Doramectin

If material not on fire and not involved in fire: Keep sparks, flames, and othersources of ignition away. Keep material out of water sources and sewers. /Organochlorine pesticide, solid, NOS/

Personnel protection: Avoid breathing dusts, and fumes from burning material. Keep upwind. Avoid bodily contact with the material. ... Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water. ... If contact with the material anticipated, wear appropriate chemical protective clothing. /Organochlorine pesticide, solid, NOS/

LC50 Eisenia foetida (earthworm) >1000 ppm/28 days, artificial soil

LC50 Onchorhynchus mykiss (rainbow trout) 5.1 ppb/96 hr, static

LC50 Lepomis macrochirus (bluegill sunfish) 11 ppb/96 hr, static

/OTHER TERRESTRIAL SPECIES/ The acute oral (single dose) LD50 of doramectin for Bobwhite quail lies in excess of 2000 mg/kg. Following doses of 500, 1000 or 2000 mg/kg, clinical signs of toxicity were mild and only infrequently observed; those receiving 2000 mg/kg were necropsied 14 days post dose and no abnormalities were observed.

/OTHER TERRESTRIAL SPECIES/ No mortality was observed in the /redworm/ Eisenia fetida exposed to 1000 ppm doramectin in an artificial soil for 28 days. The 28 day LC50 is therefore >1000 ppm. Based on weight gain, the most sensitive criteria monitored, the NOEC was 2 ppm and the LOEC was 4 ppm.

/OTHER TERRESTRIAL SPECIES/ Adult worms /Eisenia fetida (redworm)/ were exposed to doramectin for 56 days and showed no effects except for worms exposed to the highest concentration (17 mg/kg) requiring longer time to burrow. Juvenile production was reduced in worms exposed to a doramectin concentration of 1.6 mg/kg or higher. The no observed effect concentration based on fecundity data was 0.89 mg/kg doramectin.

/OTHER TERRESTRIAL SPECIES/ Adult worms /Enchytraeus albidus (whiteworm)/ were exposed to doramectin for 42 days and no effects were observed at any concentration. Juvenile production was reduced in worms exposed to a doramectin concentration of 24 mg/kg or higher. The no observed effect concentration based on fecundity data was 13 mg/kg doramectin.

For more Ecotoxicity Excerpts (Complete) data for DORAMECTIN (7 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ Doramectin was applied to normal and abraded skin of 3 New Zealand white rabbits (0.5 g under an occlusive patch) for 24 hours. Slight erythema was observed 24 and 48 hours post-dose at 1 of 3 intact sites and 2 of 3 abraded sites. There was no edema at any site and all sites appeared normal 72 hours post-dose.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Groups of CD-1 mice (10/sex/dose) were administered doramectin (purity 94.1%) in the diet for 43 days. Target doses were 0, 10, 20, 40, or 60 mg/kg bw/day on days 1 to 14; 0, 10, 20, 80 or 100 mg/kg bw/day on days 15 to 28; and 0, 100, 200, 400 or 600 mg/kg bw/day on days 29 to 43. Toxic signs included lethargy, hunched posture and tremors at 400 and 600 mg/kg bw/day, and hunched and ungroomed appearance in some mice at 100 and 200 mg/kg bw/day. A number of animals given 400 and 600 mg/kg bw/day were sacrificed moribund and the remaining mice in these groups were killed on day 33. There were no effects on body weight or food consumption. Relative liver weights were slightly higher in most treated groups but the changes were minor and not dose-related. Clinical laboratory parameters and pathological examinations were not carried out.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Groups of CD-1 mice (10/sex/group) were fed doramectin (purity 94.1%) in the diet for 92 days. Target doses were 0, 100, 200 or 300 mg/kg bw/day. Actual doramectin intake was 83-121, 154-191 or 221-322 mg/kg bw/day. Tremors, hunched posture, unkempt appearance and lethargy were observed at the mid- and high-dose groups and resulted in death or moribund sacrifice of 9 mice at 300 mg/kg bw/day and 3 mice at 200 mg/kg bw/day. The remaining animals in these two groups were killed on day 12 or 19, respectively. Body-weight gain was depressed in association with reduced food consumption at 200 mg/kg bw/day and above. Serum creatinine and BUN were slightly increased at 100 mg/kg bw/day with no effects at higher doses, presumably due to early culling of mice in these groups. Hematological parameters were unaffected. All treated groups had increased liver weights and hypertrophy of centrilobular hepatocytes, with multinucleate non-proliferative liver cells at 100 mg/kg bw/day only. Dead and moribund animals showed lymphocyte lysis in lymphoid organs, cellular depletion of bone marrow and necrosis of the adrenal cortex which may have resulted from stress and weight loss.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Groups of Long-Evans rats (10/sex/group) were fed a diet containing doramectin (purity 94.1%) at levels intended to give target doses of 0, 20, 40, 60 or 80 mg/kg bw/day for 38 days. Chromorhinorrhea, chromodacryorrhea and urogenital staining were seen at 40 mg/kg bw/day and above. Whole body tremors were also present at the two highest doses and resulted in the sacrifice of 2 rats at 60 mg/kg bw/day and all rats at 80 mg/kg bw/day. Body-weight gain and food consumption were lower at 60 mg/kg bw/day and above. Serum 5'-nucleotidase was increased at 80 mg/kg bw/day with elevated levels of blood urea nitrogen at 40 mg/kg bw/day and above. Liver weights were higher in the 40 and 60 mg/kg bw/day groups but with no dose relationship.

