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Effect of benzene and carbon tetrachloride inhalation on osmotic resistance of rabbit erythrocytes
Gen. Pharraac., Vol. I 1, pp. 197 to 199 © Pergamon Press Ltd 1980, Printed in Great Britain
0306-3623/80/0301-0197502.00/0
EFFECT OF BENZENE AND CARBON TETRACHLORIDE INHALATION ON OSMOTIC R E S I S T A N C E O F RABBIT E R Y T H R O C Y T E S ADAM KOLATAJ and HANNA STI~PKOWSKA Department of Animal Physiology, Educational University 25--518 Kielce, Rew. Paz'dziernikowej 33, Poland
(Received 6 Auyust 1979) A b s t r a c t - - I . Benzene and CC14 inhalation resulted in a decrease of erythrocytes osmotic resistance in rabbit. 2. It seems that changes observed in parallel of rabbit internal organs were also caused by the toxic effect of these substances.
INTRODUCTION Professional poisoning caused by neglecting safety rules creates a toxicological problem. The toxic effect of organic solvents on cells and, especially, erthrocytes has become dangerous to man. For toxicological investigation rabbits are often used as experimenta! animals since their reactions are similar to the physiological reactions of man. In this context it seems important to investigate more thoroughly the osmotic resistance of rabbit erythrocytes to the deleterious effects of benzene and carbon tetrachloride as these compounds become more frequent in our environment. Both benzene and CC14 are poisonous for living organisms. Even when inhaled in low concentrations they cause serious general health disturbances affecting especially the erythropoietic system. The severe benzene poisoning has the form of intoxication, shock and narcosis. Benzene, because of its lipophilic character, concentrates mostly in the brain (Supniewski, 1972) and death is caused by paralysis of the respiratory system. At lower doses and concentration the symptoms of irritation of respiratory tract, headache, vomiting and trembling are observed. If the period of benzene inhalation is long enough it causes a chronic injury of bone marrow and capillary vessels. Carbon tetrachloride poisoning through the respiratory system causes, first of all, the injury to the lungs, central nervous system and kidneys, while oral poisoning mostly affects the liver. Chronic poisoning is an effect of small "microinjuries" which after a certain time show themselves in the form of health disturbances (Rusiecki & Kubikowski, 1969; Bohosiewicz, 1970; Mayer, 1964). The safety limit of CC14 concentration in the air is 1:1000. MATERIALS AND METHODS
The experiments were carried out on 25 rabbits of different races, 1.5-2.5 kg body weight and 8-9 months old. The experimental animals derived from the same farm and during the experiment were kept under the same experimental conditions. The animals were treated with benzene (15 rabbits) or 6.P. az/2 o
197
CC14 (10 rabbits)---2 hr inhalation daily for 1 week. During the inhalation period the animal was kept in a cardboard box (with 4 apertures, dia. 3 cm) 70 × 70 × 70cm, containing a Petri dish (9cm dia.) with 5ml of benzene or CCI4.10 min after every inhalation 1 ml samples of blood was taken from the ear vein. The blood samples were centrifuged in order to separate erythrocytes from the blood serum and 2 ml of physiological solution (0.9 % NaCI) was added to the erythrocyte precipitate. Osmotic resistance of erythrocytes was measured by adding one drop of the erythrocyte suspension to I ml of NaCI solution ranging from 0.90 to 0.20~o, the difference between the consecutive concentrations being 0.02~/o. After 1 hr the results were read at 20°C temp. The NaCI concentration, which resulted in a slightly yellow solution colour, was regarded as a beginning of haemolysis and the concentration where there was no erythrocyte precipitation at the bottom as the termination of complete haemolysis. Before the experiment each animal underwent control examinations. RESULTS
