Return to Phototoxic Pesticides
Abstracts
KEYWORDS:
photocarcinogenic, photocarcinogenicity
photoclastogenic
photocytotoxic
photogenotoxic
photohemolytic
photomutagenic, photomutagenicity
phototoxic, phototoxicity
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Bay
Y3118
Ciprofloxacin
Clinafloxacin
Enoxacin
Fleroxacin |
Gemifloxacin
Grepafloxacin
Levofloxacin
Lomefloxacin |
Moxifloxacin
Norfloxacin
Ofloxacin
Pefloxacin
Sitafloxacin |
Sparfloxacin
Temafloxacin
Tosufloxacin
Trovafloxacin |
Name: |
Moxifloxacin |
CAS No. |
151096-09-2
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Formula: |
C21-H24-F-N3-O4
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Structure: |
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Other Names: |
Vigamox |
Class |
Fluoroquinolone |
Effects
(some, not all) |
Phototoxic
• May induce QT prolongation and ventricular arrhythmias |
Use: |
Antibacterial
(ophthalmic) |
Moxifloxacin
Abstracts:
Excerpts: Since noncardiovascular
drug-induced prolongation of the QT interval is often associated
with the onset of torsades de pointes resulting in life-threatening
ventricular arrhythmias (De Ponti et al., 2001; Haverkamp et al.,
2000 and Tamargo, 2000), worldwide regulatory authorities have
raised a heightened awareness on the submission of data surrounding
the ventricular repolarization process. Moreover, general nonclinical
testing strategy for delayed ventricular repolarization by human
pharmaceuticals is being discussed in draft stage guideline ICH
S7B for safety pharmacology studies (The ICH Steering Committee,
2002).
In the case of fluoroquinolone antibacterial agents, it has been
reported that sparfloxacin and grepafloxacin
can prolong the QT interval to cause lethal ventricular arrhythmias
(Bertino and Fish, 2000; Demolis et al., 1996; Dupont et
al., 1996 and Owens, 2001), which were withdrawn
in most countries. Recently, gatifloxacin and moxifloxacin
were developed as third generation of fluoroquinolones (Ball,
2000). However, in vitro studies have indicated
that gatifloxacin and moxifloxacin markedly prolonged the action
potential duration of the isolated guinea pig ventricular myocardium
and canine Purkinje fibers (Gintant et al., 2001; Hagiwara
et al., 2001 and Patmore et al., 2000). Also, gatifloxacin
and moxifloxacin inhibited the human cardiac repolarizing K+ current
(Anderson et al., 2001; Bischoff et al., 2000 and Kang et al.,
2001). Clinical studies on the safety pharmacology of gatifloxacin
and moxifloxacin indicated that these fluoroquinolones may induce
QT prolongation and ventricular arrhythmias (Bertino et
al., 2002; Démolis et al., 2000; Iannini and Circiumaru,
2001; Noel et al., 2003; Siepmann and Kirch, 2001 and Von Keutz
and Schlüter, 1999).
Ref: In vivo experimental approach for the
risk assessment of fluoroquinolone antibacterial agents-induced
long QT syndrome; by Katsuyoshi Chiba et al. European Journal
of Pharmacology Volume 486, Issue 2 , 20 February 2004, Pages
189-200.
Clinical trials in patients with community- and hospital-acquired
infections have established that the clinical effectiveness and
safety of fluoroquinolones are similar to -lactam and macrolide
agents. The most common drug-related adverse
effects (AEs) with fluoroquinolone therapy involve the
gastrointestinal troct and central nervous system and are usually
transient and mild to moderate in severity. However, serious toxic
reactions have led to the limited and restrictive use of trovafloxacin
in the United States and the withdrawal
of temafloxacin and grepafloxacin from worldwide markets.
In addition, postmarketing spontaneous AE reports have imposed
updates in the precautions and warning sections of product package
inserts of selected fluoroquinolones. This
article reviews the AEs associated with the fluoroquinolones and
compares the safety profiles of ciprofloxacin, levofloxacin, gatifloxacin,
and moxifloxacin.
Ref: Safety and tolerability of fluoroquinolones;
by Kelly A. Sprandel PharmD and Keith A. Rocivold PharmD, FCP,
FCCP. Clinical Cornerstone Volume 5, Supplement 3 , 2003, Pages
S29-S36.
