Return
to Transfluthrin Index Page
Activity:
Insecticide
(pyrethroid)
Structure:
Adverse
Effects:
Bladder
Body Weight Decrease
Bone
Brain
Cholesterol
CNS
Dermal
Endocrine: Adrenal
Endocrine: Thyroid
Genotoxic
Kidney
Liver
Lung
Spleen
Tremors
Environmental
Transfluthrin
is a synthetic pyrethroid insecticide not previously evaluated
under The Control of Pesticides Regulations (1986). The
Applicant, Bayer Plc, has applied for approval for "Baygon
Moth Paper", a product containing 0.5% transflurthin
(50 mg transflurthrin per paper strip) to be used by amateurs
in indoor situations against cloth damaging Lepidoptera
(moths) and cloth damaging Coleoptera (beetles). Each strip
is of dimensions 131 mm x 966 mm and may be used whole or
cut into sections suitable for the size of the area of use.
The product is for use indoors in domestic premises in contained
areas e.g. cupboards, boxes, suitcases, etc. where clothes,
bedding, curtains, carpets, etc. are stored.
Ref:
Evaluation on: Transfluthrin Use as a Public Hygiene Insecticide.
September 1997. Prepared by: the UK 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 at http://www.pesticides.gov.uk/citizen/evaluations/165_confirm-box.htm
Note: This was transcribed
from the copy available on the web. While one can easily
read this report on the web, the report is inaccessible,
or locked, to any attempt to copy it. Any errors are are
mine. EC.
|
---
Note from FAN: The following study seems promising (albeit
that our bodies are expected to be the unwitting repositories
of industrial chemicals and pesticides). Of interest, transfluthrin
is not registered for use in the US, yet it has been included
in this study supported by US agencies. Also, according
to the UK report (see below) animal studies showed high
levels of fluoride in the teeth and bone.
Fetal exposure
to environmental toxins & infant outcome
Source:
Crisp Data Base National Institutes of Health
Year of Publication: 2002
Authors:
OSTREA EMJR
Author
Address: EOSTREA@MED.WAYNE.EDU,
HUTZEL HOSPITAL, 4707 ST ANTOINE BOULEVARD, DETROIT, MI
48201
Supporting
Agency: U.S. DEPT. OF HEALTH AND HUMAN SERVICES; PUBLIC
HEALTH SERVICE; NATIONAL INSTITUTES OF HEALTH, NATIONAL
INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
DESCRIPTION
(provided by applicant): The exposure of pregnant women
to environmental toxins is of major concern because of their
potential harm on the fetus. However, the detection of fetal
exposure to environmental toxins still remains a major challenge.
We propose that meconium analysis is a promising tool to
meet this challenge.
Aims:
(1) To compare the prevalence and amount of fetal exposure
to environmental toxins through the analysis of meconium,
cord blood and neonatal hair and to determine the degree
of agreement among these three methods,
(2) to determine the relationship between the prevalence
and amount of maternal exposure to environmental toxins
during pregnancy, as determined by serial analyses of maternal
hair and blood, to the prevalence and amount of fetal exposure
to environmental toxins as determined by meconium, cord
blood and neonatal hair analyses, and
(3) to compare adverse immediate (birth weight, length,
head circumference, gestational age) and long term (postnatal
growth and neurobehavioral development up to 2 yrs from
enrollment) outcomes that are associated with antenatal
exposure to environmental toxins as determined by maternal
blood, maternal hair, meconium, cord blood and neonatal
hair analyses.
Study design: Pregnant
women (n=750) will be recruited, at midgestation, from the
Outpatient Clinic of the Bulacan Provincial Hospital, Philippines
and their blood and hair will be obtained at the time of
recruitment and at delivery. Umbilical cord blood, meconium
and neonatal hair will also be obtained. The samples will
be analyzed, by atomic absorption spectrometry, for lead,
mercury and cadmium and by gas chromatography/mass spectrometry
for the following pesticides and their metabolites: propoxur,
transfluthrin, Malathion, DDT,
chlorpyrifos, bioallethrin, pretilachlor, lindane, cyfluthrin
and cypermethrin. Pertinent maternal and infant data will
be obtained after birth. The infants will be subsequently
followed up at scheduled intervals for 2 years, to study
their physical growth and neurobehavioral development using
a battery of tests.
Data analysis: The relationship
between the presence/amount of environmental toxins in meconium,
maternal blood, maternal hair, cord blood or neonatal hair
to the immediate and two year outcome in the infants will
be studied, while controlling for potential confounders.
The presence/amount of environmental toxins in maternal
blood, hair, cord blood, meconium and neonatal hair will
be also evaluated to determine which substrate (s) provide(s)
the best index of exposure for a given toxin.
Expected benefits: Meconium
analysis may provide a powerful tool to study the prevalence
and degree of fetal exposure to environmental toxins and
its associated adverse effects. This project can also serve
as a model for the study of environmental pollutant problems
during pregnancy at a local, national or global level.
|
Research into fluorinated pyrethroid alcohols: An episode
in the history of pyrethroid discovery.
Author: NAUMANN K
Author Address: Landwirtschaftszentrum Monheim, Bayer AG,
D-51368 Leverkusen, Germany.
Source: PESTICIDE SCIENCE; 52 (1). 1998.
3-20.
BIOSIS
COPYRIGHT: BIOL ABS. An account of pyrethroid research from
1975 to 1985 at Bayer AG is given. The exploitation of fluorine
chemistry for this purpose led to increased activity of
known 3-phenoxybenzyl pyrethroid esters and to the commercialization
of the broad-spectrum insecticide cyfluthrin, the particularly
tick-toxic flumethrin and the rapid-acting household insecticides
fenfluthrin and transfluthrin.
The last two constituted in 1976 a novel type of pyrethroid,
based on polyfluorinated benzyl alcohols, off the mainstream
of published pyrethroid research. Transfluthrin, the single
isomer (1R)trans-permethric acid ester of 2,3,5,6-tetrafluorobenzyl
alcohol has just been introduced to the market. The
history of its discovery and structure-activity data as
well as resistance considerations regarding cyfluthrin,
are presented.
|
•••
Note:
This following excerpts were transcribed from the report available
on the web. While one can easily read this report on the web,
the report is locked to any attempt to copy it. Any errors
are mine. EC. |
Bladder
(click
on for all fluorinated pesticides)
-- The target organs were the liver
(rat, mouse and dog) and
kidney (rat). There was evidence
of liver hypertrophy in the rat from 250
mg kg d (28 study) and after administration for 90 d at 500 ppm
(equivalent to 40 mg kg d), in the dog from 350 ppm (equivalent
to 14 mg kg d) after 90 d administration and from 30 ppm (equivalent
to1 mg kg d) after 1 yr and in the mouse, from 1000 pppm (equivalent
to 280 mg kg d) after 2 yr administration. Increased kidney weights,
proximal tubule degeneration and regenertion and increases in
protein in the urine were observed in male rats from 50 ppm and
in females from 500 ppm. Similar pathological findings were seen
after 2 yr dietary administration with focal
hyperplasia in the urinary bladder in both sexes at 2000
ppm in the rat and hepatocyte hypertrophy at 1000 ppm in the mouse.
