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
|
Three rare eye disorders
are noted below. They are:
Microphthalmia
- small eye syndrome. Microphthalmia is a disorder in which
one or both eyes are abnormally small;
Anophthalmia is the absence of one or both eyes.
These rare disorders develop during pregnancy and can be
associated with other birth defects;
Coloboma - A
defect of the iris caused by a failure of the eyeball to
fuse properly during fetal development.
|
Note:
This is not an exhaustive list.
When time allows more information will be added.
Acifluorfen,
sodium -
Herbicide - CAS No. 62476-59-9
-- Acute Toxicity:
Sodium acifluorfen has been placed in Acute
Toxicity Category I for acute eye irritation and in Category
II for acute dermal irritation.
Ref:
April 4, 2002. Overview of Sodium Acifluorfen Risk Assessment.
USEPA.
http://www.fluorideaction.org/pesticides/acifluorfen.na.epa.apr.02.pdf
A developmental toxicity study in rats found qualitative evidence
of increased susceptibility of offspring because developmental
toxicity (increased resorptions, reduced fetal weights, slightly
dilated lateral ventricles of the brain, hemorrhage
in the eyeball, slight dilation of the renal pelvis, hemorrhage
in peritoneal cavity and subcutaneous spaces, and changes in ossification)
Ref: January 15, 2002. MEMORANDUM. SUBJECT:
SODIUM ACIFLUORFEN. HED Chapter for the Reregistration Eligibility
Decision Document. http://www.fluorideaction.org/pesticides/acifluorfen.na.a.red.jan.02.pdf
Severe
eye irritant;
moderate skin irritant (rabbit). /Acifluorfen/ [Tomlin, C.D.S.
(ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey,
UK: The British Crop Protection Council, 1994]
Ref: TOXNET profile from Hazardous Substances
Data Base for ACIFLUORFEN-SODIUM..
http://www.fluoridealert.org/pesticides/acifluorfen.na.toxnet.hsdb.htm
Acifluorfen is very
toxic and is labeled with a DANGER signal word due to its potential
to cause serious eye injury.
Ref: Pesticide Information Profile. Extoxnet
from Cornell Univeristy.
http://www.fluoridealert.org/pesticides/acifluorfen.extoxnet.htm
Benzotrifluoride
- Insecticide - CAS No. 98-08-8
TARGET ORGANS: Central
Nervous System, Eyes, Skin,
Respiratory Tract.
Ref: BENZOTRIFLUORIDE Material Safety Data
Sheet. OxyChem. Issue Date: 07-08-98
http://www.oxychem.com/products/msds/m7644.pdf
SYMPTOMS: This comound
is extremely destructive to the mucous membranes, upper respiratory
tract, skin and eyes. Inhalation
may be fatal as a result of spasm, inflammation and edema of the
larynx and bronchi; chemical pneumonitis and pulmonary edema.
Other symptoms include a burning sensation, coughing, wheezing,
laryngitis, shortness of breath; headache, nausea and vomiting.
Ref: 1987 Fact Sheet by National Toxicology
Program.
http://www.fluoridealert.org/pesticides/benzotrifluoride.1987.ntp.htm
Beta-cyfluthrin
- Insecticide - CAS No. 68359-37-5
--
Beta-cyfluthrin. 28-Day dog feeding study. NOAEL = 2.0 (both sexes)
LOAEL = 8.0 based on impaired movement and conjunctival
irritation.
Ref: Federal Register. September 27, 2002.
Cyfluthrin; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/cyfluthrin.fr.sept.27.2002.htm
Boron
Trifluoride
- Fumigant - CAS No. 7637-07-2
-- Boron trifluoride
is a colorless gas that is corrosive to tissues due to its rapid
hydrolysis to hydrofluoric acid and boric acid. The principal
acute effect in animals is irritation of the mucous membranes
of the respiratory tract and eyes;
post mortem examination also revealed pneumonia and degenerative
changes in renal tubules.
Ref. USEPA/OPPT. Support Document for the
Health and Ecological Toxicity Review of TRI Expansion Chemicals.
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.
Chlorodifluoromethane
-
Insecticide, Fungicide, Propellant - CAS No. 75-45-6
Chlorodifluoromethane
causes malformations of the eyes of fetal rats,
but has no reproductive effect in male rats and does not cause
prenatal toxicity in rabbits following exposure by inhalation.
Ref: 5. Summary of Data Reported and Evaluation.
International Agency for Research on Cancer IARC. 1986
http://www.fluorideaction.org/pesticides/chlorodifluoromethane.iarc.htm
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.
Palmer et al. (1978a)
conducted a large developmental study in an attempt to elucidate
the role of CFC-22 exposure in the eye lesion seen in the previous
studies (see Culik et al., 1977, and Culik and Crowe, 1978, in
the Additional Studies/Comments section). In this study, an experimental
design was used in which 34 control pregnant rats were used, and
22/group were exposed to 100, 1000, or 50,000 ppm of CFC-22 (354,
3,540, or 176,800 mg/cu.m, respectively) for 6 hours/day on gestation
days 6-15. This protocol was repeated 19 times so that more than
6000 control fetuses and 4000 fetuses from each exposed group
were thoroughly examined for the eye defect... The
eye abnormalities (small or missing eye) were noted again
in all exposure groups, but statistical significance for these
effects was achieved only in the 50,000-ppm group. The combined
incidences of microphthalmia and anophthalmia
were 3/607, 5/393, 3/390, and 10/383 in the control, 100,
1000, and 50,000-ppm groups, respectively. Additional data on
the control incidence of the eye effects during 10 years after
the Palmer et al. (1978a) study was conducted are presented in
European Chemical Industry Ecology and Toxicology Center (ECETOC)
(1989). The data were analyzed in blocks of 19 studies, and the
control incidence in the first six blocks was similar to the controls
in the Palmer study, while in later studies, the control incidence
increased (0.4-2.4% in the last four blocks) and, in one experiment,
was similar to the incidence found in the high-dose group in the
Palmer study (2.6%). The incidence of the
eye abnormality in the high-concentration group in the Palmer
et al. (1978a) study is significantly increased compared with
the overall controls in the studies conducted in the 10-year period
after the study (ECETOC, 1989), adding strength to the interpretation
that this is an adverse, treatment-related effect. This
study identifies a LOAEL for maternal weight, fetal weight, and
fetal abnormalities at 50,000 ppm. The LOAEL(HEC) is 176,800 mg/cu.m
for the fetal effects (no duration adjustment is applied) and
44,200 mg/cu.m for the maternal toxicity (exposure is adjusted
for duration).
Ref: US EPA IRIS for Chlorodifluoromethane.
http://www.fluoridealert.org/pesticides/chlorodifluoromethane.iris.htm
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).
