MATERIAL SAFETY DATA SHEET
Product Name : BRAVECTO Chewable Tablets for Dogs
MATERIAL SAFETY DATA SHEET
Version 1 issued : February , 2015 Page : 7 of 11
ORAL : Fluralaner : Oral LD50 : > 2000 mg / kg ( rat ) Polyethylene glycol 300 : Oral LD50 : 17,000 to 39,000 mg / kg ( rat , mouse , guinea pig , rabbit ) Polyethylene glycol 400 : Oral LD50 : 16,000 – 44,000 mg / kg ( rat , guinea pig , rabbit ) Glycerin : Oral LD50 : 12,600 mg / kg ( rat ) Sucrose : Oral LD50 : 29,700 mg / kg ( rat )
Clinical signs of toxicity observed include hypokinesia , prostration , cyanosis , convulsions , abdominal bloating , and diarrhea . Death results from respiratory failure . Toxic effects are always dose dependent – and exposure to Polyethylene glycol , Sucrose and Glycerin from the Bravecto chewable tablet is negligible .
DERMAL AND RESPIRATORY SENSITIZATION :
Fluralaner was not sensitizing to guinea pig skin . Polyethylene glycols did not produce skin sensitization in guinea pigs .
REPEAT DOSE TOXICITY DATA SUBCHRONIC / CHRONIC TOXICITY : In a 90 day study of Fluralaner in rats , the NOAEL was established orally at the highest dose of 400 mg / kg / body weight / day . In a 90 day study in rats , the NOAEL was established dermally at the highest dose of 500 mg / kg / body weight / day The liver is the main elimination organ of Fluralaner and a sensitive target for effects as reflected by increased liver enzyme activity in blood plasma with decreased lipid and protein concentration , increased organ weight and increased hepatocellular fatty change as the main functional endpoints in rats . In the absence of any indicator of liver injury ( Kupffer cell proliferation , necrosis , apoptosis , fibrosis , other degenerative changes , etc .) these changes are considered to represent reversible metabolic effects and hence are of non-adverse character . Polyethylene glycol 400 produced no adverse effects in dogs and rats fed 2 % in the diet for one or two years , respectively . Repeated dermal exposure to polyethylene glycol 300 for an eight-week period had no effect on mice . Repeated inhalation exposure to 1008 mg / m 3 of a higher molecular weight polyethylene glycol increased lung weight , and also produced reversible increases in neutrophil counts in male rats . Glycerin caused calcification in the renal tubules in rats given 5 % concentration of glycerin in the drinking water for 6 months . Toxic effects are always dose dependent – and exposure to Polyethylene glycol and Glycerin from the Bravecto chewable tablet is negligible .
REPRODUCTIVE / DEVELOPMENTAL TOXICITY : In prenatal development toxicity studies of Fluralaner in rats ( embryogenisis pilot and pivotal ) the final NOEL was 100 mg / kg / body weight / day in maternal and fetal organisms . No teratogenicity were recorded at up to the limit dose of 1000 mg / kg / body weight / day , and nor were any effects seen on embryo or fetus below maternal toxic dose levels . Polyethylene glycol 200 was developmentally toxic in mice , causing malformations and other fetotoxicity , but elicited no similar response in rats at higher doses . Glycerin injected into the testes of rats suppressed sperm production ; however , oral administration of 100 mg / kg had no effect on fertility . Sucrose produced fetal skeletal changes in guinea pigs exposed to high concentrations ( 5 to 10 g / kg ); however , no effects were seen in rats exposed to 10 g / kg / day . Toxic effects are always dose dependent – and exposure to Polyethylene glycol , Sucrose and Glycerin from the Bravecto chewable tablet is negligible .
MUTAGENICITY / GENOTOXICITY : Fluralaner was negative in a bacterial reverse mutation ( Ames ) study , a mouse lymphoma in vitro study , a chromosome aberration in vitro study , and a mouse erythrocyte micronucleus in vivo study .
MATERIAL SAFETY DATA SHEET Issued by : Intervet Australia Pty Limited ( trading as MSD Animal Health ) Phone : 1 800 033 461 ( Business Hours ) Poisons Information Centre : 13 11 26 from anywhere in Australia , ( 0800 764 766 in New Zealand )