In the rat, increases in fluoride content
of teeth and bone were observed from 50 ppm in oral studies
and at 200 mg m3 following inhalation exposure in 90 d studies.
-- Carcinogenicity. There is an increased incidence of
urinary blader papillomas and carcinomas (at a very low
incidence) in males and females at 2000 ppm in mice
(females only) at 1000 ppm. Both types of tumour are considered
to arise via a non genotoxic mechanism. Studies
using rat hepatocytes showed that transfluthrin
does not cause cell proliferation but acts as a weak promotor
with a NOEL of 5 ppm.
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Body
Weight Decrease
(click
on for all fluorinated pesticides)
Reproductive Toxicity.
Developmental studies in both the rat and
rabbit provided no evidence of teratogenicity when transfluthrin
was administered at 125 and 150 mg kg d respectively. One death
occurred at 125 mg kg d in the rat study and 2 deaths (1 each
at 50 and 150 mg kg d) occurred in the rabbit study. NOELs of
15 and 15 mg kg d were established for maternal toxicity in the
rat and rabbit respectively. These were based
tremors at 55 mg kg d in the rat and mortality (following severe
tremors) at 50 mg kg d in the rabbit. In a dietary multi-generation
reproductive toxicity study in the rat there was no evidence of
teratogenicity, foetotoxicity or maternal reproductive toxicity
in rats administered transfluthrin at doses up to 191 mg kg d.
NOELS of 62-191 and 9-38 mg kg d were established for maternal
reproductive and parental toxicity respectively. The NOEl for
parental toxicity was based on the following observations at 1000
ppm: - decreased body weight and
body weight gain, increased absolute and
relative liver and kidney weights, increased relative kidney weight,
decreased hepatic triglyceride content, increased incidence of
tubular pigmentation, tubular casts and pelvic calcinosis.
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Bone
(click
on for all fluorinated pesticides)
-- The target organs
were the liver (rat,
mouse and dog) and kidney
(rat)... In the rat, increases
in fluoride content of teeth and bone were observed from
50 ppm in oral studies and at 200 mg m3 following inhalation exposure
in 90 d studies.
-- Reproductive Toxicity. Developmental studies in both the rat
and rabbit provided no evidence of teratogenicity when
transfluthrin was administered at 125 and 150
mg kg d respectively. One death occurred at 125 mg kg d in the
rat study and 2 deaths (1 each at 50 and 150 mg kg d) occurred
in the rabbit study... The NOEl for parental toxicity was based
on the following observations at 1000 ppm: - decreased body weight
and body weight gain, increased absolute and relative liver and
kidney weights, increased relative kidney weight, decreased hepatic
triglyceride content, increased incidence of tubular pigmentation,
tubular casts and pelvic calcinosis.
-- In a 90 d study Bor: WISW (SPF Cpb) rats
(10 animals/sex/group) were administered diets containing 0, 10,
50, 500 or 5000 ppm transfluthrin (95% pure) in food moistened
with peanut oil to avoid dust. The main study groups were treated
for 13 w and 2 satellite groups had been intended as recovery
groups from weeks 14-18 but were treated by accident. Animals
were observed twice daily and clinical laboratory examinations
carried out at 1 and 3 months... There was a dose-dependent
increase in tooth fluoride content (significant above 50 ppm)
reaching ~ 525% in males, ~350% in females at 14 w...
The NOEL for this study was 10 ppm (0.85 mg kg d) based on the
effects at and above 50 ppm (4.0 mg kg d) of significant
increase in fluoride levels in teeth and bone in both sexes
and evidence of kidney toxicity (based on absolute and relative
weight increases in both sexes and urinary protein content increases
in males). In addition liver and thyroid toxicity was noted at
500 and 5000 pm.
-- In a 90 d study Bor: WISW (SPF-Cpb) rats
(10 animals/sex/group) were exposed via head and nose to an aerosol
of transflutrin (95^ pure) in polyethylene glycol E400 and ethanol
(1:1) for 6 h d and 5 d w. In addition 2 satellite groups were
exposed to the vehicle or the top concentration and then observed
for a further 4 w post-treatment. The measured exposure concentrations
used were 0 (air and vehicle controls), 4.9, 46.7 or 220.2 mg
m-3 (a top dose of 338.9 mg m-3 was used for 1 d. Due to a high
mortality rate this was reduced to 220.2 mg m-3, the animals replaced
and the study continued). ... Fluoride concentration
measurements of bone ash showed a significant increase of approximately
30% in males at 220.2 mg m-3 both at the end of treatment
and post treatment phases. Fluoride concentration
teeth was significantly increased in females at 220.2 mg
m-3 by approximately 50%. ... The NOEC for this study was 46.7
mg m=3. This is based on clinical signs of toxicity, increased
fluoride incorportion into teeth and bone, and non-specific
clinical chemistry changes at 220.2 mg m-3.
-- 3.3.3.4 Summary ... Following
oral administratin the major target organ in the rat and dog was
the liver, with evidence of kidney toxicity also seen in the
rat. Fluoride
determinations were undertaken in the rat
only and showed evidence of accumulation in teeth and bone
from 50 ppm (4 mg kg d)...
-- 3.2.3.2 In Vivo Studies. In a micronucleus study, Bor: NMRI
(SPF Han) mice (5/sex) received a
single gavage dose of 375 mg kg transfluthrin (95% pure) in Lutrol
E 400. This dose was chosen following a range finding study in
which mice received doses of between 250 and 2500 mg kg. In the
range finding study, mortalities (1/5) and significant signs of
toxicity (roughened fur, lateral position, twitching, spasm, salivation
and shivering) were observed at 475 mg kg
and above. In the main study similar signs of toxicity were observed
for up to 24 h post dosing. It was reported that 7/40 animals
died during this study and that a replacement group were treated
in parallel to replace the animals which died. Sampling was undertaken
at 24, 48 and 72 h post dosing. 1000 PCE's were scroed per animal
and NCE's per 1000 PCE. Individual results were not reported.
The PCE/NCE ratio as 1.06, 0.74 and 1.36 at 24, 48 and 72 h. Thus
there is some indication of bone marrow
toxicity at 48 h.
-- 3.2.4 Carcinogenicity Studies. ... In a combined chronic toxicity
and carcinogenicity study, groups of 60 Wistar
rats (strain Bor:WISW (SPF Cpb) of both sexes were administered
transfluthrin (94.5-95% pure) in the diet at concentrations of
0, 20, 200 or 2000 ppm for 109 weeks. In addition, groups of 10
male and 10 female rats were treated identically for full interim
necropsy at 52 weeks.... Fluoride accumulation
occurred in both teeth and bone (femur) at 200 and 2000
ppm in males and females at 1 and 2 yr. The reported increases
were approximately 2 and 5 fold for teeth
(from 0.1 to 0.8 mg F/g ash) and 2 and 4 fold for bone (0.5-3
mg F/g ash). The main target organs
were the liver and kidney...
