAS 320 I does not cause chromosomal aberrations
in intact animals.
Moreover,
it has also been recognized by EPA that more weight should be
placed on in vivo systems than in vitro systems as expressed in
the Agency's weight of evidence for genotoxic evaluation of a
chemical
included in the ``Guidelines for Mutagenicity Risk
Assessment'' (Federal Register, September 24, 1986, Vol. 51: 34006-34012).
Thus, the negative in vivo results (non-clastogenicity for chromosomal
aberrations) observed in the mouse micronucleus assay and the
rat hepatocytes assay, should override the
positive results obtained in the in vitro assay only without
metabolic activation. Furthermore, it has been noted that in vitro
systems may simulate abnormal physiological conditions from prolonged
exposure to a chemical in the absence of S-9 metabolic activation
(Brusick, D.J. (editor) 1987. Genotoxicity Produced in Cultured
Mammalian Cell Assay by Treatment Conditions. Mutation Research,
Vol. 189, No.1: 1-69 and Sofuni, T. 1993. Japanese Guidelines
for Mutagenicity Testing. Environmental and Molecular Mutagenesis,
Vol. 21, No.1: 2-7). Consequently, based
on the weight of the evidence presented above, BAS 320 I does
not pose a genotoxic concern.
Ref: October 27, 2004. Federal Register.
Pesticide
tolerance petition.
http://www.fluorideaction.org/pesticides/metaflumizone.fr.oct.27.04.htm
PFOA - Insecticide,
US EPA List 3 Inert
Abstract excerpt: The
effects of perfluorooctanoic acid (PFOA), a potent hepatocarcinogen
and peroxisome proliferator in rodents, on human cells have not
yet been examined. In the present study we
demonstrate that treatment of human hepatoblastoma HepG2 cells
with PFOA induces apoptosis, as well as perturbs the cell cycle...
Simultaneous flow cytometric analysis of apoptosis-associated
DNA strand breaks using the TUNEL procedure and of propidium iodide
staining of cellular DNA revealed DNA breaks
in HepG2 cells exposed to 150 microM PFOA, prior to nuclear fragmentation.
Ref: 1999. Carcinogenesis Dec;20(12):2237-46.
Effects of the rodent peroxisome proliferator and hepatocarcinogen,
perfluorooctanoic acid, on apoptosis in human hepatoma HepG2 cells;
by Shabalina IG, Panaretakis T, Bergstrand A, DePierre JW. Full
report available free at:
http://carcin.oupjournals.org/cgi/content/full/20/12/2237
Abstract:
To elucidate the relationship between peroxisome proliferation
by perfluorinated compounds and oxidative DNA damage, perfluorooctanoic
acid (PFOA), perfluorodecanoic acid (PFDA), perfluorobutyric acid
(PFBA) and perfluorooctane (PFO) were administered to 6-week-old
F-344 male rats. After a single intraperitoneal (i.p.) injection
of PFOA, PFBA or PFO in corn oil at a dose of 100 mg/kg, significant
increases of liver weight and 8-hydroxydeoxyguanosine (8-OH-dG)
levels in liver DNA were observed in PFOA-treated rats. Oral administration
of powdered diet containing 0.02% PFOA or 0.01% PFDA for 2 weeks
resulted in significant increases of liver weight and 8-OH-dG
levels in liver DNA in rats given both chemicals. On the other
hand, no increase in 8-OH-dG levels in kidney DNA was found in
either of the studies. Our results demonstrate that, as with other
peroxisome proliferators (phthalic ester plasticizers and hypolipidemic
drugs), PFOA and PFDA induced peroxisome
proliferation also leads to organ specific oxidative DNA damage.
Ref:
1991. Cancer Lett Apr;57(1):55-60. Short-term exposure
to the peroxisome proliferators, perfluorooctanoic acid and perfluorodecanoic
acid, causes significant increase of 8-hydroxydeoxyguanosine in
liver DNA of rats; by Takagi A, Sai K, Umemura T, Hasegawa
R, Kurokawa Y.
Potassium
bifluoride - Wood preservative -
CAS No. 7789-29-9
Abstract: The L5178Y
mouse lymphoma cell forward-mutation assay was used to test for
the mutagenic activity of sodium and potassium fluoride at the
thymidine kinase locus. Mutants were detected by colony formation
in soft agar in the presence of trifluorothymidine.