The data is presented in Tables I and 2. The erythrocyte osmotic resistance measured during control examinations ranged between 0.324).56% NaCl concentration, the difference between particular days being 0.02-0.08~o. Most animals reacted similarly to benzene inhalation--erythrocyte osmotic resistance decreased in the course of the experiment. Rabbits No. 6, 10 and 14 were less susceptible to benzene treatment and their erythrocyte osmotic resistance decreased to a lower degree. For example, after 3 days of benzene inhalation the erythrocyte osmotic resistance for rabbit No. 4 was 0.72-0.42~, for No. 6, 0.62q3.38~o, for No. 10, 0.60-0.40~o and No. 14, 0.604).38~ (Table 1). These differences were observed towards the end of the experiment. After 7 days of benzene treatment the erythrocyte osmotic resistance was usually less than 0.80-0.50 except rabbit No. 14, where it was much higher; 0.764).46. For animals treated with CC14 (Table 2) in 5 cases (rabbits No. 1, 2, 6, 7 and 10) there were no changes in erythrocyte osmotic resistance during the first days of inhalation. In other animals (No. 3, 4 and 5) from the
198
ADAM KOLATAJ and HANNA
STI~PKOWSKA
Table I. The values of hemolytic changes of blood red cells under the influence of benzene (in NaCI solution) Rabbits (No.l 1 II III IV V Vl VII VII1 lX X Xl XIl Xlll X1V XV
Control Min Max
1 Min
Max
Min
Max
Min
0.54 0.52 0.50 0.54 0.56 0.50 0.54 0.52 0.52 0.50 0.54 0.54 0.52 0.52 0.56
0.56 0.56 0.54 0.56 0.58 0.52 0.60 0.54 0.56 0.52 0.56 0.58 0.54 0.54 0.60
0.40 0.38 0.34 0.40 0.40 0.32 0.40 0.38 0.38 0.36 0.38 0.36 0.36 0.34 0.38
0.62 0.64 0.60 0.66 0.66 0.58 0.64 0.60 0.60 0.56 0.62 0.66 0.60 0.58 0.62
0.40 0.40 0.38 0.40 0.40 0.36 0.40 0.40 0.40 0.38 0.40 0.40 0.38 0.38 0.40
0.70 0.70 0.68 0.72 0.70 0.62 0.66 0.66 0.64 0.60 0.68 0.68 0.64 0.60 0.68
0.38 0.36 0.34 0.36 0.38 0.32 0.38 0.36 0.36 0.34 0.36 0.36 0.34 0.34 0.36
2
Max
Days 4 Min Max
Min
Max
Min
Max
Min
Max
0.42 0.44 0.40 0,42 0.42 0.38 0,42 0,42 0.42 0.40 0.42 0.42 0.38 0.38 0.42
0.72 0.74 0.72 0.74 0.74 0.68 0.72 0.72 0.66 0.66 0.72 0.72 0.66 0.66 0.70
0.78 0.78 0.74 0.76 0.78 0.72 0.76 0.74 0.70 0.72 0.76 0.76 0.74 0.68 0.74
0.46 0.48 0.42 0.46 0.46 0.42 0.46 0.44 0.46 0.48 0.46 0.44 0.44 0.40 0.48
0.82 0.82 0.80 0.80 0.82 0.76 0.80 0.80 0.76 0.78 0.80 0.80 0.76 0.70 0.76
0.52 0.54 0.46 0.52 0.52 0.44 0.52 0.46 0.48 0.50 0.50 0.48 0.46 0.42 0.48
0.86 0.84 0.82 0.86 0.84 0,80 0,86 0,84 0,80 0,80 0.82 0.82 0.82 0.76 0.82
0.54 0.54 0.48 0.52 0.54 0.48 0.54 0.46 0.52 0.52 0.52 0.52 0.50 0.46 0.62
3
