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
Food and Agricultural Organization of the United Nations
This is not an exhaustive list.
When time allows more information will be added.
fluoride - Insecticide, Wood preservative, US EPA List 4B
Inert - CAS No. 7681-49-4
Summary: Wistar rats
were given 20 ppm fluroide in drinking water, or single administration
of 115 mg/kg alloxan i.m. to induce diabetes, or single administraiton
of 115 mg/kg alloxan i.m. followed by 20 ppm fluoride for 31 days.
Blood sugar level increased in rats given alloxan and alloxan
+ fluoride. Body weight gain in rats given alloxan + fluoride
decreased significantly compared to other groups. Decrease in
haemoglobin and glutamic oxaloacetate transaminase (GOT) was seen
only in rats given alloxan + fluoride. In
this group alkaline phosphatase, the target enzyme in fluoride
toxicosis, increased considerably. The toxicity of fluoride
in diabetic rats was further reflected in organ weight data. This
investigation shows that fluoride toxicity is greater in diabetic
Fluoride 1997; 30(1):43-50. Toxicity of fluoride to diabetic rats;
by Priya CATB, Anitha K, Mohan EM, Pillai KS, Murthy PB
fluoride - Antifoulant,
Algaecide, Herbicide - CAS No. 379-52-2
...Recently we found that a single oral administration
of triphenyltin fluoride to rabbits induces transient diabetes
and diabetic lipemia by inhibiting insulin secretion from morphologically
normal pancreatic B-cells...
progress in the study of analytical methods, toxicity, metabolism
and health effects of organotin compounds
by Wada O, Manabe S, Iwai H, Arakawa Y. Sangyo Igaku 1982 Jan;24(1):24-54.
... These findings suggest that TPTF inhibits
insulin release from rabbit islets, subsequently inducing diabetic
lipemia due to the insulin deficiency. Furthermore, it
is possible to provide a new animal model for diabetes and diabetic
lipemia by administration of TPTF to rabbits.
fluoride (TPTF) as a diabetogenic agent. TPTF induces diabetic
lipemia by inhibiting insulin secretion from morphologically intact
rabbit B-cell by Manabe S, Wada O. Diabetes 1981 Dec;30(12):1013-21.
Abstract: . Phenyltin
compounds have been used as agricultural chemicals and marine
antifoulants and studied from the stand-point of toxicity. The
in vivo mechanisms of toxicity and metabolism are not understood.
Oral administration of 100 mg/kg body wt
of tripheyltin fluoride (TPTF) to rabbits evoked hypertriglyceridemia.
The mechanism of TPTF-induced hypertriglyceridemia was
studied by following the time course of fasting blood glucose
(FBS), glucose tolerance tests, serum IRI (immunoreactive insulin),
serum lipids and lipoprotein lipase (LPL) activity and by determining
the influence of insulin on TPTF-induced hypertriglyceridemia.
The pancreatic islets, liver and kidney of the rabbits were also
examined histologically. After TPTF administration, FBS
and plasma triglyceride concentration were elevated significantly
(P < 0.02) forma postheparin lipolytic activity) and LPL in adipose
tissue decreased (P < 0.02), while chyromicron and VLDL (very
low density lipoproteins) increased. Insulin treatment
for 1 or 2 days increased LPL activity to the normal level but
withdrawal of insulin from the insulin-treated rabbits again resulted
in a decrease in LPL activity. A single
oral dose of TPTF evoked diabetic lipemia and glucose intolerance
due to insulin deficiency. The IRI level decreased before
and even after glucose infusion during these periods. Microscopic
examinations revealed no remarkable changes in the pancreas islets,
liver and kidney. Pancreatic B-cells contained normal amounts
of granules at the maximal hyperlipemic stage.
TPTF interfered with insulin release from rabbit beta-cells and/or
TPTF decreased the sensitivity of islets to release insulin in
response to increasing levels of blood glucose.
Ref: MANABE S and WADA O (1981). Transient
diabetic lipemia and reversible glucose intolerance in rabbits
after a single dose of triphenyltin fluoride. J JPN DIABETIC SOC;
24 (6). 669-677.
fluoride - Antifoulant,
Fungicide, Microbiocide - CAS No. 1983-10-4
Med abstract: ...
results suggest that hyperlipidemia induced in rabbits by tributyltin
fluoride is due to decreased LPL [Lipoprotein
lipase] activity. The decrease in
LPL activity seems to be related to the inhibition of insulin
release from islets by TBTF.
and mechanism of hyperlipidemia induced in rabbits by tributyltin
fluoride] by Matsui H, Wada O, Manabe S, Ono T, Iwai H, Fujikura
T. Sangyo Igaku 1982 Mar;24(2):163-71.
= High Cholesterol
- Herbicide - CAS No. 69806-50-4
(delayed ossification and eye opacities) was also demonstrated
in New Zealand White rabbits (the LOEL was 30 mg/kg/day; the NOEL
was 10 mg/kg/day). EPA believes that there is sufficient evidence
for listing fluazifop butyl on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available hepatic and developmental toxicity data for this chemical.
