α-Naphthylthiourea (ANTU) is an organosulfur compound with the formula C10H7NHC(S)NH2. This a white, crystalline powder although commercial samples may be off-white. It is used as a rodenticide and as such is fairly toxic. Naphthylthiourea is available as 10% active baits in suitable protein- or carbohydrate-rich materials and as a 20% tracking powder.
Synthesis
Like other thioureas, ANTU can be prepared by several routes. The usual method is the reaction of 1-naphthylamine hydrochloride with ammonium thiocyanate:
[C10H7NH3]Cl + NH4SCN → C10H7NHC(S)NH2 + NH3 + HCl
It is produced from the reaction of 1-naphthyl isothiocyanate with ammonia. C10H7NCS + NH3 → C10H7NHC(S)NH2
Mechanism of action
ANTU is specifically toxic in lung cells due to its conversion to a short-lived active metabolite to which it is converted in the liver, not ANTU acting directly. This damage is focused on the endothelium of pulmonary capillaries and venules, it will lead to the formation of irreversible gaps in the endothelium of pulmonary vessels. This damage can lead to pulmonary edema. In ANTU poisoning plasma, carbon and ferritin escape through a gap in the thick part of the pulmonary capillary into the interstitial tissues of the lung
Toxicity
Alpha-Naphthylthiourea is toxic to inhalation, ingestion, or skin contact, although the intoxication may be delayed. According to the U.S. National Institute for Occupational Safety and Health (NIOSH), the recommended workplace airborne exposure limit is 0.3 mg/m3 averaged over a 10-hour workshift. Exposure to 100 mg/m3 is immediately dangerous to life and health. The lethal dose in humans is approximately 4 g/kg.
It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.
Effects on animals
An oral dose of 3 mg per kilogram of body weight causes the death of 50% of the rats exposed (), showing a very high selectivity when compared for example to monkeys ( 4000 mg per kilogram of body weight). However other studies have shown a much higher efficacy for dogs (a of 0.38 mg/kg).
The mortality of rats caused by 5 mg/kg of ANTU is reduced when allylthiourea, isopropylthiourea, ethylenethiourea, or ethylidenethiourea are administered simultaneously with ANTU. Superoxide dismutase, catalase and dimethylsulfoxide all protect against the lung damage by ANTU (although the results are diverse). This indicates that OH radicals are responsible for this type of lung injury. Given hydroxyurea over two days does not block the ANTU damage when neutrophils are decreased or when administered acutely. Cyclooxygenase pathway may generate the free radicals since ibuprofen blocked as well the ANTU damage.
ANTU causes local gastric irritation in animals and when it is absorbed, it increases permeability of the lung capillaries in all animals. The symptoms that the animals present after absorption of alpha-naphthyl thiourea are first weakness, ataxia, weak pulse and subnormal temperatures. Afterwards, they have the following symptoms: vomiting, hypersalivation, coughing and severe pulmonary edema. In the most cases a pale, mottled liver and damaged kidneys are found in animals which have ingested ANTU. Animals with an empty stomach readily vomit after ingestion of this substance. However, when there is food in the stomach of the animals the stimulation to vomit decreases, so more quantities may be absorbed. It has been found that ANTU may cause death in some animals within 2–4 hours of ingestion, while animals that survive 12 hours may recover from the poison. In a long-term, ANTU may cause pulmonary edema and pleural effusion in certain animals, such as rats. Mice treated with alpha-naphthyl thiourea with a dose of 10 mg/kg developed pulmonary edema which was maximal after 3 hours and was resolved by 12 hours. 35 mg/kg of ANTU was caused death to 60% of the animals. It also increases the blood sugar levels in rats. Dogs and pigs are occasionally poisoned with this compound while ruminants are resistant. But when the exposure of this compound in dogs is quite long they may have gastric irritation and respiratory difficulties. Death can then be followed within 6–48 hours depending on the quantity of ANTU ingested.