Some background information: The thymus gland lies in the upper
part of the mediastinum behind the sternum and extends upwards
into the root of the neck. It weighs about 10 to 15 g.(about
half an ounce) at birth and begins to grow until the individual
reaches puberty when it begins to atrophy. It’s maximum
weight is around 30 - 40g (around 1 to 1.5 ounces) by the
age of 40 it has returned to it’s weight at birth.
The thymus consists of two lobes connected by areolar tissue.
The lobes are enclosed in a fibrous capsule which dips into
their substance dividing them into lobules that consist
of an irregular branching framework of epithelial cells
Function: Lymphocytes originate from haemocytoblasts (stem cells)
in red bone marrow. Those that enter the thymus mature and
develop into activated T-lymphocytes i.e. able to respond
to antigens encountered elsewhere in the body. They then
divide into two groups :
• those that enter the
blood, some of which remain in circulation and some lodge
in other lymphoid tissue
• those that remain in
the thymus gland and are the source of future generations
The maturation of the thymus and other lymphoid tissue is
stimulated by thymosin, a hormone secreted by the epithelial
cells that form the framework of the thymus gland. Involution
of the gland begins in adolescence and, with increasing
age the effectiveness of T- lymphocyte response to antigens
declines. Ref: http://www.jdaross.mcmail.com/lymphatics6.htm
The Endocrine System:
Illustration by K. Born in Our Stolen Future
by Theo Colborn, Dianne Dumanoski and JP Myers
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.
- Acaracide, Insecticide - CAS No.
STUDIES 1. Rats Study by Dietary Repeat Dose for 90 Days Followed
by a 28-Day Recovery Period Group of 20 male and 20 female CD
(SD) rats were fed diet containing 0, 30, 100 or 300 ppm of acrinathrin
for 90 days... Other microscopic findings observed were lymphoid
deletion in the spleen and thymus
in 5 females of the 300 ppm group and medullar [marrow] atrophy
in 2 females of the 300 ppm group... The No Observed Effect Level
(NOEL) for this study was considered to be 30 ppm (male: 2.4 mg/kg/day;
female: 3.1 mg/kg/day) (Centre International de Toxicologie, 1988).
Ref: Summary of Toxicological Studies on
Acrinathrin Market Development, AgrEvo Japan Limited (Received
January 26, 1998 ; Accepted March 20, 1998).
- Herbicide - CAS No. 128639-02-1
In dogs (1/sex/group) given capsules containing carfentrazone-ethyl
at doses up to 1000 mg/kg bw/day for 28 days, food consumption
and body weight gain were decreased, plasma
urea was slightly increased and plasma glucose was slightly decreased.
Total urinary porphyrins were elevated in the male at 1000 mg/kg
bw/day and in females at ¥ 500 mg/kg bw/day. Decreased
thymus weight and cortical atrophy were observed in animals
at 1000 mg/kg bw/day and decreased uterus
weights were observed in females at this dose.
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
Herbicide - CAS No. 105512-06-9
A 90-day feeding study in rats at 1,000 ppm resulted in reduced
body weight gain, increased liver weights, hematological changes,
and increased serum activities of the alkaline phosphatase. Target
organs were liver (increased weight), thymus
(atrophy) and spleen (reduced weight). The changes were
reversible during 4 weeks of recovery. The NOAEL was 15 ppm (0.92
mg/kg in males and 0.94 mg/kg in females). The EPA HIARC suggested
the NOAEL in female rats was 8.24 mg/kg bw/day.
Ref: Federal Register: April 26, 2000 [Page
Insecticide - CAS No. 68359-37-5
inhalation study (short-term): Decreases in
body and thymus
pathology in rats
in a 28-day study (short-term) and behavioral effects in rats in
a 90-day study (intermediate/ chronic)
Ref: Federal Register: May 17, 2001, Cyfluthrin;
Pesticide Tolerances for Emergency Exemptions. Final Rule.
