Haematological studies

Lewander, K., Dave, G., Johansson, M.-L., Larsson, A. and Lidman, U. (1974). Metabolic and haematological studies on the yellow and silver phases of the European eel, Anguilla anguilla. -1. Carbohydrate, lipid, protein and inorganic ion metabolism. Comparative Biochemistry and Physiology 47B, 571-581. 

Das PM, Sadana JR, Gupta RK, et al. 1989b. Experimental selenium toxicity in guinea pigs Haematological studies. Ann Nutr Metab 33(6) 347-353. 

Stevenson AFG, Daculsi R, Monig H. 1982. Haematological studies on 90Sr-90Y-toxicity H. Femoral CFU-s kinetics and mitogen response of spleen cells. Radiat Environ Biophys 20 275-287. 

Gupta RP, Verma PC and Gupta RKP (1985) Experimental zinc deficiency in guinea-pigs diniccd signs and some haematological studies. Br J Nutr 54 421-428. 

Chliamovitch, Y.P. and C. Kuhn. 1977. Behavioural, haematological and histological studies on acute toxicity of bis(tri-n-butyltin)oxide on Salmo gairdneri Richardson and Tilapia rendalli Boulenger. Jour. Fish Biol. 10 575-585. 

AALAC certified laboratory. In-housing testing included acute, subacute, and subchronic oral, dermal and inhalation studies and specialty reproductive, behavioural, haematological and renal function toxicity studies. Preparation of risk assessment, submissions and presentations to regulatory agencies and trade association. 

Coumarin was administered in the diet for two years to Sprague-Dawley rats and CD-I mice in a study by Carlton et al. (1996) which is described more fiilly in Section 3.1.2. Histopaihological evidence of hepatotoxicity was observed in rats, with males affected more severely than females. No dose-related clinical signs were observed in the CD-I mice nor were there any changes in clinical pathology, haematology or microscopic pathology (Carlton et al, 1996). 

In a long-term study ( 20 years) of about 200 ethylbenzene production workers exposed to an undefined concentration of this compound, none of the workers showed changes in haematological parameters or serum enzyme levels as a measure of liver function (Bardodej Cirek, 1988). 

Several studies have been reported on the effects of occupational exposure to butadiene, mainly from the USSR and Bulgaria. Few are substantiated by details on the atmospheric concentration or duration of exposure, and control data are generally not provided. The effects reported include haematological disorders (Batkina, 1966 Volkova Bagdinov, 1969), kidney malfunction, laryngotracheitis, irritation of the upper respiratory tract. 

As a part of a long-term carcinogenicity study (Maltoni et al., 1980), haematological parameters and clinical chemistry parameters reflecting liver and kidney function were studied after three, six, 12 or 18 months inhalation exposure to 5,10,50 or 150-250 ppm [20, 40, 200 or 600-1000 mg/m ] 1,2-dichloroethane (Spreafico et al., 1980). No consistent treatment-related effect was observed. 

Cynomolgus monkeys showed no measurable adverse effect following inhalation of 500 ppm [1500 ing/m l dimethylformamide for 6 h per day on five days per week for two weeks (Hurtt et al., 1991). In a 13-week inhalation study, cynomolgus monkeys received whole-body exposmes of 0, 30, 100 or 500 ppm [0, 90, 300 or 1500 mg/m ] dimethylformamide for 6 h per day on five days per week (Hurtt et al., 1992). No exposure-related effect on body weight or a number of haematological parameters and serum chemistry including transaminases occurred. 

In mice, no treatment-related gross or microscopic lesions, or haematological or clinical chemistry changes were observed in 17-day (< 600 mg/kg bw per day), 13-week (< 420 mg/kg bw per day) or two-year (112 or 225 mg/kg bw per day) studies. Survival was decreased at the highest dose in 17-day and 13-week studies, but not in the long-term study (United States National Toxicology Program, 1992). 

Vinylidene chloride is a central ncr ous system depressant. Repeated exposure to low concentrations of vinylidene chloride may cause liver and renal dysfunction (Torkelson Rowe, 1981). Skin contact with vinylidene chloride causes irritation, which may be due partly to the presence of an inhibitor, hydroquinone monomethyl ether (Chivers, 1972). In one study, spirometry, blood clinical chemistry for liver and renal toxicity, haematological parameters and blood pressure measurements did not differ between vinylidene chloride-exposed workers and controls. Measured past time-weighted average vinylidene chloride concentrations ranged from < 5 to 70 ppm [< 20-280 mg/m- ] (Ott et al., 1976). 

Partly as a result of the extensive experimental and clinical studies which have been carried out on clozapine in recent years there have been two major approaches to the development of atypical neuroleptics. The first approach has been to develop drugs which broadly simulate the pharmacological profile of clozapine but which lack the adverse haematological effects. Olanzapine is an example of a drug recently... 

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