Detectable in almost all internal organs, Organs rich in adipose tissue are storage depots from which hydrocarbons are gradually released Gastrointestinal tract contains high levels of hydrocarbon and metabolites, even when PAH are administered by other routes, as a result of mucociliary clearance and swallowing or hepatobiliary excretion (IPCS, 1998)

1. Polynuclear Aromatic
Hydrocarbon (PAH)
cdfc.rug.ac.be/HealthRisk/PAHs/toxicology.htm

2. PAH Absorbtion
• Respiratory tract after inhalation of PAH-
containing aerosols or of particulates to
which a PAH, in the solid state, has
become to be absorbed
• Gastro-intestinal tract after ingestion of
contaminated food or water
• Skin as a result of contact with PAH-
bearing materials.

3. PAH Distribution
• Detectable in almost all internal organs,
• Organs rich in adipose tissue are storage
depots from which hydrocarbons are
gradually released
• Gastrointestinal tract contains high levels
of hydrocarbon and metabolites, even
when PAH are administered by other
routes, as a result of mucociliary
clearance and swallowing or hepatobiliary
excretion (IPCS, 1998)

6. Elimination
Most metabolites of PAH are excreted in feces and urine.
Target organs
Skin: Anthracene, benzo[a]pyrene and napthalene are
primary irritants. Anthracene and benzo[a]pyrene were
reported to be sensitisers (IPCS, 1998). Some PAH may
produce skin cancer (scrotum, face)
•Respiratory system: Lung cancer
•Urogenital system: Bladder cancer
•Gastro-intestinal system: Stomach cancer

7. Teratogenicity
• Embryotoxic effects have been described
in experimental animals exposed to PAH
such as benz[a]anthracene,
benzo[a]pyrene, and napthalene
• Genotoxicity: benzo(a)pyrene binds to
DNA and causes gene mutations,
chromosome aberrations, sister chromatid
exchanges; unsheduled DNA synthesis.

8. Carcinogenicity
• Cancers associated with exposure to PAHs-
containing mixtures are predominantly lung and
skin cancers,following inhalation and dermal
exposure, respectively. Bladder cancer has also
been associated with exposure to PAHs in
aluminium plants or when handling asphalt The
impact of a potentialconfounding by other
simultaneous exposures (e.g. aromatic amines,
other components of bitumen/tar...) has not
definitely been determined.

9. Holsbeek et al 1999
“Food is considered to be the primary source of PAHs
(Law and Whinnett, 1992), PAH levels probably being
diet-dependent. The observed PAHs are presumably the
ones which have escaped metabolization (Hellou et al.,
1990).”

10. Marsili et al 2001 - ? ng/g fw
(? Table 2 is microgram/g for tPAH)
• Fin whales
– 1993: 10 to 30 (RECENT SPILLS)
– 1996: 1
• S coeruleoalba
– 30’s
? Poor metabolizers. Only burn fat if pregnant,
lactating, sick or migrating
Suggest PAH may be significant stressor but
give no reasons

11. Martineau et al 2002
• High prevalence of epithelial cancers,
especially in proximal intestine, in SLE
beluga
• Epidemiologically associated with PAH
exposure to beluga and humans from
local aluminum smelters

12. Other effects
• Anti-estrogenic in flounder – Monteiro et al
2000 MER 49:453-467
• Are PAH more significant to mm than
residue data would imply?
• How can we examine their effects that are
less overt than carcinogenesis?
• Which species are most at risk?

13. PAH References
• IARC (1983) IARC Monographs on the evaluation of the carcinogenic risk of chemicals in humans, Polynuclear
aromatic compounds, Part.1, Chemical, Environmental and Experimental Data, Lyon
• IPCS (1998) Environmental Health Criteria 202 Selected non-heterocyclic polycyclic aromatic hydrocarbons,
WHO, Geneva
• ATSDR (1995), Toxicological profile for Polycyclic aromatic hydrocarbons (PAHs)Updata, U.S. Department of
Health & Human Services, Agency for Toxic Substances and Disease Registry, U.S. Governement Printing Office
Hellou, J., Stenson, G., Ni, I. H., and Payne, J. F. 1990. Polycyclic aromatic
hydrocarbons in muscle tissue of marine mammals from the Northwest Atlantic.
Marine Pollution Bulletin 21:469-473.
• Holsbeek, L., Joiris, C. R., Debacker, V., Ali, I. B., Roose, P., Nellissen, J. P., Gobert,
S., Bouquegneau, J. M., and Bossicart, M. 1999. Heavy metals, organochlorines and
polycyclic aromatic hydrocarbons in sperm whales stranded in the southern North
Sea during the 1994/1995 winter. Marine Pollution Bulletin [Mar. Pollut. Bull.]. 38:304-
313.
• Martineau, D., Lemberger, K., Dallaire, A., Labelle, P., Lipscomb, T. P., Michel, P.,
and Mikaelian, I. 2002. Cancer in Wildlife, a Case Study: Beluga from the St.
Lawrence Estuary, Quebec, Canada. Environmental Health Perspectives [Environ.
Health Perspect.]. 110:285-292.
• Mastrangelo, G., Fadda, E., and Marzia, V. 1996. Polycyclic aromatic hydrocarbons
and cancer in man. Environ Health Perspect 104:1166-1170.

14. Algal toxins
Some diatoms and dinoflagellates are
variously neurotoxic toxic to humans and
fish via diet or inhalation.