- Herbicide - CAS No. 122008-85-9
Palatability and Four-Week
Dietary Probe Study in Beagle DogsÓ; (M.J. Mizell, K.T. Hart and
J.W. Crissman; The Toxicology Research Laboratory, Health and
Environmental Sciences, The Dow Chemical
Company, Midland, MI; Study ID. DR-0298-8876-004; 9/11/90);
In a preliminary palatability study, one beagle dog/group received
250, 500 or 1000 mg/kg/day of XRD-537 nBu (Technical) (AGR 276541,
purity: 98.2%) for up to 2 weeks... In the second study, 2 beagle
dogs/sex/group received targeted doses of 0, 35, 100 or 350 mg/kg/day
for 4 weeks. Based on the food consumption, the low dose animals
received doses of 36, 36, 34 or 53 mg/kg/day, the intermediate
dose animals consumed doses of 85, 86, 133 or 138 mg/kg/day and
the high dose animals received doses of 193, 203, 37 or 292 mg/kg/day,
respectively... Gross examination of the
tissues revealed slight to very severe atrophy of the thymus in
a dose-related manner... In the microscopic examination,
multifocal vasculitis and thrombosis was noted in the kidneys
of the 2 high dose males and one intermediate and one high dose
female, respectively. Diffuse atrophy of
the thymus ranged from slight to very severe in a dose-related
manner for the males in all of the groups and from moderate
to severe for the intermediate and high dose females. In
the testes, spermatogenesis was moderately to severely reduced
in the high dose males with a concomitant increase in multinucleated
spermatids. Apparent target organs:
thymus and testes; Possible adverse effect: atrophy of the thymus
and reduced spermatogenesis in the testes; NOEL can not
be determined; Study supplemental. (Moore, 11/20/00)
Ref: February 16, 2001. California Environmental
Protection Agency Department of Peticide Regulation. Medical Toxicology
Branch. Summary of Toxicological Data. Cyhalofop-Butyl. Chemical
Code # 5748, Tolerance # 52840 SB 950 # New A.I.
- Herbicide - CAS No. 83164-33-4
studies... In a 13-week oral study in the dog, the minimum effect
level was 250 mg/kg bw based on enemis and increased
cholesterol levels at the 250 mg/kg bw/day dose level. The observed
effects at higher dose levels included impaired body weight gain,
emesis, increased plasma cholesterol and increase in the
relative thymus weights.
-- Acceptable daily intake (ADI). The acceptable daily intake
of 0.2 mg/kg bw/day is derived from the critial minimum effect
level of 500 ppm (24 mg/kg bw/day), derived from the 24-month
chronic dietary study in the rat or the multigeneration study
in the rat and allows for a 100-fold safety factor. The observed
effects included minimal reductions in body weight gain and a
slight reduction in thymus weights
at the 500 ppm dose level.
1995. Evaluation on Diflufenican.
Evaluation of fully approved or provisionally approved products.
Department for Environment, Food and Rural Affairs, Pesticides
Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green,
York YO1 7PX, UK. Available at: http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
- CAS No. 109293-97-2
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
The following results
were presented by a Monsanto scientist.
-- Four-week Feeding Study in Mice. Dithiopyr was administered
via the diet to groups of 6 male and 6 female CD-1 mice for 4
weeks at concentrations of 0, 300, 1000, 3000, 10,000 and 30,000
ppm... [No concentrations listed for the
following effects:]-- Liver enlargement and discoloration,
adrenal enlargement, and atrophy
of the thymus, spleen, seminal vesicles,
ovaries and uterus were noted on gross post-mortem examination...
(The Institute of Environmental Toxicology,
of Toxicology Studies With Dithiopyr. Dennis P. WARD. Toxicology
Department, The Agricultural Grop, A Unit of Monsanto
Company (Received February 20, 1993). Also available at
- Insecticide - CAS No. 158062-67-0
oral toxicity (nonrodents- dogs).
NOAEL is 8 mg/kg/day in males and 20 mg/kg/day for female. LOAEL
is 20 mg/kg/day in males and 50 mg/kg/day in females, based on
acute clinical signs in males and females (vomiting,
first observed on Day 1 and last observed on Day 90), clinical
pathology at 7 weeks (increased total protein
levels in males, lower red blood cells and higher reticulocytes
counts in females), increased adrenal
weights in males, decreased thymus gland
weights in males, and increased kidney tubular vacuolation
in females at study termination.
August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule.
- Herbicide - CAS
**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. Seven 125 mg/kg/day dogs (5 M, 2 F) were killed in
extremis prior to term, generally after at least 29 weeks on study...
Platelet counts were reduced by about half
in both sexes. Bone
marrow samples taken at weeks 10 and 52 for smear analyses showed
"reduced numbers of megakaryocytes," suggesting reduced
production as a reason for low platelet counts. Other hematology-related
increased incidence/degree of thymic involution,
decreased lymphocyte counts, increased degree of hemosiderin-laden
Kupffer cells, hypercellular sternal marrow, and severe extramedullary
hematopoiesis in 4 male and 1 female decedent.