Cyfluthrin
-
Insecticide - CAS No. 68359-37-5
Rat developmental studies
via inhalation. In the first two studies, pregnant female rats
at day 0 gestation were exposed head-only to cyfluthrin concentrations
of 0, 1.1, 4.7 or 23.7 mg/m3/ day (milligrams/per cubic
meter/day) for 6 hours/day on gestation days 6 through 15. In
the second study, the dams were exposed to analytical concentrations
of 0, 0.09, 0.25, 0.59 or 4.2 mg/m3 of the test material.
The dams were sacrificed on day 20 and their pups removed by caesarian
section. The maternal NOEL was 1.1 mg/ m3 and the maternal
LOEL was 4.7 mg/m3 (reduced motility, dyspnea, piloerection,
ungroomed coats and eye irritation.
The developmental NOEL was 0.59 mg/m3 and the developmental
LOEL was 1.1 mg/m3 (increases in the incidence of runts
and skeletal anomalies in the sternum (1.1 mg/m3 and
above); increases in post-implantation losses and decreases in
pup weights (4.7 mg/m3 and above) and increased incidences
of late embryonic deaths, in skeletal anomalies in the extremities,
pelvis and skull and in microphthalmia
[abnormal smallness of the eye] (23.7
mg/m3). The study was graded core minimum.
Ref: Federal Register: November 26, 1997.
Cyfluthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/cyfluthrin.fr.nov.26.1997.htm
Cyhalofop-butyl
- Herbicide - CAS No. 122008-85-9
Based on the findings of acute toxicology studies with two similar
products, and by extrapolation from the characteristics of the
individual constituents in the product, it is expected that Barnstorm
Herbicide would be of low acute oral, dermal and inhalational
toxicity. It is likely to be a slight skin irritant and a
severe eye irritant, but not to be a skin sensitiser (page
5). ... Barnstorm Herbicide is expected to be of low oral, dermal
and inhalational toxicity. It is expected
to be a severe eye, and slight skin irritant,
but not a skin sensitiser (page 9).
... Risks to workers during use.
The main acute risks arising from exposure
to Barnstorm Herbicide are slight skin irritation and severe
eye irritation. Mixer/loaders may be exposed to the product
by inhalation or by skin and ocular contact. The
main risk during this activity is skin and eye
and respiratory tract irritancy (page 17). ...Eye protection is
indicated for handling undiluted product due to the potential
for severe acute eye irritation (page 18). ... SAFETY
DIRECTIONS • Will damage the
eyes (page 35).
Ref: July
2005 - Evaluation of the new active Cyhalofop-Butyl in the product
Barnstorm Herbicide. Australian Pesticides and Veterinary Medicines
Authority (APVMA). Canberra, Australia.
http://www.fluorideaction.org/pesticides/cyhalofop.butyl.aust.2005.pdf
Cyhalothrin
- Acaricide, Insecticide - CAS
No. 68085-85-8
The physical and behavioral
effects of cyhalothrin were studied in rats. Pregnant Wistar rats
were administered 0 or 0.018% cyhalothrin topically throughout
pregnancy. After delivery the neonates were monitored for development
of fur, testes descent, and ear, eye, and vaginal opening... The
authors conclude that prenatal exposure to cyhalothrin delays
development of fur, eye and ear opening,
and testes descent and affects motivational behavior. The delays
induced in fur development and eye
and ear opening suggest that cyhalothrin interferes with maternal
or neonatal epidermal growth factor activity. The delay in testes
descent suggests that prenatal cyhalothrin exposure induces changes
in male sexual development. [da Silva Gomes M et al; Vet Human
Toxicol 33 (4): 315-7 (1991)]
Ref: TOXNET profile from Hazardous Substances
Data Base for Cyhalothrin.
http://www.fluoridealert.org/pesticides/cyhalothrin.toxnet.hsdb.htm
Cyhalothrin,
lambda -
Insecticide - CAS No. 91465-08-6
21-Day
inhalation toxicity - rat. 41387702. NOAEL: 0.08 mg/kg/day.
LOAEL: 0.90 mg/kg/day. clinical signs of neurotoxicity,
decreased body weight gains, increased incidence
of punctuate foci in cornea, slight reductions in
cholesterol in females, slight changes in selected urinalysis
parameters
Ref: Federal Register: September 27, 2002.
Lambda-cyhalothrin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/lambda.cyhalot.fr.sept27.02.htm
Flonicamid
- Insecticide - CAS No. 158062-67-0
--
Combined Chronic/ carcinogenicity (rats).
NOAEL is 200
ppm (equivalent to 7.32/8.92mg/ kg/day in males/females). LOAEL
is 1,000 ppm (equivalent to 36.5/44.1mg/ kg/day in males/females)
based on decreased body weights and body
weight gains, and increased incidences of
keratitis*
in males and striated muscle fiber
atrophy in females. At the high dose there was an incidence
(12%)of nasolacrimal duct**
squamous cell carcinomas slightly
outside the historical control range (0-10%) in male rats.
A correlation between the incidence of inflammation and the fluctuating
incidence of nasal tumors was made across dose groups. EPA did
not consider the nasolacrimal duct tumors to be treatment-related.
Female rats had a significant increasing
trend in nasolacrimal duct squamous cell carcinomas at < 0.05,
and at the high dose was slightly above the historical control
mean (0.8%) and range (0-4%). EPA considered
the nasolacrimal duct squamous cell carcinomas to be possibly
treatment related, but that a clear association with treatment
could not be made.
Ref:
August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule.
Federal Register.
http://www.fluoridealert.org/pesticides/flonicamid.fr.aug.31.2005.html
Definitions:
* Keratitis: A term used to define
a wide variety of corneal infections, irritations, and inflammations
** The
nasolacrimal duct carries tears from the
lacrimal sac into the nasal cavity.
Fluazifop-butyl
- Herbicide - CAS No. 69806-50-4
-- Fluazifop-butyl
(CAS # 69806-50-4) was evaluated for subchronic oral toxicity
in beagle dogs (4/sex/group) administered doses of 0 (vehicle
control, corn oil), 5, 25 and 250 mg/kg/day in gelatin capsules
for 13 weeks. Severe corneal ulceration,
requiring humane sacrifice of 2 males and 1 female of a 250 mg/kg/day
dosage during Week 4, prompted adjustment of this regimen to 125
mg/kg/day for the remainder of study. Prior to sacrifice, these
dogs also exhibited progressive conjunctivitis
and photophobia, and all lost weight...
Histopathological evaluation confirmed treatment-related lesions
of the eyes, liver, testes and gastrointestinal
tract. [ICI AMERS INC; Butyl 2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)
propionate: 13-Week Oral Toxicity Study in Beagle Dogs; 04/24/80;
EPA Doc No. 88-920006846; Fiche No. OTS0543851]
Ref: TOXNET profile from Hazardous Substances
Data Bank for FLUAZIFOP-BUTYL.
http://www.fluoridealert.org/pesticides/fluazifop-butyl.toxnet.hsdb.htm
**411-083 069476 Virgo,
D. M., "Fluazifop-butyl: 55 week oral toxicity study in beagle
dogs," Life Science Research, Stock, Essex, England, 10/15/82.
