| See short description and definitions on kidney
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.
- CAS No. 1341-49-7
cause salivation, nausea, vomiting, diarrhea, and abdominal pain,
followed by symptoms of weakness, tremors,
shallow respiration, carpopedal spasm, convulsions, and coma.
May cause brain and kidney damage.
Affects heart and circulatory system. Death
may be caused by respiratory paralysis. Lethal dose estimated
at between 1 teaspoonful and 1 oz.
-- Aggravation of Pre-existing Conditions: Populations that appear to be at
increased risk from the effects of fluoride are individuals that
suffer from diabetes insipidus or some forms of
Ref: Analytyka. Material Safety Data Sheet.
Online as of September 15, 2003.
Herbicide - CAS No. 62476-59-9
A 2-generation reproduction
study in rats fed diets containing 0, 25, 500 or 2,500 ppm with
no adverse effect on adult reproductive performance observed under
the conditions of the study. The NOEL was established at 25 ppm
(equivalent to 1.25 mg/kg of body weight/day) based on decreased
viability and increased incidence of kidney
lesions in high dose offspring.
Ref: Federal Register. April 17, 1996. Sodium
Salt of Acifluorfen; Pesticide Tolerance. Proposed Rule.
The chronic feeding toxicity study in rats, mice, and dogs
demonstrated that acifluorfen induced liver toxicity (acidophilic
cells in the liver and increased liver weight) and
kidney toxicity (nephritis/pyelonephritis and increased kidney
weight). An increase in the incidence of stomach ulcer
was also seen in chronic feeding study in rats.
Ref: US EPA Toxicology Chapter for RED.
November 10, 1999
- Wood Preservative - CAS No. 12125-01-8
Ingestion: May cause
salivation, nausea, vomiting, diarrhea, and abdominal pain, followed
by weakness, tremors, shallow respiration, cardopedal spasm, convulsions,
and coma. May cause brain and kidney
damage. Death may be caused by respiratory paralysis. Affects
heart and circulatory system.
Aggravation of Pre-existing Conditions: Populations that appear
to be at increased risk from the effects of fluoride are individuals
that suffer from diabetes insipidus or some forms of
Ref: 1999 Material Safety Data Sheet prepared
by Mallinckrodt Baker, Inc.
(Benefin) - Herbicide - CAS
COMBINED, RAT **208-079
167288, "Benefin: Two-Year Dietary Chronic Toxicity/Oncogenicity
Study in Fischer 344 Rats", (Michael R. Moore, Corning Hazleton
Inc, Vienna, VA., Laboratory ID # CHV 174-133, Sponsor Report
# DR-0097-3397-005, 1 July 1996). Fifty CDF ® (F-344)CrlBR rats
per sex per group received benefin in the diet at 0, 10, 100,
2500, and 5000 ppm for 2 yr. An additional 10 per sex per group
at the same dose levels were designated for 1-yr interim sacrifice.
Estimated achieved dosages were 0, 0.5, 5.4, 136, and 275 mg/kg/day
in males, and 0, 0.7, 6.8, 168, and 331 mg/kg/day in females,
respectively over weeks 1-104. Chronic NOEL = 10 ppm (0.5 and
0.7 mg/kg/day in M and F), based on increased
hyaline droplets in kidneys of both sexes at 100 ppm and above,
increased and tubular cell karyomegaly and transitional cell hyperplasia
in kidneys of males, hepatocellular hypertrophy and increased
hepatocellular pigmentation in females, and calculus of renal
pelvis in females. Substantial toxicity prompted investigators
to determine that the two highest dose levels “exceeded the maximum
tolerated dose and therefore should not be used for risk assessment”.
The study design, with no dose levels between 100 and 2500 ppm,
gave no opportunity to characterize dose-response in this range
of primary interest. These were major changes at the highest two
dose levels (in both sexes, unless indicated), in addition to
the findings for the NOEL (above) applying to both sexes. Body
weights were reduced over time (in males, primarily in last few
weeks of the study), so that at termination the deficits of 2500
and 5000 ppm groups compared to controls were 8 and 17% in males,
and 18 and 28% in females, respectively. In females only, this
was accompanied by approximately 10% food consumption reductions
at each of the higher dose levels. There were reductions in the
main hematology parameters (RBC counts, HCT, and Hb levels). Incidence
and/or degree of chronic progressive nephropathy
was increased. The majority of these rats had “slight” to “minimal”
degeneration of sciatic nerve and skeletal muscle (thigh). Males
had elevated incidence of single cell necrosis in liver.