Four of the latter 5 dogs also had substantially increased splenic
weights, "pallor" in clinical signs as part of moribund
condition, and their final hematology red cell values (RBC count,
Hb, HCT) were very low....
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY
DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide
Regulation. Medical Toxicology Branch.
-- One major change that occurs as the body ages is a process
termed "thymic involution." ... As humans age, the
thymus naturally atrophies... Once the immune system fully develops
and can protect the host against a myriad of antigens, the thymus
may be too costly to maintain, so it is evolutionarily advantageous
to decrease the amount of thymic tissue and use the energy that
would have supported the thymus for other purposes. However,
because T cells play such a prominent role in immunity, longer-lived
individuals still need a continuous supply of "fresh"
T cells to protect against newly-encountered antigens, and this
slow but progressive loss of thymic tissue has profound effects
on the entire immune system of the aged.
Immunology of Aging
involution tied to progression of pediatric HIV infection
subchronic and chronic toxicity studies, fluazinam
targeted the following organs: liver, lung, uterus, testes,
pancreas, thymus, thyroid, stomach,
eyes and brain.
Canada: Regulatory Note REG2003-12. Fluazinam. Pest
Management Regulatory Agency. Health Canada. Ottawa. October 27,
- Insecticide - CAS No. 272451-65-7
of a reproductive toxicity study in rats (exposure route not stated):
Thyroid, liver, uterine, thymus,
and spleen weight changes in 2000
and 20000 ppm F1 and F2 pups.
Ref: TSCA Health & Safety Study Cover Sheet "Public Display
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.
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
- Fungicide - CAS No. 131341-86-1
-- A carcinogenicity
study in mice administered technical fludioxonil in the diet at
0, 10, 100, 1,000, and 3,000 ppm (0, 1.1, 11.3, 112, and 360 mg/kg/day
for males and 0, 1.4, 13.5, 133, and 417 mg/kg/day for females)...
Other macroscopic changes in female mice were an increased incidence
of enlarged thymus, spleen, mediastinal
lymph node, and liver and an increased incidence of lymphoma in
these organs. The LOAEL is 112 mg/ kg/day for male mice, based
on the increased incidence of clinical toxicity and 417 mg/kg/day
for female mice, based on the increased liver weight and the increased
incidence of macroscopic pathology.
Ref: Federal Register.
October 7, 1998. Fludioxonil; Pesticide Tolerance. Final Rule.
In a 4 week dermal toxicity study, where the animals were treated
5 days per week, there were no signs of skin irritation at up
to 1000 mg/kg bw/day. The NOAEl was 200 mg/kg bw/day, based on
the presence of enlarged macrophages in the thymic
cortices of all females at 1000 mg/kg bw/day. This finding
is unexpected since it has not been reproduced in any other study
where the animals have been systemically exposed to high doses
of fludioxonil for long periods. It may be a phenomenon of high
dose exposure via the dermal route.
-- The plant metabolites CGA 192155, CGA 265378, CGA 308103, and
the chicken metabolite CGA 309565, were of low acute oral toxicity
to the rate with LD50's of >2000 mg/kg bw, except for CGA 309103
where the LD50 was >1000 mg/kg bw. At gross necropsy, spotted
thymuses were noted in all females (all of which died within
one day of dosing) treated at 2000 mg/kg bw CGA 308103, but not
at the lower dose levels, 200, 500 and 1000 mg/kg bw. The
significance of the findings in the thymuses of the animals which
died was not investigated further. In Salmonella typhimurium
reverse mutation assays, the 4 above mentioned plant metabolites
showed no evidence of mutagenic potential. The above results give
further assurance that consumer risk from exposure to these metabolites
Ref: Evaluation of Fludioxonil. UK Department
for Environment, Food and Rural Affairs, Pesticides Safety Directorate,
Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX. March
Note: this pdf document is large with no search engine.
- Herbicide - CAS No. 188489-07-8
-- EPA has not had
the opportunity to review the toxicity studies on flufenpyr-ethyl
and has not established toxic endpoints.
-- In an additional study, flufenpyr-ethyl technical was tested
in rats at dose levels of 0, 1,000, 10,000, and 20,000 ppm in
the diet for 13 weeks. Effects observed included urinary incontinence,
increased food and water consumption, and mild urinalysis, hematological
and blood biochemistry changes. Thymus weights
were slightly increased...