15. Toxicology of
Marine Mammals –
Vos et al 2003
Taylor and Francis
Source for next 13
slides

17. SAXITOXIN (STX)
• 3 dino genera
– Alexandrium
– Gymnodinium
– Pyrodinium
• 21 congeners
• Tingling and
numbness in mouth
and extremities ±
death

18. 1987/8 Humpbacks – Cape Cod
Bay
• 14 dead in a 5 week period
• Stomach mackerel, whale liver and kidney
+ve STX-like bioassay, but –ve HPLC
• Local fish had +ve HPLC
• Remains circumstantial

19. Mediterranean Monk Seal
• May/Jun 1997 - > 100 seals leaving only
70 in the population
• Morbillivirus present
• STX by bioassay and HPLC, but levels
lower than expected to cause mortaltity

20. Sea Otters
• Butter clams can sequester STX
• Sea Otters avoid areas of toxic clams
• When fed toxic clams they avoid the most
toxic clam parts such as siphon and
kidney

21. Domoic Acid (DA)
• Water soluble from various
Pseudo-nitzschia diatoms
• 17 congeners
• GI effects, dizziness,
nausea and loss of short
term memory
• Hippocampus necrosis

22. Marine animal DA events
• Pelicans & Cormorants – Monterey Bay 1991 DA,
anchovies and P-n frustules in stomach
• California Sea Lions 1998 – head weaving, scratching,
tremors and convulsions – See Gulland et al 2000 and
Scholin et al 2000. Microgram per gram levels of DA in
serum, urine and feces (it is cleared rapidly in urine)–
similar levels to LD50 in mice.
• ’78. ’86. ’92 also DA events in CA in hindsight also in
2000
• ?also mole crabs to sea otters and krill to gray whales
• Detected in humpback mortality on Georges Bank
summer 2003 at ng/g levels in feces.

23. Scholin et al Nature 2000

24. Guess who sampling a mass mortality of humpback whales
on Georges Bank 07/03 – DA found in feces at ng/g levels

25. Brevetoxin (PbTx)

26. PbTx
• 9 congeners
• Karenia brevis (aka Gymnodinium) and other
dinos
• FL, Japan, NZ and US Mid Atlantic
• Oral – perioral tingling and numbness
• Inhalational – coughing and gagging
• Fish kills. Also Manatees and Tursiops in years
of drought with poor flow of the Caloosahatchee
R
• 1987 Tt die off – PbTx, PCB, Morbillivirus,
Immunosupression

27. Ciguaterra

28. Ciguaterra
• 18 congeners Gambierdiscus toxicus a
coral epiphyte dino, grazed by reef fish
• Nausea, vomiting, diarrhea and perioral
numbness
• Speculated as involved in decline of
Hawaiian monk seal

29. Questions
• How do we get at the multi-factorial
agents?
• How do you triage the analysis of a mass
mortality event?
• What are the environmental factors that
affect algal toxin events?

30. Algal Toxins References
1989. Toxic dinoflagellates and marine mammal mortalities. Report; Conference WHOI-89-36; CRC-89-6.
Anderson, D. M., and A. W. White. 1992. Marine biotoxins at the top of the food chain. Oceanus 35:55-61.
Lefebvre, K. A., S. Bargu, T. Kieckhefer, and M. W. Silver. 2002. From sanddabs to blue whales: the
pervasiveness of domoic acid. Toxicon [Toxicon] 40:971-977.
O'Shea, T. J., G. B. Rathbun, R. K. Bonde, C. D. Buergelt, and D. K. Odell. 1991. An epizootic of Florida
manatees associated with a dinoflagellate bloom. Marine Mammal Science 7:165-179.
Rue, E., and K. Bruland. Domoic acid binds iron and copper: a possible role for the toxin produced by the
marine diatom Pseudo-nitzschia.
Rue, E., and K. Bruland. 2001. Domoic acid binds iron and copper: a possible role for the toxin produced by
the marine diatom Pseudo-nitzschia. Marine Chemistry [Mar. Chem.]. 76:1-2.
Scholin, C. A., F. Gulland, G. J. Doucette, S. Benson, M. Busman, F. P. Chavez, J. Cordaro, R. DeLong, A.
De Vogelaere, J. Harvey, M. Haulena, K. Lefebvre, T. Lipscomb, F. M. Van Dolah, and et al. 2000. Mortality of
sea lions along the central California coast linked to a toxic diatom bloom. Nature [Nature]. no. 6765:80-84.
Steidinger, K. A. Implications of 1986-87 Ptychodiscus brevis red tide and 1987-88 mass bottlenose dolphin
mortalities.
Trainer, V. L., N. G. Adams, B. D. Bill, C. M. Stehr, J. C. Wekell, P. Moeller, M. Busman, and D. Woodruff.
Domoic acid production near California coastal upwelling zones, June 1998.
Trainer, V. L., N. G. Adams, B. D. Bill, C. M. Stehr, J. C. Wekell, P. Moeller, M. Busman, and D. Woodruff.
1998. Domoic acid production near California coastal upwelling zones, June 1998. Limnology and
Oceanography [Limnol. Oceanogr.]. 45:1818-1833.
Van Dolah, F. M., G. J. Doucette, F. M. Fulland, T. L. Rowles, and G. D. Bossart. 2003. Impacts of algal toxins
on marine mammals. In: Toxicology of Marine Mammals. J. Vos, G. Bossart, M. Fournier and T. O'Shea.
Taylor and Francis, NY.247-269.