Chronic inflammation of the lungs was seen in the majority of
these rats, whereas low incidences of congestion of the
abdominal cavity, and urinary bladder hyperplasia were limited
to these dose levels. Numerous clinical chemistry changes mirrored
the above pathology in kidneys, liver,
and perhaps other tissues at the higher two dose levels. Tumor
incidence: thyroid follicular tumors (adenomas and carcinomas)
increased in males (incidences of 1, 1, 1, 7, and 8 in controls
through high dose, respectively) and females (incidences of 0,
0, 1, 5, and 4). Hepatocellular tumors (primarily adenomas) were
increased in males (incidences of 2, 2, 1, 5, and 11 in controls
through high dose, respectively). There were no statistically
significant increases in epithelial cell tumors in kidneys nor
urinary bladder, however the low incidences of transitional cell
papilloma and tubule cell adenoma or carcinoma
were predominantly found in 2500 and 5000 ppm groups (compare
to the congener, trifluralin). Study is acceptable. Tumors are
possible adverse effects, which should be evaluated in perspective
of the many indications of excessive exposures at effective dose
levels. Green and Aldous, 4/11/00.
Summary of Toxicological Data: Benefin. California EPA, Department
of Pesticide Regulation, Medical Toxicology Branch. Revised April
- Fungicide -
In a chronic/oncogenicity study Fisher rats
received 0, 50, 200, 5,000,
or 10,000 ppm of benthiavalicarb- isopropyl for up to 104 weeks.
The NOAEL was 200 ppm (9.9 mg/kg/day and 12.5 mg/kg/day in males
and females respectively), based on a
of toxic effects, primarily in the liver and kidney,
and adenocarcinomas of the uterus at
• In an oncogenicity
study in mice, the dietary
doses were 0, 20, 100, 2,500 or 5,000 ppm. The NOAEL was 100 ppm
(13.7 mg/kg/day and 18.6 mg/kg/day in males and females, respectively)
based on a variety of toxic effects, primarily
in the liver and kidney, and hepatocellular
blastoma and carcinoma at 2,500 ppm.
Ref: March 9, 2005. Petition
for the establishment of Tolerances on Imported Grapes and Tomatoes.
Federal Register: March 9, 2005.
- (also known as Trifluoromethylbenzene)
- Insecticide - CAS No. 98-08-8
was studied for oral toxicity in Crj:CD (SD) rats in an OECD combined
repeat dose and reproductive/developmental toxicity screening
test at doses of 0, 20, 100 and 500 mg/kg/day. With regard to
repeated dose toxicity, effects on liver and kidney
were observed in both sexes given more than 100 mg/kg, indicating
a NOEL is of 20 mg/kg/day for both sexes. In the reproductive/developmental
toxicity study, there were no effects of
the test article on the reproductive performance of the parents.
Depression of body weight gain in offspring of all treatment groups
was observed without any necropsy findings. The NOELs are
considered to be 500 mg/kg/day for reproductive performance of
the parents and less than 20 mg/kg/day for offspring development.
-- Test Results: ... As necropsy findings,
renal hypertrophy and discoloration were observed in males of
the 500 mg/kg group. Increase kidney weights
in males given more than 100 mg/kg and in females of the
500 mg/kg group, and increased liver weights in males given more
than 100 mg/kg were observed. On histopathological examination,
centrilobular hepatocyte hypertrophy in both sexes, and hyaline
droplets, necrosis, basophilic change and dilatation of renal
proximal tubules in males were noted in the 100 and 500
mg/kg groups. Therefore, the NOEL is considered to be 20 mg/kg/day
for both sexes.
1988. GINC: Global Information Network on Chemicals. The Databases
- Fumigant - CAS No. 7637-07-2
-- Exposure of 6 animal
species to 100 ppm, 4-7 hr/day, 5 days/wk in a 30 day experiment
killed all animals, most within the test period. Guinea pigs were
most susceptible ... dogs least ... The primary site of damage
was the lung ... Kidney damage ...
also occurs. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge,
Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical
Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington,
DC: U.S. Government Printing Office, Jan. 1981.
-- An acute study of boron trifluoride (BF3) in rats indicated
the 4 hr LC50 to be 1.21 mg/l. In a 2 week study, all animals
exposed to 180 mg/cu m died prior to the sixth exposure, rats
exposed at concn of 66 and 24 mg/cu m showed clinical signs of
respiratory irritation, body weight gain depressions, increased
lung weights, and depressed liver weights. Histopathology showed
necrosis and pyknosis of the proximal tubular
epithelium of the kidneys. This effect was limited to the
high-concn exposure group. Based on the results of these studies,
Fischer 344 rats were exposed 6 hr/day, 5 days/week for 13 weeks
to a respirable, liquid aerosol of BF3 at concn of 0, 2.0, 6.0,
and 17 mg/cu m. One rat in the high exposure group died. The
most significant finding in this group was necrosis of the proximal
tubular epithelium of the kidneys....