-- Mice. In a 4-week study, CD-1 mice were fed pure flufenpyr-
ethyl at dose levels of 0, 300, 1,000, 3,000, and 7,000 ppm. Effects
were slight anemia, changes in blood biochemistry, increased liver
and thymus weights, and enlarged
Federal Register: June 25, 2003 (Volume 68, Number 122)] [Notices]
[Page 37813-37820]. Flufenpyr-ethyl; Notice of Filing a Pesticide
Petition to Establish a Tolerance for a Certain Pesticide Chemical
in or on Food.
- Herbicide - CAS No. 103361-09-7
Subacute Toxicity Study of S-53482 by Dietary Administration in
Rats"; (Haruhiko Adachi; Sumitomo Chemical Co., Environmental
Health Science Laboratory,, Ltd., Osaka, Japan; Study No. 1760;
4/26/91); Sixteen Crj:CD (SD) rats/sex/group were treated in the
diet with 0, 30, 300, 1000 or 3000 ppm of S-53482 (lot no. PYG-89021-M,
purity: 94.8%). Six of these animals/sex/group were treated for
5 weeks. The remaining 10 animals/sex/group were treated for 13
weeks ((M): 0, 1.94, 19.4, 65.2, 197.3 mg/kg/day, (F) 0, 2.22,
22.4, 72.8, 218.4 mg/kg/day)... Other noted lesions for the 3000
ppm females were... atrophy of the thymus
and the presence of thymal foam cells (0:0/10
vs. 3000: 3/10), sinus histiocytosis in the mesenteric
lymph node (0:0/10 vs. 3000: 3/10), and cytoplasmic
vacuolation in the adrenal cortex
(0:0/10 vs. 3000: 3/10)...
January 32, 2003 (revised) -
Summary of Toxicological
Data. California EPA, Department of
Pesticides Regulation, Medical Toxicology Branch.
insect Chemosterilant; now used as a pharmaceutical - CAS
EFFECTS ON FETUS: Exposure in first trimester resulted in skeletal
abnormalities; hypoplasia of aorta, lungs, thymus,
and gastrointestinal tract; and urinary tract abnormalities. Fetus
exposed in third trimester had cyanosis and clonus.
Ref: TOXNET profile from Hazardous Substances
- CAS No. 67485-29-4
-In a prenatal developmental
toxicity study, MRID 00061790, groups of 26 pregnant female Sprague-Dawley
rats were given oral administration of hydramethylnon at doses
of 0, 3, 10, or 30 mg/kg/day on gestation days 6-15. The vehicle
controls were dosed with corn oil. The dams were sacrificed and
examined on gestation day 20... At 30 mg/kg/day, a 16% decrease
in maternal body weight, increased incidence of clinical signs
(nasal mucus, alopecia, soft stool, staining of the ano-genital
fur), yellowish discoloration of the fat, and small
thymus were observed. For developmental toxicity, the NOAEL
was 10 mg/kg/day and the LOAEL was 30 mg/kg/day, based on decreased
mean fetal weights, increased incidence of rudimentary structures,
and increased incidence of incompletely ossified supraoccipital.
This study is classified as acceptable and satisfies guideline
requirement 83-3(a) for a developmental toxicity study in rats.
Ref: US EPA. Reregistration Eligibility
Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
- Insecticide - CAS No. 173584-44-6
"Combined Chronic Toxicity/Oncogenicity Study with DPX-JW062-106
(50% DPX-KN128, 50% DPX-KN127) Two-Year Feeding Study in Rats"
(Frame, S. 835-E. I. du Pont de Nemours and Company, Haskell Laboratory,
Elkton Road, Newark, Delaware, Study HLR 1174-96, 11/19/97). DPX-JW062-106
technical (Batch DPX-JW062-106, 47.5% DPX-KN128) was given in
the diet daily to males at 0, 20, 40, 60, 125 or 250 ppm and females
at 0, 10, 20, 40, 60 or 125 ppm for 24 months. Deaths of one female
at 60 ppm and seven at 125 ppm during the first year were associated
with bone marrow atrophy, splenic lymphoid depletion and
thymic necrosis... After two years, secondary changes were
seen in the liver, spleen, bone marrow, kidneys and thymus
in high dose groups.
11, 1999: Summary
of Toxicology Data - Indoxycarb.