LSR Report No. 81/ILK019/620. Six dogs/sex/group were dosed for
55 weeks with Fluazifop-butyl, 99.6% purity, by gelatin capsules
at dose levels of 0, 5, 25, and 125 mg/kg/day in a chronic study.
Test article within capsules was dissolved in 0.4 ml/kg corn oil
vehicle. NOEL = 5 mg/kg/day... All
other noteworthy findings were limited to the high dose group,
as follows... Eyes of eight high dose dogs
had cataracts, usually accompanied by miliary ("seed-like"
appearance) vacuolation of the lens... Possible adverse
effects (many-faceted toxicity, including mortalities, at 125
mg/kg/day). Acceptable. Aldous, 5/20/02.
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY
DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide
Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.caepa.02.pdf
Fluazifop-P-butyl
- Herbicide - CAS No. 79241-46-6
-- 018 994244: Tesh,
J. M., Ross, F. W. and Tesh, S. A. "PP009: Effects of Oral Administration
upon Pregnancy in the Rabbit, Final report". Life Science Research
report No. 80/ILK 027/498 [November 28, 1980]. PP009, purity 94.8%,
administered via gavage at concentrations of 10, 30 or 90 mg/kg/day
to 20-24 artificially inseminated female New Zealand rabbits during
gestation days 6 through 28. Adverse effects: increased incidence
of cloudy eyes (12.7%), small
fetuses, delayed ossification and enlarged anterior and posterior
fontanelle. Maternal NOEL = >90 mg/kg/day (no toxicity).
UNACCEPTABLE (No MTD, too few pregnant dams at scheduled sacrifice).
(C. Aldous, 8/27/85).
-- ONCOGENICITY, MOUSE [OR HAMSTER] 411-125 180756 Rattray, N.
J., ÒFluazifop-p-butyl: 80 week carcinogenicity study in hamsters,Ó
Central Toxicology Laboratory (CTL), Alderley Park Macclesfield,
2/1/01. Lab Study ID: Syngenta No.1606-01. Golden Syrian hamsters,
51/sex/group, were dosed in diet with 0, 0, 200, 750, or 3000
ppm fluazifop-p-butyl (91.6%) for 81-83 weeks. The dual control
groups were treated identically. An additional 12/sex/group (same
doses) were allocated for 1-yr sacrifice (for hematology only).
Estimated achieved doses were 12.5, 47, and 194 mg/kg/day (M)
and 12.1, 46, and 181 mg/kg/day (F). No NOEL was established...
Findings at the higher two dose levels only included decreased
testes weights, reduced spermatozoa counts in epididymides and
increased
cataract development in males...
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY
DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide
Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.caepa.02.pdf
4.2.3.8 Fluazifop-P-butyl - Rabbit In a developmental toxicity
study [MRID 46082904] [fluazifop-p-butyl (90.1% a.i., batch/lot
# P12)] was administered to [(20 females) New Zealand White] rabbits/group
by gavage in corn oil vehicle [1 ml/kg] at dose levels of 0, 2,
10 or 50 mg a.i./kg bw/day from days 8 through 20 of gestation.
Day sperm was found was designated as day 1. On day 30 of gestation,
dams were killed and the uterine contents examined for live and
dead fetuses. Fetuses were weighed, examined for external and
visceral abnormalities, sexed, eviscerated and stained for skeletal
examination. ... Treatment related effects on development were
seen in the 50 mg/kg/day group only. Statistically significant
extra 13 th rib and delayed ossification was seen in sternebrae
2 and 5. An increase in partially ossified 5 sternebrae was seen
at 10 mg/kg/day, but the litter incidence was not increased. A
nominal increase in malformations were seen at 50 mg/kg/day, such
as acephaly [1 fetus/1 litter], cebocephaly
[1 fetus/1 litter], cleft palate [1 fetus/1 litter], microphthalmia
[1 fetus/1 litter], gastroschisis [1 fetus/1
litter], and multiple anomalies in 1 fetus/1 litter. None
were duplicated and all could have occurred 1 to 3 times in the
same litter, with 0 in control. Since individual
animal data was not submitted, this incidence in litters could
not be verified. For developmental toxicity, the
NOAEL is 10 mg/kg/day and the LOAEL is 50 mg/kg/day based on increased
13 th rib and increased incidence of delayed ossification of sternebrae
2 and 5. (page 39).
Ref:
December 10, 2004. US
EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance
Reassessment Eligibility Decision (TRED) Document. EPA Docket
number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf
Definitions:
Acephaly:
literally means absence of the head. The acephalic fetus is
a parasitic twin attached to an otherwise intact fetus. The
acephalic fetus has a body but lacks a head and a heart; the
fetus’s neck is attached to the normal twin. The blood
circulation of the acephalic fetus is provided by the heart
of the twin. The acephalic fetus can not exist independently
of the fetus to which it is attached.
Ref:
http://www.icomm.ca/geneinfo/acep.htm
Cebocephaly:
A facial anomaly, characterized by a small, flattened nose with
a single nostril situated below incomplete
or underdeveloped closely set eyes.
Ref: http://www.icomm.ca/geneinfo/cephaly.htm
Gastroschisis: is an abdominal
wall defect located to the side of the umbilical cord (umbilicus).
The infant is born with intestines protruding through this defect
and no protective sac is present.
Ref: http://www.nlm.nih.gov/medlineplus/ency/article/002924.htm
Microphthalmia - small eye syndrome.
Microphthalmia is a disorder in which one or both eyes are abnormally
small.
Fluazinam
- Fungicide
- CAS
No. 79622-59-6
In subchronic and chronic
toxicity studies, fluazinam targeted the following organs: liver,
lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes
and brain...
Ref:
Canada: Regulatory
Note REG2003-12. Fluazinam. Pest
Management Regulatory Agency. Health Canada. Ottawa. October 27,
2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf
Acute
eye irritation
rabbits. Technical grade fluazinam. Extremely irritating. Corneal
opacity did NOT reverse in 21 days. Toxicity
Category I.
Ref: US EPA Pesticide Fact Sheet. Fluazinam.
August 10, 2001.
http://www.epa.gov/opprd001/factsheets/fluazinam.pdf
Flubendiamide
- Insecticide - CAS No. 272451-65-7
Results
of a reproductive toxicity study in rats (exposure route not stated):
Increased incidence of eyeball enlargement
and dark-colored liver in 2000 and 20000
ppm F1 and F2 pups.
