Animal studies oximes toxicity

Use of oximes is well accepted for OP exposures, but their role in carbamate poisoning is controversial. Animal studies have shown oxime use can increase toxicity when treating carbaryl exposure (Lifshitz et al., 1994). Therefore, there is a general guideline that oximes should be avoided if a carbamate exposure is suspected. One case series reported the routine use of oxime therapy for carbamate exposures in children (Lifshitz et al., 1994). Marked clinical improvement was observed in all patients, regardless of whether they were exposed to an OP or a carbamate. In addition to the retrospective review of cases, the authors completed an in vitro study of oxime use with carbamate toxicity and discovered that oximes play a minor role in direct reactivation of human carbamylated AChE. Due to this finding, the authors concluded that the current guideline to avoid oxime use in a carbamate exposure is valid. 

At both these times, thigh muscle contained a higher concentration of 2-PAM I than abdominal muscle, but a lower concentration of III. Dogs and rabbits appear, therefore, to tolerate repeated daily intravenous doses of 2-PAM I at 30 mg/kg or of III at 10 mg/kg during a period of 6-8 wk when the dally doses are suspended during each weekend. Because in this and the other studies reviewed the animals were killed at or soon after the end of the period of administration of an oxime, there has been no opportunity to judge whether repeated administration of an oxime may initiate some alteration in normal structure or function that will result eventually in a definite lesion. No truly chronic study of the toxicity of an oxime has been found. Thus, possible cryptic toxic effects of this type of compound have never been assessed. 

MMB-4 was less toxic in mice (LD50 = 441mg/kg, intramuscular) than obidoxime (188mg/kg, intramuscular) but more toxic compared with HI-6 (671 mg/kg, intramuscular) (Bartosova etal., 2006). It was shown that MMB-4 was inferior to HI-6 in reactivation of peripheral AChE from soman-poisoned animals, although both oximes were better than 2-PAM. In soman-poisoned rats MMB-4 was not successful in protection or reactivation of soman-inhibited AChE (Shih, 1993). Luo et al. (2008) foxmd that MMB-4 was not a good reactivator of soman-inhibited AChE obtained fromhmnan and three monkey species, in which it was found to be less effective compared with HI-6. This is consistent with the findings reported in other studies (Lundy et al., 2011). 

---