Name: |
Norfloxacin |
CAS No. |
70458-96-7
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Formula: |
C16-H18-F-N3-O3
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Structure: |
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Other Names: |
AM-715
BRN 0567897
Baccidal
Barazan
CCRIS 6302
Chibroxin
Fulgram
MK 0366
MK-366
Noroxin
Sebercim |
Class |
Fluoroquinolone |
Effects
(some, not all) |
•
Photogenotoxic
• Photohemolytic
• Phototoxic
• Retarded fracture healing in rats
|
Use: |
Anti-infective
agents, fluoroquinolone
Antibacterial
Drug / Therapeutic Agent
1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic
acid. Quinoline-derived synthetic antibacterial agent with
a very broad spectrum of action. Oral administration yields
highly bactericidal plasma, tissue, and urine levels. Norfloxacin
inhibits bacterial DNA-gyrase and is used in gastrointestinal,
eye, and urinary infections. |
Norfloxacin
Abstracts:
The phototoxic potential
of eight fluoroquinolones (norfloxacin,
ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin,
sparfloxacin and gatifloxacin) was evaluated by using three
in vitro methods of cytotoxicity against mammalian cells, erythrocyte
lysis and DNA strand breakage. All fluoroquinolones
tested with the exception of gatifloxacin, an 8-methoxy quinolone,
showed DNA strand breaking activities under UV-A irradiation.
Their cytotoxicity against HeLa cells was also enhanced by UV-A
irradiation. In particular, the phototoxic
potential of sparfloxacin, enoxacin and lomefloxacin was high
in both methods. Ofloxacin is very
photocytotoxic against HeLa cells, while it has low potential
to cause DNA strand breakage. Norfloxacin,
ciprofloxacin and enoxacin were very photohemolytic, but
sparfloxacin was not, indicating that the in vivo phototoxic potencies
of fluoroquinolones might not be predictable by the photohemolysis
study. Gatifloxacin, a non-phototoxic quinolone, showed no phototoxic
potential in any of these three in vitro tests. These results
suggest that determination of DNA strand breaking activity, combined
with cytotoxicity against mammalian cells, is available to predict
the phototoxic potential of fluoroquinolones without laboratory
animals.
Ref: In vitro method for prediction of the
phototoxic potentials of fluoroquinolones; by T. Yamamoto et al.
Toxicology in Vitro - Volume 15, Issue 6 , December 2001, Pages
721-727.
BACKGROUND: The objective
of the present study was to test and compare the effect of floroquinolones
on fracture healing as assessed histopathologically. METHODS:
A total of twenty five Wistar rats were arbitrarily assigned to
five groups with five animals each. Bilateral closed femoral fracture
was constructed manually in all groups. The first group did not
receive any drug as control (C). The 2nd, 3rd, 4th, and the last
group were treated with norfloxacin (N),
ofloxacin (O), pefloxacin (P) and ciprofloxacin (Ci) respectively.
Antibiotic administration was started on the 7th day after the
fracture incident. All the treatments were discontinued twenty
days after the incident all the rats were sacrificed , and the
fracture calluses together with affected femurs were resected
en bloc at the fourth week after fracture. RESULTS: Average healing
grades of control group was higher than all the other antibiotic
groups. Mean healing grades of control ( 5 ; n:8), ofloxacin (4.1;
n:7), ciprofloxacin (3.9; n:8), norfloxacin (3.4 ; n:9) and pefloxacin
groups (2.6 ; n:10) were recorded.. Statistically significant
differences between antibiotherapy groups ( excluding. norfloxacin)
and the control group were detected. CONCLUSIONS: The current
histopathological study has shown that all
the studied floroquinolones retarded fracture healing in rats.
Ref: A Comparison of effects of floroquinolones
on fracture healing (An experimental study in rats). By Tuncay
I, Ozbek H, Kosem M, Unal O. Ulus Travma Derg. 2005 Jan;11(1):17-22.
Name: |
Ofloxacin |
CAS No. |
82419-36-1
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Formula: |
C18-H20-F-N3-O4
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Structure: |
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Other Names: |
BRN 3657947
CCRIS 5233
DL 8280
DL-8280
Floxin
HOE 280
ORF 18489
Ocuflox
Oflocet
Oxaldin
PT 01
Tarivid
Visiren |
Class |
Fluoroquinolone |
Effects
(some, not all) |
•
Photogenotoxic
• Photocytotoxic
• Phototoxic
• Teratogenic
• Chondrotoxicity
• Significantly impaired testicular function and structure
in rats.