For more Non-Human Toxicity Excerpts (Complete) data for DORAMECTIN (9 total), please visit the HSDB record page.

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

LD50 Mouse (CD-1) oral >2000 mg/kg bw /in 0.1% aqueous methylcellulose/ /from table/

LD50 Rat (Sprague-Dawley, male) ip >300 mg/kg bw /in 0.1% aqueous methylcellulose/ /from table/

Implantation or injectable dosage form new animal drugs. Doramectin: Conditions of use (1) cattle ... Indications for use. For treatment and control of gastrointestinal roundworms, lungworms, eyeworms, grubs, sucking lice, and mange mites. To control infections and to protect from reinfection with Cooperia oncophora and Haemonchus placei for 14 days, Ostertagia ostertagi for 21 days, and C. punctata, Oesophagostomum radiatum, and Dictyocaulus viviparus for 28 days after treatment. ... (2) Swine ... Indications for use. For treatment and control of gastrointestinal roundworms, lungworms, kidney worms, sucking lice, and mange mites.

Ophthalmic and topical dosage form new animal drug. Doramectin: Conditions of use in cattle ... Indications for use. For treatment and control of gastrointestinal roundworms: Ostertagia ostertagi (adults and fourth-stage larvae), Ostertagia ostertagi (inhibited fourth-stage larvae), Ostertagia lyrata (adults), Haemonchus placei (adults and fourth-stage larvae), Trichostrongylus axei (adults and fourth-stage larvae), Trichostrongylus colubriformis (adults and fourth-stage larvae), Cooperia oncophora (adults and fourth-stage larvae), Cooperia punctata (adults and fourth-stage larvae), Cooperia pectinata (adults), Cooperia surnabada (adults), Bunostomum phlebotomum (adults), Oesophagostomum radiatum (adults and fourth-stage larvae), Trichuris spp. (adults); lungworms: Dictyocaulus viviparus (adults and fourth-stage larvae); eyeworms: Thelazia gulosa (adults), Thelazia skrjabini (adults); grubs: Hypoderma bovis and Hypoderma lineatum; sucking lice: Linognathus vituli, Haematopinus eurysternus, and Solenopotes capillatus; biting lice: Bovicola (Damalinia) bovis; mange mites: Chorioptes bovis and Sarcoptes scabiei; horn flies: Haematobia irritans; and to control infections and to protect from reinfection with Cooperia oncophora, Dictyocaulus viviparus, Ostertagia ostertagi, and Oesophagostomum radiatum for 28 days; and with Cooperia punctata and Haemonchus placei for 35 days after treatment; and to control infestations and to protect from reinfestation with Linognathus vituli for 42 days and with Bovicola (Damalinia) bovis for 77 days after treatment.

Tolerances for residues of new animal drugs in food. Doramectin. a) Acceptable daily intake (ADI). The ADI for total residues of doramectin is 0.75 microgram per kilogram of body weight per day. (b) Tolerances - (1) Cattle. A tolerance of 100 parts per billion is established for parent doramectin (marker residue) in liver (target tissue) and of 30 parts per billion for parent doramectin in muscle. (2) Swine. A tolerance is established for parent doramectin (marker residue) in liver (target tissue) of 160 parts per billion.

Therap cat (vet): antiparasitic

... Control of certain gastrointestinal roundworms, lungworms, eyeworms, kidney worms, grubs, lice, and mange mites (in cattle and swine)[US FDA; Animal Drugs, Feeds, and Related Products: Doramectin. Federal Register: November 21, 1997 (Volume 62, Number 225)] [Rules and Regulations]

MEDICATION (VET)

... S.P. Gibson et al., European patent 214,731; /corresponds to/ US patent 5,089,480 (1987, 1992 both to Pfizer).

... Fermentation product of a specific strain of Streptomyces avermitilis ... .

Doramectin is not approved for use in female dairy cattle 20 months of age or older. If a lactating cow is exposed to Doramectin, milk from the cow may have detectable residues of the drug for as long as 60 days. Any detectable level of Doramectin in milk is considered by FDA to be illegal.

The avermectin eprinomectin, which is analogous to doramectin, can reduce dung beetle populations in pastures where the cattle have been treated with pour-on formulations.