Ref: TSCA Health & Safety
Study Cover Sheet "Public Display Copy"
http://www.epa.gov/opptintr/tsca8e/doc/8ehq/2004/november04/8ehq-1004-15768a.pdf
••
This
document was cited at EPA's
site: "TSCA 8(e) and FYI Submissions Received from 11-15-04-11-26-04".
It is important to note this as the document itself does not identify
flubendiamide or its CAS No.
•• This
study was conducted in the laboratory of The Institute of Environmental
Toxicology - Japan
•• Source of Data/Study
Sponsor: Bayer Material Science Corporation, 100 Bayer Road, Pittsburg
PA 15205
Flufenacet
- Herbicide - CAS No. 142459-58-3
A 1-year dog chronic
feeding study with a NOEL was 40 ppm (1.29 mg/kg/day in males
and 1.14 mg/kg/day in females) and a LOEL of 800 ppm (27.75 mg/kg/day
in males and 26.82 mg/kg/day in females) based on increased alkaline
phosphatase, kidney, and liver weight in both sexes, increased
cholesterol in males, decreased T2, T4 and ALT values in both
sexes, and increased incidences of microscopic lesions in the
brain, eye, kidney, spinal cord,
sciatic nerve and liver.
Ref: Federal Register: September 23, 1998.
Flufenacet; Time-Limited Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/flufenacet.fr.sept.23.1998.htm
In a mouse carcinogenicity
study the NOAEL was less than 50 ppm (7.4 mg/kg/day) for males
and the NOAEL was 50 ppm (9.4 mg/kg/day) for females. The LOAEL
was 50 ppm (7.4 mg/kg/day) for males and the LOAEL was 200 ppm
(38.4 mg/kg/day) for females based on cataract
incidence and severity. There was no evidence of carcinogenicity
for flufenacet in this study.
Ref:
Federal Register. March 29, 2000. Notice of Filing a Pesticide
Petition to Establish a Tolerance for Certain Pesticide Chemicals
in or on Food.
http://www.fluoridealert.org/pesticides/flufenacet.fr.mar.29.2000.htm
Flumequine
- Microbiocide - CAS No. 42835-25-6
--PubMed Abstract:
Flumequine (1 200 mg/day) was prescribed
as treatment for infection of the urinary tract to three patients
with chronic renal failure, who reported positive scotoma
three days later. Ophthalmologic examination
evinced bilateral symmetrical macular bullae. A characteristic
yellow papule was present at foveal level. In all three cases,
visual acuity was impaired (down to 4/10), without any angiographic
alteration. Foveolas showed a moderate persistent hyperfluorescence.
All patients recovered a normal visual acuity, within two days
after treatment cessation, and bullae disappeared without sequelae
within 5 days. The chronology and kinetics of clinical manifestations
were clearly and reproducibly correlated with flumequine therapy
in all patients, and suggest that this drug may be considered
responsible for the ocular symptom reported. Chronic renal
failure (creatinine clearance lower than 25 ml/mn) most certainly
favoured the appearance of visual troubles,
but other factors may possibly play a similar role: hepatic failure,
individual hypersensitivity... Quinolones used as urinary antiseptics
(nalidixic acid, oxolinic acid, pipemidic acid...), and other
flumequine analogues may possibly
be involved in such side-effects. This was reported by Bouissou
et al. in an experimental model with nalidixic acid, where transient
bullae appeared on young animals' articular cartilage. Such lesions
are related to focal alterations of the C2 intermediary layer
of cartilage, with marked edema of the interstitial material.
The volume of synovial fluid increases concomitantly. These
alterations suggest a direct cytotoxic effect at the intercellular
level of target organs, a mechanism possibly also occurring in
the retina.
• FAN Note: Scotoma definition: An
island-like blind gap in the visual field. Taber's Medical
Dictionary
Ref: J Fr Ophtalmol 1983;6(10):829-36. [Serous
macular detachment of the neuro-epithelium and flumequine]. [Article
in French]. Sirbat D et al.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6672059&dopt=Abstract
Fluometuron
- Herbicide - CAS No. 2164-17-2
Primary
eye irritation: Induces corneal opacity,
Toxicity Category I. Fluometuron
(Cotoran, Lanex) Herbicide Profile 12/85.
Ref: Chemical Fact Sheet for Fluometuron.
Fact Sheet Number 88. December 1985.
http://pmep.cce.cornell.edu/profiles/herb-growthreg/fatty-alcohol-monuron/fluometuron/herb-prof-fluometuron.html
• Fluometuron is of low to moderate toxicity with toxicity
categories of III and IV, except for dermal and eye
irritation (II). (page 2)
• Primary eye irritation studies indicate fluometuron produces
corneal opacity, iris irritation, redness,
chemosis, and discharge, all of which cleared from day
4 to day 10 (Tox Category II) (page
8)
Ref.
February 1, 2005. US EPA: Fluometuron: Revised HED Risk Assessment
for Phase III of the Reregistration Eligibility Decision. Docket
Identification Number: OPP-2004-0372-0008.
http://www.fluorideaction.org/pesticides/fluometuron.opp-2004-0372-0008.pdf
Fluometuron is a mild
skin and eye irritant. It has caused skin sensitization in guinea
pigs and in humans. It affects the cornea
of the eye in such a way that light cannot pass through
it. This condition is referred to as corneal opacity. Skin or
eye contact with it may cause burning... Prolonged or repeated
exposure to fluometuron may cause conjunctivitis.
Ref: Pesticide Informationnn Profile. Fluometuron.
March 1994. EXTOXNET.
http://www.fluoridealert.org/pesticides/fluometuron.extoxnet.1994.htm
Fluosilicic
acid -
Wood Preservative - CAS No. 16961-83-4
-- Rabbits, New Zealand,
fluorosilicic acid (~ 23%, neat), purity n. p. instillation; 0.1
mL (0.8 mol) into the left eye. Eyes were observed at 24, 48,
and 72 h following treatment. Severe and
permanent corneal opacity with scar tissue occurred. Rhone-
Poulenc Inc. (1971)
Ref: Review of Toxicological Literature.
October 2001. Sodium Hexafluorosilicate [CASRN 16893-85-9] and
Fluorosilicic Acid [CASRN 16961-83-4]. Prepared for Scott Masten,
Ph.D. National Institute of Environmental Health Sciences P.O.
Box 12233 Research Triangle Park, North Carolina 27709. Contract
No. N01-ES-65402. Submitted by Karen E. Haneke, M.S. (Principal
Investigator) Bonnie L. Carson, M.S. (Co-Principal Investigator)
Integrated Laboratory Systems P.O. Box 13501 Research Triangle
Park, North Carolina 27709.
http://www.fluoridealert.org/pesticides/fluorosilicates.nih.2001.pdf
Fluridone
- Aquatic Herbicide - CAS No. 59756-60-4
Fluridone
was shown to cause slight to moderate corneal dullness, iritis,
and conjunctivitis, and it was toxicity
category II for primary eye irritation.