-- Boron trifluoride is primarily a respiratory irritant which
predisposed the exposed /guinea pigs/ to respiratory infection.
Exposure at 100 ppm (277 mg/cu m) was fatal to all animals. Physiological
responses prior to death included respiratory irritation and infection,
kidney damage, retarded growth, and
severe progressive fluorosis in rat teeth...
Ref: TOXNET profile from Hazardous Substances
Data Bank for Boron Trifluoride.
-- 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.
The kidneys are most severely affected because
boric acid concentrates in this organ.
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.
- Herbicide - CAS No. 128639-02-1
-- Repeat-dose studies
indicate that the primary targets for carfentrazone-ethyl toxicity
are the liver, kidney,
and the red blood cell
forming system... Increased kidney weight and the presence of
pigment in kidney cells typified
kidney toxicity in rats and dogs...
April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL
in the product AFFINITY 400 DF HERBICIDE. National Registration
Authority for Agricultural and Veterinary Chemicals. NRA Ref.
available at http://www.apvma.gov.au/publications/prscar.pdf
Insecticide, Fungicide, Propellant - CAS No. 75-45-6
kidney, adrenal and pituitary weights...
The female rats in the 50,000-ppm group exhibited a statistically
significant increase in liver (absolute and relative), kidney
(absolute), adrenal (absolute), and pituitary (absolute, at interim
sacrifice--pituitaries were not weighed at terminal sacrifice)
weights. No nonneoplastic histopathological changes attributable
to exposure to HCFC-22 were observed. The liver weight effect
was not considered adverse because it did not exceed a 10% weight
change and there was no histopathology observed. Based on effects
on kidney, adrenal, and pituitary
weight, a NOAEL
of 10,000 ppm [NOAEL(HEC) = 5260 mg/cu.m] and a LOAEL of 50,000
ppm [LOAEL(HEC) = 26,300 mg/cu.m] can be estimated.
Ref: US EPA IRIS for Chlorodifluoromethane.
4-,Alpha,Alpha,Alpha - (CTFT)
- Intermediate used in herbicides
In 14-day toxicity
studies, 1 of 10 female rats given the top dose of 1000 mg/kg
CTFT in corn oil died on day 8; no deaths of male rats or of mice
of either sex were attributable to the administration of CTFT.
Body weight gains in all groups of rats and mice were similar
with the exception of the top dose (1000 mg/kg) groups of male
and female rats, which lost weight during the first week and resumed
weight gain during the second. CTFT was
found to accumulate in the kidneys of male rats, and there
was a linear relationship between the kidney
CTFT concentrations and the kidney levels of a2u-globulin,
as determined by an ELISA assay. Microscopic changes in male rats
included a dose-related toxic nephropathy consistent with that
previously described as "hyaline droplet nephropathy." Dosed male
and female rats also had hepatocyte hypertrophy and cytoplasmic
vacuolization of the adrenal cortex. Clinical pathology
findings suggested a mild anemia and cholestasis in rats. In contrast
to rats, mice did not show appreciable CTFT concentrations in
any tissue evaluated, suggesting a more rapid elimination of the
chemical. However, hepatocellular hypertrophy, and clinical pathology
findings consistent with cholestasis and mild liver injury, were
noted in mice in the 400 and 1000 mg/kg dose groups. These studies
demonstrated that oral doses of CTFT of 400 mg/kg or higher caused
liver hypertrophy in rats and mice and adrenal changes in rats.
Doses of 50 mg/kg or higher caused "hyaline droplet nephropathy"
in male rats. The results were similar with CTFT administered
either in corn oil or in -CD (although absorption of CTFT was
somewhat more rapid with -CD), suggesting that -CD may be an appropriate
vehicle for toxicity studies with other chemicals.
Ref: National Toxicology Program. July 1992.
Toxicity Studies of p-Chloro-,,Trifluorotoluene (CAS NO: 98-56-6)
Administered in Corn Oil and -Cyclodextrin to F344/N Rats and
B6C3F1 Mice in 14-Day Comparative Gavage Studies.
Herbicide - CAS No. 105512-06-9
Reproductive and developmental
toxicity... Target organs were liver
(adults) and kidney (adults and pups).
