Table 7. Benchmark doses (BMD), lower and upper 90% confidence interval (BMDL and BMDU, respectively) and No Observed (Adverse) Effect Level (NOAEL/NOEL) for relevant responses in Atlantic salmon (Salmo salar L.) exposed to graded levels of ethoxyquin (EQ) through their diet for 90 day.
Values are given in mg EQ/kg BW/day estimated from feed intake.
| BMD05 | BMDL05 | BMDU05 | BMD10 | BMDL10 | BMDU10 | BMD20 | BMDL20 | BMDU20 | NOAEL (NOEL) | |
|---|---|---|---|---|---|---|---|---|---|---|
| Endpoint | ANOVA | |||||||||
| Growth parameters (EQ 0 –EQ 3) | ||||||||||
| Condition factor (k) | 11.4 | 0.8 | 121.0 | 11 | ||||||
| Hematological parameters (EQ 0 –EQ 5) | ||||||||||
| Hct | 28.2 | 13.1 | 40.0 | |||||||
| HGB | 26.8 | 14.9 | 36.0 | |||||||
| MCV | 7.4 | 1.1 | 63.8 | |||||||
| MCH | 28.8 | 2.6 | 80.3 | |||||||
| Biomarkers of liver function (EQ 0- EQ 5) | ||||||||||
| Bile acids | none | none | none | none | none | none | 0.4 | |||
| ALT | 26.4 | 14.5 | 32.5 | n.s. (30) | ||||||
| AST | 25.8 | 10.9 | 29.3 | n.s. (30) | ||||||
| Bilirubin | 17.8 | 5.5 | 30.5 | n.s. (11) | ||||||
| Albumin | 45.1 | 41.5 | 49.7 | 30 (p = 0.058) | ||||||
| Total protein | 31.6 | 28.7 | 33.6 | 30 | ||||||
| Creatinine | 2.0 | 0.5 | 9.2 | 1.2 | ||||||
| Liver oxidative stress markers (EQ 0- EQ 5) | ||||||||||
| TBARS | 8.0 | 2.3 | 13.1 | 1.2 | ||||||
| Liver alpha-tocopherol | 4.6 | 1.7 | 9.2 | 1.2 | ||||||
| Markers of oxidative DNA damage (EQ 0- EQ 5) | ||||||||||
| 8-oxo-dG | none | none | none | n.s. (40) | ||||||
| AP sites | none | none | none | n.s. (40) | ||||||
| Histopathology (EQ 0- EQ 5) | ||||||||||
| Liver: Depletion of vacuoles | 6.0 | 3.2 | 17.9 | 11 | ||||||
| Kidney: Severe presence of pigmented macrophage aggregates | 38.4 | 36.7 | 39.3 | 30 | ||||||
| Spleen: Severe congestion of spleen tissue | 12.1 | 2.7 | 35.8 | 30 | ||||||
Taking the width of the 90% confidence intervals (BMDU/BMDL) into consideration, benchmark responses were set at the default of 5%, or adjusted to 10 or 20%. For derivation of the critical BMDL, the width of the confidence interval was taken into account as an indicator of precision. The No-observed-(adverse)-effect-levels (NOAEL/NOEL) was determined from statistical comparisons of responses in each predetermined dose group with the control group. Raw data and the Akaike Information Criteria for all models assessed, as well as models for the critical endpoints included into the evaluation for the critical BMDL are available in S16 Table.
Abbreviations: Hct, Hematocrit; HGB, Hemoglobin; MCV, Mean corpuscular volume; MCH, Mean corpuscular hemoglobin; ALT, Alanine amino-transferase; AST, Aspartate aminotransferase; TBARS, Thiobarbituric acid reactive substances; GSH, Reduced glutathione; GSSG, Oxidized glutathione; 8-oxo-dG, 8-hydroxy-2’-deoxyguanosine; AP, apurinic/apyrimidinic.