Page 110 - The Toxicology of Fishes

90 The Toxicology of Fishes

A B C D
1000

100
CLr : GFR 10

1

0.1
1 2 3 4 5 6 7 8 9 10 11 12 13 14
FIGURE 3.17 Influence of tubular transport, biotransformation, and plasma binding on renal excretion in marine teleosts
(A–C) (Pritchard and Renfro, 1984) and freshwater teleosts (D) (McKim et al., 1999b). Data for each compound are
expressed as the ratio of renal clearance (CL r ) to glomerular filtration rate (GFR). (A) Reference compounds: (1) glucose,
reabsorbed by active transport; (2) 2-deoxyglucose, with no net tubular transport; (3) p-aminohippuric acid, a prototypical
substrate for active anion secretion pathway. (B) Effect of metabolism: (4) benzo(a)pyrene (BaP), reabsorbed passively; (5)
BaP-7-phenol conjugates (largely glucuronide), limited anion secretion; (6) BaP-7,8-dihydroxydiol conjugates (largely
sulfate), a better substrate for anion secretion; (7) DDT, passive reabsorption; (8) DDA, effective tubular secretion. (C)
Effect of plasma protein binding: (9) DDA, plasma binding of 97%; (10) 2,4-D, plasma binding of 70%. DDA and 2,4-D
are transported similarly in vitro (without binding). (D) Effects of reabsorption and metabolism: (11) hydroquinone, strong
passive reabsorption; (12) phenol, slight passive reabsorption; (13) phenyl glucuronide, limited anion secretion; (14) phenyl
sulfate, better substrate for anion secretion.

Renal Clearance
The mechanisms responsible for renal excretion of chemicals can be distinguished by dividing measured
renal clearance rates (CL ) by the GFR (McKim et al., 1999b; Pritchard and Renfro, 1984). CL is the
r
r
volume of plasma completely cleared of chemical by the kidney in a given period of time and is calculated
by dividing the excretion rate of chemical in urine by the chemical concentration in plasma at the
midpoint of a sampling period. The GFR is the total amount of plasma filtered by the kidney and may
14
be estimated using an in vivo [ C]-polyethylene glycol method (Beyenbach and Kirschner, 1976). Figure
3.17 shows CL -to-GFR ratios for several compounds in both freshwater and saltwater fish. A CL -to-
r
r
GFR ratio less than 1 suggests that a chemical is reabsorbed within the kidney tubule, a ratio of 1
indicates no net tubular transport, and a ratio greater than 1 signifies active secretion into the tubular
fluid. Chemical binding in plasma can reduce renal tubular secretion as well as chemical filtration at the
glomerulus. Generally, however, the effect of plasma binding on CL is greater than that on GFR,
r
decreasing the ratio of CL to GFR. For a given mechanism of renal excretion, CL -to-GFR ratios in
r
r
saltwater fish tend to exceed those of freshwater fish. This pattern appears to be due primarily to higher
GFR values in freshwater fish.
Dermal Excretion
The extent to which chemicals and their metabolites are eliminated across the skin is poorly known;
however, anatomical and physiological factors that promote chemical uptake across the skin of some
fish species (e.g., high degree of vascularization and large ratio of skin area to gill area) also might be
expected to facilitate chemical elimination. Lead and cadmium diffuse across the skin of juvenile
rainbow trout and into the mucous layer, which is then sloughed from the fish (Varanasi and Markey,
1978). Naphthalene was recovered from the mucus of rainbow trout soon after it was administered by