Organophosphates (Toxicity)

The maximum nontoxic oral dose is 0.44 mg/kg for calves, 2.2 mg/kg for cattle and goats, and 4.8 mg/kg for sheep. The oral LD₅₀ in rats is 5 mg/kg, and the dermal LD₅₀ in rabbits is 220 mg/kg.

Carbophenothion has been used as a spray for fruit trees and as a dip or spray for sheep blowfly, keds, and lice. Dairy calves <2 wk old sprayed with water-based formulations showed poisoning at concentrations ≥0.05%, and adult cattle were poisoned by spraying with 1%. Sheep and goats have been poisoned by 22 mg/kg, PO, but not by 8 mg/kg. In sheep, 0.1% as a dip produces no signs of poisoning. The LD₅₀ for rats is ~31 mg/kg; a daily dosage of 2.2 mg/kg for 90 days produced poisoning. Dogs tolerated a diet containing 32 ppm for 90 days. A single application of a powder containing 1% of carbophenothion is lethal to cats.

Adult cattle were poisoned by 5% or higher sprays, whereas young calves were poisoned at concentrations of 2%. The minimum oral toxic dose appears to be ~22 mg/kg for cattle of all ages. The acute oral LD₅₀ for rats is 12 mg/kg, and the dermal LD₅₀ in rabbits is 3,200 mg/kg.

The oral LD₅₀ is 500 mg/kg in goats and 941 mg/kg in rats. In comparison with calves, steers, and cows, bulls (particularly of the exotic breeds) are highly susceptible to a single dose of chlorpyrifos. The maximum tolerated dose of chlorpyrifos in sheep is 750 mg/kg. Sheep given 850 mg/kg died 5 days after dosing, those given 900 mg/kg died on the third day, and a dose of 1,000 mg/kg was lethal within 30 hours. Onset of poisoning signs is usually delayed compared with that of many other commonly used organophosphates because of the conversion of chlorpyrifos to the active cholinesterase inhibitor chlorpyrifos-oxon. Chlorpyrifos produces reproductive and developmental toxicity.

Coumaphos is used against cattle grubs and a number of other ectoparasites and for treatment of premises. The maximum concentration that may be safely used on adult cattle, horses, and pigs is 0.5%. Young calves and all ages of sheep and goats must not be sprayed with concentrations >0.25%; 0.5% concentrations may be lethal. Adult cattle may show mild toxicity at 1% concentrations. The minimum lethal dose for calves appears to be between 10 and 40 mg/kg. A dose of 25 mg/kg is usually fatal in sheep. The oral LD₅₀ in rats is 13 mg/kg.

Crotoxyphos is used as a spray or powder for the control of ectoparasites on cattle and pigs. Crotoxyphos is of rather low toxicity; however, Brahman cattle are markedly more susceptible than European breeds. Cattle (except as above), sheep, goats, and pigs all tolerate sprays containing crotoxyphos at 0.5% levels or higher. Crotoxyphos is safe at a level of 1%, although skin lesions have been found in pigs. Toxic doses appears to be in the 2% range, except for in Brahman cattle, in which 0.144%–0.3% may be toxic.

Demeton is used as a systemic insecticide against sucking insects and mites. Demeton is used mainly as a foliage spray and has a relatively long residual life. It is a mixture of demeton-O and demeton-S and is highly toxic to mammals. The oral LD₅₀ is 8 mg/kg in goats and 2 mg/kg in rats; the dermal LD₅₀ in rats and rabbits is 8 mg/kg. Demeton-O poisoning developed in several hundred cattle grazing near cotton treated with this insecticide. The corresponding analogues of demeton (demeton-O-methyl and demeton-S-methyl) are also used for similar purposes but are less toxic than demeton.

Young calves appear to tolerate 0.05% spray but are poisoned by 0.1% concentrations. Adult cattle may be sprayed at weekly intervals with 0.1% concentrations without inducing poisoning. Young calves tolerate 0.44 mg/kg, PO, but are poisoned by 0.88 mg/kg. Cattle tolerate 8.8 mg/kg, PO, but are poisoned by 22 mg/kg. Sheep tolerate 17.6 mg/kg but are poisoned by 26 mg/kg. The oral LD₅₀ in rats is 300 mg/kg, and the dermal LD₅₀ in rabbits is 379 mg/kg.