Mutagenic and toxic responses were observed in the concentration
range of 300-600 micrograms/ml with both sodium and potassium
fluoride. Approximately 3-fold increases in mutant frequency
were observed for concentrations in the 500-700 micrograms/ml
range that reduced the relative total growth to approximately
10% in the absence or presence of a rat-liver S9 activation system.
A sample of 30% sodium fluoride-70% sodium
bifluoride (NaHF2) induced a similar mutagenic response
but was more toxic with respect to the fluoride concentration.
A specificity for fluoride ions in causing mutagenesis was indicated
by the fact that much higher concentrations of sodium or potassium
chloride were necessary to cause toxicity and increases in the
mutant frequency. The possible involvement of chromosomal changes
was signaled by the predominant increase in the small colony class
of mutants.
Ref: Caspary WJ et al. (1987).
Mutagenic
activity of fluorides in mouse lymphoma cells. Mutat Res.
Mar;187(3):165-80.
Sodium
bifluoride - Insecticide, Former US EPA
List 3 Inert -
CAS No.
1333-83-1
Abstract: The L5178Y
mouse lymphoma cell forward-mutation assay was used to test for
the mutagenic activity of sodium and potassium fluoride at the
thymidine kinase locus. Mutants were detected by colony formation
in soft agar in the presence of trifluorothymidine.
Mutagenic and toxic responses were observed in the concentration
range of 300-600 micrograms/ml with both sodium and potassium
fluoride. Approximately 3-fold increases in mutant frequency
were observed for concentrations in the 500-700 micrograms/ml
range that reduced the relative total growth to approximately
10% in the absence or presence of a rat-liver S9 activation system.
A sample of 30% sodium fluoride-70% sodium
bifluoride (NaHF2) induced a similar mutagenic response but was
more toxic with respect to the fluoride concentration.
A specificity for fluoride ions in causing mutagenesis was indicated
by the fact that much higher concentrations of sodium or potassium
chloride were necessary to cause toxicity and increases in the
mutant frequency. The possible involvement of chromosomal changes
was signaled by the predominant increase in the small colony class
of mutants.
Ref: Caspary WJ et al. (1987).
Mutagenic
activity of fluorides in mouse lymphoma cells. Mutat Res.
Mar;187(3):165-80.
--
GENOTOXICITY - DNA damage and chromosome aberrations have been
reported in insect studies.
Ref:
Hazardous Substances Data Bank for SODIUM HYDROGEN DIFLUORIDE
CASRN:
1333-83-1 http://www.fluorideaction.org/pesticides/sodium.bifluoride.toxnet.htm
Sodium fluoroacetate
(Compound
1080)
- Insecticide, Rodenticide - CAS No.
62-74-8
Abstract: 1080 has
been used in New Zealand to control vertebrate pests since 1954,
and although a large historical database exists, little is known
about the developmental toxicity of this pesticide. This investigation
was intended to evaluate the developmental toxicity and teratogenic
potential of 1080 in Sprague-Dawley rats following oral intubation.
A pilot study was performed to help select doses for the subsequent
study and consisted of groups of 5 time-mated females. Animals
received 1080 at concentrations ranging from 0.1 to 1.0 mg/kg/day
from Days 6 to 17 of gestation. A 60% mortality rate and
reductions in maternal body weight and body weight gain as well
as decreased litter size and increased resorptions were observed
at 1.0 mg/kg/day. Consequently, the doses selected for the main
study were 0.1, 0.33 and 0.75 mg/kg/day. Groups of 26 time-mated
females received 1080 from Days 6 to 17 of gestation. On Day 20
of gestation, litters were delivered via laparohysterectomy. The
results of this study have not been fully evaluated, but visceral
and skeletal evaluation results will be presented. Significant
reductions in maternal body weight, body weight gain and food
consumption were noted at 0.75 mg/kg/day. No changes in litter
size or resorptions were observed, but fetal body weight was significantly
reduced at 0.75 mg/kg/day. No external fetal abnormalities were
noted. Available data indicate that 1080 is maternally toxic at
0.75 mg/kg/day and higher. Embryolethality
was noted at 1.0 mg/kg/day, but not at 0.75 mg/kg/day.