• Retarded fracture healing in rats
|
Use: |
Anti-infective
agents, fluoroquinolone
Anti-infective agents, urinary
Antibacterial
An Orally
administered broad-spectrum quinolone antibacterial drug active
against most gram-negative and gram-positive bacteria. Clinical
efficacy has been confirmed in a variety of systemic infections
as well as in acute and chronic urinary tract infections.
|
Ofloxacin
Abstracts:
The
anti-bacterial drug ofloxacin is teratogenic in experimental animals.
The aim of this study was to evaluate the teratogenic effects
on the developing chick tail bud. ... The defects consist of a
blunt ending neural tube, dysplasia of the caudal structures and
absence of caudal vertebrae and ganglia. The
notochord is severely affected at its caudal end. It exits
the vertebral column ventro-laterally, and follows an S-shaped
course to fuse with the tail gut. The incidence of defects is
more pronounced at higher dosages. Care should be taken in prescribing
the drug to pregnant women, as ofloxacin
may cause embryonic abnormalities.
Ref: Effect of ofloxacin on chick tail bud
development. By Vorster W and Lizamore DJ. J Morphol 1997;232(3):337.
Ofloxacin
and ciprofloxacin are two closely-related fluoroquinolones which
both induce chondrotoxicity in juvenile dogs.
In immature rats, however, cartilage lesions
have been described with ofloxacin only...
Ref: Ciprofloxacin and N-methyl-ciprofloxacin
induce joint cartilage lesions in immature rats. By E Lozo et
al. Teratology 1996 May;53(5):32A.
The phototoxic potential
of eight fluoroquinolones (norfloxacin, ofloxacin,
enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin,
sparfloxacin and gatifloxacin) was evaluated by using three
in vitro methods of cytotoxicity against mammalian cells, erythrocyte
lysis and DNA strand breakage. All fluoroquinolones
tested with the exception of gatifloxacin, an 8-methoxy quinolone,
showed DNA strand breaking activities under UV-A irradiation.
Their cytotoxicity against HeLa cells was also enhanced by UV-A
irradiation. In particular, the phototoxic
potential of sparfloxacin, enoxacin and lomefloxacin was high
in both methods. Ofloxacin is very
photocytotoxic against HeLa cells, while it has low potential
to cause DNA strand breakage. Norfloxacin, ciprofloxacin and enoxacin
were very photohemolytic, but sparfloxacin was not, indicating
that the in vivo phototoxic potencies of fluoroquinolones might
not be predictable by the photohemolysis study. Gatifloxacin,
a non-phototoxic quinolone, showed no phototoxic potential in
any of these three in vitro tests. These results suggest that
determination of DNA strand breaking activity, combined with cytotoxicity
against mammalian cells, is available to predict the phototoxic
potential of fluoroquinolones without laboratory animals.
Ref: In vitro method for prediction of the
phototoxic potentials of fluoroquinolones; by T. Yamamoto et al.
Toxicology in Vitro - Volume 15, Issue 6 , December 2001, Pages
721-727.
n the last few years,
a marked decrease in male fertility has been reported. Environmental
factors were recently suspected for this effect. Among those factors
is the misuse of drugs and in particular antibiotics. Quinolones
are a group of antibacterial agents with broad-spectrum activity.
Testicular impairment of some quinolone members is controversial;
a matter which stimulated our attention to investigate the adverse
testicular effects of the most familiar quinolone members, namely:
ofloxacin, ciprofloxacin and pefloxacin. They were given to rats
in doses of 72, 135 and 72 mg kg-1day-1p.o., respectively, for
15 consecutive days. Ofloxacin was also used to establish a dose–response
relationship in doses of 36, 72 and 360 mg kg-1day-1p.o. for 15
consecutive days. Results revealed that
ofloxacin, ciprofloxacin and pefloxacin reduced testicular LDH-X
activity by 39.8%, 62.7% and 60.7%, respectively. Moreover, sperm
count, motility and daily sperm production were markedly decreased.
Ofloxacin induced a dose-dependent decrease in testicular LDH-X
activity, sperm count and motility. Furthermore, daily sperm production
showed a marked reduction which amounted to 26.1% and 40.0% following
administration of ofloxacin (72, 360 mg kg-1day-1*15 days), respectively.
Moreover, administration of ofloxacin resulted in marked testicular
histopathological changes. It is concluded that, ofloxacin, ciprofloxacin
and pefloxacin significantly impaired both testicular function
and structure in rats.
Ref: ADVERSE TESTICULAR EFFECTS OF SOME
QUINOLONE MEMBERS IN RATS; by ADEL R. A. ABD-ALLAH et al. Pharmacological
Research Volume 41, Issue 2 , February 2000, Pages 211-219.