beginning of the experiment minimal haemolysis increased. After 4 days, i.e. after 8 hr of CCI4 inhalation rabbit No. 3 died and its final erythrocyte osmotic resistance was 0.72-0.24°/0 NaCI. Rabbit No. 10 died after 5 days and its respective value was 0.76-0.34°~, NaC1. Before the death of these animals a very low activity was observed (partial leg paralysis). All animals showed a decrease of erythrocyte osmotic resistance, as compared with the control values, and it may be assumed to be caused by the toxic effect of CC14. DISCUSSION It has been found that toxic substances cause some changes in various hematological parameters (Brendel & Stepniewicz, 1969: Kontek et al., 1973; Norkowski et al., 1973). These changes also comprise the changes in erythrocyte resistance. Our experiments have shown the decrease of erythrocyte osmotic resistance caused by benzene and CC14 treatment. One may suppose it can also be caused by dissolving the lipid c o m p o n e n t of the cell membrane, which resulted in increased hemolysis. Kwiatkowski (1962) pointed out that cell mem-
0.44 0.44 0.40 0.46 0.44 0.40 0.44 0.44 0.44 0.42 0.44 0.44 0.40 0.40 0.44
5
6
7
brane permeability is the main factor of osmotic pressure. He investigated the erythrocyte osmotic resistance in horses with different pathological symptoms. He found that in certain illnesses of the alimentary canal, proceeding with the symptoms of self-poisoning, the decrease of erythrocyte osmotic resistance was also observed. The erythrocyte osmotic resistance decreases also during infection, and this may suggest the presence of a great number of old erythrocytes and an action of bacterial toxis (Dyszy, 1956). Toxic substance penetrating from damaged tissues during or after surgical operation may affect the erythrocyte osmotic resistance of a patient (Kad[ubowska & Pietz, 1956). Our experiments showed that the erythrocyte osmotic resistance was related to the quantity of inhaled benzene and CC14. As more benzene was inhaled its solubilising effect on the lipid component of the cell membrane was stronger and this decreased the erythrocyte resistance. The changes in erythrocyte resistance may also be explained by damage of bone marrow cells producing erythrocytes. Latta & Dawies (1941) and Moeschlin & Speck (1967) stated that benzene caused damage to the bone and even leukaemia in laboratory animals. Are other
Table 2. The values of hemolytic changes of blood red cells under the influence of CC14 (in NaCl solution) Rabbits (No.)
Control Min Max
1 Min
2 Max
Min
3 Max
Min
Max
I II Ill
0.56 0.64 0.60
0 . 1 8 0 . 5 6 0 . 1 8 0 . 5 6 0 . 1 8 0 . 5 6 0.20 0 , 1 8 0 . 6 2 0 . 1 8 0 . 6 2 0 . 1 8 0 . 6 2 0.20 0 . 1 8 0 . 6 2 0 . 2 0 0 . 6 2 0 . 2 2 0 . 6 4 0.22
IV V VI VII VIII IX X
0.54 0.54 0.62 0.52 0.58 0.68 0.52
0.18 0.18 0.18 0.20 0.20 0.18 0.18
0.50 0.56 0.62 0.52 0.58 0.68 0.52
0.20 0.18 0.18 0.22 0.20 0.20 0.18
0.55 0.56 0.62 0.52 0.60 0.68 0.52
0.20 0.20 0.20 0.22 0.20 0.22 0.20
0.60 0.58 0.62 0.52 0.60 0.70 0.54
0.24 0.22 0.20 0.22 0.20 0.22 0.22
Day 4 Min Max 0.64 0.66 0.72 died 0.62 0.60 0,64 0.56 0,60 0.70 0,66
5 Min
6 Max
Min
7 Max
Min
Max
0 . 2 4 0 . 6 4 0 . 2 4 0 . 6 7 0 . 2 8 0 . 7 0 0.28 0 . 2 4 0 . 7 2 0 . 2 4 0 . 7 2 0 . 2 8 0 . 7 6 0~28 0.24 . . . . . . . 0.22 0.24 0.20 0.22 0.22 0.22 0.24
0.64 0.62 0.66 0.58 0.62 0.70 0.76 died
0.24 0.24 0.22 0.22 0.22 0.24 0.34
0.66 0.64 0.68 0.60 0.64 0.72 . .
0.24 0.24 0.22 0.24 0.26 0.26 . .
0.68 0.72 0.74 0,64 0.64 0.78 . .
0.24 0,30 0.30 0,30 0,30 0,32
Effect of benzene and carbon tetrachloride inhalation \
paper (Nomiyama, 1965) describing experiments on rats suggested that the harmful agents causing bone marrow damage are the toxic benzene derivatives of phenolic character, mostly diphenol and pyrocatechol. In man, benzene causes a n u m b e r of haematologic disturbances like haemolytic anemia, hyperplasia of bone marrow and leucopaemia (Goldwater, 1965; Aksoy et al., 1970; De Gawin, 1963; Vigliam & Forni, 1969; Vigliam & Saita, 1964).