At this stage, there is no evidence of developmental toxicity.
Reductions in fetal body weight at 0.75 mg/kg/day are probably
linked to maternal toxicity rather than a direct effect on the
fetus.
Ref: Turck PA et al. (1998). Assessment
of the developmental toxicity of sodium monofluoroacetate (1080)
in rats. Toxicologist 1998 Mar;42(1-S):258-9.
Sulfluramid
- Acaricide, Insecticide - CAS No. 4151-50-2
Abstract: Oral administration
of sulfluramid, an insecticide, has been shown to produce transient
sterility in dogs. The present study in
rabbits was designed to evaluate the potential adverse
effects of maternal exposure to sulfluramid during late gestation
on the growth, viability, development and sperm quality of the
F1 generation. Sulfluramid, suspended in 1% CMC/0.1% Tween 80,
was administered by gavage to three groups of 22 timed-pregnant,
"litter-experienced" New Zealand White rabbits from gestation
days 19-28 at levels of 0.3, 1.0 and 3.0
mg/kg/day. The F0 females were allowed to deliver naturally
and rear their bunnies to PND (postnatal day) 42. Selected F1
bunnies were evaluated for developmental landmarks, and a longitudinal
quantitative assessment of spermatogenesis was performed on semen
from all selected F1 males. The number of
bunnies stillborn or found dead on PND 0 was increased, and the
viability on PND 1 was decreased in the 3.0 mg/kg/day group.
In addition, postnatal viability indices
in all treated groups were decreased throughout the pre-weaning
period (PND 4-42). No treatment-related effects were noted on
the age at which balanopreputial separation or vaginal patency
occurred. The numbers of sperm/ejaculate, percentages of motile
sperm, numbers of motile sperm/ejaculate and percentages of sperm
with normal morphology were apparently unaffected by treatment
during the 4-week longitudinal assessment
of spermatogenesis. No adverse effects were apparent on
mean testicular and epididymal sperm numbers, and no treatment-related
histopathological findings were noted in the reproductive organs
at any dose level. Although significant
neonatal toxicity (mortality) was noted in all treatment groups,
no treatment-related effects were noted on sexual maturation
or testicular function of the F1 generation in this study.
Ref: Stump DG et al. (1997). Study of the
effects of sulfluramid on pre- and postnatal development, maturation
and fertility in the rabbit. Toxicologist Mar;36(1 Pt 2):357.
tau-Fluvalinate
- Acaricide, Insecticide - CAS No. 102851-06-9
-- Teratogenicity studies
on tau fluvalinate in rabbits showed incidences of delayed ossification,
and visceral and skeletal malformations at an overt maternotoxic
dose (125 mg/kg bw). This dose also caused increased numbers of
resorptions and poorer viability of fetuses. No teratogenic effects
occurred at lower doses. No reproduction
studies with tau fluvalinate in other species were submitted and
the compound has to be classified as possibly teratogenic. No
teratogenic effects of the less toxic racemic fluvalinate were
seen in rats. Doses of 10 and 50 mg/kg bw/day
were materno- and fetotoxic.
Ref:
Revised
Summary Report. EMEA/MRL/021-REV1/95. Committee for Veterinary
Medicinal Products. The European Agency for the Evaluation of
Medicinal Products.
http://www.fluorideaction.org/pesticides/tau.fluvalinate.1995.review.pdf
Teratogenicity studies
on tau fluvalinate in rabbits showed incidences of delayed ossification,
and visceral and skeletal malformations at an overt maternotoxic
dose (125 mg/kg bw). This dose also caused increased numbers of
resorptions and poorer viability of fetuses. No teratogenic effects
occurred at lower doses. No reproduction studies with tau fluvalinate
in other species were submitted and the
compound has to be classified as possibly teratogenic.
No teratogenic effects of the less toxic racemic fluvalinate were
seen in rats. Doses of 10 and 50 mg/kg bw/day were materno- and
fetotoxic.
Ref:
Revised
Summary Report. EMEA/MRL/021-REV1/95. Committee for Veterinary
Medicinal Products. The European Agency for the Evaluation of
Medicinal Products.
http://www.fluorideaction.org/pesticides/tau.fluvalinate.1995.review.pdf
TFM
(3-Trifluoro-Methyl-4-Nitro-Phenol)
- Lampricide, Piscicide - CAS No. 88-30-2
Mutagenicity. In an
in vitro cytogenetic assay (MRID 40999201), cultured CHO cells
were exposed to TFM (86%) at concentrations of 49.6, 99.2, 149,
or 198 Fg/ml for 17.25 hrs. in absence of the S9 metabolic activation.