Dichlorvos has many uses on both plants and animals. It is rapidly metabolized and excreted, and residues in meat and milk are not a problem if label directions are followed. It is of moderate toxicity, with a minimum toxic dose of 10 mg/kg in young calves and 25 mg/kg in horses and sheep. The oral LD₅₀ in rats is 25 mg/kg, PO, and the dermal LD₅₀ in rabbits is 59 mg/kg. A 1% dust was not toxic to cattle. Flea collars containing dichlorvos may cause skin reactions in some pets. Cats wearing dichlorvos-impregnated collars can develop signs of ataxia-depression syndrome, followed by death.

Dimethoate is used extensively in horticulture as a systemic insecticide, but it also kills insects by contact. When administered PO, the minimum toxic dose for young dairy calves was ~48 mg/kg, while 22 mg/kg was lethal for cattle 1 yr old. Daily doses of 10 mg/kg for 5 days in adult cattle lowered blood cholinesterase activity to 20% of normal but did not produce poisoning. Horses have been poisoned by doses of 60–80 mg/kg, PO. When applied topically, 1% sprays have been tolerated by calves, cattle, and adult sheep. The oral LD₅₀ in rats is 215 mg/kg, and the dermal LD₅₀ in rabbits is 400 mg/kg.

Dioxathion is a nonsystemic acaricide and insecticide for the control of ticks. Dioxathion is a mixture of cis- and trans-isomers, usually in the ratio of 1:2. The cis-isomer is more toxic than the trans-isomer. Used on both plants and animals, it is rapidly metabolized and not likely to produce residues in meat greater than the 1 ppm official tolerance. Concentrations of ≥0.15% are generally used on animals. The minimum toxic dose in calves is 5 mg/kg. Sprays of 0.5% in cattle and sheep or 0.25% in goats and pigs are nontoxic. Sprays at concentrations up to 0.1% are usually safe for calves and lambs. Twice this concentration may produce signs of poisoning. Dioxathion at 8.8 mg/kg, PO, has killed young calves, and it produced intoxication at 4.4 mg/kg. Emaciated cattle with severe tick infestation are more frequently poisoned than healthy animals. Maximum residues of dioxathion in adipose tissue of cattle occur 2–4 days after dipping. The elimination half-life, after obtaining maximum concentrations, is ~16 days.

The maximum nontoxic oral dose is 0.88 mg/kg for young calves, 2.2 mg/kg for cattle and goats, and 4.8 mg/kg for sheep. Poisoning has occurred in cattle after consuming harvested forages previously sprayed with this insecticide. The oral LD₅₀ in rats is 2 mg/kg, and the dermal LD₅₀ in rabbits is 6 mg/kg. Chronic exposure to disulfoton may result in tolerance to toxicity.

EPN is a nonsystemic insecticide and acaricide structurally related to parathion. The acute oral LD₅₀ in rats is 8–36 mg/kg. EPN at a dosage of 10 mg/kg was found to be nontoxic to adult cattle and sheep. The minimum oral toxic dose of EPN is 2.5 mg/kg in calves and 25 mg/kg in sheep and yearling cattle. Sprays containing 0.025%–0.05% EPN are toxic to young calves, and 0.25% EPN is lethal. Dogs were not poisoned at dosages >100 mg/kg.

The oral LD₅₀ in rats is 35 mg/kg, and the dermal LD₅₀ in rabbits is 2,730 mg/kg. The maximum nontoxic dose is 10 mg/kg in calves and 50 mg/kg in cattle, sheep, and horses. In general, Brahman cattle are especially susceptible to famphur toxicity. This compound is effective against warbles in cattle, but (as for all grubicides) directions must be followed as to time of application; larvae killed while migrating and the resultant local reaction can cause serious problems. In several instances, famphur poisoning occurred in birds (mainly magpies and robins) shortly after cattle had been treated with a pour-on preparation containing famphur.