The treatment had no effect on reproductive organs. The NOAEL
for toxicity to the parental rats and offspring was 50 ppm, corresponding
to a mean daily intake of 3.2 mg/kg clodinafop-propargyl. The
NOAEL for reproductive toxicity was 1,000 ppm (64.2 milligram/kilogram
body weight/day (mg/kg bw/day))... The EPA HIARC concluded that
based on hepatocellular hypertrophy and
kidney findings, the NOAEL was 1 ppm (0.031 in males and
0.034 in females.
Ref: Federal Register. April 26, 2000. [PF-938;
SUBCHRONIC AND CHRONIC
-- 870.4300 Chronic/ Oncogenicity in the Rat. NOAEL = M:0.03 mg/kg/day
; F: 0.03 mg/kg/day LOAEL = M: 0.3 mg/kg/day; F: 0.4 mg/kg/day
based on hepatocytic hypertrophy,
and tubular pigmentation. Under the conditions of this study,
treatment with clodinafop-propargyl increased the incidence of
prostate and ovarian tumors in rats at 750 ppm. For males, an
increased incidence of prostate adenoma was seen in the high-dose
group. The chemical was administered at a dose sufficient to
test its carcinogenic potential.
Ref: US EPA Pesticide Fact Sheet. Reason
for Issuance: Conditional Registration.
June 6, 2000.
- Herbicide - CAS No. 147150-35-4
84% DF was not found to be carcinogenic, teratogenic or to cause
reproductive effects. In-vitro and animal mutagenicity studies
were negative. Target organ effects have
been reported in the blood, kidney,
liver, testes and thyroid gland...
Ref: Material Safety Data Sheet for Gauntlet
Herbicide. MSDS Ref. No: F18-20-2. Date Approved: 09/25/2000.
Revision No. 1. FMC Corporation, Agricultural Products Group,
1735 Market Street, Philadelphia, PA 19103, USA.
Also available at http://www.cdms.net/ldat/mp48J001.pdf
-- In the rat Chronic
Feeding / Carcinogenicity study the NOEL was equal to 75 mg/kg/day
and the Lowest Observed Effect Level (LOEL) was 325 mg/kg/day
based on significant increase in hemoglobin,
hematocrit, and red cell count in males, activities of the liver
enzymes aspartate and alanine aminotransferase as well as alkaline
phosphatase were decreased in males, cholesterol was decreased
in females, specific gravity of urine was decreased in
females, increased relative wight in liver
and relative weight of testes in males,
males exhibited an increased incidence of collecting duct hypertrophy
and females exhibited increased incidence of vacuolation in the
kidney. There was no evidence of carcinogenicity for cloransulam-methyl
in this study. In the mouse carcinogenicity study the NOEL was
10 mg/kg/day and the LOEL was 108 mg/kg/day based on based on
a decrease in renal tubule vacuolation in
male mice, increased size of centrilobular and midzonal
hepatocytes accompanied by altered tinctorial properties in females
hepatocyte hypertrophy in males.
Total tumor incidence
(adenoma + carcinoma) was not increased by dosing with cloransulam-methyl.
-- Two Generation Reproduction (rat): Parental Systemic NOEL =
10 mg/kg/day Parental Systemic LOEL = 100 mg/kg/day based on
hypertrophy of the collecting ducts and vacuolation consistent
with fatty changes. Reproductive and Developmental NOEL = 100
mg/kg/day Reproductive and Developmental LOEL = 500 mg/kg/day
based on decreased live pups and increased pup deaths.
-- Chronic Feeding/ Carcinogenicity (rat):
NOEL = 75 mg/kg/day LOEL = 325 mg/kg/day based on significant
increase in hemoglobin, hematocrit, and red cell count in males,
activities of the liver enzymes aspartate and alanine aminotransferase
as well as alkaline phosphatase were decreased in males, cholesterol
was decreased in females, specific gravity of urine was
decreased in females, increased relative wight in liver
and relative weight of testes in males, males exhibited an increased
incidence of collecting duct hypertrophy and females exhibited
increased incidence of vacuolation in the kidney. There
was no evidence of carcinogenicity for cloransulam-methyl in this
-- Carcinogenicity (mouse): NOEL = 10 mg/kg/day LOEL = 108 mg/kg/day
based on a decrease in renal tubule vacuolation
in male mice, increased size of centrilobular
and midzonal hepatocytes accompanied by altered tinctorial properties
in females and centrilobular hepatocyte hypertrophy in males.
Total tumor incidence (adenoma + carcinoma) was not increased
by dosing with cloransulam-methyl.