In the presence of the S9 activation, the CHO cells were exposed
to TFM at concentrations of 115, 384, 769, 1150, or 1540 Fg/ml
for 2 hrs. After exposure to TFM, the treated cells were washed
with buffered saline, and complete McCoyÕs a medium containing
0.1 Fg/ml Colcemid was added to the washed cells. The cells were
then incubated for 2.5 hrs (without S9) or 7.5 hrs (with S9).
The metaphase cells were then harvested, and slides prepared for
analysis. The results showed that, without S9 activation, TFM
at concentrations of 149 and 198 Fg/ml induced
chromosomal aberrations, consisting mainly of simple chromatid
breaks. In the presence of S9 activation, 1150 and 1540 Fg/ml
of TFM caused a statistically significant
and dose-related increase in chromosomal aberrations, consisting
of simple chromatid and chromosome breaks. (pp 10--11)
Ref: November 1999 US EPA's Reregistration
Eligibility Decision (RED) for 3-Trifluoro-Methyl-4-Nitro-Phenol
and Niclosamide).
http://www.fluoridealert.org/pesticides/tfm.red.1999.pdf
Tolylfluanid
- Fungicide - CAS No. 731-27-1
--
Bacterial gene mutation assay. Tolylfluanid was cytotoxic
to all strains at = 8 [mu]g/plate +/ - S9 and precipitated from
solutions in all strains at 5,000 [mu]g/plate +/- S9. There were
no reproducible, dose- related differences in the number of revertant
colonies in any strain or dose over the background. Positive controls
induced appropriate response.
-- Metabolite--WAK 6698. Bacterial
gene mutation assay. Metabolite was cytotoxic at doses £=158 [mu]g/plate
in the initial assay and 1,581 [mu]g/plate in the repeat assay.
There was no evidence of a significant increase in mutant colonies
over background in any strains tested in the initial or repeat
mutagenicity assays. Positive controls induced appropriate response.
-- Technical. In vitro mammalian cell gene mutation assay. Cytotoxicity
was observed at concentrations 1 to 10 [mu]g/milliliter (mL) -S9
and 5 to 10 [mu]g/mL +S9. Over the ranges tested clastogenic effects
included increased incidences of metaphases with aberrations including
gaps, metaphases excluding gaps, metaphases with exchanges, and
metaphases with polyploidy were observed.
Tolyfluanid is clastogenic both in the presence
and in the absence of S9 activation.
Ref: Federal Register: September 25, 2002.
Tolylfluanid; Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/tolylfluanid.fr.sept25.2002.htm
Transfluthrin
- Insecticide - CAS No. 118712-89-3
Abstract: ...
Our study describes the genotoxic effects
of PCP, lindane, transfluthrin,
cyfluthrin, and natural pyrethrum
on human mucosal cells of the inferior and
middle nasal conchae.
METHODS: Epithelial cells were isolated from nasal mucosa, which
was removed in the surgical treatment of chronic sinusitis and
nasal concha hyperplasia. After the cells had been tested for
vitality using the trypan blue exclusion test, the short-term
culture method was used. The material was incubated with PCP (0.3,
0.75, and 1.2 mmol), lindane (0.5, 0.75, and 1.0 mmol), transfluthrin
(0.05, 0.1, 0.5, 0.75, and 1.0 mmol), cyfluthrin (0.05, 0.1, 0.5,
0.75, and 1.0 mmol), natural pyrethrum (0.001, 0.005, 0.01, 0.05,
and 0.1 mmol), and N-methyl-N'-nitro-N-nitrosoguanidine for 60
minutes. Substance-induced DNA damage (single-strand and double-strand
breaks) were determined using single-cell microgel electrophoresis.
A fluorescence microscope was used together with an image processing
system to analyze the results obtained.
