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2-chloroethanol Animal Subchronic Toxicity

Time:2015/9/24 8:28:20

 2-chloroethanol Animal Subchronic Toxicity (Re- peated doses for a period not exceeding1 year)


2-chloroethanol has been administered subchronically by the oral route. both by gavage and in the diet.to the ra$. dog, and monkey. parenter- ally to the dog and rat; and by inhalation to rats (Refs. 4. 32. 41-44). Effects include depressed weight gain and increased mortality. subacute myocardi- tis. and changes in organ weights. Data from the 30-day subcutaneous dosing (27 mg/kg) of 2-chloroethanol to dogs indicated hepatocellu- lar degenerative changes and increased sexm alkaline phosphatase and bilirubin levala One dog died. No hepatic effects were seen with signifi- cantly lower .doses (9 mg or 3 mg/kg). ~emi;lLferous tubular - degeneetion was detected at the 27 and 9 mg/kg dose levels.

In another study (Feuer. G. et al..Ref. 39). subcutaneous dally dosing of rats (20 -/kg of ethylene chlorohy- drin for 7 days) caused a reduction in the activities of hepatic drug-metabo- llzing enzymes and of glucose 6-phos- phatase. A trend of reduction was seen also at 3 or 10 mg/kg in male rats.

A 21-day ocular irritation study has been performed in rabbits with solutions of 2-chloroethanol. ethylene glycol, and combinations of 2-chloroethanol and ethylene glycol (Ref. 7). The concentrations of the 2-chloroethanol solutions raqged from 0.1 to 40 percent; of the ethylene glycol solutions. from 0.5 to 80 perceneand of the combination solution of ethylene chlorohydrlrr and ethylene glycol, from 0.1 percent/0.5 percent to 30 percent/?O percent. Maxhial conjunctival congestion and

discharge, moderate swellins, increasing corneal cloudiness, damage as eddenced by fluorescein statning, and pannus were obsemed with solutions of 40 percent ethylene chlorohydrln; moderate conjunctival congestion. minimal discharge and mfnlmal swelling with solutions of 80 percent ethylene glycol; and moderate conjunctival congestion, moderate discharge, minimal swelling, flare. hitis. corneal cloudiness, damage as evidenced by fluorescein staining, and moderate pannus wlth solutions of 30 percent/TO percent 2-chloroethanol/ethylene glycol.