California EPA Department of Pesticide Regulation, Medical Toxicology
- Herbicide - CAS No. 77501-63-4
-- Subchronic feeding--
Mice-- 3-month. Groups of Male and female mice were fed diets
containing Lactofen Technical at concentrations of 0, 40, 200,
1,000, 5,000, and 10,000 for 13-weeks. At week 5, the dosage of
the 40 ppm groups was increased to 2,000 ppm. Treatment related
mortality occurred at dosages above 1,000 ppm. The LOEL was 200
ppm based on: increased WBC; decreased hematocrit, hemoglobin
and RBC; increased alkaline phosphatase, SGOT, SGPT, cholesterol
and total serum protein levels; increased weights or enlargement
of the spleen, liver, adrenals, heart
and kidney; histopathological changes of the liver, kidney, thymus,
and testes. In general, effects were slight in the 200
ppm groups, and moderate to severe in the 1,000 ppm groups.
Ref: Federal Register: February 25, 1998
[Page 9532-9540]. Notice of Filing of Pesticide Petition.
- Herbicide - CAS No. 42874-03-3
Absolute and relative
thymus weights were decreased in mid-dose males (-14%/-10%)and
high-dose males (-32%/- 18%)...Vacuolation of the
adrenal cortex was present in high-dose
females. Thymic atrophy
occurred in high-dose males and females.... Fine vacuolation
of adrenal glands (slight)and cortical
atrophy of the thymus (slight)
were increased in high-dose males...
Ref: US EPA. Toxicology Chapter for RED.
August 8, 2001.
- Fungicide - CAS No. 124495-18-7
-- (Corlett, 8/27/01)
030; 181171; "XR-795: Palatability and Toxicity Probe Study
in Beagle Dogs" (Szabo, J.R. and Rachunek,
B.L., Health and Environmental Sciences-Texas Lake Jackson Research
Center, The Dow Chemical Company,
Freeport, Texas, Laboratory Project Study ID: DR-0325-7474-001,
2/28/92). XR-795 (TSN100008, Lot # DECO-36-111, purity
= 98.8%) was admixed to the diet at dose levels of 0 (untreated
diet only), 100, 500, or 1000 mg/kg/day and fed continuously to
1 beagle dog per sex per dose for 30 days. No clinical signs were
observed. A treatment-related decrease in
body weight gain or outright body weight loss at all dose levels
in males and at 500 and 1000 mg/kg/day in females was observed.
A treatment-related decrease in feed consumption in males at all
dose levels and in females at 500 and 1000 mg/kg/day was observed.
Macroscopic examination revealed a small/atrophic
thymus in both the male and the female at 1000 mg/kg/day
and small/atrophic testes in the male at
1000 mg/kg/day. Microscopic examination revealed vacuolation of
midzonal and centrilobular hepatocytes at 500 and 1000
mg/kg/day in both sexes and thymic lymphoid
depletion in the male and female at 1000 mg/kg/day. No
adverse effects. NOEL (M) < 100 mg/kg/day, NOEL (F) = 100 mg/kg/day
(based on body weight and feed consumption data). Supplemental
(only 1 animal per sex per dose was used and the animals were
only dosed for 30 days). (Corlett, 8/28/01)
Ref: October 4, 2001 - SUMMARY
OF TOXICOLOGY DATA QUINOXYFEN (XDE-795 & XR-795). California
EPA, Department of Pesticide Regulation, Medical Toxicology Branch
PFOS - PFOA
- Insecticide, US EPA List 3 Inert
Abstract: The effects
of peroxisome proliferators on the immune system of male C57B1/6
mice have been investigated. Significant
atrophy of the thymus and spleen was observed in animals treated
with potent peroxisome proliferators (e.g. perfluorooctanoic acid
(PFOA), di(2-ethylhexyl)phthalate (DEHP), Wy-14643 and
nafenopin), whereas the effects of a moderate peroxisome proliferator
(i.e. acetylsalicylic acid (ASA)) were relatively weak. The time
course of thymic and splenic atrophy caused by PFOA was found
to resemble the time course of the increase in liver weight and
of peroxisome proliferation... Interestingly, in vitro exposure
to PFOA for up to 24 h did not produce analogous effects in either
thymocytes or splenocytes. Thus, the thymic
and splenic atrophy caused by PFOA appears to involve an indirect
Ref: 2000. Clin Exp Immunol Nov;122(2):219-26. Effects
of peroxisome proliferators on the thymus and spleen of mice;
by Yang Q, Xie Y, Depierre JW.