RESULTS: After exposure to all tested substances, a high percentage
of the cells of the middle nasal concha in particular were found
to have severely fragmented DNA as a result of strong genotoxic
effects. Although the reaction of the cells of the inferior nasal
concha was significantly less strong (p < 0.001), the tested
substances were nevertheless found to have a notable genotoxic
effect on these cells too.
CONCLUSION: Our study strongly suggests
that exposure to PCP, lindane, transfluthrin, cyfluthrin, and
natural pyrethrum has a genotoxic effect on the epithelial cells
of human nasal mucosa. In addition, we have shown that
nasal structures differ in susceptibility to the various pesticides
used in the tests. Thus, the study provides new evidence supporting
the biological plausibility of PCP- and lindane-induced effects,
thereby helping evaluate potential PCP- and lindane-induced mucous
membrane carcinomas of these parts of the nose. In addition, our
study shows that other substances that today are widely used for
controlling pests have a considerable genotoxic effect on human
target cells. The results obtained indicate the need for additional
studies on the genotoxicity of these substances and their adverse
effects on human health.
Ref: Genotoxic effects of pentachlorophenol,
lindane, transfluthrin, cyfluthrin, and natural pyrethrum on human
mucosal cells of the inferior and middle nasal conchae; by Tisch
M, Faulde MK, Maier H. Am J Rhinol. 2005 Mar-Apr;19(2):141-51.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15921213&query_hl=2
3-Trifluoromethyl
aniline - Intermediate
for herbicides (eg, Fluometron
& Norflurazon); Intermediate
for pharmaceuticals; Breakdown product - CAS No. 98-16-8
--
GENOTOXICITY. m-Trifluoromethylaniline
induced dominant lethal mutations in flies.
-- ACUTE EXPOSURE. m-Trifluoromethylaniline is toxic by the oral,
inhalation, dermal, or IP routes.
-- Non-Human Toxicity Excerpts: WHEN ADDED TO FOOD OF LARVAL &
IMAGO DROSOPHILA, M-TRIFLUOROMETHYLANILINE INCR INCIDENCE OF DOMINANT
LETHAL MUTATIONS AMONG OFFSPRING & INCR PERCENTAGE OF UNFERTILIZED
EGGS. [ILICHKINA AG ET AL; MOL MEKH GENET PROTSESSOV 291 (1976)].
Ref: TOXNET profile from Hazardous Substances
Data Bank.
http://www.fluoridealert.org/pesticides/3-trifluoromethyl.an.toxnet.htm
Trifluralin
- Herbicide - CAS No. 1582-09-8
Abstract: The genotoxicity
of trifluralin (1582098) was examined in human lymphocytes. Lymphocyte
cultures were established from blood samples drawn from two healthy
young male donors. These were treated with 0 to 200 micrograms
per milliliter (microg/ml) trifluralin with or without metabolic
activation from S9 mix for up to 72 hours (hr). Induction of sister
chromatid exchanges (SCEs) was assessed after 2 or 48hr of incubation
with trifluralin. Micronuclei induction was evaluated after 72hr
of trifluralin treatment. Induction of chromosome aberrations
was assessed after 30hr of incubation with trifluralin. Cytotoxicity
was assessed by measuring changes in the proliferative rate index
(PRI), determined by examination of the first three metaphases,
and the cytokinesis block proliferative index (CBPI). Trifluralin
treatment for 48hr in the absence of S9 mix caused a slight, but
statistically significant increase in SCE frequency in lymphocytes
from both donors at 50microg/ml, the highest concentration tested.
Treatment with 25microg/ml trifluralin in the absence of S9 mix
also caused a significant increase in SCE frequency in lymphocytes
from one donor. Treatment with 200microg/ml trifluralin for 2hr
in the presence of S9 mix caused a significant increase in SCE
frequency in lymphocytes from both donors. These effects were
accompanied by slight decreases in the PRI and CBPI. Trifluralin
did not increase the frequency of chromosome aberrations or micronuclei
above the background level. The authors
conclude that trifluralin is able to exert weak cytotoxic and
genotoxic effects in cultured human lymphocytes. The SCE
assay seems to be more sensitive for detecting these types of
effects than the chromosome aberration or micronucleus assays.
Ref: Ribas G et al. (1996). Genotoxic Evaluation
of the Herbicide Trifluralin on Human Lymphocytes Exposed In Vitro.
Mutation Research, Vol. 371, Nos. 1/2, pages 15-21, 30 references,
1996.
