9.6.2 HEALTH EFFECTS
Chronic Be disease, commonly known as berylliosis, is manifested by
pulmonary and systemic granulomatous disease caused by exposure to Be by
inhalation. The duration of exposure may be from several months to years. The
interval between initial exposure and clinical manifestations of disease varies
with individuals. Some patients may not become symptomatic until up to 25
years after their last exposure. The average latency is 10 to 15 years. The most
common symptom of chronic Be disease is dyspnea (shortness of breath).
Other symptoms include cough, fatigue, weight loss, chest pain, signs of
pulmonary hypertension, nodular skin lesions, and conjunctivitis.
In acute Be disease, nasopharyngitis, tracheobronchitis, or chemical
pneumonitis may occur, resulting in edema, inflammation, and necrosis. The
severity of clinical disease depends largely on the dose of Be exposure.
Symptoms and signs are nonspecific, identical to those found in any case of
chemical pneumonitis secondary to a lung irritant, and include dyspnea, cough,
chest pain, blood-tinged sputum, and cyanosis. Acute Be disease is currently
uncommon. Evidence from both animal experiments and human epidemiologic
studies suggests a link between Be and lung cancer in humans.
9.6.3 BIOLOGICAL EFFECTS
In animal studies, Be has been shown to cause ultrastructural changes in the
liver. Alterations included vacuolization and dense deposits in lysosomes, loss
of fibrils and appearance of dense plaques in some nucleoli, and distortion of
bile canaliculi.
15 Changes in lysosomal morphology were found to correlate
with the biochemical evidence of localization of Be within lysosomes. Increases
in serum gammaglobulins, elevated erythrocyte sedimentation rate, and
erythrocytosis, hyperuricemia, and transient hypercalcemia and hypercalciuria,
have also been noted.
Be affects the enzyme that leads to DNA synthesis and can act as a
competitive inhibitor of magnesium (Mg
2þ
), a cofactor for DNA polymerase.
DNA polymerase catalyzes the formation of a polynucleotide from a single
DNA template strand and a short complementary DNA or RNA primer. It
also functions to ‘‘proofread’’ the base pairing as a new strand of DNA is
formed. In this way, it can remove an incorrectly base-paired nucleotide before
the next nucleotide is added to the DNA strand. Therefore, when Be
competitively inhibits Mg
2þ , a base-substitution mutation may occur. It has
been reported that the physical properties of DNA are affected by 0.1 to 1 mM
beryllium sulfate (BeSO 4 ).
9.6.4 THERAPY
One of the remedies for berylliosis is the use of chelating agents, such as
aurintricarboxylic acid (ATA) (Figure 9.2a). In an animal experiment,
researchers injected mice with enough Be salt to kill them within a few days.
142
Environmental Toxicology
[16:52 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-009.3d]
Ref: 4365 MING-HO YU Chap-009 Page: 142 135-148
Chronic Be disease, commonly known as berylliosis, is manifested by
pulmonary and systemic granulomatous disease caused by exposure to Be by
inhalation. The duration of exposure may be from several months to years. The
interval between initial exposure and clinical manifestations of disease varies
with individuals. Some patients may not become symptomatic until up to 25
years after their last exposure. The average latency is 10 to 15 years. The most
common symptom of chronic Be disease is dyspnea (shortness of breath).
Other symptoms include cough, fatigue, weight loss, chest pain, signs of
pulmonary hypertension, nodular skin lesions, and conjunctivitis.
In acute Be disease, nasopharyngitis, tracheobronchitis, or chemical
pneumonitis may occur, resulting in edema, inflammation, and necrosis. The
severity of clinical disease depends largely on the dose of Be exposure.
Symptoms and signs are nonspecific, identical to those found in any case of
chemical pneumonitis secondary to a lung irritant, and include dyspnea, cough,
chest pain, blood-tinged sputum, and cyanosis. Acute Be disease is currently
uncommon. Evidence from both animal experiments and human epidemiologic
studies suggests a link between Be and lung cancer in humans.
9.6.3 BIOLOGICAL EFFECTS
In animal studies, Be has been shown to cause ultrastructural changes in the
liver. Alterations included vacuolization and dense deposits in lysosomes, loss
of fibrils and appearance of dense plaques in some nucleoli, and distortion of
bile canaliculi.
15 Changes in lysosomal morphology were found to correlate
with the biochemical evidence of localization of Be within lysosomes. Increases
in serum gammaglobulins, elevated erythrocyte sedimentation rate, and
erythrocytosis, hyperuricemia, and transient hypercalcemia and hypercalciuria,
have also been noted.
Be affects the enzyme that leads to DNA synthesis and can act as a
competitive inhibitor of magnesium (Mg
2þ
), a cofactor for DNA polymerase.
DNA polymerase catalyzes the formation of a polynucleotide from a single
DNA template strand and a short complementary DNA or RNA primer. It
also functions to ‘‘proofread’’ the base pairing as a new strand of DNA is
formed. In this way, it can remove an incorrectly base-paired nucleotide before
the next nucleotide is added to the DNA strand. Therefore, when Be
competitively inhibits Mg
2þ , a base-substitution mutation may occur. It has
been reported that the physical properties of DNA are affected by 0.1 to 1 mM
beryllium sulfate (BeSO 4 ).
9.6.4 THERAPY
One of the remedies for berylliosis is the use of chelating agents, such as
aurintricarboxylic acid (ATA) (Figure 9.2a). In an animal experiment,
researchers injected mice with enough Be salt to kill them within a few days.
142
Environmental Toxicology
[16:52 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-009.3d]
Ref: 4365 MING-HO YU Chap-009 Page: 142 135-148