-- B6C3F1 mice (60/group/sex) received
0, 10, 100 or 1000 ppm mg kg transfluthrin (94.8-95%) pure in
the diet for up to 104 weeks with 10/sex/dose killed after one
yar. Two additional groups(10/sex) received 0 or 1000 ppm for
13 weeks. ... Fluoride accumulation in bone
and teeth of both sexes were observed (in the 13 week study
at 1000 ppm) and at 53 and 104 weeks from 100 ppm (approximately
2 fold at 100 ppm and 4-5 fold at 1000 ppm with respect to controls).
... Based on the chronic toxicity, in males the NOEL is 10 ppm
(2 mg kg d based on increases in liver weight
and hepatocyte hypertrophy, at 1000 ppm and increased
fluoride accumulation at 100 ppm). It is not possible to
set a NOEL for females as increases in serum
cholesterol, protein and albumin were reported at the lowest
dose.
-- 3.2.4 Carcinogenicity Studies. The two available studies, in
the rate and mouse both combine chronic toxicity and carcinogenicity...
Single incidences of tumours occurring in treated groups but not
controls were reported in the kidneys, ovaries, brain, parathyroid
and skeletal muscle. Neither these,
nor the occasional incidences of systemic tumors presented in
Table 3.3 were considered to be treatment related (page 23).
-- 3.2.5 Reproductive Toxicology. 3.2.5.1 Developmental Studies.
3.2.5.1.1 Rat. In an adequately conducted
developmental toxicology study, rats (28.group) were administered
transfluthrin )95%) purity in 5% (v/v) aqueous Emulphor EL 719
vehicle by gavage at doses of 0, 25, 55 and 125 mg kg d during
days 6-15 of gestation. Control animals received vehicle alone...
Necropsy of the dams and examination of the foetuses were performed
on day 20 of gestation. ... A significant
increase in delayed ossification was observed for 3 skeletal elements
(cervical arches, first and second sternebrae) at 55 mg
kg d. However, this finding was not dose-dependent and there was
no indication of delayed systemic ossificaiton. Therefore, this
observation is considered incidental.. Transfluthrin was not teratogenic
under the conditions of study. The NOEL for maternal toxicity
was 25 mg kg d based upon tremors observed at 55 mg kg d and above.
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Brain
(click
on for all fluorinated pesticides)
-- 3.2.4 Carcinogenicity
Studies. The two available studies, in the rate and mouse both
combine chronic toxicity and carcinogenicity... Single incidences
of tumours occurring in treated groups but not controls were reported
in the kidneys, ovaries, brain, parathyroid
and skeletal muscle. Neither these, nor the occasional incidences
of systemic tumors presented in Table 3.3 were considered to be
treatment related (page 23).
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Cholesterol
(click
on for all fluorinated pesticides)
-- In 2 yr studies
the NOEL for non-neoplastic findings in the
rat was 20 ppm (1 mg kg d) based on efffects in the kidney
(increased organ weight, pigment deposition and glomerulonephrosis)
at 200 ppm and above). In the mouse, the NOEL was 10 ppm in males
(based on increases in liver weight, hepatocyte hypertrophy at
1000 ppm and fluoride accumulation at 100 ppm). It
was not possible to set a NOEL
for females as increases in serum cholesterol, protein
and albumin were reported at the lowest dose.
-- In 90 d study Beagles (4/sex/group)
were administered transfluthrin (94.5%0 pure via their food at
nominal concentrations of 0, 50, 350 or 2500 ppm. Haematological
and urine examinations were carried out on all grops pre study
and at 3, 6 and 13 w. Ophthalmological examinations were carried
out pre study, 6 and 13 w, and hearing tests were carried out
pre study and 13 w. ... The haematological and urine examinations
showed no treatment related changes. The clinical chemistry examination
indicated treatment related effects on the
liver. At 2500 ppm increases in cholesterol
levels were noted in both sexes which increased with time
(~ 35-70% in males and ~ 60-80% in females
over `- 13 w). In addition at 13
w plasma lipid and triglyceride levels were increased in both
sexes (~ 110-120%). N-demethylase activity was increased in both
sexes at 2500 ppm (~ 35%). At 13 w the examination also noted
a decrease in thyroxine levels in females (~ 45%) and a non-significant
decrease in triiodothyronine (~ 40%) at 2500 ppm. At necropsy,
gross pathological examination noted no treatment related changes.
At 2500 ppm relative (to the brain) liver weights increased in
both sexes (~ 30% in males and ~50% in females) and thyroid weight
increased non-significantly in females (~ 70%). Histopathological
examination showed centrilobular hypertrophy in all animals at
2500 ppm and 1 female from this group with minimal hepatocytic
single cell necrosis. The NOEL for this study was 50 ppm
(1.9 kg d) based on the increase in N-demethylase activity in
males at 350 ppm (14 mg kg d).
-- B6C3F1 mice (60/group/sex) received
0, 10, 100 or 1000 ppm mg kg transfluthrin (94.8-95%) pure in
the diet for up to 104 weeks with 10/sex/dose killed after one
yar. Two additional groups(10/sex) received 0 or 1000 ppm for
13 weeks... Serum cholesterol levels were
significantly raised from 13 weeks at 1000 ppm (20%
in males and 54% in females) and from 100 ppm from week
53 (approximately 11 - 30%) and at week
103 from 10 ppm in females (approximately 50 - 70%) and
at 1000 ppm in males )~ 20%). ... Based on the chronic toxicity,
in males the NOEL is 10 ppm (2 mg kg d based on increases in
liver weight and hepatocyte hypertrophy, at 1000 ppm and increased
fluoride accumulation at 100 ppm). It
is not possible to set a NOEL for females as increases in serum
cholesterol, protein and albumin were reported at the lowest dose.
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
CNS
(click
on for all fluorinated pesticides)
3.2.5.1.2 Rabbit. In
an adequately conducted teratology study, pregnant Himalayan rabbits
(15/group) were administered transfluthrin (94% purity) in 0.5%
(v/v) aqueous Cremophor EM emulsion by gavage at doses of 0, 15,
50 and 150 mg kg d during days of 6-18 of gestation. Control animals
received vehicle alone... Dams were necropsied on day 29 of gestation
following delivery of the foetuses by caesarean section. Two deaths
occurred, one on day 18 at 50 mg kg d and one on day 19 at 150
mg kg d. Immediately prior to death both animals displayed symptoms
consistent with CNS involvement inclusing
spasms, severe tremor and prostration (animals found lying on
their side). Autopsy of these animals revealed an enlarged lobulated
liver and pale lobulated lungs at 50 mg kg d whereas no
pathological fingings were observed at 150 mg kg d.
