Adverse Effects
Transfluthrin
CAS No. 118712-89-3

 
 

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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

 
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