Ref: US EPA. August
30, 2004.
FLURIDONE:
Toxicology Chapter for RED and Updating Executive Summaries for
11 Studies
-- Three studies were
conducted concurrently, using Fischer rats fed the same dietary
levels of Fluridone [0, 200, 650, 2000 ppm (0, 8, 25, 81 mg/kg/day)].
The first study was a 1-year feeding study (R-1126) in which 120
animals were divided into four groups of 15 animals/sex/dietary
level. The other two studies were reported to be replicate 2-year
oncogenic assays (Nos. R-1136 and R-1146), in which 240 animals
per assay were divided into four groups of 30 animals/sex/dietary
level. These three studies constitute a 2-year study with 75 animals/sex/dietary
level of which 15 animals/sex/dietary level were sacrificed at
12 months. Effects observed at 650 ppm included glomerulonephritis
[kidney], atrophic testes,
eye keratitis,
decreased body weight and organ weights. [Elanco Products Company,
Division of Eli Lilly and Company. 1980a. MRID No. 00103251, 00103305.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.]
Ref: US EPA IRIS for Fluridone. 1990.
http://www.fluoridealert.org/pesticides/fluridone.epa.iris.1990.htm
•
Note:
Eye keratitis = inflammation of the cornea.
Flusilazol
/ Flusilazole - Fungicide - CAS No. 85509-19-9
Parents
believe that exposure to Flusilazol during pregnacy resulted in
severe eye deformities such as microphthalmia
(small eyes) and coloboma,
a defect in the structure of the eyes.
Ref: Scottish Daily Record & Sunday
Mail Ltd. - Sunday Mail. October 15, 2000
http://www.fluoridealert.org/pesticides/flusilazole.scot.eye.2000.htm
• Definitions:
Coloboma - A defect of the iris
caused by a failure of the eyeball to fuse properly during fetal
development. These are developmental anomalies and do not worsen
as the child grows older.
Microphthalmia - An unnatural
smallness of the eyes, occurring as the result of disease or
of imperfect development.
Abstract: This report
describes the first part of a study which was undertaken to examine
the teratogenic potential of triazole compounds used as fungicides
in agriculture. Pregnant Wistar rats were given single oral dosages
of flusilazole or bitertanol on days 9, 10, 11 or 13th of gestation
(positive vaginal smear=day 1) at levels of 1/5, 1/10 and 1/50
LD50. The dosages were calculated from the reported LD50 values
of 1272 mg/kg for flusilazole and
5000 mg/kg for bitertanol. The results of the study demonstrated
that both compounds induce congenital anomalies
when given on days 9, 10 or 11th at levels corresponding to 1/5
and 1/10 LD50. The types of the registered
malformations after flusilazole treatment
were exophthalmus, hypognathia,
macroglossia and cleft
palate and after bitertanol treatment micro- and
acaudia and in rare cases exophthalmus, hypognathia and cleft
palate. A clear dose effect relationship was established for both
compounds.
Ref: Vergieva T (1990). Vergieva T. eratology
1990 Aug;42(2):27A-28A. Abstract from Toxnet.
•
Definitions:
Exophthalmia (n.) The protrusion
of the eyeball so that the eyelids will not cover it, in consequence
of disease.
Hypognathus - Unequal conjoined
twins in which the rudimentary parasite is attached to the mandible
of the autosite.
Macroglossia
-
Excessively large tongue.
Much of what is known
about the possible dangers of flusilazole
is considered a trade secret -- unavailable even to state
agents investigating health complaints. What is known about the
fungicide -- which is not approved for use in the United States
-- offers little comfort to those who applied it to Florida farmland
as an undisclosed ingredient in some lots of Benlate 50 DF. According
to a study conducted in Bulgaria, oral doses of flusilazole given
to pregnant rats produced congenital
defects such as protruding
eyes, twins of unequal size joined at the jaw and
grossly enlarged tongues...
Ref: Jan Hollingsworth. Fungicide studies
offer little comfort. Memo: BURIED SECRETS PURSUING A MEDICAL
MYSTERY. December 18, 1995. Tampa Tribune (Florida). page 4
Flutolanil
- Fungicide - CAS No.
66332-96-5
Chronic toxicity. A
1-year dog chronic feeding study with a NOEL was 40 ppm [1.29
mg/kg/day in males and 1.14 mg/kg/day in females] and a LOEL of
800 ppm [27.75 mg/kg/day in males and 26.82 mg/kg/day in females]
based on increased alkaline phosphatase, kidney, and liver weight
in both sexes, increased cholesterol in males, decreased T2, T4
and ALT values in both sexes, and increased incidences of microscopic
lesions in the brain, eye, kidney,
spinal cord, sciatic nerve and liver.
Federal Register: June 23, 1998 [Page 34176-34184].
Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/flutolanil.fr.june.23.1998.htm
Flutriafol
- Fungicide
-
CAS No. 76674-21-0
Ophthalmoscopic examinations,
performed on 20 males and 20 femals from the control and top dosage
groups after 52 and 104 weeks of the study, found a variety of
ocular changes. Apart from retinal
pallor, changes were regarded as age-related (or the incidence
of the changes was within the historical data). At 52 weeks, very
pale to pale retinal pallor was found in 3/20 male and
2/20 female animals in the hgh dosage group compared to nil in
the control animals. On termination, slightly
pale to pale retinal pallor was seen in 6/19 male and 5/18 female
rats from the high dosage group compared to 1/18 males
in the control group. No opthalmoscopic examinations were carried
out on the low and intermediate dosage groups. In the absence
of abnormalities in the retinal vessels and hyper-reflection of
the retina, the study authros concluded that the retinal pallor
was not toxicologically significant. No treatment-related histopathological
abnormalities were detected in eyes at termination in any dosage
group... Data requirements: To be submitted within 6 months of
the date of issue of approval: The applicant must address the
increased retinal pallor seen in
the two chronic two year feeding study in rats or provide a reasoned
argument as to why it is not of toxicological significance.
