Is Spinosad safe for dogs and cats?
Low risk for petsSpinosad is the active ingredient in Comfortis (spinosad alone) and Trifexis (spinosad + milbemycin oxime) — FDA-approved oral flea prevention tablets for dogs. At label doses, spinosad is well-tolerated in most dogs; vomiting is the most commonly reported adverse effect (recommend feeding with a full meal to reduce GI upset). Ivermectin-sensitive dog breeds (Collies, Australian Shepherds with MDR1/ABCB1 mutations) should use spinosad-containing products cautiously when combined with ivermectin or milbemycin — there is a potential for synergistic CNS toxicity at high doses through combined GABA chloride channel effects. Comfortis is beef-flavored and chewable; palatability may increase risk of dose-doubling if dogs access extra tablets.
What is spinosad?
The IUPAC name is (1S,2S,5R,7S,9S,10S,14R,15S,19S)-15-[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-19-ethyl-4,14-dimethyl-7-[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy-20-oxatetracyclo[10.10.0.02,10.05,9]docosa-3,11-diene-13,21-dione;(1S,2R,5S,7R,9R,10S,14R,15S,19S)-15-[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-19-ethyl-14-methyl-7-[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy-20-oxatetracyclo[10.10.0.02,10.05,9]docosa-3,11-diene-13,21-dione.
Also known as: (1S,2S,5R,7S,9S,10S,14R,15S,19S)-15-[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-19-ethyl-4,14-dimethyl-7-[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy-20-oxatetracyclo[10.10.0.02,10.05,9]docosa-3,11-diene-13,21-dione;(1S,2R,5S,7R,9R,10S,14R,15S,19S)-15-[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-19-ethyl-14-methyl-7-[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy-20-oxatetracyclo[10.10.0.02,10.05,9]docosa-3,11-diene-13,21-dione, Natroba, Blackhawk, Comfortis.
- IUPAC name
- (1S,2S,5R,7S,9S,10S,14R,15S,19S)-15-[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-19-ethyl-4,14-dimethyl-7-[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy-20-oxatetracyclo[10.10.0.02,10.05,9]docosa-3,11-diene-13,21-dione;(1S,2R,5S,7R,9R,10S,14R,15S,19S)-15-[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-19-ethyl-14-methyl-7-[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy-20-oxatetracyclo[10.10.0.02,10.05,9]docosa-3,11-diene-13,21-dione
- CAS number
- 168316-95-8
- Molecular formula
- C83H132N2O20
- Molecular weight
- 1477.9 g/mol
- SMILES
- CCC1CCCC(C(C(=O)C2=CC3C4CC(CC4C=CC3C2CC(=O)O1)OC5C(C(C(C(O5)C)OC)OC)OC)C)OC6CCC(C(O6)C)N(C)C.CCC1CCCC(C(C(=O)C2=CC3C4CC(CC4C(=CC3C2CC(=O)O1)C)OC5C(C(C(C(O5)C)OC)OC)OC)C)OC6CCC(C(O6)C)N(C)C
- PubChem CID
- 17754356
Risk for dogs
Low riskSpinosad is the active ingredient in Comfortis (spinosad alone) and Trifexis (spinosad + milbemycin oxime) — FDA-approved oral flea prevention tablets for dogs. At label doses, spinosad is well-tolerated in most dogs; vomiting is the most commonly reported adverse effect (recommend feeding with a full meal to reduce GI upset). Ivermectin-sensitive dog breeds (Collies, Australian Shepherds with MDR1/ABCB1 mutations) should use spinosad-containing products cautiously when combined with ivermectin or milbemycin — there is a potential for synergistic CNS toxicity at high doses through combined GABA chloride channel effects. Comfortis is beef-flavored and chewable; palatability may increase risk of dose-doubling if dogs access extra tablets.
Risk for cats
Low riskComfortis for Cats (spinosad oral flea tablet) is FDA-approved for cats 14 weeks and older, weighing at least 2 lbs. Safety studies in cats demonstrate good tolerance at label doses. Vomiting is the most commonly reported adverse effect; giving with food minimizes this. The same MDR1 mutation caution applies when combining with macrocyclic lactones in cats. Spinosad does not pose the pyrethroid-class toxicity concern, making it a valued option for cat flea control in households where pyrethroid avoidance is prioritized.
Regulatory consensus
3 regulatory and scientific bodies have classified Spinosad. The classifications differ — that's the data.
| Agency | Year | Classification | Notes |
|---|---|---|---|
| IRAC | — | Group 5 | Mode of action classification for insecticides |
| US EPA | — | Toxicity Category III–IV | Acute mammalian toxicity classification |
| OMRI | — | Certified for use in certified organic production | Approved by Organic Materials Review Institute |
Regulators apply different standards of evidence — animal-data weighting, exposure-pattern assumptions, epidemiological power thresholds — which is why two scientific bodies can review the same data and reach different conclusions. The disagreement is the data.
Where pets encounter spinosad
- Industrial Facilities — Manufacturing plants, Chemical storage areas, Waste treatment sites
- Occupational Environments — Factories, Warehouses, Transportation vehicles
Safer alternatives
Lower-risk approaches that achieve a similar outcome to Spinosad:
-
Physical/mechanical pest control (IPM)
Trade-offs: More labor-intensive. May not be sufficient for severe infestations.Relative cost: 1.2-2×
Frequently asked questions
Is spinosad safe for pets?
Spinosad is the active ingredient in Comfortis (spinosad alone) and Trifexis (spinosad + milbemycin oxime) — FDA-approved oral flea prevention tablets for dogs. At label doses, spinosad is well-tolerated in most dogs; vomiting is the most commonly reported adverse effect (recommend feeding with a full meal to reduce GI upset). Ivermectin-sensitive dog breeds (Collies, Australian Shepherds with MDR1/ABCB1 mutations) should use spinosad-containing products cautiously when combined with ivermectin or milbemycin — there is a potential for synergistic CNS toxicity at high doses through combined GABA chloride channel effects. Comfortis is beef-flavored and chewable; palatability may increase risk of dose-doubling if dogs access extra tablets.
What products contain spinosad?
Spinosad appears in: Manufacturing plants (Industrial facilities); Chemical storage areas (Industrial facilities); Factories (Occupational environments); Warehouses (Occupational environments).
Why do regulators disagree about spinosad?
Spinosad has been classified by 3 agencies including IRAC, US EPA, OMRI, with differing conclusions. Regulators apply different standards of evidence (animal data weighting, exposure-pattern assumptions, epidemiological power thresholds), which is why two scientific bodies can review the same data and reach different conclusions. See the regulatory consensus table on this page for the full picture.
See Spinosad in the pets app
Look up products containing spinosad, compare to alternatives, and explore the full data record.
Open in pets View raw API dataSources (2)
- US EPA: Spinosad Registration Review — biological insecticide (Saccharopolyspora spinosa fermentation); IRAC Group 5; nAChR + GABA chloride channel mechanism; bee acute contact toxicity; aquatic invertebrate toxicity; organic certification; pet product safety (Comfortis, Trifexis); human lice treatment; label timing restrictions for pollinator protection (2019) (2019) — regulatory
- ASPCA Animal Poison Control Center: Neonicotinoid Insecticide Toxicosis — imidacloprid, nitenpyram, dinotefuran; pet product safety (Advantage, Capstar, Vectra); nAChR mechanism; mammalian vs. insect selectivity; clinical signs and management (2023) (2023) — veterinary
Reference data, not professional advice. Aggregates publicly available regulatory and scientific data; not a substitute for veterinary, medical, legal, or regulatory advice. Why we built ALETHEIA →