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Dermal
(click
on for all fluorinated pesticides)
3.2.2.2 Dermal. In a repeat dose study groupsof HC:NZW New Zealand
white rabbits (5 animals/sex/group)
received applications of 0, 20, 200 or 1000 mg kg transflurthrin
(95% pure) in cremophor E1 (2 ml kg) under a gauze dressing for
6 h d 5 d w for 3 w. Further groups were treated with 0 and 1000
mg kg and then observed for a further 14 day. ... At necropsy
white, yellow, glazing and/or cratering were noted in kidneys
at the end of both the treatment and post treatment periods. Kidney
weights were increased by ~ 35% relative in males at 20
mg kg at the end of the treatment period but not at the end of
the post-treatment period. These were attributed to an infestation
of Nosema cuniculi. Histopathological examination revealed
effects on the kidney (unspecified nephropathy at the end of both
treatment and post treatment in all groups). Epidermal
thickening was noted in 7/10 animals at 200 mg kg and all
animals at 1000 mg kg. Hyperkeratosis was
observed in 2/10 animals at 200 mg kg and 7/10 a 1000 mg kg. Apart
from 1 female case of epidermal erosion, skin pathology was absent
at the end of the post-treatment period. The NOEL was 20 mg kg
based on the epidermal thickening and hyperkeratosis
seen at and above 200 mg kg in both sexes.
-- B6C3F1 mice (60/group/sex) received
0, 10, 100 or 1000 ppm mg kg transfluthrin (94.8-95%) pure in
the diet for up to 104 weeks with 10/sex/dose killed after one
yar. Two additional groups(10/sex) received 0 or 1000 ppm for
13 weeks... Serum
cholesterol levels were significantly raised from
13 weeks at 1000 ppm (20% in males and 54% in females) and from
100 ppm from week 53 (approximately 11 - 30%) and at week 103
from 10 ppm in females (approximately 50 - 70%) and at 1000 ppm
in males )~ 20%). ... Fluoride accumulation in bone and teeth
of both sexes were observed (in the 13 week study at 1000 ppm)
and at 53 and 104 weeks from 100 ppm (approximately 2 fold at
100 ppm and 4-5 fold at 1000 ppm with respect to controls). ...
The only gross pathological findings considered to be treatment
related were nodules in the livers of females at 1000 ppm (incidence
6/42, 4/39, 3/42 and 15/44). On histopathological examination,
at 1000 ppm, non neoplastic findings were periacinar hepatocyte
hypertropy was observed at 53 weeks (slight to moderate in all
males and minimal in 6/10 females) and more marked but consistent
with liver enzyme induction at 104 weeks (38/50 males, 26/50 females).
... The incidences of hepatocellular carcinoma were within the
historical control range for the laboratory (1 - 5 in females
for studies using 50 animals), whereas the adenoma incidence of
13/50 exceeded the range (1 - 9). The low incidences of
other tumours (haemangiosarcoma in the spleen,
sarcoma of the subcutis and
adenoma of the harderian gland) observed
at the top dose in females were not statistically significant.
... Based on the chronic toxicity, in males the NOEL is 10 ppm
(2 mg kg d based on increases in liver weight and hepatocyte hypertrophy,
at 1000 ppm and increased fluoride accumulation at 100 ppm). It
is not possible to set a NOEL for females as increases in serum
cholesterol, protein and albumin were reported at the lowest
dose.
Ref: Evaluation on: Transfluthrin Use as a Public Hygiene Insecticide.
September 1997. Prepared by: the UK 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.
Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
•
Defintion of Subcutis:
The skin has 3 layers called the epidermis, dermis, and subcutis.
The last and deepest layer of the skin is called the subcutis.
The subcutis and the lowest part of the dermis form a network
of collagen and fat cells. The subcutis conserves heat and has
a shock-absorbing effect that helps protect the body's organs
from injury.
Ref: What is Nonmelanoma Skin Cancer? American
Cancer Society.
http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_skin_cancer_51.asp
Endocrine:
Adrenal (click
on for all fluorinated pesticides)
3.2.4 Carcinogenicity
Studies. ... In a combined chronic toxicity and carcinogenicity
study, groups of 60 Wistar rats (strain
Bor:WISW (SPF Cpb) of both sexes were administered transfluthrin
(94.5-95% pure) in the diet at concentrations of 0, 20, 200 or
2000 ppm for 109 weeks. In addition, groups
of 10 male and 10 female rats were treated identically for full
interim necropsy at 52 weeks... Benign
adrenal tumours seen in males are within the control ranges
for Wistar rats...
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Endocrine:
Thyroid (click
on for all fluorinated pesticides)
3.2.2.1 Oral Route
... At 250 mg kg and 28 d, in both sexes, there were absolute
and body weight relative increases in liver
(15-20%) and kidney weights (~ 10%). In males absolute
and body weight relative thyroid weight
increases were also observed (20-25%). These changes were reversed
by 56 d... In all males at 500 ppm and
5000 ppm and in three males treated
for 19 w the thyroid follicular epithelium was hypertrophied and
colloid was depleted. The NOEL for this study was 10 ppm
(0.85 mg kg d) based on the effects at and above 50 ppm (4.0 mg
kg d) of significant increase in fluoride
levels in teeth and bone in both sexes and evidence of
kidney toxicity (based on absolute and relative weight increases
in both sexes and urinary protein content increases in
males). In addition liver and
thyroid toxicity was noted at 500 and 5000 pm.
-- In 90 d study Beagles (4/sex/group)
were administered transfluthrin (94.5%0 pure via their food at
nominal concentrations of 0, 50, 350 or 2500 ppm. Haematological
and urine examinations were carried out on all grops pre study
and at 3, 6 and 13 w. Ophthalmological examinations were carried
out pre study, 6 and 13 w, and hearing tests were carried out
pre study and 13 w. ... The haematological and
urine examinations showed no treatment related changes. The clinical
chemistry examination indicated treatment related effects on the
liver. At 2500 ppm increases in cholesterol levels were noted
in both sexes which increased with time (~ 35-70% in males and
~ 60-80% in females over `- 13 w). In addition at 13 w plasma
lipid and triglyceride levels were increased in both sexes (~
110-120%). N-demethylase activity was increased in both sexes
at 2500 ppm (~ 35%). At 13 w the examination also noted
a decrease in thyroxine levels in females
(~ 45%) and a non-significant decrease in triiodothyronine
(~ 40%) at 2500 ppm. At necropsy, gross pathological examination
noted no treatment related changes. At 2500 ppm
relative (to the brain) liver weights increased in both sexes
(~ 30% in males and ~50% in females) and thyroid
weight increased non-significantly in females (~ 70%)...
-- 3.3.3.4 Summary ... Following
oral administratin the major target organ in the rat and dog was
the liver, with evidence of kidney toxicity also seen in the rat.
Fluoride determinations were undertaken in the rat only and showed
evidence of accumulation in teeth and bone from 50 ppm
(4 mg kg d). In the rat, mortalities and body tremors
were seen at 250 mg kg d following gavage dosing. ... In
the liver, absolute and relative organ weight increases (recovering
following cessation of treatment) together with clinical chemistry
and histopathological evidence of hepatocyte hypertrophy were
observed from 500 ppm and at 250 mg kd d. There was also evidence
of kidney toxicity from 50 ppm (absolute and body weight relative
increases in kidney weight in both sexes ... In the thyroid,
hypertrophy of the thyroid follicular epithelium and colloid depletion
was reported from 500 ppm. The NOEl was 10 ppm (0.85 kg d).