BACKGROUND: The objective
of the present study was to test and compare the effect of floroquinolones
on fracture healing as assessed histopathologically. METHODS:
A total of twenty five Wistar rats were arbitrarily assigned to
five groups with five animals each. Bilateral closed femoral fracture
was constructed manually in all groups. The first group did not
receive any drug as control (C). The 2nd, 3rd, 4th, and the last
group were treated with norfloxacin (N),
ofloxacin (O), pefloxacin (P) and ciprofloxacin (Ci) respectively.
Antibiotic administration was started on the 7th day after the
fracture incident. All the treatments were discontinued twenty
days after the incident all the rats were sacrificed , and the
fracture calluses together with affected femurs were resected
en bloc at the fourth week after fracture. RESULTS: Average healing
grades of control group was higher than all the other antibiotic
groups. Mean healing grades of control ( 5 ; n:8), ofloxacin (4.1;
n:7), ciprofloxacin (3.9; n:8), norfloxacin (3.4 ; n:9) and pefloxacin
groups (2.6 ; n:10) were recorded.. Statistically significant
differences between antibiotherapy groups ( excluding. norfloxacin)
and the control group were detected. CONCLUSIONS: The current
histopathological study has shown that all
the studied floroquinolones retarded fracture healing in rats.
Ref: A Comparison of effects of floroquinolones
on fracture healing (An experimental study in rats). By Tuncay
I, Ozbek H, Kosem M, Unal O. Ulus Travma Derg. 2005 Jan;11(1):17-22.
Name: |
Pefloxacin |
CAS No. |
70458-92-3
|
Formula: |
C17-H20-F-N3-O3
|
Structure: |
|
Other Names: |
1584RB
BRN 0567618
EINECS 274-611-8
EU 5306
Pefloxacine |
Class |
Fluoroquinolone |
Effects
(some, not all) |
•
Phototoxic
• Significantly
impaired testicular function and structure in rats.
• Retarded
fracture healing in rats
|
Use: |
Anti-infective
agents, urinary
Antibacterial
An Orally
administered broad spectrum quinolone antibacterial agent
active against most gram-negative and gram-positive bacteria.
It is effective against urinary tract infections as well as
against many other systemic infections. The drug is well tolerated
in adults, but should not be given to children and pregnant
women. |
Pefloxacin
Abstracts:
In the last few years,
a marked decrease in male fertility has been reported. Environmental
factors were recently suspected for this effect. Among those factors
is the misuse of drugs and in particular antibiotics. Quinolones
are a group of antibacterial agents with broad-spectrum activity.
Testicular impairment of some quinolone members is controversial;
a matter which stimulated our attention to investigate the adverse
testicular effects of the most familiar quinolone members, namely:
ofloxacin, ciprofloxacin and pefloxacin. They were given to rats
in doses of 72, 135 and 72 mg kg-1day-1p.o., respectively, for
15 consecutive days. Ofloxacin was also used to establish a dose–response
relationship in doses of 36, 72 and 360 mg kg-1day-1p.o. for 15
consecutive days. Results revealed that
ofloxacin, ciprofloxacin and pefloxacin reduced testicular LDH-X
activity by 39.8%, 62.7% and 60.7%, respectively. Moreover, sperm
count, motility and daily sperm production were markedly decreased.
Ofloxacin induced a dose-dependent decrease in testicular LDH-X
activity, sperm count and motility. Furthermore, daily sperm production
showed a marked reduction which amounted to 26.1% and 40.0% following
administration of ofloxacin (72, 360 mg kg-1day-1*15 days), respectively.
Moreover, administration of ofloxacin resulted in marked testicular
histopathological changes. It is concluded that, ofloxacin, ciprofloxacin
and pefloxacin significantly impaired both testicular function
and structure in rats.
Ref: ADVERSE TESTICULAR EFFECTS OF SOME
QUINOLONE MEMBERS IN RATS; by ADEL R. A. ABD-ALLAH et al. Pharmacological
Research Volume 41, Issue 2 , February 2000, Pages 211-219.
The fluoroquinolone
antibacterial agents possess photosensitizing properties that
lead to phototoxic responses in both human and animal subjects.
The phototoxicity order reported in humans is: fleroxacin >
lomefloxacin, pefloxacin >>
ciprofloxacin > enoxacin, norfloxacin and ofloxacin. Studies
both in vivo and in vitro have related this phototoxicity to the
generation of reactive oxygen species including hydrogen peroxide
and the hydroxyl radical. ...
Ref: Fluoroquinolone
antimicrobials: singlet oxygen, superoxide and phototoxicity.
