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Management Regulatory Agency. Alternative Strategies &
Regulatory Affairs Division, Ottawa (Ontario).
note no. REG2003-12.
note provides a summary of data reviewed and the rationale
for the proposed regulatory decision regarding the active
ingredient fluazinam and the associated end-use product
Allegro 500F for control of late blight on potatoes. It
includes information on the active substance, its properties,
& uses; methods of analysis of the substance &
its residues; the impact of fluazinam on human & animal
health; residues; fate & behaviour of fluazinam in
the environment; effects on non-target species; efficacy
of the product; and considerations related to the Toxic
Substances Management Policy.
- INITIAL SUBMISSION: B-1216: 13-WEEK TOXICITY STUDY IN
ORAL ADMINISTRATION WITH COVER LETTER DATED 07-31-92
CAS Registry No: 79622-59-6
SUBMISSION: B-1216: FOUR-WEEK TOXICITY STUDY IN DIETARY
ADMINISTRATION TO CD RATS (FINAL REPORT) WITH COVER LETTER
CAS Registry No: 79622-59-6
SUBMISSION: TERATOLOGY STUDY OF 3-CHLORO-N-(5-CHLORO-2,6-DINITRO-4-TRIFLUORO-METHYL-PHENYL)-5-TRIFLUOROMETHYL-PYRIDINAMINE
IN RATS WITH COVER LETTER DATED 08-19-92
CAS Registry No: 79622-59-6
Toxline at Toxnet
BIOPHYS ACTA; 1056 (1). 1991.
activity of a newly developed fungicide, fluazinam (3-chloro-N-(3-chloro-2,6-dinitro-4-trifluoromethylphenyl)-5-trifluoromethyl-2-pyridinamine).
GUO Z-J, MIYOSHI H, KOMYOJI T,
HAGA T, FUJITA T
Agric. Chem., Kyoto Univ., Kyoto 606, Japan.
BIOSIS COPYRIGHT: BIOL ABS. A very unusual uncoupling
activity was found in a newly developed phenylpyridylamine
fungicide for agricultural use, fluazinam. The compound
had extraordinarily strong uncoupling activity, but
the activity rapidly disappeared with rat-liver mitochondria
isolated by the usual method with centrifugation. Treatment
that lowered the concentration of glutathione (GSH),
in the mitochondrial matrix prevented the disappearance
of the uncoupling activity. The activity of an analog
of fluazinam in which the 3-chloro substituent on the
phenyl moiety, probably works as a leaving substituent,
was replaced by the i-propoxy group lacking such a function,
did not disappear. These results suggest that fluazinam
was metabolically transformed on the mitochondrial level,
probably by a GSH conjugation mechanism. When GSH was
completely eliminated, fluazinam
had powerful uncoupling potency, greater than that of
SF 6847, the most potent acidic uncoupler known until
free report at
Med 2003 Jan;60(1):76-7
asthma from fungicides fluazinam and chlorothalonil.
Draper A, Cullinan P, Campbell C, Jones
M, Newman Taylor A.
Department of Occupational & Environmental Medicine, Royal Brompton
Hospital & NHLI, 1b Manresa Road, London SW3 6LR, UK Syngenta
International AG, WRO 1007.1.37, Werk Rosental, Schwarzwaldallee
215, CH-4025 Basel, Switzerland.
We report two cases of occupational asthma caused by sensitisation
to powdered fungicides fluazinam and chlorothalonil, from the
same fungicide formulation plant. Both developed work related
lower respiratory symptoms after a latent interval of asymptomatic
exposure. The diagnosis in each case was confirmed with a serial
peak flow record in the workplace followed by specific inhalation
tests. These fungicides are known to cause dermatitis; this
report indicates that these compounds can induce specific immunological
reactions in the airways as well as skin.
PMID: 12499462 [PubMed - in process]
Food Chem 2000 Apr;48(4):967-73
residues in grapes, wine, and their processing products.
Cabras P, Angioni A.
Dipartimento di Tossicologia, Universita di Cagliari, viale
Diaz 182, 09126 Cagliari, Italy. firstname.lastname@example.org
In this review the results obtained in the 1990s from research
on the behavior of pesticide residues on grapes, from treatment
to harvest, and their fate in drying, wine-making, and alcoholic
beverage processing are reported. The fungicide residues on
grapes (cyproconazole, hexaconazole, kresoxim-methyl, myclobutanil,
penconazole, tetraconazole, and triadimenol), the application
rates of which were of a few tens of grams per hectare, were
very low after treatment and were not detectable at harvest.