-- 3.2.4 Carcinogenicity
Studies. ... In a combined chronic toxicity and carcinogenicity
study, groups of 60 Wistar rats (strain
Bor:WISW (SPF Cpb) of both sexes were administered transfluthrin
(94.5-95% pure) in the diet at concentrations of 0, 20, 200 or
2000 ppm for 109 weeks. In addition, groups of 10 male and 10
female rats were treated identically for full interim necropsy
at 52 weeks... At 52 weeks at 2000 ppm in males there was an increased
incidence of "cuboidal follicular epithelium"
in the thyroid (in 7/10 animals) and at the end of the
study, a slight increase in thryoid follicular
cell hyperplasia in males and females at 200 and 2000 ppm
(incidences 0, 0, 3. 3 and 0. 0, 1, 2 at 0, 20, 200 and 2000 ppm).
... There is no evidence of a treatment related increase in thyroid
tumour incidence and the low numbers of
hepatocellular adenoma/carcinoma are considered to be within the
historical control range. Benign adrenal tumours seen in males
are within the control ranges for Wistar rats. There is a low
but increased incidence of urinary bladder tumours at 2000 ppm
in both sexes. The mechanixm is considered to be non genotoxic
given the increased incidence of urinary epithelial hyperplasia
in both sexes, at this dose. ... A NOEL for non-neoplastic findings
is 20 ppm ( 1 mg kg d, based on effects in the kidney (increased
organ weight, pigment deposition and glomerulonephrosis) at 200
ppm and above).
-- 3.2.4 Carcinogenicity Studies. The two available studies, in
the rate and mouse both combine chronic toxicity and carcinogenicity...
Single incidences of tumours occurring in treated groups but not
controls were reported in the kidneys, ovaries, brain, parathyroid
and skeletal muscle. Neither these, nor the occasional incidences
of systemic tumors presented in Table 3.3 were considered to be
treatment related (page 23).
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Genotoxic
(click
on for all fluorinated pesticides)
Abstract: ...
Our study describes the genotoxic effects
of PCP, lindane, transfluthrin,
cyfluthrin, and natural pyrethrum
on human mucosal cells of the inferior and
middle nasal conchae.
METHODS: Epithelial cells were isolated from nasal mucosa, which
was removed in the surgical treatment of chronic sinusitis and
nasal concha hyperplasia. After the cells had been tested for
vitality using the trypan blue exclusion test, the short-term
culture method was used. The material was incubated with PCP (0.3,
0.75, and 1.2 mmol), lindane (0.5, 0.75, and 1.0 mmol), transfluthrin
(0.05, 0.1, 0.5, 0.75, and 1.0 mmol), cyfluthrin (0.05, 0.1, 0.5,
0.75, and 1.0 mmol), natural pyrethrum (0.001, 0.005, 0.01, 0.05,
and 0.1 mmol), and N-methyl-N'-nitro-N-nitrosoguanidine for 60
minutes. Substance-induced DNA damage (single-strand and double-strand
breaks) were determined using single-cell microgel electrophoresis.
A fluorescence microscope was used together with an image processing
system to analyze the results obtained.
RESULTS: After exposure to all tested substances, a high percentage
of the cells of the middle nasal concha in particular were found
to have severely fragmented DNA as a result of strong genotoxic
effects. Although the reaction of the cells of the inferior nasal
concha was significantly less strong (p < 0.001), the tested
substances were nevertheless found to have a notable genotoxic
effect on these cells too.
CONCLUSION: Our study strongly suggests
that exposure to PCP, lindane, transfluthrin, cyfluthrin, and
natural pyrethrum has a genotoxic effect on the epithelial cells
of human nasal mucosa. In addition, we have shown that
nasal structures differ in susceptibility to the various pesticides
used in the tests. Thus, the study provides new evidence supporting
the biological plausibility of PCP- and lindane-induced effects,
thereby helping evaluate potential PCP- and lindane-induced mucous
membrane carcinomas of these parts of the nose. In addition, our
study shows that other substances that today are widely used for
controlling pests have a considerable genotoxic effect on human
target cells. The results obtained indicate the need for additional
studies on the genotoxicity of these substances and their adverse
effects on human health.
Ref: Genotoxic effects of pentachlorophenol,
lindane, transfluthrin, cyfluthrin, and natural pyrethrum on human
mucosal cells of the inferior and middle nasal conchae; by Tisch
M, Faulde MK, Maier H. Am J Rhinol. 2005 Mar-Apr;19(2):141-51.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15921213&query_hl=2
Kidney
(click
on for all fluorinated pesticides)
-- The target organs
were the liver (rat,
mouse and dog) and kidney
(rat). There was evidence of
liver hypertrophy in the rat from 250 mg kg d (28 study) and after
administration for 90 d at 500 ppm (equivalent to 40 mg
kg d), in the dog from 350 ppm (equivalent to 14 mg kg d) after
90 d administration and from 30 ppm (equivalent to1 mg kg d) after
1 yr and in the mouse, from 1000 pppm (equivalent to 280 mg kg
d) after 2 yr administration. Increased kidney
weights, proximal tubule degeneration
and regenertion and increases in protein in the urine were observed
in male rats from 50 ppm and in females
from 500 ppm. Similar pathological findings were seen after
2 yr dietary administrationwith focal hyperplasia in the urinary
bladder in both sexes at 2000 ppm in the rat and hepatocyte hypertrophy
at 1000 ppm in the mouse. In the rat, increases in fluoride content
of teeth and bone were observed from 50 ppm in oral studies and
at 200 mg m3 following inhalation exposure in 90 d studies.
-- In 2 yr studies the NOEL for non-neoplastic findings in the
rat was 20 ppm (1 mg kg d) based on efffects in the kidney
(increased organ weight, pigment
deposition and glomerulonephrosis) at 200 ppm and above).
In the mouse, the NOEL was 10 ppm in males
(based on increases in liver weight, hepatocyte hypertrophy at
1000 ppm and fluoride accumulation at 100 ppm). It was not possible
to set a NOEL for females as increases in serum cholesterol, protein
and albumin were reported at the lowest dose.
-- Reproductive Toxicity. Developmental studies in both the rat
and rabbit provided no evidence of teratogenicity when
transfluthrin was administered at 125 and 150 mg kg d respectively.
One death occurred at 125 mg kg d in the rat study and 2 deaths
(1 each at 50 and 150 mg kg d) occurred in the rabbit study.
NOELs of 15 and 15 mg kg d were established for maternal toxicity
in the rat and rabbit respectively. These were based tremors at
55 mg kg d in the rat and mortality (following severe tremors)
at 50 mg kg d in the rabbit. In a dietary multi-generation reproductive
toxicity study in the rat there was no evidence of teratogenicity,
foetotoxicity or maternal reproductive toxicity in rats administered
transfluthrin at doses up to 191 mg kg d. NOELS of 62-191 and
9-38 mg kg d were established for maternal reproductive and parental
toxicity respectively. The NOEl for parental toxicity was based
on the following observations at 1000 ppm: - decreased body weight
and body weight gain, increased absolute and relative liver and
kidney weights, increased relative
kidney weight, decreased hepatic
triglyceride content, increased incidence of tubular
pigmentation, tubular casts and pelvic
calcinosis.