Ref: USEPA. Pesticide Fact sheet. Cloransulam-methyl.
Reason for Issuance: Conditional Registration Date Issued: October
Insecticide - CAS No. 68359-37-5
A 24 month chronic
feeding/carcinogenicity study in rats demonstrated a NOAEL of
2.5 mg/kg/bwt/day and LEL of 6.2 mg/kg/bwt/day, based on decreased
body weights in males, decreased food consumption in males, and
inflammatory foci in the kidneys in females...
4. Subchronic toxicity. Thirteen-week dietary toxicity studies
in rats, mice and dogs were conducted. The primary
target organs identified in these studies were the kidneys (rat),
and the liver (rat, mouse and dog)... Chronic toxicity. In a 2-year
combined chronic toxicity/ oncogenicity study in the rat, the
NOAEL for chronic toxicity was 5 mg/ kg/day based upon kidney
effects characterized as slight, subtle alteration in kidney tubular
morphology, mostly within the corticomedullary junction which
likely represented more a physiologic adaptation than a pathological
change indicative of a toxic injury... In a 2-year dietary
feeding study in B6C3F1 mice conducted at 50, 100, 250 and 500
mg/kg/ day, 50 mg/kg/day was considered the NOAEL in males and
the NOAEL in females based upon histologic
changes in the kidney. The lesion
noted in male mice was a reduced vacuolation of the kidney tubular
epithelium at all dose levels. Decreased absolute and relative
kidney weights were seen at 100 mg/kg/day and above. In female
mice, focal dilation with hyperplasia of the lining epithelium
of the renal cortical tubules was seen at 100 mg/kg/day and above.
Ref: Federal Register. November 20, 1998.
- CAS No. 122008-85-9
-- Chronic dietary
all populations: Carcinogenicity in mice
based on kidney effects in females including tubular dilatation,
chronic glomerulonephritis, and hyaline casts. LOAEL =
Ref: Federal Register. September 27, 2001.
Cyhalofop-butyl; Pesticide Tolerances for Emergency Exemptions.
Preservative, Antifoulant, Fungicide, Acaracide -
CAS No. 1085-98-9
In the chronic
studies, the most consistent findings were
cranial osteosclerosis in the rat, and findings consistent with
fluorosis in a 2-year mouse study. Clinical chemistry findings
with supportive histopathology were observed in a 1-year study
in the dog which were indicative of
renal and liver damage.
A detailed assessment of cranial osteosclerosis
was performed in a 2-year study in the rat; a LOEL was
established at 10-14 mg kg -1 d -1..
-- A detailed assessment of cranial osteosclerosis was performed
in a rat 2-year study (summarised in section 184.108.40.206) in which
a LOEL was established at 10-14 mg kg -1 d -1 . A clear increase
in the incidence of cranial osteosclerosis was observed in the
low- and middle-dose groups, with almost all animals affected
at the top dose. These findings are likely to be secondary to
fluorosis in these animals. In terms of interspecies comparisons,
in a mouse 2- year study, thickening of both the appositional
bone of the cranial vault and nasal turbinates, and tooth alveolitis
were observed at the top dose of 1,731-1,873 mg kg -1 d -1 . These
findings are also considered to be a secondary consequence of
fluorosis in these animals. No evidence of fluorosis was observed
in the dog studies. It is considered that these findings are likely
to represent a fluoride mediated perturbation of bone metabolism
but are not considered to be of concern for human health.
It is considered that the observed liver and renal damage is of
concern to human health.
-- In a 1-year dog study clinical chemistry findings with supportive
histopathology, indicative of nephrotoxicity
and liver damage, were observed. In this study a NOAEL
of 2.5 mg kg -1 d -1 was established.
-- Two-year Study The following study is considered to be flawed
due to the lack of histopathological evaluation and it was not
GLP compliant. Beagles (4/sex/group) received dietary administration
of either 0, 100, 300, 1000 or 3000 ppm dichlofluanid (90 % purity);
equivalent to 3.6, 10.5, 34 and 107 mg kg -1 d -1 (males) and
3.4, 11, 34 and 101.4 mg kg -1 d -1 (females) respectively, for
a two year study period. Interim blood sampling was carried out
at 6 weeks, 6 months and 12 months for haematology, with interim
clinical chemistry analysis being performed at 12 months... Changes
reported in clinical chemistry parameters at 3000 ppm including
increased ALP, ALT, bilirubin,
cholesterol levels and BSP retention time, indicative of impaired
hepatic function... Against a background of variable data,
increases in serum creatinine (27 % males and 33 % females, at
3000 ppm) and urea levels (34 % males and 50 % females, at 3000
ppm) were reported, this being suggestive of impaired
renal function. Direct measurements of kidney function
at study termination revealed a decrease in both p-aminohippuric
acid (PAH) and inulin clearance; (5 and 17 %) in males and (19
and 32 %) females at 24 months at 3000 ppm. These data provide
further evidence for impaired renal function...