Pyrimethanil residues were constant up to harvest, whereas fluazinam,
cyprodinil, mepanipyrim, azoxystrobin, and
showed different disappearance rates (t(1/2) = 4.3,
12, 12.8, 15.2, and 24
days, respectively). The decay rate of the organophosphorus
insecticides was very fast with t(1/2) ranging between 0.97
and 3.84 days. The drying process determined a fruit concentration
of 4 times. Despite this, the residue levels of benalaxyl, phosalone,
metalaxyl, and procymidone on sun-dried grapes equalled those
on the fresh grape, whereas they were higher for iprodione (1.6
times) and lower for vinclozolin and dimethoate (one-third and
one-fifth, respectively). In the oven-drying process, benalaxyl,
metalaxyl, and vinclozolin showed the same residue value in
the fresh and dried fruit, whereas iprodione and procymidone
resides were lower in raisins than in the fresh fruit. The wine-making
process begins with the pressing of grapes. From this moment
onward, because the pesticide on the grape surface comes into
contact with the must, it is in a biphasic system, made up of
a liquid phase (the must) and a solid phase (cake and lees),
and will be apportioned between the two phases. The new fungicides
have shown no effect on alcoholic or malolactic fermentation.
In some cases the presence of pesticides has also stimulated
the yeasts, especially Kloeckera apiculata, to produce more
alcohol. After fermentation, pesticide residues in wine were
always smaller than those on the grapes and in the must, except
for those pesticides that did not have a preferential partition
between liquid and solid phase (azoxystrobin, dimethoate, and
pyrimethanil) and were present in wine at the same concentration
as on the grapes. In some cases (mepanipyrim, fluazinam,
and chlorpyrifos) no detectable residues were found in the wines
at the end of fermentation. From a comparison of residues in
wine obtained by vinification with and without skins, it can
be seen that their values were generally not different. Among
the clarifying substances commonly used in wine (bentonite,
charcoal, gelatin, polyvinylpolypyrrolidone, potassium caseinate,
and colloidal silicon dioxide), charcoal allowed the complete
elimination of most pesticides, especially at low levels, whereas
the other clarifying substances were ineffective. Wine and its
byproducts (cake and lees) are used in the industry to produce
alcohol and alcoholic beverages. Fenthion, quinalphos, and vinclozolin
pass into the distillate from the lees only if present at very
high concentrations, but with a very low transfer percantage
(2, 1, and 0.1%, respectively). No residue passed from the cake
into the distillate, whereas fenthion and vinclozolin pass from
the wine, but only at low transfer percentages (13 and 5%, respectively).
Publication Types: Review, Tutorial
[PubMed - indexed for MEDLINE]
J AOAC Int
chromatographic determination of azoxystrobin, fluazinam, kresoxim-methyl,
mepanipyrim, and tetraconazole in grapes, must, and wine.
Cabras P, Angioni A, Garau VL, Pirisi
FM, Brandolini V.
Universita di Cagliari, Dipartimento di Tossicologia, Italy.
Azoxystrobin, fluazinam, kresoxim-methyl,
mepanipyrim, and tetraconazole were determined in grapes,
must, and wine by a gas chromatographic method with nitrogen-phosphorus
(NP) and mass spectrometric (MS) detectors. Pesticides were
isolated from the matrixes by online microextraction with acetone-hexane
(50 + 50, v/v). Because of the high selectivity of NP and MS
detectors, no interferent peaks were present and no cleanup
was necessary. Recoveries from fortified grapes, must, and wine
ranged from 80 to 111%, with coefficients of variation ranging
from 1 to 14%. Limits of determination were 0.05 mg/kg for kresoxim-methyl
and 0.10 mg/kg for the other compounds.
PMID: 9850581 [PubMed - indexed for MEDLINE]
Dermatitis 1995 Jul;33(1):8-11
Dermatitis 1996 Jul;35(1):70
dermatitis due to a new fungicide used in the tulip bulb industry.
Bruynzeel DP, Tafelkruijer J, Wilks MF.
Department of Occupational Dermatology, Free University Academic
Hospital, Amsterdam, The Netherlands.
We describe an outbreak of contact dermatitis in a tulip bulb
processing company. Shortly after the introduction of a new
pesticide, the fungicide fluazinam, employees started to complain
of dermatitis of the arms and the face. 8 employees were investigated
and showed positive patch tests to fluazinam. The dermatitis
disappeared quickly when they stopped work, but returned as
soon they restarted. Subsequent investigations showed that the
fungicide had not been used according to the manufacturer's
recommendations. Fluazinam was shown to be a strong sensitizer
under these circumstances.