REFERENCES
AKSOY M., DINCOL K., ERDEM S., AKGUN T. & DINGOL G. (19701 Clinical laboratory observation in 32 patients with aplastic anemia and 2 with acute myeloblastic leukemia due to chronic benzene poisoning. Abstracts of the Xlllth International Congress on Hematology, p. 134. BOHOSIEWlCZ U. (1970) Toksykologia Weterynarkjna. pp. 20--20 & 119-120 PRRiL W-wa. BRENDEL B. & STEPNIEWWZ W. (1969) Wpiyw zabiegu operacyjnego i znieczulenia og61nego na wzrgst hemolizy wewn,~trznaczyniowej i aktywnog6 katalazy w surowicy krwi. Lekarz Wojsk. 4, 308-312. Dvszv B. (1956) Opornog~: krwinek czerwonych w ~wietle przypadk6w klinicznych. Pol. Przeol. Chirurg. 3, 26(~268. DE GAWIN R. L. (1963) Benzene exposure and aplastic anemia followed by leukemia fifteen years later. J.A.M.A. 185, 748. GOLDWATER L. J. (1965) Disturbances in the blood following exposure to benzol. Clin. Med. 26, 957.
199
KADLUBOWSKA M. & PIETZ M. (1956)Zmiany osmotycznej oporno~,ci krwinek czerwonych w stanach pooperacyjnych. Pol. Przegl. Chirury. 8, 857-85~8. KONTEK M., MIETRASZEK Z. & PARADOWSKI S. (1973) Zachowanie sit aktywnogci cholinesteraz osoczowej i krwinkowej u pracownik6w rolnych nara~onych na dzialanie insektycydow fosforoorganicznych. Med. Praey 24, 113-218. KWIATKOWSKI T. (1962} Opornogc' osmotyczna krwinek czerwonych i poziom rezerwy alkalicznej koni Archs Weter. I, 8. LATIA J. DAWIES L. T. (1941) Effects on the blood and hemopoietic organs of the albino rat of repeated administration of benzene. Archs. Path. Chicago 31, 55. MAYER J. (1964) Farmakoloyia im Farmakoterapie Weterynar~jna, pp. 605-609 PWRiL, W-wa. 605-609. MOESCHLIN S. & SPECK B. (1967) Experimental studies on the mechanism of action of benzene on the bone marrow (radioautoraphic studies using H 3 thymidyne). Acta Haemat., Basel 38-104. NOMJYAMA K. (1965) Studies on poisoning by benzene and its homologues. Industr. Health 3, 53. NORKOWSKI S., KOSSAKOWSKIS. & PATYRA S. (1973) Badania had toksykologia ostrych zatru6 zwierzat foschlorem. Pestycydy 1, 125-126. RUSIECK! W. & KUBIKOWSK! P. T. 0969) Toksykolo~lia Wsp61czesna. pp. 63-71 & 632-636 PZWL W-wa, 63-71, 632 636. SUPNIEWSKI J. (1972) Farmakolo(tia. PZWL, W-wa. VIGLIAM C. & FORN! A. (1969) Benzene chromosom changes and leukomia. J. Occup. Med. 17, 148. VIGL!AM E. C. & SA!TA G. (1964) Benzene and leukemia. New Eng. J. Med. 271,872.
0306-3623/80/0301-0197502.00/0
EFFECT OF BENZENE AND CARBON TETRACHLORIDE INHALATION ON OSMOTIC R E S I S T A N C E O F RABBIT E R Y T H R O C Y T E S ADAM KOLATAJ and HANNA STI~PKOWSKA Department of Animal Physiology, Educational University 25--518 Kielce, Rew. Paz'dziernikowej 33, Poland
(Received 6 Auyust 1979) A b s t r a c t - - I . Benzene and CC14 inhalation resulted in a decrease of erythrocytes osmotic resistance in rabbit. 2. It seems that changes observed in parallel of rabbit internal organs were also caused by the toxic effect of these substances.
