Research general

The toxicity of substances is mainly tested on rats and mice. Catastrophes (like the Gulf War, the Vietnam War, industrial accidents) offer more insight too. The test data offer insight in the ‘normal’ human state but not exactly. For instance rabbits are more sensitieve to amphetamines as rats (Franklin MR 1977). And humans are bad metabolizers, in case of some toxic substances, compared to rats and mice (IARC, 1993, Mendrala AL 1993, Rossi R et al 2001).

The harm a certain substance, a certain person does, depends on his/her detoxifing system, the liver function, former hepatitis b infestation (IARC 2002, Groopman JD et al 2007, Wu HC et al 2007), former and/or actual exposure to other toxic components (environment, drugs). All these factors and many more can make a potentially quite harmless chemical, a toxic one.

Quote:
“Chemicals that were relatively harmless when used independently of each other could become highly toxic to the brain when used together… governments should consider restricting the availability of some household chemicals until more was known about their interaction in the brain with each other and with other substances such as over-the-counter medicines.„ (Mohamed Abou-Donia, a professor of pharmacology, cancer biology and neurobiology at Duke University Medical Centre. 2001)

Other factors making relative harmless substances highly toxic include stress, hypertension, and exposure to nicotine, which all disrupt the BBB (Blood Brain Barrier) (Abdel-Rahman A et al 2002, Esposito P et al 2002, Hawkins BT et al 2004, 2005). As do Diesel exhaust particles (Anika M. S. Hartz et al 2008) and does homocysteine (Tyagi N, 2008) and histamin (Sharma HS 1992).
The BBB (blood-brain barrier) protects the brain from drugs and other chemicals that enter the circulatory system. This is what got a lot of Gulf War Veterans (see at Permethrin).

And of cause if you do not know where to look at you will not find it. Behaviour for instance is a rather new subject and certain effects just become obvious in a second or even third generation!!!!!! (see at Permethrin and Piperonyl-butoxide)

To illustrate

A tale of two cities Safety testing in Britain and Germany Howell J Pesticides News, 1998, Vol 40, p3. http://www.pan-uk.org/pestnews/Issue/pn40/pn40p3.HTM

Safety testing in Britain and Germany Safety tests on permethrin use in homes in Britain and Germany have produced strikingly different results and recommendations. In the UK, water-based permethrin timber treatment formulations have been given eight-hour re-entry time approval, whilst in Germany permethrin has been declared a persistent human health risk for up to two years after application. Jeff Howell visited both institutes to investigate these differences.

References

Abdel-Rahman A, Shetty AK, Abou-Donia MB (2002)
Disruption of the blood brain barrier and neuronal cell death in cingulated cortex, dentate gyrus, thalamus and hypothalamus in a rat model of Gulf-War syndrome.
Neurobiol Dis 10: 306–326.

Esposito P, Chandler N, Kandere K, Basu S, Jacobson S, et al. (2002)
Corticotropin-relasing hormone and brain mast cells regulate blood-brain-barrier permeability induced by acute stress.
J Pharmacol ExpTher 303: 1061–1066.

Franklin MR (1977)
Dep. Biopharm. Sci., Coll. Pharm., Univ. Utah, Salt Lake City, UT 84112
The inhibition of mixed-function oxidation reactions by amphetamines in liver and lung microsomes.
Microsomes and Drug Oxidations. Ullrich, V., Roots, I., Hildebrandt, A., Estabrook, R. W., Conney, A. H., eds. (New York: Pergamon Press): pp. 284-291 1977

Groopman JD, Kensler TW, Wild CP (2007)
Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland 21205 jgroopma@jhsph.edu.
Protective Interventions to Prevent Aflatoxin-Induced Carcinogenesis in Developing Countries.
Annu Rev Public Health. 2007 Oct 3

Anika M. S. Hartz, Björn Bauer, Michelle L. Block, Jau-Shyong Hong and David S. Miller (2008)
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA;
Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier.
The FASEB Journal. 2008;22:2723-2733.

Hawkins BT, Abbruscato TJ, Egleton RD, Brown RC, Huber JD, et al. (2004)
Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution.
Brain Res 1027: 48–58.

Hawkins BT, Davis TP (2005)
The blood-brain barrier/neurovascular unit in health and disease.
Pharmacol Rev 57: 173–185.

IARC, (1993)
International Agency for Research on Cancer (IARC) - Summaries & Evaluations AFLATOXINS
Naturally Occurring Aflatoxins (Group1) Aflatoxin M1 (Group 2B) For definition of Groups, see Preamble Evaluation. VOL.: 56 (1993) (p. 245) http://www.inchem.org/documents/iarc/vol56/09-afl.html

IARC (2002) International Agency for Research on Cancer (IARC) - Summaries & Evaluations
AFLATOXINS (Group 1) For definition of Groups, see Preamble Evaluation.
VOL.: 82 (2002) (p. 171) http://www.inchem.org/documents/iarc/vol82/82-04.html

Mendrala AL Langvardt PW Nitschke KD Quast JF Nolan RJ (1993)
Toxicology Research Laboratory, Dow Chemical Company, Midland, MI 48674.
In vitro kinetics of styrene and styrene oxide metabolism in rat, mouse, and human.
Arch Toxicol. 1993; 67(1):18-27. [Archives of toxicology]

Rossi R Milzani A Dalle-Donne I Giannerini F Giustarini D Lusini L Colombo R Di Simplicio P (2001)
Department of Neuroscience, Pharmacology Unit, Via A. Moro 4, University of Siena, Italy.
Different metabolizing ability of thiol reactants in human and rat blood: biochemical and pharmacological implications.
J Biol Chem. 2001, Mar 9; 276(10):7004-10. [The Journal of biological chemistry]

Sharma HS, Nyberg F, Cervos-Navarro J, Dey PK. (1992)
Department of Neuropathology, Free University Berlin, F.R.G.
Histamine modulates heat stress-induced changes in blood-brain barrier permeability, cerebral blood flow, brain oedema and serotonin levels: an experimental study in conscious young rats.
Neuroscience. 1992 Sep;50(2):445-54.

Neetu Tyagi, Munish Kumar, SB Pushpakumar, David Lominadze, Karni S Moshal, Utpal Sen, Thomas Paul Vacek and Suresh C Tyagi (2008)
Physiology & Biophysics, University of Louisville, Louisville, KY
Homocysteine attenuates blood brain barrier function by inducing oxidative stress and the junctional proteins.
The FASEB Journal. 2008;22:734.7

Wu HC, Wang Q, Wang LW, Yang HI, Ahsan H, Tsai WY, Wang LY, Chen SY, Chen CJ, Santella RM. (2007)
Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, NY, USA.
Polycyclic aromatic hydrocarbon- and aflatoxin-albumin adducts, hepatitis B virus infection and hepatocellular carcinoma in Taiwan.
Cancer Lett. 2007 Jul 8;252(1):104-14. Epub 2007 Jan 23.

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