Fenitrothion, also known as sumithion, is used as a contact insecticide in agriculture and horticulture. The oral LD₅₀ in rats is 250 mg/kg, and the dermal LD₅₀ in rabbits is 1,300 mg/kg. When applied to cattle, its metabolites are excreted at low levels in milk and urine. Fenitrothion produces reproductive and developmental toxicity in chickens.

Fenthion is commonly applied topically to control warble infestation in cattle and fleas in dogs. The minimum toxic dose, PO, is 25 mg/kg for cattle; 50 mg/kg is lethal to sheep. The oral LD₅₀ in rats is 255 mg/kg, and the dermal LD₅₀ in rabbits is 330 mg/kg.

Malathion is one of the safest organophosphates because of its selective toxicity; it is highly toxic to insects but much less toxic to mammalian species. The oral LD₅₀ in rats is 885 mg/kg, and the dermal LD₅₀ in rabbits is 4,000 mg/kg. The oral acute toxic dose in calves is 10–20 mg/kg and in adult cattle and sheep is 50–100 mg/kg. In a chronic study in buffalo calves (6–9 mo old), daily oral administration of malathion at 0.5 mg/kg for 1 yr produced no biochemical or clinical effects. Dosages >1 mg/kg inhibited blood acetylcholinesterase (AChE) activity and increased liver enzymes (ALT and AST). A 20 mg/kg dose produced clinical signs after 10 days. The acute oral LD₅₀ in buffalo calves is 53 mg/kg. Dermal application by spray containing 0.5% or 1% of malathion had no apparent effect on calves, but 5% spray caused death within 75 hr. Malathion at 0.5% or 1% should not be sprayed on calves for more than 3 consecutive days. Malathion is excreted in cow’s milk.

Methyl parathion is less toxic than parathion (diethyl parathion). The LD₅₀ in rats from a single oral dose is 9–25 mg/kg, and the dermal LD₅₀ in rabbits is 63 mg/kg. Methyl parathion at 2.5 mg/kg had no ill effect, but 10 mg/kg daily quickly led to toxic signs. The lethal dose in cattle is 100 mg/kg. Methyl parathion is excreted in cow’s milk. Methyl parathion produces reproductive and developmental toxicity.

The LD₅₀ in rats is 3 mg/kg, and the dermal LD₅₀ in rabbits is 16 mg/kg. Mevinphos has been commonly used to control the population of birds, and thereby caused poisoning in nontarget species. Mevinphos at 200 ppm in the diet is lethal in dogs.

Naled is essentially a dibrominated dichlorvos, which has the ability to act as a contact insecticide. It has a broad spectrum of insecticidal action. Because it has a short residual life, it poses relatively little hazard to fish and wildlife. The oral LD₅₀ in rats is 191 mg/kg, and the dermal LD₅₀ in rabbits is 390 mg/kg.

The maximum nontoxic oral dose is 0.88 mg/kg for young calves, 2.2 mg/kg for cattle, and 4.8 mg/kg for sheep and goats.

Parathion (diethyl parathion) is widely used for control of plant pests and is approximately one-half as toxic as tetraethyl pyrophosphate (see Tetraethyl pyrophosphate (TEPP)). The oral LD₅₀ in rats is 3 mg/kg, and the dermal LD₅₀ in rabbits is 6.8 mg/kg. It is used as a dip and spray for cattle in some countries (not in the USA). Most cases of occupational insecticide poisonings in people have been attributed to parathion or its degradation products. The minimum toxic dose in calves is 0.25–0.5 mg/kg and in cattle is 25–50 mg/kg. The minimum oral lethal dose in sheep is 20 mg/kg and in goats is 50 mg/kg. The LD₅₀ in dogs is 23–35 mg/kg and in cats is 15 mg/kg. Dermal sprays containing 0.02%, 1%, and 1% of parathion are lethal to calves, sheep, and goats, respectively. Parathion is used extensively to control mosquitoes and insects in orchards and on market garden crops. Normally, because so little is used per acre, it presents no hazard to livestock. However, because of the potency of parathion, care should be taken to prevent accidental exposure. Parathion does not produce significant residues in animal tissues.