Evaluation
on: Flutriafol. October 1996. Issue No. 158, UK Department for
Environment, Food and Rural Affairs, Pesticides Safety Directorate,
Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX.
http://www.pesticides.gov.uk/citizen/evaluations/158_confirm-box.htm
Hexaflumuron
- Insecticide, Plant Growth Regulator - CAS No. 86479-06-3
Recruit (hexaflumuron)
Health Effects: eye irritant, liver
and kidney damage
Ref: Physical Properties And Health Effects
of Pesticides Used On National Park Service Collections. Conserve
O Gram. U.S. National Park Service. September 2001. Number
2/17.
http://www.fluoridealert.org/pesticides/Natl.Park.Serv.Pesticides01.pdf
Isoxaflutole
- Herbicide - CAS No. 141112-29-0
-- In a combined chronic
toxicity/carcinogenicity study in rats, evidence of systemic toxicity
was observed at 500 mg/kg/day and included: abnormal gait, limited
use of limbs, lower body weight gains and
food consumption, decreased food efficiency during the first 14
weeks of the study, elevated cholesterol levels throughout the
104-week study, increased absolute and relative liver weights,
and thyroid hyperplasia. Increased incidence of periacinar hepatocytic
hypertrophy, portal tract (senile) bile duct changes, focal cystic
degeneration of the liver was observed in males at 20 mg/kg/day
and greater, females at 500 mg/kg/day. Eye
opacity, gross necropsy changes in eyes, corneal lesions, degeneration
of sciatic nerve and thigh muscles was observed in males at 20
mg/kg/day and higher doses and in females at 500 mg/kg/day.
The chronic LOAEL is 20 mg/kg/day based on liver, thyroid,
ocular, and nervous system toxicity in males
and liver toxicity in females.
The chronic NOEL is 2.0 mg/kg/day.
-- Reproductive Toxicity. In a 2-generation reproduction study
in rats, evidence of toxicity was observed in the male and female
parental rats of both generations: at 20 and 500 mg/kg/day, increased
absolute and relative liver weights associated
with liver hypertrophy was observed; at 500 mg/kg/day (HDT), decreased
body weight, body weight gain and food consumption during
premating and gestation, and increased incidence of subacute inflammation
of the cornea of the eye in F0 adults
as well as keratitis in F1 adults
were reported. There were no other systemic effects that were
attributed to treatment, nor was there any indication, at any
treatment level, of an effect on reproductive performance of the
adults. Treatment-related effects were observed in F1 and F2 offspring:
at 20 and 500 mg/kg/day, reduction in pup survival was noted;
at 500 mg/kg/day, decrease in body weights
of F1 and F2 pups throughout lactation, increased incidence of
chronic keratitis, low incidence
of inflammation of the iris, as well
as retinal and vitreous bleeding
in F2 pups and weanlings were observed. Necropsy of F1 and F2
pups culled on Day 4 revealed an increased number of pups with
no milk in the stomach and underdeveloped
renal papillae. The Systemic LOAEL is 17.4 mg/kg/day for
males and females, based upon increased
liver weights and hypertrophy and the Systemic NOEL is 1.76 mg/kg/day
for males and females. The Reproductive LOAEL is greater than
437 mg/kg/day, based on lack of reproductive effects and
the Reproductive NOEL is greater than or equal to 437 mg/kg/day.
Ref: US EPA. Pesticide Fact Sheet. Isoxaflutole
Reason for Issuance: Conditional Registration Date Issued: September
15, 1998.
http://www.epa.gov/opprd001/factsheets/isoxaflutole.pdf
Lactofen
- Herbicide - CAS No. 77501-63-4
At 37.5 mg/kg/day,
there was also an increased incidence of cataracts
and renal pigmentation. Based on the LOEL, an oral RfD of 0.002
mg/kg/day was derived.
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.
Mefluidide,
diethanolamine salt - Herbicide - CAS
No. 53780-36-2
The studies reviewed
below were conducted with either the free acid or the diethanolamine
salt of mefluidide. The diethanolamine salt is the registered
active ingredient in California. Possible toxicological differences
between the free acid and diethanolamine salt were not considered
in the following reviews. The free acid and diethanolamine salt
have been grouped by the US EPA (Morris, 10/5/93)...
-- 386-004 987263, "Two Year Feeding study in Rats", (International
Research and Development Corporation, Mattawan, MI, study no.
102-208, report no. 225, 6/14/79). Mefluidide (MBR 12325) technical,
purity 93%, fed in the diet to 50/sex/group at 0, 600, 1800 or
6000 ppm over two (2) years starting at in utero from a reproductive
study. ADVERSE EFFECT: retinal degeneration.
Eye effect NOEL = 600 ppm.
Ref: Summary of Toxicology Data. 1986. California
EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/mefluidide.ca.epa.1986.pdf
Noviflumuron
- Insecticide - CAS No. 121451-02-3
-- “XDE-007: Two-year Dietary Chronic
Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer
344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.;
Toxicology & Environmental Research and Consulting, The Dow
Chemical Company, Midland, MI; Laboratory Project Study ID: 011168;
4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea;
XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose)
for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day.
Subchronic toxicity was assessed after 90 days of treatment on
10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose
(chronic toxicity group), and 5/sex/dose (chronic neurotoxicity
group) were necropsied. The remaining 50/sex/dose were necropsied
after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day
(At > 75 mg/kg/day there were decreased body weights and body
weight gains along with increases or decreases
in absolute and/or relative organ weights
(liver, kidney, brain, heart, adrenal, testes, spleen, epididymides
were affected) at 12 and/or 24 months. Skin/tail papules and pustules
were observed in males (300 mg/kg/day) and females (> 75 mg/kg/day)
in the second year. Females showed an increase
in phthisis bulbi*
at 300 mg/kg/day...
Ref:
August 2005 - Summary of toxicological data. California EPA, Department
of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/noviflumuron.ca.epa.2005.pdf
*
Definition: Phthisis
bulbi is an end-stage ocular response
to severe ocular disease, inflammation, or insult. Clinically,
the globe will be soft and hypotonus with minimal or no vision
and loss of much of the normal architecture of the eye.
Histopathologically, the globe is small and shrunken with marked
thickening of the sclera, as well as disorganization and atrophy
of much of the intraocular contents. The intraocular contents
are markedly dirupted and difficult to recognize. Commonly,
the retinal pigment epithelium may undergo a metaplasia leading
to intraocular ossification or bone formation in the end-stage
of phthisis bulbi.
Ref: University of Utah. John A. Moran
Eye Center.
http://insight.med.utah.edu/opatharch/uvea/phthisis_bubli.htm
PFOS
- PFOA - Insecticide, US EPA List 3 Inert
" DuPont tested
for and found PFOA in the blood of female plant workers in Parkersburg.
The company followed and documented pregnancy outcomes in exposed
workers. Two of seven children born to female plant workers between
1979 and 1981 had birth defects, one an
“unconfirmed” eye and tear duct defect, and one a
nostril and eye defect. [Dupont
Document] In 1981 fifty women were reassigned in the plant."
Ref: Environmental Working Group.
2003
report: PFCs:
a family of chemicals that contaminate the planet. Part 4: PFC
Health Concerns
3.6 Developmental Toxicity.
Three prenatal developmental toxicity studies of PFOS have been
conducted, two studies in rats and one study in rabbits. In addition,
preliminary results are available for developmental toxicity studies
in rats and mice. The first study administered four groups of
22 time-mated Sprague-Dawley rats 0, 1, 5, and 10 mg/kg/day PFOS
in corn oil by gavage on gestation days (GD) 6-15 (Gortner, 1980).