INTRODUCTION Professional poisoning caused by neglecting safety rules creates a toxicological problem. The toxic effect of organic solvents on cells and, especially, erthrocytes has become dangerous to man. For toxicological investigation rabbits are often used as experimenta! animals since their reactions are similar to the physiological reactions of man. In this context it seems important to investigate more thoroughly the osmotic resistance of rabbit erythrocytes to the deleterious effects of benzene and carbon tetrachloride as these compounds become more frequent in our environment. Both benzene and CC14 are poisonous for living organisms. Even when inhaled in low concentrations they cause serious general health disturbances affecting especially the erythropoietic system. The severe benzene poisoning has the form of intoxication, shock and narcosis. Benzene, because of its lipophilic character, concentrates mostly in the brain (Supniewski, 1972) and death is caused by paralysis of the respiratory system. At lower doses and concentration the symptoms of irritation of respiratory tract, headache, vomiting and trembling are observed. If the period of benzene inhalation is long enough it causes a chronic injury of bone marrow and capillary vessels. Carbon tetrachloride poisoning through the respiratory system causes, first of all, the injury to the lungs, central nervous system and kidneys, while oral poisoning mostly affects the liver. Chronic poisoning is an effect of small "microinjuries" which after a certain time show themselves in the form of health disturbances (Rusiecki & Kubikowski, 1969; Bohosiewicz, 1970; Mayer, 1964). The safety limit of CC14 concentration in the air is 1:1000. MATERIALS AND METHODS
The experiments were carried out on 25 rabbits of different races, 1.5-2.5 kg body weight and 8-9 months old. The experimental animals derived from the same farm and during the experiment were kept under the same experimental conditions. The animals were treated with benzene (15 rabbits) or 6.P. az/2 o
197
CC14 (10 rabbits)---2 hr inhalation daily for 1 week. During the inhalation period the animal was kept in a cardboard box (with 4 apertures, dia. 3 cm) 70 × 70 × 70cm, containing a Petri dish (9cm dia.) with 5ml of benzene or CCI4.10 min after every inhalation 1 ml samples of blood was taken from the ear vein. The blood samples were centrifuged in order to separate erythrocytes from the blood serum and 2 ml of physiological solution (0.9 % NaCI) was added to the erythrocyte precipitate. Osmotic resistance of erythrocytes was measured by adding one drop of the erythrocyte suspension to I ml of NaCI solution ranging from 0.90 to 0.20~o, the difference between the consecutive concentrations being 0.02~/o. After 1 hr the results were read at 20°C temp. The NaCI concentration, which resulted in a slightly yellow solution colour, was regarded as a beginning of haemolysis and the concentration where there was no erythrocyte precipitation at the bottom as the termination of complete haemolysis. Before the experiment each animal underwent control examinations. RESULTS
The data is presented in Tables I and 2. The erythrocyte osmotic resistance measured during control examinations ranged between 0.324).56% NaCl concentration, the difference between particular days being 0.02-0.08~o. Most animals reacted similarly to benzene inhalation--erythrocyte osmotic resistance decreased in the course of the experiment. Rabbits No. 6, 10 and 14 were less susceptible to benzene treatment and their erythrocyte osmotic resistance decreased to a lower degree. For example, after 3 days of benzene inhalation the erythrocyte osmotic resistance for rabbit No. 4 was 0.72-0.42~, for No. 6, 0.62q3.38~o, for No. 10, 0.60-0.40~o and No. 14, 0.604).38~ (Table 1). These differences were observed towards the end of the experiment. After 7 days of benzene treatment the erythrocyte osmotic resistance was usually less than 0.80-0.50 except rabbit No. 14, where it was much higher; 0.764).46. For animals treated with CC14 (Table 2) in 5 cases (rabbits No. 1, 2, 6, 7 and 10) there were no changes in erythrocyte osmotic resistance during the first days of inhalation. In other animals (No. 3, 4 and 5) from the
