Chemistry Reference
In-Depth Information
studies have one or more of the following shortcomings:
a small number of subjects examined, no control group
or an inadequate control group because of relatively high
blood lead levels, the inclusion of subjects with current
or recent urogenital tract infections, and/or a lack of con-
trol for other common factors capable of affecting repro-
ductive parameters. The fi ndings were mainly related
to dose-response trend(s) on a group basis for different
exposure categories, so that insuffi cient evidence was
presented for establishing a quantitative dose-response
curve and no-adverse-effect exposure threshold, particu-
larly concerning the range of very low to moderate blood
lead levels.
Some data suggest that the reproductive effects of
lead in men are reversible; a trend toward normaliza-
tion was found in subjects treated with a lead-chelat-
ing agent (Cullen
et al.,
1984; Fisher-Fischbein
et al
.,
1987) or after cessation of occupational lead exposure
(Viskum
et al
., 1999).
A cross-sectional study of 149 industrial work-
ers with low to moderate chronic lead exposure
(Telišman
et al
., 2000) showed signifi cant lead-
related reproductive effects even at blood lead levels
<400
In contrast, an international cross-sectional study
of 362 lead workers and 141 control subjects from 10
companies in Belgium, Italy, and the United Kingdom
(Bonde
et al.,
2002) reported that, although median
sperm concentration was reduced by 49% in men
with blood lead >500
µ
g/L, a likely threshold as high
as 440
g/L was found for this parameter of semen
quality. The mean (range) blood lead values were 44
(0-198)
µ
µ
g/L in the control subjects and 310 (46-645)
µ
g/L in lead workers. Abnormal sperm chromatin
structure was not signifi cantly related to blood lead
levels. However, it seems possible that differences in
some lifestyle factors and the body burden of other
relevant metals, not controlled for in this study, might
have contributed to variations in reproductive param-
eters among the study population, thereby weakening
or masking the relationship between blood lead and
reproductive effects.
Recent data indicate that lead can adversely affect
human semen quality even at blood lead levels
<150
g/L (Jurasovic
et al
., 2004; Telišman
et al.,
2003).
In a study of 123 men who had never been occupa-
tionally exposed to metals, the median (range) blood
lead values were 57 (range 25-149)
µ
g/L. The median (range) of current blood lead
values were 103 (67-208)
µ
g/L. After adjust-
ing for confounding variables (age, smoking, alcohol,
blood cadmium, and serum copper, zinc, and sele-
nium), an increase in blood lead was signifi cantly asso-
ciated with decreasing percentages of morphologically
normal and subnormal sperm and with increasing
percentages of slow sperm and overly wide sperm. A
decrease in ALAD activity was signifi cantly associated
with decreasing size of testes and seminal plasma lev-
els of the lactate dehydrogenase isoenzyme LDH-C
4
. In
another study (Benoff
et al
., 2003), the seminal plasma
lead levels of subjects not occupationally exposed to
lead were found to inversely correlate with fertilizing
capacity of sperm (sperm acrosome reaction) and the
fertilization rate when using IVF technique, but also
with seminal plasma zinc levels. Taken together, these
studies suggest that lead may signifi cantly reduce
human semen quality even at low-level lead exposure
that is common for general populations worldwide.
Several studies of lead workers have indicated
that paternal blood lead levels of approximately 300-
400
µ
µ
g/L in 51 control subjects
and 367 (119-659)
g/L in 98 lead workers; their
long-term average blood lead values were <400
µ
g/
L. Changes in reproductive parameters were more
pronounced at relatively low-level lead exposure
(<350
µ
g/L) compared with higher levels. For exam-
ple, the dose-response relationship between sperm
count and blood lead in the 149 subjects showed
a decrease of approximately 65 × 10
6
sperm in the
blood lead range 50-350
µ
g/L. A decrease in sperm
count was signifi cant even at blood lead levels of
240
µ
g/L. After adjusting
for age, smoking, alcohol, blood cadmium, serum
zinc, and serum copper, an increase in blood lead
was signifi cantly associated with decreasing sperm
concentration, counts of total sperm and progres-
sively motile sperm, seminal plasma levels of zinc,
acid phosphatase and citric acid, and increasing per-
centage of pathological sperm with abnormal sperm
head morphology. A better correlation of reproduc-
tive parameters was found with respect to delta-
aminolevulinic acid dehydratase (ALAD) activity in
blood, indicating that the reproductive effects were
in part mediated through lead interference with
zinc metabolism (Telišman
et al.,
2000). In a similar
study, Alexander and coworkers (1996a) showed
that sperm concentration and sperm count in lead
workers were inversely related to both current blood
lead and long-term average blood lead, even at lev-
els <400
µ
g/L compared with <100
µ
g/L are a most likely threshold for increased
rate of spontaneous abortions (Lindbohm
et al
., 1991),
reduced rate of live births (Gennart
et al
., 1992b; Lin
et al
., 1996), and prolonged TTP (Sallmén
et al
., 2000;
Shiau
et al
., 2004), although inconsistent fi ndings
(Bonde and Kolstad, 1997; Coste
et al.,
1991; Joffe
et al
.,
2003) or a minor incompatibility were also reported.
An Italian study (Apostoli
et al
., 2000) reported that,
although shorter TTP was found in lead workers com-
pared with control subjects, within the group of lead
µ
µ
g/L.
