Chemistry Reference
In-Depth Information
6.3.3 Toxicological Signifi cance
human tissues and fl uids. This age-old practice has
been used by the Centers for Disease Control and Pre-
vention (CDC) to study the presence of natural and
synthetic chemicals in human populations (CDC, 2005
the NHANES report). This has led to the development
of programs to control emission of certain environmen-
tal pollutants such as lead, when the cause and effect
has been established. The measurement of metals in
biological fl uids is the primary means of quantifying
exposure for metals by occupational health organiza-
tions, such as the American Congress of Governmental
Industrial Hygienists, and is the basic tool for popu-
lation or molecular epidemiology studies of effects of
exposure to humans of various metals.
A study in occupationally exposed men given a low
oral dose of zinc did not provide evidence of an effect
on blood lead or urinary ALA. However, the inhalation
route of exposure for lead circumvents potential interac-
tions at the level of absorption, and the dose of zinc was
very low in this study. In another study, an increase in
urinary ALA above the normal range was signifi cantly
associated with a decrease in the chelatable zinc/lead
ratio to 18.45 or less in children given chelation ther-
apy for lead poisoning (Chisolm, 1981). Supplemental
zinc protected against the inhibiting effects of lead on
ALAD activity and against lead-induced increases in
zinc protoporphyrin and urinary ALA excretion in rats
given both metals orally for intermediate durations
(Cerklewski and Forbes, 1976; El-Gazzar
et al.
, 1978;
Flora
et al.
, 1982; 1989). These protective effects were
seen at higher but not lower lead doses and when basal
levels of zinc in the diet were adequate. The potential
public health hazard of the joint toxic action of this mix-
ture must also recommend inclusion of estimation of
endpoint-specifi c hazard indexes (HIs) for neurological
effects of lead and manganese and for hematological
effects of lead and zinc. The HIs are estimated by use of
exposure data and health guidance values:
References
Abdulla, M., Stevensson, S. and Haeger-Aronsen, B. (1979).
Arch. En-
viron. Health
34,
464-469.
Agency for Toxic Substances and Disease Registry. (ATSDR 2001).
“Guidance Manual for the Assessment of Joint Toxic Action of
Chemical Mixtures.” ATSDR.
Ahmad, S., Kitchin, K. T., and Cullen, W. R. (2002).
Toxicol. Lett
.
133,
47-57.
Ahsan, H., Chen, Y., Kibriya, M. G.,
et al.
(2003).
Cancer Lett.
201,
57-65.
Ahsan, H., Chen, Y., Wang, Q.,
et al.
(2003).
Toxicol. Lett.
143,
123-131.
Åkesson, A., Berglund, M., Schutz, A.
et al.
(2002).
Am. J. Publ. Health
92,
284-287.
Åkesson, A., Stål, P., and Vahter, M. (2000).
Environ. Health Perspect.
108,
289-291.
Alexander, B. H., Checkoway, H., Costa-Mallen, P.,
et al.
(1998).
Envi-
ron. Health Perspect.
106,
213-216.
Ames, S. K., Ellis, K. J., Gunn, S. K
., et al.
(1999).
J. Bone Miner. Res.
14,
740-746.
Amicosante, M., Berretta, F., Rossman, M.,
et al.
(2005).
Respir Res.
6,
94.
An, Q., Wang, Z., Liu, B.,
et al.
(1998).
Wei Sheng Yan Jiu.
27,
312-314.
Anghileri, L. J., Mayayo, E., Domingo, J. L.,
et al.
(2002).
Drug Chem.
Toxicol
.
25,
267-279.
Bal, W., Lukszo, J., Jezowska-Bojczuk, M.,
et al.
(1995).
Chem. Res.
Toxicol.
8,
683-692.
Bal, W., Lukszo, J., and Kasprzak, K. S. (1996).
Chem. Res. Toxicol
.
9,
535-540.
Barton, J. C., Patton, M. A., Edwards, C. Q.,
et al.
(1994).
J. Lab Clin.
Med.
124,
193-198.
Bellinger, D., Hu, H., Titlebaum, L.,
et al.
(1994).
Arch. Environ. Health.
49,
98-105.
Belman, S., and Nordberg, G. F. (Eds.). (1981).
Environ. Health Per-
spect.
40,
3-42.
Bergdahl, I. A., Gerhardsson, L., Schutz, A.,
et al.
(1997).
Arch. Envi-
ron. Health.
52,
91-96.
Bergdahl, I. A., Grubb, A., Schutz, A.,
et al.
(1997).
Pharmacol. Toxicol.
81,
153-158.
Bergdahl, I. A., Sheveleva, M., Schutz, A.,
et al.
(1998).
Toxicol. Sci.
46,
247-253.
Beutler, E., Felitti, V. J., Koziol, J. A.,
et al.
(2002).
Lancet.
359,
211-218.
Beyrouty, P., and Chan, H. M. (2006).
Neurotoxicol. Teratol
.
28 (1),
49-58.
Björkman, L., Vahter, M., and Pedersen, N. L. (2000).
Environ. Health
Perspect.
108,
719-22.
Exposure
Pb
Guidance value
Pb
Exposure
Mn
HI
neuro
=
+
Guidance value
Mn
This HI approach should be used when the hazard
quotients (HQ) of at least two of the components equal
or exceed 0.1. If only one or if none of the mixture com-
ponents has a hazard quotient that equals or exceeds
0.1, further assessment of the joint toxic action is not
needed, because additivity and/or interactions are
unlikely to result in signifi cant health hazard (ATSDR,
2001a). With the information from the WOE matrix, the
following summarizations can be made regarding the
impact of interactions on some specifi c toxicities.
A deductive method such as the WOE should have
built-in capabilities to integrate all observations on
interactions, refl ect the underlying principles and
mechanisms that are operative, allow the users to
express uncertainty comparable to existing methods,
be able to be applied consistently in varying exposure
scenarios, be used qualitatively and if possible quanti-
tatively, and, most importantly, be able to be verifi ed
and validated through experimental studies.
6.4 Perspectives and Future Needs
The best measurement of exposure comes through
biomonitoring, the measurement of chemicals in