-- 3.2.2.1 Oral Route ... At 250 mg kg and 28 d, in both sexes,
there were absolute and body weight relative increases
in liver (15-20%) and kidney
weights (~ 10%). In males absolute and body weight relative
thyroid weight increases were also observed (20-25%). These changes
were reversed by 56 d. Of animals dying during treatment that
could be examined (5/7), the females exhibited slight congestion
and haemorrhage of the lung with 2 cases of focal alveolar emphysema
and 1 of alveolar oedema. The male had congested
kidneys. There was no other treatment-related pathology
during treatment or at the end of the post-treatment periods.
The NOEL was 50 mg kg d based on the effects seen at 250 mg kg
d (organ weight changes in both sexes which had reversed by 46
d).
-- In a 90 d study Bor: WISW (SPF Cpb) rats
(10 animals/sex/group) were administered diets containing 0, 10,
50, 500 or 5000 ppm transfluthrin (95% pure) in food moistened
with peanut oil to avoid dust. The main study groups were treated
for 13 w and 2 satellite groups had been intended as recovery
groups from weeks 14-18 but were treated by accident. Animals
were observed twice daily and clinical laboratory examinations
carried out at 1 and 3 months. An opthalmological examination
was carried out at the start of the study, at 13 w and in the
satellite group at 17 w. At necropsy fluoride levels in teeth
and bone were measured. During the study 2 female, treated at
10 and 0 ppm, died during weeks 6 and 18 respectively. One died
during blood sampling, the other was sacrified due to eye trauma...
There was a dose-dependent increase in tooth fluoride content
(significant above 50 ppm) reaching ~ 525% in males, ~350% in
females at 14 w. ... At necropsy there was evidence of
effects on the liver and
kidney at 500 and 5000 ppm... In addition at 5000 ppm there
was a significant increase (50%) in the numbers of animals of
both sexes with degenerated hepatocytes.
Relative and absolute kidney
weights were increased in males at
13 and 19 w by 10-15% at and above 50 ppm. In females a slight
increase (! 5%) was reported in relative weight only at 19 w.
Histopathological examination showed proximal
convoluted tubule degeneration in both sexes at 13 w not
19 w and a significant increase (~ 30%) in animals with basophilic
tubules. In all males at 500 ppm and
5000 ppm and in three males treated for 19 w the thyroid follicular
epithelium was hypertrophied and colloid was depleted. The NOEL
for this study was 10 ppm (0.85 mg kg d) based on the effects
at and above 50 ppm (4.0 mg kg d) of significant increase in fluoride
levels in teeth and bone in both sexes and evidence of
kidney toxicity (based on absolute
and relative weight increases in both sexes and urinary protein
content increases in males). In addition
liver and thyroid toxicity was noted at 500 and 5000 pm.
-- 3.2.2.2 Dermal. In a repeat dose study groupsof HC:NZW New
Zealand white rabbits (5 animals/sex/group)
received applications of 0, 20, 200 or 1000 mg kg transflurthrin
(95% pure) in cremophor E1 (2 ml kg) under a gauze dressing for
6 h d 5 d w for 3 w. Further groups were treated with 0 and 1000
mg kg and then observed for a further 14 day. ... At necropsy
white, yellow, glazing and/or cratering
were noted in kidneys at the end of both the treatment
and post treatment periods. Kidney weights
were increased by ~ 35% relative in males at 20 mg kg at the end
of the treatment period but not at the end of the post-treatment
period. These were attributed to an infestation of Nosema cuniculi.
Histopathological examination revealed effects on the kidney
(unspecified nephropathy at the end of both treatment and post
treatment in all groups)...
-- 3.3.3.4 Summary ... Following oral administratin
the major target organ in the rat and dog was the liver, with
evidence of kidney toxicity also
seen in the rat.
Fluoride determinations were undertaken in the rat only and showed
evidence of accumulation in teeth and bone from 50 ppm (4 mg kg
d). In the rat, mortalities and body tremors were seen at 250
mg kg d following gavage dosing. ... In the liver, absolute and
relative organ weight increases (recovering following cessation
of treatment) together with clinical chemistry and histopathological
evidence of hepatocyte hypertrophy were observed from 500 ppm
and at 250 mg kd d. There was also evidence of
kidney toxicity from 50 ppm (absolute and body weight relative
increases in kidney weight in both sexes ...
In the thyroid, hypertrophy of the thyroid follicular epithelium
and colloid depletion was reported from 500 ppm. The NOEl was
10 ppm (0.85 kg d).
-- 3.2.4 Carcinogenicity Studies. ... In a combined chronic toxicity
and carcinogenicity study, groups of 60 Wistar
rats (strain Bor:WISW (SPF Cpb) of both sexes were administered
transfluthrin (94.5-95% pure) in the diet at concentrations of
0, 20, 200 or 2000 ppm for 109 weeks. In addition, groups of 10
male and 10 female rats were treated identically for full interim
necropsy at 52 weeks.... Fluoride accumulation
occurred in both teeth and bone (femur) at 200 and 2000 ppm in
males and females at 1 and 2 yr. The reported increases were approximately
2 and 5 fold for teeth (from 0.1 to 0.8 mg F/g ash) and 2 and
4 fold for bone (0.5-3 mg F/g ash). The
main target organs were the liver and kidney. ... A NOEL
for non-neoplastic findings is 20 ppm ( 1 mg kg d, based on effects
in the kidney (increased organ weight, pigment
deposition and glomerulonephrosis) at 200 ppm and above).
-- 3.2.4 Carcinogenicity Studies. The two available studies, in
the rate and mouse both combine chronic toxicity and carcinogenicity...
Single incidences of tumours occurring in treated groups but not
controls were reported in the kidneys,
ovaries, brain, parathyroid and skeletal muscle. Neither these,
nor the occasional incidences of systemic tumors presented in
Table 3.3 were considered to be treatment related (page 23).
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Liver
(click
on for all fluorinated pesticides)
-- The target organs
were the liver (rat,
mouse and dog) and kidney (rat).
There was evidence of liver hypertrophy
in the rat from 250 mg kg d (28 study) and after administration
for 90 d at 500 ppm (equivalent to 40 mg kg d), in the dog from
350 ppm (equivalent to 14 mg kg d) after 90 d administration and
from 30 ppm (equivalent to1 mg kg d) after 1 yr and in the mouse,
from 1000 pppm (equivalent to 280 mg kg d) after
2 yr administration. Increased kidney weights, proximal tubule
degeneration and regenertion and increases in protein in the urine
were observed in male rats from 50 ppm and in females from 500
ppm. Similar pathological findings were seen after 2 yr dietary
administrationwith focal hyperplasia in the urinary bladder in
both sexes at 2000 ppm in the rat and hepatocyte hypertrophy at
1000 ppm in the mouse. In the rat, increases in fluoride content
of teeth and bone were observed from 50 ppm in oral studies and
at 200 mg m3 following inhalation exposure in 90 d studies.