198
ADAM KOLATAJ and HANNA
STI~PKOWSKA
Table I. The values of hemolytic changes of blood red cells under the influence of benzene (in NaCI solution) Rabbits (No.l 1 II III IV V Vl VII VII1 lX X Xl XIl Xlll X1V XV
Control Min Max
1 Min
Max
Min
Max
Min
0.54 0.52 0.50 0.54 0.56 0.50 0.54 0.52 0.52 0.50 0.54 0.54 0.52 0.52 0.56
0.56 0.56 0.54 0.56 0.58 0.52 0.60 0.54 0.56 0.52 0.56 0.58 0.54 0.54 0.60
0.40 0.38 0.34 0.40 0.40 0.32 0.40 0.38 0.38 0.36 0.38 0.36 0.36 0.34 0.38
0.62 0.64 0.60 0.66 0.66 0.58 0.64 0.60 0.60 0.56 0.62 0.66 0.60 0.58 0.62
0.40 0.40 0.38 0.40 0.40 0.36 0.40 0.40 0.40 0.38 0.40 0.40 0.38 0.38 0.40
0.70 0.70 0.68 0.72 0.70 0.62 0.66 0.66 0.64 0.60 0.68 0.68 0.64 0.60 0.68
0.38 0.36 0.34 0.36 0.38 0.32 0.38 0.36 0.36 0.34 0.36 0.36 0.34 0.34 0.36
2
Max
Days 4 Min Max
Min
Max
Min
Max
Min
Max
0.42 0.44 0.40 0,42 0.42 0.38 0,42 0,42 0.42 0.40 0.42 0.42 0.38 0.38 0.42
0.72 0.74 0.72 0.74 0.74 0.68 0.72 0.72 0.66 0.66 0.72 0.72 0.66 0.66 0.70
0.78 0.78 0.74 0.76 0.78 0.72 0.76 0.74 0.70 0.72 0.76 0.76 0.74 0.68 0.74
0.46 0.48 0.42 0.46 0.46 0.42 0.46 0.44 0.46 0.48 0.46 0.44 0.44 0.40 0.48
0.82 0.82 0.80 0.80 0.82 0.76 0.80 0.80 0.76 0.78 0.80 0.80 0.76 0.70 0.76
0.52 0.54 0.46 0.52 0.52 0.44 0.52 0.46 0.48 0.50 0.50 0.48 0.46 0.42 0.48
0.86 0.84 0.82 0.86 0.84 0,80 0,86 0,84 0,80 0,80 0.82 0.82 0.82 0.76 0.82
0.54 0.54 0.48 0.52 0.54 0.48 0.54 0.46 0.52 0.52 0.52 0.52 0.50 0.46 0.62
3
beginning of the experiment minimal haemolysis increased. After 4 days, i.e. after 8 hr of CCI4 inhalation rabbit No. 3 died and its final erythrocyte osmotic resistance was 0.72-0.24°/0 NaCI. Rabbit No. 10 died after 5 days and its respective value was 0.76-0.34°~, NaC1. Before the death of these animals a very low activity was observed (partial leg paralysis). All animals showed a decrease of erythrocyte osmotic resistance, as compared with the control values, and it may be assumed to be caused by the toxic effect of CC14. DISCUSSION It has been found that toxic substances cause some changes in various hematological parameters (Brendel & Stepniewicz, 1969: Kontek et al., 1973; Norkowski et al., 1973). These changes also comprise the changes in erythrocyte resistance. Our experiments have shown the decrease of erythrocyte osmotic resistance caused by benzene and CC14 treatment. One may suppose it can also be caused by dissolving the lipid c o m p o n e n t of the cell membrane, which resulted in increased hemolysis. Kwiatkowski (1962) pointed out that cell mem-
0.44 0.44 0.40 0.46 0.44 0.40 0.44 0.44 0.44 0.42 0.44 0.44 0.40 0.40 0.44
5
6
7
brane permeability is the main factor of osmotic pressure. He investigated the erythrocyte osmotic resistance in horses with different pathological symptoms. He found that in certain illnesses of the alimentary canal, proceeding with the symptoms of self-poisoning, the decrease of erythrocyte osmotic resistance was also observed. The erythrocyte osmotic resistance decreases also during infection, and this may suggest the presence of a great number of old erythrocytes and an action of bacterial toxis (Dyszy, 1956). Toxic substance penetrating from damaged tissues during or after surgical operation may affect the erythrocyte osmotic resistance of a patient (Kad[ubowska & Pietz, 1956). Our experiments showed that the erythrocyte osmotic resistance was related to the quantity of inhaled benzene and CC14. As more benzene was inhaled its solubilising effect on the lipid component of the cell membrane was stronger and this decreased the erythrocyte resistance. The changes in erythrocyte resistance may also be explained by damage of bone marrow cells producing erythrocytes. Latta & Dawies (1941) and Moeschlin & Speck (1967) stated that benzene caused damage to the bone and even leukaemia in laboratory animals. Are other
Table 2. The values of hemolytic changes of blood red cells under the influence of CC14 (in NaCl solution) Rabbits (No.)