Abstract:
In the present study, the herbicides bentazone, molinate, thiobencarb
and trifluralin were evaluated for mutagenic and recombinagenic
effects using the wing spot test of Drosophila melanogaster (somatic
mutation and recombination test, SMART). Both
standard (ST) and high-bioactivation (HB) fly crosses were used,
the latter cross is characterised by a high sensitivity to promutagens
and procarcinogens. Three-day-old larvae, transheterozygous
for the multiple wing hairs (mwh, 3-0.3) and flare-3 (flr(3),
3-38.8) genes, were chronically fed with six different concentrations
of each herbicide. Feeding ended with pupation of the surviving
larvae and the genetic changes induced in somatic cells of the
wing's imaginal discs lead to the formation of mutant clones on
the wing blade. Point mutation, chromosome breakage and mitotic
recombination produce single spots; while twin spots are produced
only by mitotic recombination. Bentazone, usually considered as
a non-mutagen, gave positive results in the wing spot test with
the high-bioactivation cross. Molinate, about which information
on mutagenic effects is inconclusive, gave positive responses
in both the standard and the high-bioactivation crosses, while
the other thiocarbamate, thiobencarb, gave positive results only
in the standard cross and at the highest concentration tested
(10 mM). Finally, trifluralin, one of the
most widely studied herbicides for genotoxic effects, gave positive
results in the wing spot test with both crosses. Apart
from the interest of the results found in the genotoxic evaluation
of the four selected herbicides, our results also contribute to
extend the existing database on the Drosophila wing spot test,
and corroborate the utility of the use of high-bioactivation strains
for the genotoxic evaluation of xenobiotics.
Ref: Evaluation of the genotoxicity of four
herbicides in the wing spot test of Drosophila melanogaster using
two different strains; by Kaya B, Marcos R, Yanikoglu A, Creus
A. Mutat Res. 2004 Jan 10;557(1):53-62.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14706518
2.4 GENOTOXICITY. In the DAR, 11 in vitro studies and five in
vivo studies have been evaluated and presented. There
was evidence of aneuploidy induction from an in vitro chromosome
aberration study, positive effects in a comet tail test, as well
as weak positive effects in an in vivo micronucleus study.
In order to clarify these effects, the need of performing of a
new micronucleus study was requested by the rapporteur Member
State. This was stated as a data requirement in level 4 of the
DAR “An in vivo bone marrow micronucleus assay in mice with
kinetochore or centromeric staining in order to ascertain the
nature of the micronuclei induced”. The new study was performed
and submitted by the notifier and the rapporteur Member State
has evaluated and presented it in the Addendum. No increase in
the incidence of micronuclei formation or the aneuploidy was recorded,
when it was administered as a single dose
to male and female mice. Hence, trifluralin is considered
negative for clastogenic and aneugenic potential in the present
study (page 10)
Ref:
March 14, 2005. European
Food Safety Authority: Conclusion regarding the
peer review of the pesticide risk assessment of the active substance
trifluralin. EFSA Scientific Report (2005) 28, 1-77.
http://www.fluoridealert.org/pesticides/trifluralin.eu.long.2005.pdf
Triflusulfuron-methyl
- Herbicide
- CAS No. 126535-15-7
-- A human lymphocyte
cytogenetic assay was performed using 0.5, 1.5, 1.7, 1.85, or
2.0 mg/mL DPX-66037-59 (98.7%) with and without metabolic activation.
Cytotoxicity was observed at 1.85 mg/mL, indicated by a lower
mitotic index than controls. Triflusulfuron-methyl, with metabolic
activation, was clastogenic at 2.0 mg/mL
under the conditions of this test.
-- A human lymphocyte cytogenetic assay was performed using 0.1Ð2.0
mg/mL DPX-66037-24 (95.6%) with and without metabolic activation.
Cytotoxicity was observed at 2.0 mg/mL,
indicated by a lower mitotic index than controls. Triflusulfuron-methyl,
with metabolic activation, was clastogenic at $1.7 mg/mL in a
dose-dependent manner under the conditions of this test.
-- ... It was genotoxic in mammalian in
vitro chromosomal aberrations assays (same assay performed twice),
but not in a mammalian in vivo assay.
Ref:
Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note
REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf
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