-- The NOEL's following 90 d oral administration were 10 ppm (equivalent
to 0.85 mg kg d) in the rat and 50
ppm (equivalent to 1.9 mg kg d) in the dog.
It was not possible to set a NOEL following dietary administration
for 1 yr in the dog as there was some slight evidence of
liver hypertrophy at the lowest dose (10 ppm)...
-- In 2 yr studies the NOEL for non-neoplastic findings in the
rat was 20 ppm (1 mg kg d) based on efffects in the kidney
(increased organ weight, pigment deposition and glomerulonephrosis)
at 200 ppm and above). In the mouse, the NOEL was 10 ppm in males
(based on increases in liver weight,
hepatocyte hypertrophy at 1000 ppm
and fluoride accumulation at 100 ppm). It
was not possible to set a NOEL for females as increases in serum
cholesterol, protein and albumin were reported at the lowest
dose.
-- Reproductive Toxicity. Developmental studies in both the rat
and rabbit provided no evidence of teratogenicity when
transfluthrin was administered at 125 and 150 mg kg d respectively.
One death occurred at 125 mg kg d in the rat study and 2 deaths
(1 each at 50 and 150 mg kg d) occurred in
the rabbit study. NOELs of 15 and 15 mg kg d were established
for maternal toxicity in the rat and rabbit respectively. These
were based tremors at 55 mg kg d in the rat and mortality (following
severe tremors) at 50 mg kg d in the rabbit. In a dietary multi-generation
reproductive toxicity study in the rat there was no evidence of
teratogenicity, foetotoxicity or maternal reproductive toxicity
in rats administered transfluthrin at doses up to 191 mg kg d.
NOELS of 62-191 and 9-38 mg kg d were established for maternal
reproductive and parental toxicity respectively. The NOEl
for parental toxicity was based on the following observations
at 1000 ppm: - decreased body weight and
body weight gain, increased absolute and relative liver
and kidney weights, increased
relative kidney weight, decreased hepatic triglyceride content,
increased incidence of tubular pigmentation, tubular casts and
pelvic calcinosis..
-- 3.2.2.1 Oral Route ... At 250 mg kg and 28 d, in both sexes,
there were absolute and body weight relative increases in
liver (15-20%) and kidney weights
(~ 10%). ... At necropsy there was evidence of effects
on the liver and kidney
at 500 and 5000 ppm. Relative and absolute liver
weights were increased by ~ 15% at 500 ppm, ~45% at 5000
ppm (males at 13 w) and up to ~55%
at 19 w. Histopathological examination showed centrilobular
hepatocyte hypertrophy in all males, 9/10 females at 5000
ppm and 8/10 males, 4/10 females at 500 ppm. In addition at 5000
ppm there was a significant increase (50%) in the numbers of animals
of both sexes with degenerated hepatocytes...
-- In 90 d study Beagles (4/sex/group)
were administered transfluthrin (94.5%0 pure via their food at
nominal concentrations of 0, 50, 350 or 2500 ppm. Haematological
and urine examinations were carried out on all grops pre study
and at 3, 6 and 13 w. Ophthalmological examinations were carried
out pre study, 6 and 13 w, and hearing tests were carried out
pre study and 13 w. ... The haematological and urine examinations
showed no treatment related changes. The clinical chemistry examination
indicated treatment related effects on the liver...
Histopathological examination showed centrilobular
hypertrophy in all animals at 2500 ppm and 1 female from
this group with minimal hepatocytic single
cell necrosis. The NOEL for this study was 50 ppm (1.9
kg d) based on the increase in N-demethylase activity in males
at 350 ppm (14 mg kg d).
-- 3.2.4 Carcinogenicity Studies. ... In a combined chronic toxicity
and carcinogenicity study, groups of 60 Wistar
rats (strain Bor:WISW (SPF Cpb) of both sexes were administered
transfluthrin (94.5-95% pure) in the diet at concentrations of
0, 20, 200 or 2000 ppm for 109 weeks. In addition, groups of 10
male and 10 female rats were treated identically for full interim
necropsy at 52 weeks.... Fluoride accumulation
occurred in both teeth and bone (femur) at 200 and 2000
ppm in males and females at 1 and 2 yr. The reported increases
were approximately 2 and 5 fold for teeth
(from 0.1 to 0.8 mg F/g ash) and 2 and 4 fold for bone (0.5-3
mg F/g ash). The main target organs
were the liver and kidney. ... Microscopic pathology showed
"ground galss cytoplasm" in the
liver in both sexes at 2000 ppm (approx. 9/60 for males
and females) and hepatocyte hyperplasia
in males (0, 2, 1, 1 at 0, 20, 200 and 2000 ppm)...
-- B6C3F1 mice (60/group/sex) received
0, 10, 100 or 1000 ppm mg kg transfluthrin (94.8-95%) pure in
the diet for up to 104 weeks with 10/sex/dose killed after one
yar. Two additional groups(10/sex) received 0 or 1000 ppm for
13 weeks... Serum
cholesterol levels were significantly raised from
13 weeks at 1000 ppm (20% in males and 54% in females) and from
100 ppm from week 53 (approximately 11 - 30%) and at week 103
from 10 ppm in females (approximately 50 - 70%) and at 1000 ppm
in males )~ 20%). ... Fluoride accumulation in bone and teeth
of both sexes were observed (in the 13 week study at 1000 ppm)
and at 53 and 104 weeks from 100 ppm (approximately 2 fold at
100 ppm and 4-5 fold at 1000 ppm with respect to controls).
... The only gross pathological findings considered to be treatment
related were nodules in the livers of females
at 1000 ppm (incidence 6/42, 4/39, 3/42 and 15/44). On histopathological
examination, at 1000 ppm, non neoplastic findings were periacinar
hepatocyte hypertropy was observed at 53 weeks (slight
to moderate in all males and minimal in 6/10 females) and more
marked but consistent with liver enzyme
induction at 104 weeks (38/50 males, 26/50 females). ...
Based on the chronic toxicity, in males the NOEL is 10 ppm (2
mg kg d based on increases in liver weight
and hepatocyte hypertrophy, at 1000 ppm and
increased fluoride accumulation at 100 ppm). It is not possible
to set a NOEL for females as increases in serum cholesterol, protein
and albumin were reported at the lowest dose.
-- 3.2.4.1 Promotion Studies ... 3.2.3.2 Summary. An increased
incidence of urinary bladder papillomas
and carcinomas was seen following dietary administration of 2000
ppm to the rat. The mechanism of tumourigenicity is considered
to be non genotoxic. Studies using
rat hepatocytes showed that transfluthrin does not cause cell
proliferation but acts as a weak promoter with a NOEL of 5 ppm.
Transfluthrin is not carcinogenic in the mouse. In the rat the
NOEL for non-neoplastic findings is 20 ppm (1 mg kg d), based
on effects in the kidney (increased organ
weight, pigment deposition and glomerulonephrosis) at 200 ppm
and above). In the male mouse the NOEL is 10 ppm (2 mg kg d, based
on increases in liver weight
and hepatocyte hypertrophy,
at 1000 ppm and increased fluoride accumulation
at 100 ppm). It is not possible to set a NOEL for females as increases
in serum cholesterol, protein and albumin were reported at the
lowest dose.