-- In a teratogenicity study in Sprague-Dawley rats exposed via
oral gavage, delayed ossification and an increased incidence of
were observed in fetuses (the fetotoxic
LOEL was 5 mg/kg/day; the NOEL 1 mg/kg/day) and a teratogenic
LOEL of 200 mg/kg/day (the NOEL was 10 mg/kg/day) was determined
based on the incidence of diaphragmatic hernia.
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
In a teratogenicity
study in Sprague-Dawley rats exposed via oral gavage, delayed
ossification and an increased incidence of hydroureter
were observed in fetuses (the fetotoxic LOEL was 5 mg/kg/day;
the NOEL 1 mg/kg/day) and a teratogenic
LOEL of 200 mg/kg/day (the NOEL was 10 mg/kg/day) was determined
based on the incidence of diaphragmatic
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.
fluoride - Antifoulant, Algaecide, Herbicide - CAS
2. Comment. American Hoechst Corporation disagrees with the
Agency's [US EPA] position that TPTH produces teratogenic effects
and that a NOAEL has not been determined in the two previously
reviewed rat teratogenicity studies [Refs. 5 and 46]. American
Hoechst and M&T Chemicals had the rat teratology study by
Battelle Columbus Laboratories [Ref. 3] peer reviewed by two independent
sources and submitted the results of those reviews. One
reviewer found that 2.8 mg/ kg/day was clearly a NOAEL for teratogenicity
while the second reviewer was unable to identify a no effect
level from the data available. In addition, American Hoechst submitted
the results of a teratology study of triphenyltin
fluoride (TPTF) that had been previously submitted to EPA.
The NOAEL for this study was 3.0 mg/kg/day.
Response. The submissions from American Hoechst Corporation do
not satisfactorily eliminate concerns regarding the teratogenicity
of TPTH because no new information was presented to the Agency.
Although these studies provided sufficient data to assure that
TPTH is not teratogenic in rats at dose levels up to and including
8.0 mg/kg/day, these studies did result in developmental and maternal
toxicity. Second, the registrant did not provide new information
indicating that a NOAEL exists in the two rat studies. Third,
the teratology study with TPTF also indicated hydroureter
as a fetal lesion. The initial reviewer of this study classified
this compound as a teratogen.
Ref: Federal Register: October 20, 2000.
Triphenyltin Hydroxide; Proposed Determination To Terminate
Special Review. Proposed Determination to Terminate Special Review.
- CAS No. 181274-17-9
-- Study # 870.3100. 28-Day oral toxicity in rodents (rats) NOAEL
= 27 mg/kg/day in males and 25 mg/kg/day in females. LOAEL = 266
mg/kg/day in males and 251 mg/kg/day in females based on
immunological changes in both sexes.
-- Study # 870.3100. 90-Day oral toxicity in rodents (rats) NOAEL
= 73.5 mg/kg/day in males and 102 mg/kg/day in females LOAEL =
287 mg/kg/day in males and 358 mg/kg/day in females based on immunological
findings in both sexes
-- Study # 870.4300. 2-Year Chronic toxicity/carcinogenicity in
rats NOAEL = 125 mg/kg/day in males and females LOAEL = 1,000
mg/kg/day in males and females based on
decreased body weight and increased food consumption in females,
thickened mucosa of the glandular stomach in both sexes, inflammatory
infiltrates (males), vacuolation of the squamous epithelium in
the fore-stomach (females) and immunological
effects in males. no evidence of carcinogenicity
Ref: US EPA Pesticide Fact Sheet for Flucarbazone-sodium.
September 29, 2000.
(HFC-134a) - Propellant; Inert - CAS No. 811-97-2
-- The adverse events observed during the exposures to HFC-134a
and HFC-227ea were unexpected and inconsistent with the published
data. Based on the published data on HFC-134a and HFC-227ea, no
adverse effects should have been observed at the 0.4% v/v and
0.6% levels, respectively, used in this study.
-- Subject #3 reported problems with dizziness and balance following
the exposure. At the time of this report (6 weeks post exposure),
both the dizziness and balance problems still persisted. Subject
#5 reported chest tightness and a headache with associated dizziness
immediately following the exposure. The headache subsided by the
time the subject woke up the day following the exposure. The day
following the exposure, subject #5 reported unusual feelings in
the chest resembling "flutters". The chest tightness was reported
to subside within 3 days of the exposure and the "flutters" within
2 weeks of the exposure. As with subject #3, subject #5 was still
experiencing dizziness and balance problems at the time of this
report (6 weeks post exposure). Subject #5 also reported persistent
ringing in the ears which was still
present at the time of this report.
-- The presence of HFC-134a in the blood 1 hour after exposure
-- In summary, all 7 human volunteers completed the Halon 1301
exposures without incident while both the HFC-134a and HFC-227ea
exposures were terminated due to the adverse effects described
in this report.
Ref: 1997. Human Inhalation of Halon 1301,
HFC-134a and HFC-227ea for Collection of Pharmacokinetic Data.
19 Aug 97.