Chemwatch : 34-9443 Version No : 4.1.1.1
Page 8 of 12 Fido ' s Fre-Itch Rinse Concentrate For Dogs , Cats , Puppies , Kittens And Cage Birds
Issue Date : 02 / 13 / 2014 Print Date : 06 / 27 / 2016 pyrethrin I
TOXICITY Oral ( rat ) LD50 : 260 mg / kg [ 2 ]
IRRITATION Nil reported water
TOXICITY Oral ( rat ) LD50 : > 90000 mg / kg [ 2 ]
IRRITATION Not Available
Legend : 1 . Value obtained from Europe ECHA Registered Substances - Acute toxicity 2 .* Value obtained from manufacturer ' s SDS . Unless otherwise specified data extracted from RTECS - Register of Toxic Effect of chemical Substances
2-ETHYLHEXYL BICYCLOHEPTENE
DICARBOXIMIDE
PIPERONYL BUTOXIDE
PYRETHRIN I
The material may cause skin irritation after prolonged or repeated exposure and may produce a contact dermatitis ( nonallergic ). This form of dermatitis is often characterised by skin redness ( erythema ) and swelling the epidermis . Histologically there may be intercellular oedema of the spongy layer ( spongiosis ) and intracellular oedema of the epidermis . For 2-ethylhexyl ( or N-octyl ) bicycloheptene dicarboximide ( MGK-264 ) Dermal Absorption : A study with human volunteers indicated that the dermal absorption factor for MGK-264 is approximately 10 % based on the combination of radiolabelled material in the urine ( about 1 %) and unaccounted for radioactivity ( about 9 %, assumed to be retained in the body ). Subchronic Inhalation Toxicity : A 90-day rat inhalation toxicity study demonstrated that at the lowest dose tested , there were indications of metaplasia / hyperplasia and changes in the larynx . At higher doses , histopathology of the larynx revealed additional changes and more intense changes in the epithelium and throat . Thus , inhalation exposure is capable of causing alterations in the respiratory tract . Immunotoxicity and Neurotoxicity : There were no indications of immunotoxicity or specific neurotoxicity Subchronic and Chronic Oral Toxicity : The liver is the target organ of MGK-264 . Liver effects were noted in the adults in the rat chronic / oncogenicity study , the mouse chronic / oncogenicity study , the rat multi-generation reproduction study and subchronic and chronic dog studies . The dog appeared to be the most sensitive species for liver alterations but these alterations were limited to slight to moderate brown pigment and circulating enzyme changes . The dog study did not include histopathology of the liver to verify the presence of degenerative conditions . In the mouse , liver changes include bile duct histological changes including liver tumors , as well as kidney weight effects and brown pigment . Carcinogenicity : MGK-264 has been identified as a possible human carcinogen based on statistically significant increases mainly in benign liver adenomas in both sexes of mice at doses approaching the limit dose and on increases in benign thyroid follicular tumors in male rats at doses considered to be adequate to assess carcinogenic potential . Developmental Toxicity : The rat and rabbit developmental toxicity studies did not demonstrate developmental toxicity for MGK-264 . Maternal toxicity consisted of body weight and food consumption decreases . However , at higher doses , abortions , resorptions , and deaths were noted . Reproductive Toxicity : There were no effects on the reproductive performance of either males or females in the multigeneration reproduction study . Systemic effects were related to body weight decrease as well as histopathological changes in the liver similar to those seen in the rat chronic feeding study . However , offspring for all generations indicated decreased body weight during lactation at a lower dose than parental systemic effects . The effect was reversible after weaning as pups regained weight and their weights were comparable to control animal weights after weaning . Mutagenicity : Mutagenicity and genotoxicity were not evident in the Ames test for bacterial mutations , in the unscheduled DNA synthesis , or in a chromosome aberration studies . Although MGK-264 was considered weakly positive in the mouse lymphoma assay , there was a low concern for mutagenic or genetic toxicity . Metabolism : The metabolism and pharmacokinetics data for MGK-264 in rats demonstrated that MGK-264 is absorbed and excreted with little retention of metabolites
The substance is classified by IARC as Group 3 : NOT classifiable as to its carcinogenicity to humans . Evidence of carcinogenicity may be inadequate or limited in animal testing . Dermal ( rabbit ) LD50 : > 1880 mg / kg [ Handbook of Toxicology ] * Published value - probably not peer-reviewed ADI : 0.03 mg / kg
For pyrethrins The term " pyrethrin " refers to all six isomers found in pyrethrum , extracts which are obtained from the dried and ground flowers of the pyrethrum plant , Chrysanthemum cinerariaefolium . The CAS Registry No . for the mixture is 8003-34-7 . The individual isomers are referred to by the common names of the acid followed by an Arabic number 1 or 2 ( i . e ., pyrethrin 1 , pyrethrin 2 , cinerin 1 , cinerin 2 , jasmolin 1 , jasmolin 2 ). If the term pyrethrins is followed by a roman numerical designation , than it refers to all of the isomers of that number in the pyrethrum extract ( e . g ., pyrethrins I includes pyrethrin 1 , cinerin 1 , and jasmolin 1 ). Pyrethrins have low to moderate acute toxicity via the oral , dermal , and inhalation routes . Mammalian toxicity data suggest that pyrethrins are slightly toxic to small mammals on an acute oral basis ( LD50 = 700 mg / kg body weight ). They are a moderate eye irritant , a mild dermal irritant , and are not a skin sensitisers . Toxic Effects The critical toxicological effects of pyrethrins are neurobehavioral effects ( tremors , labored breathing , hyperactivity , secretory signs , matted coats ), following acute , short-term , and chronic exposure , with nervous system lesions observed in the rat and mouse following acute exposure ; thyroid effects , following chronic exposure in the rat and dog ; and liver effects , following short- and long-term exposure in the rat , dog , and mouse . Following inhalation exposure , neurobehavioral effects were observed initially , and respiratory tract lesions were observed at all dose levels . The neurobehavioral effects and the mode of action on the sodium channel are considered relevant to humans because the effects are observed in both the rat and mouse , and the mode of action affects a basic function of the nervous system that is common to all animals . Toxic Mixtures Effects : The U . S . EPA considered the possibility for increased toxicity due to the presence of synergists such as MGK-264 and piperonyl butoxide in pyrethrins formulations . In order for synergistic effects to be observed in humans ,