Control Min Max
1 Min
2 Max
Min
3 Max
Min
Max
I II Ill
0.56 0.64 0.60
0 . 1 8 0 . 5 6 0 . 1 8 0 . 5 6 0 . 1 8 0 . 5 6 0.20 0 , 1 8 0 . 6 2 0 . 1 8 0 . 6 2 0 . 1 8 0 . 6 2 0.20 0 . 1 8 0 . 6 2 0 . 2 0 0 . 6 2 0 . 2 2 0 . 6 4 0.22
IV V VI VII VIII IX X
0.54 0.54 0.62 0.52 0.58 0.68 0.52
0.18 0.18 0.18 0.20 0.20 0.18 0.18
0.50 0.56 0.62 0.52 0.58 0.68 0.52
0.20 0.18 0.18 0.22 0.20 0.20 0.18
0.55 0.56 0.62 0.52 0.60 0.68 0.52
0.20 0.20 0.20 0.22 0.20 0.22 0.20
0.60 0.58 0.62 0.52 0.60 0.70 0.54
0.24 0.22 0.20 0.22 0.20 0.22 0.22
Day 4 Min Max 0.64 0.66 0.72 died 0.62 0.60 0,64 0.56 0,60 0.70 0,66
5 Min
6 Max
Min
7 Max
Min
Max
0 . 2 4 0 . 6 4 0 . 2 4 0 . 6 7 0 . 2 8 0 . 7 0 0.28 0 . 2 4 0 . 7 2 0 . 2 4 0 . 7 2 0 . 2 8 0 . 7 6 0~28 0.24 . . . . . . . 0.22 0.24 0.20 0.22 0.22 0.22 0.24
0.64 0.62 0.66 0.58 0.62 0.70 0.76 died
0.24 0.24 0.22 0.22 0.22 0.24 0.34
0.66 0.64 0.68 0.60 0.64 0.72 . .
0.24 0.24 0.22 0.24 0.26 0.26 . .
0.68 0.72 0.74 0,64 0.64 0.78 . .
0.24 0,30 0.30 0,30 0,30 0,32
Effect of benzene and carbon tetrachloride inhalation \
paper (Nomiyama, 1965) describing experiments on rats suggested that the harmful agents causing bone marrow damage are the toxic benzene derivatives of phenolic character, mostly diphenol and pyrocatechol. In man, benzene causes a n u m b e r of haematologic disturbances like haemolytic anemia, hyperplasia of bone marrow and leucopaemia (Goldwater, 1965; Aksoy et al., 1970; De Gawin, 1963; Vigliam & Forni, 1969; Vigliam & Saita, 1964).
REFERENCES
AKSOY M., DINCOL K., ERDEM S., AKGUN T. & DINGOL G. (19701 Clinical laboratory observation in 32 patients with aplastic anemia and 2 with acute myeloblastic leukemia due to chronic benzene poisoning. Abstracts of the Xlllth International Congress on Hematology, p. 134. BOHOSIEWlCZ U. (1970) Toksykologia Weterynarkjna. pp. 20--20 & 119-120 PRRiL W-wa. BRENDEL B. & STEPNIEWWZ W. (1969) Wpiyw zabiegu operacyjnego i znieczulenia og61nego na wzrgst hemolizy wewn,~trznaczyniowej i aktywnog6 katalazy w surowicy krwi. Lekarz Wojsk. 4, 308-312. Dvszv B. (1956) Opornog~: krwinek czerwonych w ~wietle przypadk6w klinicznych. Pol. Przeol. Chirurg. 3, 26(~268. DE GAWIN R. L. (1963) Benzene exposure and aplastic anemia followed by leukemia fifteen years later. J.A.M.A. 185, 748. GOLDWATER L. J. (1965) Disturbances in the blood following exposure to benzol. Clin. Med. 26, 957.
199
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