Martinez LJ, Sik RH, Chignell CF.1998 Photochem Photobiol; Apr;67(4):399-403.
BACKGROUND: The objective
of the present study was to test and compare the effect of floroquinolones
on fracture healing as assessed histopathologically. METHODS:
A total of twenty five Wistar rats were arbitrarily assigned to
five groups with five animals each. Bilateral closed femoral fracture
was constructed manually in all groups. The first group did not
receive any drug as control (C). The 2nd, 3rd, 4th, and the last
group were treated with norfloxacin (N),
ofloxacin (O), pefloxacin (P) and ciprofloxacin (Ci) respectively.
Antibiotic administration was started on the 7th day after the
fracture incident. All the treatments were discontinued twenty
days after the incident all the rats were sacrificed , and the
fracture calluses together with affected femurs were resected
en bloc at the fourth week after fracture. RESULTS: Average healing
grades of control group was higher than all the other antibiotic
groups. Mean healing grades of control ( 5 ; n:8), ofloxacin (4.1;
n:7), ciprofloxacin (3.9; n:8), norfloxacin (3.4 ; n:9) and pefloxacin
groups (2.6 ; n:10) were recorded.. Statistically significant
differences between antibiotherapy groups ( excluding. norfloxacin)
and the control group were detected. CONCLUSIONS: The current
histopathological study has shown that all
the studied floroquinolones retarded fracture healing in rats.
Ref: A Comparison of effects of floroquinolones
on fracture healing (An experimental study in rats). By Tuncay
I, Ozbek H, Kosem M, Unal O. Ulus Travma Derg. 2005 Jan;11(1):17-22.
In electrophysiological
and behavioral experiments on rats we studied the effects of pefloxacin,
a member of fluoroquinolone family, on the nociceptive system.
Intraperitoneal injection of pefloxacin (80 mg/kg) decreased the
thresholds of nociceptive response to noxious stimulation in the
hot-plate test. In addition, it decreased the threshold of the
late component of nociceptive flexor reflex. Intrathecal application
of pefloxacin in a dose of 20 microg provoked allodynia, while
the higher dose of 400 microg induced behavioral pattern characteristic
of central pain syndrome. It was hypothesized
that pain induced by pefloxacin results from disturbances in GABAergic
inhibition in the central subdivisions of the nociceptive system.
Ref: Mechanisms of pefloxacin-induced pain.
By Kukushkin ML, Igonkina SI, Guskova TA. Bull Exp Biol Med. 2004
Apr;137(4):336-8.
Name: |
Sitafloxacin |
CAS No. |
127254-12-0
(and 163253-35-8) |
Formula: |
C19-H18-Cl-F2-N3-O3
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Structure: |
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Other Names: |
DU 6859
DU 6859a |
Class |
Fluoroquinolone |
Effects
(some, not all) |
•
Photoclastogenic
• Phototoxic |
Use: |
|
Sitafloxacin
Abstracts:
The photochemical
clastogenic potential of 12 quinolone antibacterial agents with
or without light irradiation was assessed by an in vitro chromosomal
aberration test using cultured CHL cells. Exposure to all test
compounds, except for DK-507k, increased the incidence of cells
with structural aberrations excluding gap (TA) following light
irradiation. Test compounds used in the present study under light
irradiation were divided into three groups based on their ED50
values, doses inducing chromosomal aberrations in 50% of cells.
The first group with ED50 values below 30 g/ml
includes sparfloxacin (SPFX), clinafloxacin (CLFX), gemifloxacin
(GMFX), lomefloxacin (LFLX), sitafloxacin
(STFX), grepafloxacin (GPFX) and fleroxacin (FLRX); the second
group with ED50 values of 100 g/ml, enoxacin (ENX) and levofloxacin
(LVFX); the third group with little or no potency, moxifloxacin
(MFLX), trovafloxacin (TVFX) and DK-507k. The
photochemical clastogenicity of these compounds correlates well
with their reported in vivo phototoxic potentials.
In the chemical structure and clastogenicity relationships, substitution
of a methoxy group at the C-8 position in the quinolone nucleus
was confirmed to reduce not only photochemical clastogenicity,
but also the clastogenic potential of quinolone antibacterial
agents.
Ref: In vitro photochemical clastogenicity
of quinolone antibacterial agents studied by a chromosomal aberration
test with light irradiation. By Satoru Itoh et al. Mutation Research/Genetic
Toxicology and Environmental Mutagenesis Volume 517, Issues 1-2
, 27 May 2002, Pages 113-121.
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