title: Analysis of cataract and keratotic damage induced by 4-diethylaminoethoxy-alpha-ethyl-benzhydrol (RGH-6201) in rats.
abstract: RGH-6201 (4-diethylaminoethoxy-alpha-ethyl-benzhydrol) in the first dose-range finding study on rats produced severe, irreversible ophthalmic damage. The underlying mechanism was studied in a series of experiments with daily doses of 50, 100 and 200 mg/kg in rats by gavage. Lenticular damage appeared as a moderate nuclear degeneration during Week 4 of treatment with 50 mg/kg RGH-6201. This could be detected in the isolated eye and in histological examination but not by ophthalmoscopy. Keratitis and iridocyclitis developed about the 2nd week of treatment followed by epithelial proliferation in the lens under the anterior capsule in the higher dose groups. Nuclear and total cataract developed from the 2nd week on in the 200 mg/kg group and from the 3rd week on in the 100 mg/kg group. Further gross pathological changes in the high dose group were characterized by marked hairloss, desquamation in the cardiac region of the stomach and diarrhoea. It has to be emphasized that fine lenticular changes were unrelated to keratitis and iridocyclitis. Since other benzhydrol derivatives such as 2,5-dimethyl-alpha-ethylbenzhydrol and 3-trifluoro-methyl-alpha-ethyl-benzhydrol do not induce similar changes, the diethyl-amino-ethoxy group was assumed to be the toxic part of the molecule. Intravenous studies with equimolar doses of diethyl-aminoethanol revealed no similar symptoms.
mesh_terms: D000505:Alopecia / Q000139:chemically induced; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002386:Cataract / Q000139:chemically induced*; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D007634:Keratitis / Q000139:chemically induced; D007907:Lens Nucleus, Crystalline / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014606:Uveitis, Anterior / Q000139:chemically induced
chemical_list: D001559:Benzhydryl Compounds; C047790:4-diethylaminoethoxy-alpha-ethylbenzhydrol