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Mechanisms of renal toxicity
Plenary Lectures (5 March 1981) 1700-1720 Hall I
A7
SYMPTOMS AND SIGNS OF LEAD N E U R O T O X I C I T Y
Philippe G r a n d j e a n and J~rn B e c k m a n n Danish N a t i o n a l I n s t i t u t e of O c c u p a t i o n a l Health, Hellerup, Odense U n i v e r s i t y Hospital, Denmark
and
S i x t y - s e v e n healthy men (age, 18-50 years) with d i f f e r e n t degrees of o c c u p a t i o n a l exposure to inorganic lead were e x a m i n e d by means of an e x t e n s i v e neuropsychological test battery (Grandjean et al., 1978). D e m e n t i a l symptoms were recorded on a scale from O (excellent) to 9 (severe). C u r r e n t lead exposure was e s t i m a t e d by the lead c o n c e n t r a t i o n in blood. This exposure p a r a m e t e r c o r r e l a t e d closely with lead levels in hair and zinc p r o t o p o r p h y r i n in blood. P e r f o r m a n c e in almost all n e u r o p s y c h o l o g i c a l tests d e c r e a s e d with a u g m e n t e d blood lead concentrations. However, m e m o r y p r o b l e m s and alcohol i n t o l e r a n c e were the only symptoms s i g n i f i c a n t l y related to increased lead exposure. A m u l t i p l e r e g r e s s i o n analysis and a split analysis showed that symptoms of insomnia, lack of concentration, m e m o r y problems, alcohol intolerance, etc., were related to reduced test results. A n d e r s e n ' s (1978) Graphic C o n t i n u o u s Performance Test a p p e a r e d to be the best estimator of d e m e n t i a l symptoms in the l e a d - e x p o s e d men examined. These results support the notion that lead n e u r o t o x i c i t y is a d o s e - r e l a t e d effect w h i c h may occur at very low e x p o s u r e levels. N e u r o p s y c h o l o g i c a l tests provide a more sensitive e s t i m a t e of lead n e u r o t o x i c i t y than does s u b j e c t i v e symptoms. R.Andersen, Neuropsych., 1978, 16, 439. P . G r a n d j e a n et al., S c a n d . J . W o r k Environ.Hlth,
1978, ~, 295.
PLENARY LECTURES (5 March 1981) 0900-0940 Hall 1
MECHANISMS ~ RENALTOXICITY JERRY B. HO~ M.D., Center for Environmental Toxicology & Department of Phamacology and Toxicoiogy: Michigan State University, East Lansing, Michigan 48824, U,S.A.
Because of its high rate of blood flow and unique physi~logical functions of
filtration, reabaorption and secretion, the ceiis
of the kidney are often exposed to concentrations of chemicals far in excess of other cells of the body.
Sites of action of nephro-
toxic chemicals vary according to their renaI handling and/or due to the location of specific biochemical targets.
A specific lesion
~long the nephron will often produce a characteristic physiological alteration;
the glomerular lesion of puromycin aminenucleoside
produces changes different than the tubular effects of chlorinated hydrocarbons or the medullary effects of bremoethyIamine.
Devel-
opment and utilization of renal function tests designed to definitely evaiuate tubular integrity should aid in the evaluation of the effects of new, potentially toxic chemicals on the kidney.
A7
SYMPTOMS AND SIGNS OF LEAD N E U R O T O X I C I T Y
Philippe G r a n d j e a n and J~rn B e c k m a n n Danish N a t i o n a l I n s t i t u t e of O c c u p a t i o n a l Health, Hellerup, Odense U n i v e r s i t y Hospital, Denmark
and
S i x t y - s e v e n healthy men (age, 18-50 years) with d i f f e r e n t degrees of o c c u p a t i o n a l exposure to inorganic lead were e x a m i n e d by means of an e x t e n s i v e neuropsychological test battery (Grandjean et al., 1978). D e m e n t i a l symptoms were recorded on a scale from O (excellent) to 9 (severe). C u r r e n t lead exposure was e s t i m a t e d by the lead c o n c e n t r a t i o n in blood. This exposure p a r a m e t e r c o r r e l a t e d closely with lead levels in hair and zinc p r o t o p o r p h y r i n in blood. P e r f o r m a n c e in almost all n e u r o p s y c h o l o g i c a l tests d e c r e a s e d with a u g m e n t e d blood lead concentrations. However, m e m o r y p r o b l e m s and alcohol i n t o l e r a n c e were the only symptoms s i g n i f i c a n t l y related to increased lead exposure. A m u l t i p l e r e g r e s s i o n analysis and a split analysis showed that symptoms of insomnia, lack of concentration, m e m o r y problems, alcohol intolerance, etc., were related to reduced test results. A n d e r s e n ' s (1978) Graphic C o n t i n u o u s Performance Test a p p e a r e d to be the best estimator of d e m e n t i a l symptoms in the l e a d - e x p o s e d men examined. These results support the notion that lead n e u r o t o x i c i t y is a d o s e - r e l a t e d effect w h i c h may occur at very low e x p o s u r e levels. N e u r o p s y c h o l o g i c a l tests provide a more sensitive e s t i m a t e of lead n e u r o t o x i c i t y than does s u b j e c t i v e symptoms. R.Andersen, Neuropsych., 1978, 16, 439. P . G r a n d j e a n et al., S c a n d . J . W o r k Environ.Hlth,
1978, ~, 295.
PLENARY LECTURES (5 March 1981) 0900-0940 Hall 1
MECHANISMS ~ RENALTOXICITY JERRY B. HO~ M.D., Center for Environmental Toxicology & Department of Phamacology and Toxicoiogy: Michigan State University, East Lansing, Michigan 48824, U,S.A.
Because of its high rate of blood flow and unique physi~logical functions of
filtration, reabaorption and secretion, the ceiis
of the kidney are often exposed to concentrations of chemicals far in excess of other cells of the body.
Sites of action of nephro-
toxic chemicals vary according to their renaI handling and/or due to the location of specific biochemical targets.
A specific lesion
~long the nephron will often produce a characteristic physiological alteration;
the glomerular lesion of puromycin aminenucleoside
produces changes different than the tubular effects of chlorinated hydrocarbons or the medullary effects of bremoethyIamine.
Devel-
opment and utilization of renal function tests designed to definitely evaiuate tubular integrity should aid in the evaluation of the effects of new, potentially toxic chemicals on the kidney.