The relative kidney and liver weights were elevated at both 1000
(21 and 3.4 %) and 3000 ppm (18 and 10 %).
2003 - Evaluation
on: Booster biocides in antifouling products. Full review of Dichlofluanid.
No. 206. Evaluation of Fully Approved or Provisionally Approved
Products. Prepared by : The Health and Safety Executive Biocides
& Pesticides Assessment Unit, Magdalen House, Stanley Precinct
Bootle Merseyside L20 3QZ Available from: Department for Environment,
Food and Rural Affairs, Pesticides Safety Directorate, Mallard
House, Kings Pool, 3 Peasholme Green, York YO1 7PX, UK. Also available
Propellent, EPA List 2 Inert - CAS
McAlack, J.W. and P.W. Schneider, Jr. 1982. Two-year inhalation
study with ethane, 1,1-difluoro (FC-152a) in rats. E.I. Du
Pont de Nemours and Co., Inc. Haskell Laboratory for Toxicology
and Industrial Medicine. Haskell Laboratory Report No. 8-82. CD
rats (30/sex/group) were exposed to 0, 2000, 10,000, or 25,000
ppm 1,1- difluoroethane (HCFC-152a) (99.88% pure) (0, 5399, 26,994,
or 67,485 mg/cu.m, respectively) for 6 hours/day, 5 days/week,
for 2 years (McAlack and Schneider, 1982). Duration-adjusted concentrations
are 0, 964, 4821, or 12,051 mg/cu.m, respectively. Interim sacrifices
were performed on 10 rats/sex/group after 3 or 12 months of exposure.
The animals were exposed in 4.6-cu.m stainless steel and glass
chambers using a one-pass, flow-through mode of air flow (air
flow rate = 1200 L/minute). The test atmosphere was generated
by diluting HCFC-152a vapor with air. The concentration of the
test atmosphere was analyzed approximately every 30 minutes during
each exposure period by gas chromatography, and mean chamber concentrations
were found to be within 15% of nominal concentrations. Animals
were observed twice daily and several times during exposure for
clinical signs of toxicity and moribundity. Body weights and food
consumption were measured biweekly for the first 14 weeks and
monthly thereafter. Hematology, clinical chemistry, and urinalysis
were conducted at 1, 3, 6, 12, 18, and 24 months on 10 rats/sex/group.
Gross and microscopic evaluation of approximately 40 tissues was
conducted in all animals at terminal sacrifice and in the high-concentration
and control animals at the 3- and 12-month sacrifices (10 rats/sex).
Kidney and nasal tissues from the low- and intermediate-concentration
groups were also examined microscopically. The number of cross-sections
examined in the nasal tissue ranged from three to six (Trochimowicz,
1992). ... Urinary fluoride was increased
statistically in both sexes at all concentrations, indicating
metabolism of HCFC-152a. Biochemical changes (significant
increases in serum creatinine in the females exposed to 10,000
and 25,000 ppm HCFC-152a), increased urine volume, and decreased
urine osmolality seen throughout the study suggested
renal toxicity. The only organ weight or histopathology
data to support this functional deficit was decreased
kidney weight and renal tubular damage noted in the high-concentration
animals at the 3-month sacrifice. The tubular
lesions were reported in the original report as "slight cytoplasmic
vacuolation, luminal dilation, and the presence of occasional
vesiculated nuclei" and were
seen in 4/10 males and 7/10 females. These changes were
not seen at the other scheduled evaluations, however, and a subsequent
peer review of these data (Bruner, 1992) determined that the renal
tubular changes reported at the 3-month sacrifice were artifactual
changes due to tissue processing rather than a treatment-related
Ref: US EPA IRIS for
(Freon 152) - List 3 Inert - CAS No. 624-72-6
Abstract: The inhalation toxicity of a series of fluorinated
ethanes which are metabolized to fluoroacetate (144490) were studied
in the male CD-rat. When the rats were exposed
by inhalation to 1,2-difluoroethane (624-72-6), 1-chloro-2-fluoroethane
(762505), 1-bromo-2-fluoroethane (762492), or 1-chloro-1,2-difluoroethane
(338647) for 4 hours, the lethal concentrations for each compound
were less than 100 parts per million (ppm). Tests with
1,1-difluoroethane (75376) showed a 4 hour median lethal dose
of over 400,000ppm in rats. Clinical signs of fluoroacetate toxicity
were noted including lethargy, hunched posture, and convulsions.