Doses were adjusted according to body weight. Dams were monitored
on GD 3-20 for clinical signs of toxicity. Individual body weights
were recorded on GD 3, 6, 9, 12, 15, and 20. Animals were sacrificed
on GD 20 by cervical dislocation and the ovaries, uteri and contents
were examined for the number of corpora lutea, number of viable
and non-viable fetuses, number of resorption sites, and number
of implantation sites... The most notable sign of developmental
toxicity observed in all dose groups consisted of abnormalities
of the lens of the eye, which was not seen in controls.
The proportion of fetuses with the lens abnormality in one or
both lenses was significantly higher in the high dose group. All
eye abnormalities appeared to be localized to the area of the
embryonal lens nucleus, although
a variety of morphological appearances were present within that
location. According to the authors, this
abnormality appeared to be an arrest in development of the primary
lens fibers forming the embryonal lens nucleus. Secondary lens
fiber development progressed normally except immediately surrounding
the abnormal embryonal nucleus. Under the conditions of
the study, a LOAEL for developmental toxicity of 1 mg/kg/day was
indicated; a developmental NOAEL could not be established.
Ref: November 21, 2002 report:
Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its
salts. Organisation for Economic Co-operation and Development.
ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf
Pyraflufen-ethyl
- Herbicide - CAS No. 129630-19-9
Human Health Effects. The U.S. Environmental Protection Agency
(EPA) classifies Edict [which contains pyraflufe-ethyl] as category
I (High Toxicity) with a signal word of DANGER
because of irreversible damage to the eyes and harm if
swallowed or absorbed through the skin.
Ref: Pyraflufen. Roadside Vegetation Management
Herbicide Fact Sheet. Washington State Department of Transportation.
http://www.fluorideaction.org/pesticides/pyraflufen.fact.sheet.washington.pdf
Sulfuryl
fluoride -
Fumigant insecticide - CAS No. 2699-79-8
- (870.4100) Chronic
toxicity--rodents. NOAEL = 3.5 for M and 16 for F mg/kg/
day
LOAEL = 20 ppm or 14 for M and 80 ppm or 62 for F mg/kg/day based
on dental fluorosis* in males and for females greatly increased
mortality (due mostly to severe kidney toxicity which led to kidney
failure); and histopathology in brain (vacuolation in cerebrum
and thalmus/hypothalmus), adrenal cortex, eyes,
liver, nasal tissue and respiratory tract; and, dental fluorosis*.
- (870.4300) 2-Year
combined chronic/carcinogenicity--rat. NOAEL = 3.5 for
M and 16 for F mg/kg/day. LOAEL = 20 ppm or 14 for M and 80 ppm
or 62 for F mg/kg/day based on dental fluorosis* in males and
for females greatly increased mortality (due mostly to severe
kidney toxicity which led to kidney failure); and histopathology
in brain (vacuolation in cerebrum and thalmus/hypothalmus), adrenal
cortex, eyes, liver, nasal tissue
and respiratory tract; and, dental fluorosis*.
Ref: January
23, 2004. Sulfuryl Fluoride; Pesticide Tolerance.
40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal
Register
tau-Fluvalinate - Acaricide, Insecticide - CAS No. 102851-06-9
Acute & Chronic Dietary (general population). LOAEL = 1 mg/kg/day.
Clinical signs in the rat chronic feeding study coupled with a
LOAEL of 2 mg/kg/day based on excessive grooming and bulging
eyes in the subchronic neurotoxicity study.
Ref:
October 28, 2005. Reregistration Eligibility Decision (RED) for
Tau-fluvalinate. List A. Case No. 2295. US EPA. Federal Register
Docket No. OPP-2005-0230-0002. (Page
1).
http://www.fluorideaction.org/pesticides/tau-fluvalinate.red.2005.pdf
Tembotrione - Herbicide - CAS No. 335104-84-2
• Long-term dietary administration of tembotrione resulted in an increased incidence of thyroid adenomas and squamous cell carcinomas of the cornea in male rats. Since the incidence of thyroid adenomas was not statistically significant, they were considered unrelated to treatment. The levels of the doses tested were adequate. No tumors were noted in female rats or in male and female mice after long-term dietary administration of tembotrione. The HED CARC (April 11, 2007) classified tembotrione as "Suggestive Evidence of Carcinogenic Potential" by the oral route based on the occurrence of eye tumors in male rats; therefore, the quantification of cancer risk is not required.
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.
• The eye, liver and kidney are the primary target organs of tembotrione. In the subchronic, chronic and reproduction rat studies, and the subchronic dog study, corneal opacity, edema of the cornea, neovascularization, and keratitis were seen at various doses indicating ocular toxicity. Males appear to be more susceptible to ocular toxicity than females. Also, corneal opacity was completely reversible following subchronic and chronic exposures in rats and some neovascularizations were reversible following subchronic exposure in rats; but these effects were not reversible following chronic exposure (page 15).
• In a combined chronic/carcinogenicity study (MRID 46695708)
AE 0172747 was administered to 60 Rj: WI (IOPS HAN) Wistar male rats/dose in the diet at dose levels of 0, 1, 20, 200 or 800 ppm (equivalent to 0, 0.04, 0.79, 8.3 or 31.7 mg/kg bw/day) in the diet for 104 weeks. Gross necropsy revealed a higher incidence of ocular opacity at 20, 200, and 800 ppm. The incidence of minimal to marked keratitis of the eye(s) was significantly increased (p≤0.01) in males in the 20, 200, and 800 ppm groups (97-98%) when compared to controls (3%). Keratitis included one or more of the following changes in the cornea: acute inflammation, epithelial hyperplasia, keratinization, epithelial vacuolization, erosion and/or ulceration. Generally, the keratitis observed in this study was a multifocal to diffuse chronic active superficial keratitis, involving the corneal epithelium and superficial aspects of the corneal stroma, which did not penetrate the cornea. A slight non-statistically significant elevation (3-5%) of hyperplastic lesions was noted on the cornea of the eye at 200 and 800 ppm, when compared to controls (0 %). In addition, a minimal to moderate retinal degeneration, mostly located in the ora serrata area of the retina, was significantly increased (p≤0.05) in the 800 ppm group (15%) when compared to controls (3%) (page 79-80).
• Dose and Endpoint for Establishing RfD: (page 22)
-- Study Selected: Chronic Toxicity/Carcinogenicity (Feeding)/Rat MRID No.: 46695708
-- The NOAEL of 0.04 mg/kg/day was based on neovascularization and edema of the cornea and snow flake-like corneal opacity, unilateral or bilateral keratitis of the eye, decreased mean body weight and mean body-weight gain, increased total cholesterol, higher ketone levels and lower pH values, higher protein levels, increased kidney weight, kidney to body weight and kidney to brain weight ratios, chronic nephropathy and atrophy of the sciatic nerve observed in the male at 0.79 mg/kg/day (LOAEL).