Phorate is closely related to demeton (see Demeton). It is a systemic insecticide and miticide. The oral LD₅₀ in rats is 1.6 mg/kg, and the dermal LD₅₀ in rabbits is 2.5 mg/kg. The minimum toxic dose PO is 0.25 mg/kg in calves, 0.75 mg/kg in sheep, and 1 mg/kg in cattle.

Phosmet is a nonsystemic acaricide and insecticide. The minimum oral toxic dose is 25 mg/kg in cattle and calves and 50 mg/kg in sheep. Spraying with a 0.5% solution has no toxic effect, but a 1% solution of phosmet produces intoxication in cattle. Phosmet is not excreted in milk.

Ronnel is an excellent oral systemic insecticide. It is effective against many ecto- and endoparasitic arthropods, including cattle grubs, screw worms, and sucking lice. Ronnel is also used as a residual spray insecticide to control flies, fleas, and cockroaches. The oral LD₅₀ in rats is 1,250 mg/kg, and the dermal LD₅₀ in rabbits is 2,000 mg/kg. Ronnel produces mild signs of poisoning in cattle at 132 mg/kg, but severe signs do not appear until the dosage is >400 mg/kg. The minimum toxic dose in sheep is 400 mg/kg. Concentrations as high as 2.5% in sprays have failed to produce poisoning of cattle, young dairy calves, or sheep. Poisoning usually occurs in two stages. The animal first becomes weak and, although able to move about normally, may be placid. Diarrhea, often flecked with blood, may also be seen. Salivation and dyspnea then appear if the dose was high enough. Blood cholinesterase activity declines slowly over 5–7 days. Ronnel produces residues in meat and milk; strict adherence to label restrictions is essential. The residues may be removed by giving the animal activated charcoal for several days.

Ruelene is active both as a systemic and contact insecticide in livestock, has some anthelmintic activity, and has rather low toxicity. Dairy calves have been poisoned by 44 mg/kg, PO, while adult cattle require 88 mg/kg for the same effect. Sheep are moderately intoxicated by 176 mg/kg; Angora goats are about twice as sensitive. Pigs have been poisoned by 11 mg/kg and horses by 44 mg/kg. Most livestock tolerate a 2% topical spray.

Temephos is used as an insecticide against mosquitoes and midges. It is of low toxicity to mammalian species. The oral LD₅₀ for rats is 1 g (or more)/kg, while the dermal LD₅₀ is >4 g/kg. Daily exposure of cattle for 1 yr at 1–1.5 mg/kg is known to produce clinical signs of poisoning and affect fertility in heifers.

This soil insecticide is used to control corn rootworms. The oral LD₅₀ in rats is 1.6 mg/kg. The minimum oral toxic dose is ~1.5 mg/kg for sheep and cattle. Cases of intoxication in cattle have occurred. Ingestion of 7.5 mg/kg was lethal to heifers.

Tetrachlorvinphos has low toxicity in dogs; chronic feeding studies indicate the lowest effect level was 50 mg/kg/day, and the no observed effect level (NOEL) was 3.13 mg/kg/day. The minimum toxic dose in pigs is 100 mg/kg.

Tetraethyl pyrophosphate (TEPP) is one of the most acutely toxic insecticides. Although not used on animals, accidental exposure occurs occasionally. One herd of 29 cattle (including calves and adults) was accidentally sprayed with 0.33% TEPP emulsion; all died within 40 min.

Trichlorfon is used as a systemic insecticide and anthelmintic in domestic animals. It is also used as an acaricide in sheep at the dose rate of 80 mg/kg at weekly intervals for not more than 4 wk. The oral LD₅₀ in rats is 630 mg/kg, and the dermal LD₅₀ in rabbits is >2,000 mg/kg. As a spray, trichlorfon at a 1% concentration is tolerated by adult cattle; given PO, it is tolerated by young dairy calves at 4.4 mg/kg but produces poisoning at 8.8 mg/kg. Adult cattle, sheep, and horses appear to tolerate 44 mg/kg, while 88 mg/kg produces poisoning. Dogs were unaffected when fed 1,000 ppm of trichlorfon for 4 mo. Administration of trichlorfon at 75 mg/kg, PO, produces adverse clinical signs in dogs. Trichlorfon is metabolized rapidly.