Concentrations of citrate increased in serum and heart tissue
on exposure to 1,2-difluoroethane, 1-chloro-2-fluoroethane, 1-chloro-1,2-difluoroethane,
and 1-bromo-2-fluoroethane. Fluoroacetate was present in the urine
of rats exposed to each of the toxic compounds. Rats
exposed to 1,2-difluoroethane showed fluorocitrate in the kidneys.
Rats exposed to 1,2-difluoroethane showed
a concentration related elevation of serum and heart citrate up
to 1000ppm of the compound. Serum citrate was up five fold and
heart citrate 11 fold over control levels. The authors
suggest that the metabolism of the toxic fluoroethane was initiated
at the carbon/hydrogen bond, with metabolism to fluoroacetate
via an aldehyde or an acyl fluoride. The authors conclude that
1-(di)halo-2-fluoroethanes are highly toxic to rats and should
be viewed as a hazard to humans.
Ref: Fluoroacetate-Mediated Toxicity of
Fluorinated Ethanes; by Keller DA, Roe DC, Lieder PH. Fundamental
and Applied Toxicology, Vol. 30, No. 2, pages 213-219, 1996.
- Propellant, EPA List 2 Inert - CAS
/GUINEA PIGS/ ... EXPOSED /UP TO 2 HR/ @ CONCN OF 10.2% DIED &,
ON AUTOPSY, CONGESTED LUNGS, CONGESTED KIDNEYS,
CONGESTED LIVER, DISCOLORED SPLEEN, & HIGHLY CONTRACTED HEART
WERE FOUND. [American Conference of Governmental
Industrial Hygienists. Documentation of the Threshold Limit Values
for Substances in Workroom Air. Third Edition, 1971. Cincinnati,
Ohio: AmericanConference of Governmental Industrial Hygienists,
1971. (Plus supplements to 1979) 81
Ref: TOXNET profile from Hazardous
Substances Data Base for DICHLOROFLUOROMETHANE
- CAS No. 145701-21-9
Based on oral feeding
studies, the primary target organs are the
liver and kidney. In a subchronic rat feeding study, the
primary target organ is the liver including increased relative
organ weight, hepatocellular hypertrophy, and slight multifocal
necrosis. Decreased body weight and kidney
lesions were also noted. Liver effects were also noted
in a subchronic dog study and included increased relative liver
weight, centrilobular hepatocellular changes, and hepatocellular
necrosis accompanied by elevated ALP, AST, and ALT... In
a chronic toxicity/oncogenicity study in the rat, the kidney is
identified as a target organ... The
kidney was also a target organ in a mouse carcinogenicity study.
Among the observed kidney effects were reduced vacuolization
in the tubular epithelium, lower absolute and relative kidney
weights, and focal dilatation with hyperplasia of the epithelial
lining in the cortical tubules.
Ref: Federal Register. March 8, 2000. Diclosulam;
Pesticide Tolerance. Final Rule.
Herbicide - CAS No. 109293-97-2
Chronic toxicity. A
52-week feeding study in the dog at doses of 0, 1, 5, 40, or 80
mg/kg. Liver and kidney were identified
as target organs and the NOEL was established at 5 mg/kg...
A 90-day feeding study in the dog at approximate doses of 0, 0.25,
1, 5, 50, 150, or 400 mg/kg/day. Liver,
kidney, stomach, and thymus were identified as target organs.
The NOEL was 50 mg/kg/day. The maximum tolerated dose was
exceeded at > 150 mg/kg/day...
Ref: Federal Register. November 21, 1997.
- Herbicide -
CAS No. 97886-45-8
... In a 13-week dog
feeding study, increased alkaline phosphatase, discolored livers,
and cholestasis was observed at 10
mg/kg/day (LOEL). The NOEL was 1 mg/kg/day. In addition, at 30
mg/kg/day, increased serum glutamic-pyruvic transaminase and serum
glutamic oxaloacetic transaminase, increased liver and kidney
weights, and decreased cholesterol and albumin were observed.
EPA believes that there is sufficient evidence for listing dithiopyr
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based
on the available hepatic and renal
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.
The following results
were presented by a Monsanto scientist.