-- UF(s): An UF of 100 was applied to account for interspecies extrapolation (10
-- Comments about Study/Endpoint/UF: This study provided the lowest NOAEL in the database (most sensitive endpoint) and will also provide the most protective limits for human effects.
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.
1,1,1,2-Tetrafluoroethane
(HFC-134a) - Propellant, US
EPA List 4B Inert - CAS No. 811-97-2
-- In the perinatal
and postnatal part of the study, groups of 41 female rats were
administered concentrations of 1,800, 9,900, or 64,400 ppm of
HFC-134a (99.3% pure) for 1 h daily during days 17 to 20 of pregnancy
and days 1 to 21 postpartum (Alexander et
al. 1996). Females were allowed to deliver and rear their
young. Selected F1 animals were mated; these animals were sacrified
on day 20 of pregnancy, and the uterine contents were examed...
There was a statistically significant delay
in the occurrence of pinnae detatchment,
eye-opening, and startle response
in the F1 generation, whose dams inhaled 64,400 ppm....
-- Alexander
DJ, Libretto SE, Adams MJ, Hughes EW, Bannerman M. 1996. HFA-134a
(1,1,1,2-tetrafluoroethane): effects of inhalation exposure upon
reproductive performance, development and maturation of rats.
Human Exp Toxicol 15:508-517.
Ref:
National Research Council. 2002. Acute Exposure Guideline Levels
for Selected Airborne Chemicals. Volume 2. Subcommittee on Acute
Exposure Guideline Levels, Committee on Toxicology, Board of Environmental
Studies and Toxicology, Division of Earth and Life Studies. Available
from: National Academy Press, 2101 Constitution Ave, NW, Box 285,
Washington DC 20055. ISBN 0-309-08511-X. Online at:
http://books.nap.edu/books/030908511X/html/index.html
Thiazopyr
- Herbicide - CAS No. 117718-60-2
-- It is considered
to be moderately irritating to the skin and substantially
irritating to the eye.
-- A two year rat carcinogenicity study at doses of 0, 0.04, 4.4,
44.2 or 136.4 mg/kg/day (Males) 0, 0.06, 0.6, 5.6, 56.3 or 177.1
mg/kg/day (female) with a NOEL of 4.4 mg/kg/day.
The effects were protruding eyes,
evidence of mild anemia, increased GGT and cholesterol, increased
absolute and relative liver, kidney and thyroid weights and significant
increase in microscopic lesions in the liver (hypertrophy and
vacuolar changes), kidney (nephropathy) and thyroid (hypertrophy
and hyperplasia); decreased mean body weight and body weight gain
and food consumption. A statistically significant increase in
thyroid follicular cell adenomas/cystadenomas were observed in
males at 44.2 and 136.4 mg/kg/day. A nonsignificant increase in
renal tubular adenomas in high-dose females was considered to
be equivocal.
Ref: US EPA Pesticide Fact Sheet.
February 20, 1997.
http://www.epa.gov/opprd001/factsheets/thiazopyr.pdf
Tolylfluanid
- Fungicide - CAS No. 731-27-1
-- Prenatal developmental
toxicity/rabbit LOAEL = 70 mg/kg/day based
on increased
malformations (arthrogryposis of front extremities and small
orbital cavity/folded retina) and variations
(floating ribs and accelerated ossification).
Ref: Federal Register: September 25, 2002.
Tolylfluanid; Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/tolylfluanid.fr.sept25.2002.htm
Tributyltin
fluoride - Antifoulant, Fungicide,
Microbiocide - CAS No. 1983-10-4
Abstract: The acute
and chronic toxicities of anti fouling coatings were studied in
animals. The acute oral median lethal dose (LD50) was determined
for bis(tri-n-butyltin)oxide (56-35-9), tributyltin-fluoride
(1983-10-4) and triphenyltin-fluoride
(379-52-2) for rats and rabbits...
All were severe or extreme eye irritants
and most were moderate to severe skin irritants.
Ref: 1975
Journal of Paint Technology, Vol. 47, No. 600, pages 54-58. Effects
Of Organotin Anti-Fouling Coatings On Man And His Environment
by Sheldon AW.
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AAAjCaaO4:1
Trifloxystrobin
- Fungicide - CAS No. 141517-21-7
--
Reproductive toxicity. Target
/ critical effect - Reproduction: Decreased bodyweight
gain of pups and delayed eye opening at
parental toxic doses. Lowest relevant reproductive NOAEL
/ NOEL: 50 ppm(2.3 mg/kg bw/day)...
-- Medical data New active substance.
Limited data. Some evidence of skin and
eye irritation in 3 people during field trials (but 120
people without effects).
Ref:
Review report for the active substance trifloxystrobin. Trifloxystrobin.
SANCO/4339/2000-Final. 7 April 2003. Finalised in the [European
Commission] Standing Committee on the Food Chain and Animal Health
at its meeting on 15 April 2003 in view of the inclusion of trifloxystrobin
in Annex I of Directive 91/414/EEC.
http://www.fluorideaction.org/pesticides/trifloxystrobin.eu.april.03.pdf
Triphenyltin
fluoride - Antifoulant,
Algaecide, Herbicide - CAS No. 379-52-2
Abstract: The acute
and chronic toxicities of anti fouling coatings were studied in
animals. The acute oral median lethal dose (LD50) was determined
for bis(tri-n-butyltin)oxide (56-35-9),
tributyltin-fluoride (1983-10-4) and triphenyltin-fluoride
(379-52-2) for rats and rabbits...
All were severe or extreme eye irritants
and most were moderate to severe skin irritants.
Ref: 1975
Journal of Paint Technology, Vol. 47, No. 600, pages
54-58. Effects Of Organotin Anti-Fouling Coatings On Man And His
Environment by Sheldon AW.
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AAAjCaaO4:1
Abstract.
An
acute dust inhalation toxicity study using albino rats as experimental
animals was performed for the compound triphenyltin-fluoride.
The acute dust inhalation median lethal concentration of the test
compound is 0.29 milligrams per liter of air based on a four hour
exposure period. Untoward behavioral reactions
exhibited by the animals included gasping, bloody nasal discharge,
bloody ocular discharge, and weakness. Body
weight gains of the survivors of the 14 day observation period
were less than normal. Gross pathologic
observation revealed mild to severe focal discoloration of the
lungs in all test animals.
Ref: Acute Dust Inhalation
Toxicity Study with Triphenyltin Fluoride in Albino Rats; by Elliott
CB. Source: M and T Chemicals, Inc. (Unpublished report submitted
to NIOSH), Rahway, N. J., IBT No. N1632, 14 pages, 1 reference,
1972. [Toxline abstract at Toxnet]
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