Table 1 Metabolism, toxicology, and residue depletion studies of febantel and fenbendazole

Toxicity

FBT

Japanese Amberjack (S. quinqueradiata & S. dumerili); 0–10 mg/kg bw/day for 5 day; feed

Concentration of FBT was dependent on cumulative mortality at the end of experiment

Kawakami et al. [18]

Toxicity

FBT

Juvenile Japanese Amberjack (S. Quinqeradiata); 0–1000 mg/kg bw/day (6 experiments) for 3–28 day; feed

Increased mortality over 50 mg/kg bw/day;

decreased growth rate in all treated groups; histopathological change in liver (absence of vacuoles) and brain (rarely Nissl bodies distribution in medulla oblongata);

effective dose and duration were demonstrated: max 15 mg/kg bw/day for 10 days

Shirakashi et al. [19]

Toxicity

FBT

Japanese Amberjack (S. quinqueradiata, S. dumerili); 0, 10 mg/kg bw/da for 5 day; feed (different four locations, total four trials)

No apparent avoidance to medicated feed and no signs of toxicity in treated group

Shirakashi et al. [20]

Toxicity

FBZ

Silver perch (Bidyanus bidyanus); bath at 10 mg/L for 48 h or feed at 75 mg kg bw/day for 6 day

Neither behavioral abnormalities nor adverse physical signs of toxicity were observed by bath or oral application of FBZ; no impact on survival rate by both application

Forwood et al. [36]

Toxicity

FBT

Zebrafish embryo (Danio rerio); 0.02–2.0 mg/L for 144 hpf; WB (flow-through system)

NOEC for 0.20 mg/L at 144 hpf;

EC₅₀ [95% CI] 0.34 mg/L [0.26–0.044 mg/L] at 144 hpf

Carlsson et al. [21]

Toxicity

FBZ

Zebrafish embryo (Danio rerio); 0.002–0.2 mg/L for 144 hpf; WB (flow-through system)

NOEC for 0.02 mg/L at 144 hpf;

EC₅₀ [95% CI] 0.024 mg/L [0.021–0.030 mg/L] at 144 hpf

Carlsson et al. [21]

Toxicity

OXF

Zebrafish embryo (Danio rerio); 0.1–10 mg/L for 144 hpf; WB (flow-through system)

NOEC for 4.6 mg/L at 144 hpf;

EC₅₀ [95% CI] 6.8 mg/L [5.6–8.3 mg/L] at 144 hpf

Carlsson et al. [21]

Toxicity

FBT

Tiger puffer (T. rubripes); 0, 12.5, or 25 mg/kg bw/day for 5 day; feed (total six trials)

No adverse effects observed [i.e., good appetite, all feed eaten with 5–10 min.; high survival, low daily mortality (< 0.1%)]

Kimura et al. [35]

Toxicity

FBZ

Young and adult three-spined sticklebacks (G. aculeatus); 0–50 μg/mL for 2 or 6 day; bath

*tolerance test, 1–100 μg/mL for 100 h; bath

Misshapen sporogonial plasmodia under treatment with FBZ at 5 μg/mL for 2 h, and malformation of the prespores under 1 μg/mL for 1 h;

In tolerance test, no visible adverse effects or other negative effects on the vital functions or on behavior

Günter Schmahl and Jochen Benini, [32]

Toxicity

FBT

Gyrodactylus sp. obtained from infected rainbow trout (O. mykiss); 2.5 or 10 mg/L for 3 h; WB (noncirculating system)

Observation of signs of toxicity at the highest concentration

Santamarina et al. [28]

Toxicity

FBZ

Rainbow trout (O. mykiss); 25 mg/L for 3 or 12 h; 0.77, 1.5, 6.2, or 12.5 mg/L for 12 h; WB (non-circulating system)

Presence of signs of toxicity at a concentration of 25 mg/L

Tojo et al. [29]

Metabolism

FBT

Juvenile Japanese Amberjack (S. Quinqeradiata); 0–20 mg/kg bw/day for 5 day; feed or intubation

FBT was not detected in muscle, liver, and kidney after 1d from last treatment;

FBZ and its metabolites were detected in the liver and kidney until 7d after last treatment;

20 mg/kg bw/day, higher total BL, lower TG, and lower plasma CRE observed but not change of histopathology

Shirakashi et al. [22]

Metabolism

FBT

Tiger puffer (T. rubripes); 12.5 and 25 mg/kg/day for 5 day; 50 mg/kg/day for 3 day; feed

FBT peaked at 4 h after admin. and decreased to 30% of the peak at 8 h and gradually reduced thereafter in plasma; OXFSO₂ peaked at 12 h in plasma and was detected until 72 h after admin

Kimura et al. [5]

Metabolism

FBZ

Channel catfish (Ictalurus punctatus); intravenously 1 mg/kg bw or orally 5 mg/kg bw

FBZ was detected in muscle at all sampling time; but it appeared in urine at a low concentration; OXFSO₂ was main metabolite in urine and intestinal contents

Kiztman et al. [25]

Comparative Metabolism

FBZ

Liver tissue from catfish (young nonbreeding) at 25 or 37

OXF was the majority; OXFSO₂ with small quantities; absence of FBZNH₂; no metabolic difference of temperature

Short et al. [26]

Residue depletion

FBZ

Rainbow trout (O. mykiss); 6 mg/kg bw/day (single) or 1.5 mg/L (12 h); intubation or bath

FBZ was detected in muscle until 4d after last treatment per oral; Tmax (24 h) and sharply reduced thereafter in both routes; the concentration of skin was more than that of muscle; FBZ was detected until 1d after last treatment via bath exposure;

OXF was observed in muscle up to 1d after cessation; OXF was detected in skin until 4d after cessation

Iosifidou et al. [23]

Residue depletion

FBZ

Rainbow trout (O. mykiss); 50 mg/kg bw/day (single); intubation

FBZ was detected in liver and muscle at 24 h after treatment, and concentration of both organs sharply declined thereafter; appropriate withdrawal period as 497.6-degree days was confirmed

Soukupova-markova et al. [24]

Residue depletion

FBT

Japanese amberjack (S. quinqueradiata); 10 mg/kg bw/day for 5 day; feed

Residues were detectable until 14 days in liver and kidney, but not in muscle; highest concentration of residues were reported in liver followed by kidney and muscle

FSCJ [27]

Residue depletion

FBT

Greater amberjack (S. dumerili); 10 mg/kg bw/day for 5 day; feed

In muscle, OXFSO₂ was detectable no longer than 5 day after cessation

FSCJ [27]

Residue depletion

FBT

Greater amberjack (S. dumerili); 10 mg/kg bw/day for 5 day; feed

Residues were not detectable in muscle over 5d after last treatment; highest concentration: liver > kidney > muscle at 3 day after cessation; residues were detected until 14 day in liver and kidney

FSCJ [27]

Residue depletion

FBT

Japanese pufferfish (T. rubripes); 50 mg/kg bw/day for 5 day; feed

Absence of FBT in muscle and skin after 24 h after cessation, and OXFSO₂ was detectable in both tissues ranging from 0.51 to 2.64 μg/g (skin > muscle)

FSCJ [27]

Residue depletion

FBT

Japanese pufferfish (T. rubripes); 50 mg/kg bw/day for 5 day; feed

Absence of FBT in muscle and skin; OXFSO₂ was detected in one muscle sample among five samples at a concentration of 0.08 μg/g at 7 day after cessation; none of residues were observed at 14 day after cessation

FSCJ [27]