-- Four-week Feeding Study in Rats. Dithiopyr was administered
via the diet to groups of 6 male and 6 female Fischer-344 (F-344)
rats for 4 weeks at concentrations of 0, 300, 1000, 3000, 10,000
and 30,000 ppm. Decreased body weight and food consumption, as
well as clinical signs of toxicity were observed at the higher
dose levels. Liver enlargement and discoloration, thymic atrophy,
emaciation, and increased liver,
kidney and thyroid/parathyroid weights
were noted on gross postmortem examination. Due to an elevation
in liver and kidney weights at the
low dose level, the no observable effect level (NOEL) is considered
to be less than 300 ppm. (The Institute of Environmental Toxicology,
-- Thirteen-week Feeding Study in Mice Dithiopyr was administered
via the diet to groups of 12 male and 12 female CD-1 mice for
13 weeks at concentrations of 0, 10, 100, 1000 and 5000 ppm...
Postmortem examination revealed primarily liver and
kidney toxicity. Elevated
plasma AP, alanine aminotransferase (ALT), aspartate aminotransferase
(AST), urea nitrogen and cholesterol levels were indicative of
cholestasis and liver toxicity. These biochemical changes were
accompanied by a significant increase in liver weight, hepatocellular
swelling, vacuolation and necrosis, dissociation of hepatocellular
cords, and bile duct proliferation. Increased
kidney weights, decreased urine protein and specific gravity,
and acidophilia of proximal tubular cells were indicative of mild
renal toxicity... (The Institute of Environmental Toxicology,
-- CHRONIC TOXICITY AND ONCOGENICITY STUDIES. Twenty-four-month
Feeding Study in Rats •In a combined chronic toxicity and oncogenicity
study, dithiopyr was administered via the diet to groups of 90
male and 90 female F-344 rats for 104 weeks at concentrations
of 0, 3, 10, 100 and 300 ppm... Postmortem examination provided
evidence of liver and kidney toxicity.
There were no statistically significant or biologically significant
increases in neoplastic lesions.
-- Twelve-month Oral Study in Dogs •Dithiopyr was administered
orally via gelatin capsule to groups of 6 male and 6 female beagle
dogs for 52 weeks at dose levels of 0, 0.5, 5 and 25 mg/kg/day...
Postmortem examination revealed liver toxicity and cholestasis.
Specific findings included : increased AP levels in plasma, liver
enlargement and discoloration, the presence of black sandy materials
in the gallbladder, hepatocellular necrosis and fibrosis, pseudo-bile
duct formation, bile duct proliferation, and increased mucoidal
secretion in the gallbladder. Brown pigment deposition was also
found in the bile canaliculi, Kupffer cells and the kidneys.
The chronic NOEL in dogs is considered to be 0.5 mg/kg/day. (The
Institute of Environmental Toxicology, 1989)
-- REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDIES 1. Two-generation
Reproduction Study in Rats •Dithiopyr was administered via the
diet to groups of 24 male and 24 female S-D rats over 2 consecutive
generations at concentrations of 0, 25, 250 and 2500 ppm... Postmortem
examination of parental animals revealed primarily liver toxicity,
consisting of organ enlargement and discoloration, hepatocellular
swelling and necrosis, and bile stasis. Other findings included
: increased kidney weight, focal
renal tubular atrophy, thyroid follicular hypertrophy, and adrenal
cortical hypertrophy... (The Institute of Environmental Toxicology,
Ref: Summary of Toxicology Studies With
Dithiopyr Dennis P. WARD. Toxicology Department, The Agricultural
Grop, A Unit of Monsanto Company (Received February 20, 1993)
- Herbicide - CAS No. 55283-68-6
C -- Possible Human Carcinogen.
Mammary tumors (F); Suggestion of
bladder tumors (F) and kidney
tumors (M & F); Fischer 344 rats.
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
- Rodenticide - CAS No. 371-62-0
An increase in sternebral ossification defects,
hydronephrosis, runting (pup weight
less than 2.7 g), variant rib ossifications, extra vertebral ossification
centers, cardiac septal defects,
and intrauterine growth retardation were noted in rats.
Ref: TOXNET profile from Hazardous Substances
Data Base. http://www.fluoridealert.org/pesticides/ethylene.fluorohydri.toxnet.htm
HYDRONEPHROSIS - Pathological chronic
enlargement of the collecting channels of a kidney, leading to
compression and eventual destruction of kidney tissue, and diminishing
- Acaracide - CAS No. 153233-91-1
-- Subchronic toxicity.
Effects observed at high dose levels consisted primarily of
anemia and histological changes in the adrenal
Ref: August 13, 2003. [Federal Register:
August 13, 2003 (Volume 68, Number 156)] [Notices]. Etoxazole;
Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food.