-- 3.2.5.1.2 Rabbit. In an adequately conducted teratology study,
pregnant Himalayan rabbits (15/group) were administered transfluthrin
(94% purity) in 0.5% (v/v) aqueous Cremophor EM emulsion by gavage
at doses of 0, 15, 50 and 150 mg kg d during days of 6-18 of gestation.
Control animals received vehicle alone... Dams were necropsied
on day 29 of gestation following delivery of the foetuses by caesarean
section. Two deaths occurred, one on day 18 at 50 mg kg d and
one on day 19 at 150 mg kg d. Immediately prior to death both
animals displayed symptoms consistent with
CNS involvement inclusing spasms, severe tremor and prostration
(animals found lying on their side). Autopsy of these animals
revealed an enlarged lobulated liver
and pale lobulated lungs
at 50 mg kg d whereas no pathological fingings were observed
at 150 mg kg d.
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Lung
(click
on for all fluorinated pesticides)
-- 3.2.2.1 Oral Route ... At 250 mg kg and 28 d, in both sexes,
there were absolute and body weight relative increases
in liver (15-20%) and kidney weights
(~ 10%). In males absolute and body weight relative thyroid weight
increases were also observed (20-25%). These changes were reversed
by 56 d. Of animals dying during treatment that could be examined
(5/7), the females exhibited slight congestion and haemorrhage
of the lung
with 2 cases of focal alveolar emphysema and 1 of alveolar oedema.
The male had congested kidneys. There was no other treatment-related
pathology during treatment or at the end of the post-treatment
periods. The NOEL was 50 mg kg d based on the effects seen at
250 mg kg d (organ weight changes in both sexes which had reversed
by 46 d).
-- 3.2.5.1.2 Rabbit. In an adequately conducted teratology study,
pregnant Himalayan rabbits (15/group) were administered transfluthrin
(94% purity) in 0.5% (v/v) aqueous Cremophor EM emulsion by gavage
at doses of 0, 15, 50 and 150 mg kg d during days of 6-18 of gestation.
Control animals received vehicle alone... Dams were necropsied
on day 29 of gestation following delivery of the foetuses by caesarean
section. Two deaths occurred, one on day 18 at 50 mg kg d and
one on day 19 at 150 mg kg d. Immediately prior to death both
animals displayed symptoms consistent with
CNS involvement inclusing spasms, severe tremor and prostration
(animals found lying on their side). Autopsy of these animals
revealed an enlarged lobulated liver and
pale lobulated lungs at 50 mg kg d whereas no pathological
fingings were observed at 150 mg kg d.
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Spleen
(click
on for all fluorinated pesticides)
B6C3F1 mice
(60/group/sex) received 0, 10, 100 or 1000 ppm mg kg transfluthrin
(94.8-95%) pure in the diet for up to 104 weeks with 10/sex/dose
killed after one yar. Two additional groups(10/sex) received 0
or 1000 ppm for 13 weeks... Serum cholesterol
levels were significantly raised from 13 weeks at 1000 ppm (20%
in males and 54% in females) and from 100 ppm from week 53 (approximately
11 - 30%) and at week 103 from 10 ppm in females (approximately
50 - 70%) and at 1000 ppm in males )~ 20%)... The incidences
of hepatocellular carcinoma were within
the historical control range for the laboratory (1 - 5 in females
for studies using 50 animals), whereas the adenoma incidence of
13/50 exceeded the range (1 - 9). The low incidences of other
tumours (haemangiosarcoma in the spleen,
sarcoma of the subcutis and adenoma
of the harderian gland) observed
at the top dose in females were not statistically significant...
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Tremors
(click
on for all fluorinated pesticides)
-- Reproductive Toxicity.
Developmental studies in both the rat and
rabbit provided no evidence of teratogenicity when transfluthrin
was administered at 125 and 150 mg kg d respectively. One death
occurred at 125 mg kg d in the rat study and 2 deaths (1 each
at 50 and 150 mg kg d) occurred in the rabbit study. NOELs of
15 and 15 mg kg d were established for maternal toxicity in the
rat and rabbit respectively. These were based tremors
at 55 mg kg d in the rat and mortality (following severe
tremors) at 50 mg kg d in the rabbit...
-- 3.3.3.4 Summary ... Following
oral administratin the major target organ in the rat and dog was
the liver, with evidence of kidney toxicity also seen in the rat.
Fluoride determinations were undertaken in the rat only and showed
evidence of accumulation in teeth and bone from 50 ppm (4 mg kg
d). In the rat, mortalities and body tremors
were seen at 250 mg kg d following gavage dosing...
-- 3.2.3.2 In Vivo Studies. In a micronucleus study, Bor: NMRI
(SPF Han) mice (5/sex) received a
single gavage dose of 375 mg kg transfluthrin (95% pure) in Lutrol
E 400. This dose was chosen following a range finding study in
which mice received doses of between 250 and 2500 mg kg. In the
range finding study, mortalities (1/5) and significant signs of
toxicity (roughened fur, lateral position, twitching, spasm, salivation
and shivering) were observed at 475
mg kg and above. In the main study similar signs of toxicity were
observed for up to 24 h post dosing. It was reported that 7/40
animals died during this study and that a replacement group were
treated in parallel to replace the animals which died. Sampling
was undertaken at 24, 48 and 72 h post dosing. 1000 PCE's were
scroed per animal and NCE's per 1000 PCE.
Individual results were not reported. The PCE/NCE ratio as 1.06,
0.74 and 1.36 at 24, 48 and 72 h. Thus there is some indication
of bone marrow toxicity at 48 h.
-- 3.2.5.1.2 Rabbit. In an adequately conducted teratology study,
pregnant Himalayan rabbits (15/group) were administered transfluthrin
(94% purity) in 0.5% (v/v) aqueous Cremophor EM emulsion by gavage
at doses of 0, 15, 50 and 150 mg kg d during days of 6-18 of gestation.
Control animals received vehicle alone... Dams were necropsied
on day 29 of gestation following delivery of the foetuses by caesarean
section. Two deaths occurred, one on day 18 at 50 mg kg d and
one on day 19 at 150 mg kg d. Immediately prior to death both
animals displayed symptoms consistent with CNS
involvement inclusing spasms, severe
tremor and prostration (animals found lying on their side).
Autopsy of these animals revealed an enlarged
lobulated liver and pale lobulated lllungs at 50 mg kg d whereas
no pathological fingings were observed at 150 mg kg d.
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK 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. Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Environmental
(click
on for all fluorinated pesticides)
Environmental
toxicity tests demonstrated that all products containing
transfluthrin should be classified as 'Extremely
dangerous to fish and other aquatic life', with a
48 h EC50 for Daphnia magna of 1.7 ug1 and a 96 h LC50 for
rainbow trout (Oncorhynchus mykiss) of 0.7 ug 1.
Ref: Evaluation on: Transfluthrin
Use as a Public Hygiene Insecticide. September 1997. Prepared
by: the UK 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.
Available
online at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
|
|