PMID: 7493485 [PubMed - indexed for MEDLINE]
Dermatitis 1995 Mar;32(3):160-2
contact dermatitis from the newly introduced fungicide fluazinam.
van Ginkel CJ, Sabapathy NN.
Department of Dermatology, University Hospital Utrecht, The
In spring 1992, several farmers in the western part of The Netherlands
developed dermatitis on their hands, forearms and face. In some,
the legs, trunk and genitals were also affected. Complaints
ranged from a mildly itchy, papular rash to a painful, weeping
and blistering dermatitis. Medical aid was needed by 5/9 of
them. Some of the farmers grew seed potatoes, the others cultivated
lilies. All of them had in common that
their complaints emerged after repeated application of a new
fungicide over several weeks. The fungicide was Shirlan,
with fluazinam as its active ingredient. 9 farmers were patch
tested with a concentration range of the whole formulation (aq.)
and of the active ingredient (pet.). In
7 of 9 farmers, positive patch tests were scored with both the
whole formulation (down to 0.01% aq.) and fluazinam itself (down
to 0.1% pet.). Patch tests in consecutive control patients
(n = 10) were all negative. As it was impossible to substitute
fluazinam as the active ingredient, farmers are now supplied
with detailed information as to how to avoid skin contact as
much as feasible.
PMID: 7774188 [PubMed - indexed for MEDLINE]
Biophys Acta 1992 Jul 6;1101(1):41-7
activity and physicochemical properties of derivatives of fluazinam.
Brandt U, Schubert J, Geck P, von Jagow
Universitatsklinikum Frankfurt, Zentrum der Biologischen Chemie,
Frankfurt am Main, Germany.
The physico-chemical properties and uncoupling activity of eight
derivatives of N-phenyl-2-pyridinamines related to the fungicide
fluazinam were analyzed using rat liver mitochondria. The uncoupling
activity of these compounds relies on the deprotonable secondary
amino group. One of the derivatives tested (B-3) was slightly
more efficient than fluazinam. By phase-distribution analysis
we could show that the N-phenyl-2-pyridinamines are chemicals
with moderate hydrophobicity. Deprotonation of the compound
reduces the water/octanol partition coefficient by about one
order of magnitude. The pKA value of the deprotonable group
is affected equally by electron withdrawing substituents of
the phenyl- and the pyridinyl-ring, and could be predicted simply
from the sum of the Hammett coefficients. The uncoupling efficiency
was not dependent on the hydrophobicity of the compound, but
appeared to be governed by the pKA of the deprotonable group.
This structure/uncoupling characteristic is different from that
of the generally more hydrophobic uncouplers of the salicylanilide-type.
The pKA resulting in the most efficient uncoupling was found
to lie in the range of the pH of the reaction medium. A model
based on a solution complexation mechanism, which describes
this behaviour, is presented. We conclude that the N-phenyl-2-pyridinamines
uncoupled the mitochondria by a simple protonophoric cycle involving
protonation/deprotonation in the bulk phase, and that the kinetics
of uncoupling were primarily governed by the total concentration
of the limiting uncoupler species.
PMID: 1633176 [PubMed - indexed for MEDLINE]
Biophys Acta 1991 May 6;1057(3):377-83
transport inhibition of the cytochrome bc1 complex of rat-liver
mitochondria by phenolic uncouplers.
Tokutake N, Miyoshi H, Fujita T.
Department of Agricultural Chemistry, Kyoto University, Japan.
The respiration inhibition of rat-liver mitochondria by a series
of substituted phenolic uncouplers was studied. The inhibitory
effects were classified into three types, I-III, depending on
the pattern of the changes in inhibitory potency observed when
the potent uncoupler SF6847 was simultaneously applied. The
extent of inhibition by type I phenols did not change as the
transmembrane potential was dissipated by SF6847, but the extent
of inhibition by type II and III phenols was decreased and increased,
respectively. With the addition of another
potent uncoupler, fluazinam, the uncoupling activity
of which disappears with time, the inhibitory potency of type
II phenols was decreased, but increased reversibly with the
disappearance of the uncoupling effect of fluazinam. However,
the inhibitory potency of type III phenols
increased by fluazinam was not reduced. The inhibitory
site of the phenols studied here was the cytochrome bc1 complex.
This complex undergoes conformational changes when the transmembrane
potential changes. The findings suggested that inhibition by
substituted phenolic uncouplers depends partially on conformational
changes of the cytochrome bc1 complex that accompany variations
in the transmembrane potential.
PMID: 1851439 [PubMed - indexed for MEDLINE]
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