3.5 Reproductive Toxicity
Studies in Animals
York (2002) conducted an oral two-generation reproductive toxicity
study of APFO, which is summarized below. Although this preliminary
risk assessment focuses on developmental toxicity, the summary
below of the two generation reproductive toxicity study includes
all endpoints. Five groups of 30 Sprague-Dawley rats per sex per
dose group were administered APFO by gavage at doses of 0,1,3,10,
and 30 mg/kg/day six weeks prior to and during mating. Treatment
of the F0 male rats continued until mating was confirmed,and treatment
of the F0 female rats continued throughout gestation, parturition,
Parental Males (F0)... At necropsy,
reductions in terminal body weights were
seen at 3,10,and 30 mg/kg/day. Absolute weights of the left and
right epididymides, left cauda epididymis, seminal vesicles (with
and without fluid), prostate, ,left and right adrenals, spleen,
were also significantly reduced at 30 mg/kg/day... All
organ weight-to-terminal body weight and ratios were significantly
increased in all treated groups...
F1 Males ...
The absolute weight of the thymus was also
significantly decreased in the 10 and 30
mg/kg/day dose groups... The ratios of the spleen weight-to-brain
weight were significantly decreased at 1 mg/kg/day and higher,
and the ratios of the thymus weight-to-brain
weight were significantly decreased at 10 and 30 mg/kg/day...
10, 2003: Preliminary
Risk Assessment of the Developmental Toxicity associated with
Exposure to Perfluorooctanoic Acid and its Salts. US
EPA Office of Pollution Prevention and Toxics. 63 pages.
In the rat subchronic study, Goldenthal et al. (1978b) administered
CD rats, 5/sex/group, dietary
levels of 0, 30, 100,
300, 1000 or 3000 ppm PFOS (FC-95) for 90 days. The males
232 g and the females weighed 165-206 g at study initiation. The
dietary levels were equivalent
to doses of 0, 2, 6, 18, 60 and 200 mg/kg/day... The rats were
sacrificed after 90 days of treatment and a gross necrospy was
conducted... All of the rats in the 300,
1000 and 3000 ppm groups died. Death occurred between days 13-25
and days 18-28 for the males and females, respectively, in the
300 ppm group...
The rats in all groups showed signs of toxicity including emaciation,
handling, hunched back, red material around the eyes, yellow material
around the anogenital
region, increased sensitivity to external stimuli, reduced activity
and moist red material around
the mouth or nose. Three males and two females in the 100 ppm
group died prior to scheduled sacrifice. Two of the males and
the two females died during week 5 and the third male died during
week 11 of the study... All rats in the 30 ppm group survived
until the end of the study... Histologic examination also showed
lesions in all treated groups. Centrilobular to midzonal cytoplasmic
hypertrophy of hepatocytes and focal necrosis was observed in
the liver; the incidence and relative severity were greater in
the males. In addition, especially among rats in the 300, 1000
and 3000 ppm groups, treatment related histologic lesions were
noted in the primary
marrow) and secondary (spleen, mesenteric
lymph nodes) lymphoid organs, stomach, intestines, muscle
and skin. In the thymus, this consisted
of depletion in the number and size of the lymphoid follicles
and in the bone marrow hypocellularity was
noted. The spleen was slightly atrophied
with a corresponding decrease in the size and number of lymphoid
follicles and cells and a similar depletion was noted in the mesenteric
Ref: August 31, 2000.
SUBJECT: Hazard Assessment of PFOS. FROM: Jennifer Seed, Branch
Chief, Existing Chemical Assessment Branch, Risk Assessment Division
(7403). THRU: Oscar Hernandez , Division Director, Risk Assessment
Division (7403). TO: Charlie Auer, Division Director, Chemical
Control Division (7405).
- Insecticide, Rodenticide - CAS No.
-- An acute dermal
toxicity study with rabbits used technical sodium fluoroacetate.
The LD was 277.1 mg/kg for males and 324.2 mg/kg for 50 females.
The animals showed lethargy, diarrhea, and convulsions preceding
death, along with extensive hemorrhage of the
thymus and congestion of the lungs. This is toxicity category
II (MRID 152129).
Ref: US EPA Reregistration Eligibility Decision
(RED) for Sodium fluoroacetate. September 1995.
-Fungicide - CAS No. 112281-77-3
-- A chronic feeding/carcinogenicity
study was conducted with tetraconazole in Crl:CD-l (ICR)BR mice
at dietary levels of 10, 90, 800, and 1,250 ppm for 80 weeks.
Treatment-related non-neoplastic changes were also seen at 1,250
ppm in the lungs, kidneys,
testes, epididymides, ovaries and
bone, particularly the cranium;
a compression of the brain was noted in a number of mice reflecting
the extent of cranial bone changes and an increased
thymic involution was seen in male mice that
died on test.
The 1,250 ppm
dietary level for tetraconazole, because of the substantial bwt
gain changes and increased mortality (more
in males), appeared to be above the maximum tolerated dose
(MTD). At 800 ppm, there were increases in non neoplastic changes
in lungs, kidneys,
testes, epididymides, ovaries and bone.
In addition, there was substantial reduction in weight gain as
compared with zero-dose control animals, but the mortality rate
was unaffected. Eight hundred ppm appeared to be a reasonable
estimate of the MTD for mouse.
Ref: Federal Register: October 14, 1999.
Notice of Filing Pesticide Petitions to Establish a Tolerance
for Certain Pesticide Chemicals in or on Food. PP 9F5066, 9F6023,
- Fungicide - CAS No. 141517-21-7
Target / critical effect - Developmental toxicity: Enlarged
thymus (rat) and skeletal effects (rabbit) at maternally
toxic dose levels. Lowest relevant developmental NOAEL / NOEL:
50 mg/kg bw/day (rabbit)
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.
subchronic studies, several mortality related changes were reported
for the top dose in dogs (500 mg/kg) and rats (800 mg/kg). At
these dose levels, excessive toxicity has resulted in body weight
loss and mortality with the associated and non-specific changes
in several organs (such as atrophy in the
thymus, pancreas, bone marrow, lymph node, and spleen)
which are not considered specific target organs for the test compound.
Ref: Federal Register: November 14, 2001
[Page 57074-57079]. Notice of Filing a Pesticide Petition to Establish
a Tolerance for a Certain Pesticide Chemical in or on Food.
- Herbicide - CAS No. 199119-58-9
-- Short Term Studies.
Trifloxysulfuron applied to the skin of rats at doses of 0, 10,
100 or 1000 mg/kg bw/day for 28 days did not result in any deaths,
abnormal clinical signs, skin irritation, changes in food consumption,
macroscopic changes or microscopic lesions attributable to treatment.
Body weight gain was lower in females at 1000 mg/kg/day and haemoglobin
and phosphate were slightly lower in males at 1000 mg/kg bw/day.
Thymus weights were lower in males at 100
and 1000 mg/kg bw/day and in females at 1000 mg/kg bw/day.
-- Dogs were given trifloxysulfuron at doses of 0, 50, 200 or
500 mg/kg bw/day in gelatin capsules for 28 days. There were no
mortalities, changes in food consumption, clinical signs of toxicity
or effects on body weight gain. A white material in the faeces
of animals at 500 mg/kg bw/day was confirmed by analysis to be
the test material. Red blood cell count, haematocrit, haemoglobin,
platelet counts and clotting times, plasma bilirubin, protein
and albumin were lower and globulin and chloride were higher in
both sexes at 500 mg/kg bw/day. Plasma bilirubin was also lower
in females at 200 mg/kg bw/day and plasma potassium and calcium
were lower in males at 500 mg/kg bw/day. Liver weights were higher
in both sexes at 200 and 500 mg/kg bw/day. Thymus
weights were marginally lower with one of
two males and one of two females at 500 mg/kg bw/day having slight
cortical atrophy in the thymus. Testes weight
was lower in one of the two males at 500 mg/kg bw/day along with
markedly reduced spermatogenesis and some single cell necrosis
of tubular cells. This male also had slight follicular hypertrophy
in the thyroid. Spleen weights were higher in females at
500 mg/kg bw/day with lymphoid hyperplasia observed in the spleen
of males at 200 and 500 mg/kg bw/day and females at all doses.
Pneumonia was observed in dogs at 500 mg/kg bw/day.
Ref: August 2002 -
Evaluation of the new active Trifloxysulfuron-sodium in the product
ENVOKE HERBICIDE. Public Release Summary.
National Registration Authority for Agricultural and Veterinary
Chemicals 2002 ISSN1443-1335.