Table 2.
Effects of orally administered furan (by gavage) in acute, subacute and subchronic (&le 90 days) studies in experimental animals
| Species (number of animals per group) | Dosage (mg/kg bw) | Duration/time of observation | Outcomea | NOAEL (LOAEL) in mg/kg bw per dayb | Reference |
|---|---|---|---|---|---|
|
B6C3F1/CrIBR male mouse (5) Fischer 344/CrIBR male rat (5) |
Single 30 (rats), 50 (mice) | 12, 24, 48 h, 4 and 8 days |
Increased plasma liver enzymes after 12 h and later LI increased after 48 h |
One dose level only | Wilson et al. (1992) |
|
B6C3F1/CrIBR male mouse (5) Fischer 344/CrIBR male rat (5) |
Single, 15, 27, 39. 50 (mice) 0, 8, 15, 22, 30 (rats) | 24 h | Increased plasma liver enzymes at 27 mg/kg bw (male mice) and 15 mg/kg bw (male rats) | (15; mice) (8; rats) | |
|
B6C3F1/CrIBR male mouse (5) Fischer 344/CrIBR male and female rat (5) |
30 (rats), 50 (mice) | 6 weeks, 5 days a week | Hepatic necrosis and inflammation, bile duct hyperplasia and metaplasia in rats | One dose level only | |
|
B6C3F1/CrIBR male mouse (5) Fischer 344/CrIBR male rat (5) |
30 (rats), 50 (mice) | 1, 3 and 6 weeks, 5 days a week | increased hepatocellular LI (proliferation) | One dose level only | |
|
B6C3F1 male and female mouse (5) Fischer 344 male and female rat (5) |
0, 5, 10, 20, 40 or 80 mg (male rats) 0, 10, 20, 40, 80 and 160 (mice and female rats) |
16 days, 5 days a week |
Rats (observation): mottled and enlarged livers Mice: no organ changes |
Range‐finding study | NTP (1993) |
|
B6C3F1 male and female mouse (10) Fischer 344 male and female rat (10) |
0, 4, 8, 15, 30 or 60 (rats and female mice) 0, 2, 4, 8, 15 or 30 (male mice) |
13 weeks, 5 days a week | Increase in relative and absolute liver weight, histopathological changes in the liver | (2; male mice) (4; rats and female mice) | NTP (1993) |
| Fischer 344 male rat (3–6) | 45 | 6 weeks, 5 days a week | Reduced liver weight, cholangiofibrosis, biliary metaplasia, biliary cirrhosis | One dose level only | Sirica et al. (1994b) |
| B6C3F1 female mouse (6–11) | 4, 8 and 15 | 3 weeks, 5 days a week | Increase in serum ALT, SDH, apoptotic index, subcapsular inflammation | 4 | Fransson‐Steen et al. (1997) |
| 15 | 3–5 days a week over 2 weeks – 2 days (15 days in total) | Increase in liver weight, serum ALT, SDH and bile acids | One dose level only | ||
| B6C3F1 female mouse (15) | 0.5, 1, 2 and 4 | 3 weeks, 5 days a week | Increased serum ALT, subcapsular inflammation | (0.5) | Moser et al. (2009) |
| B6C3F1 male mouse (3–11) | 2, 4, 8 and 15 | 28 days, 5 days a week | Hepatic necrosis, hepatocellular proliferation | 4 | Cordelli et al. (2010) |
| Sprague–Dawley Crl CD1 BR male rat (3–5) | 30 | 8 h, 1, 3, 7, 10, 12 and 20 days, and 1, 2 and 3 months, 5 days a week | Hepatic necrosis, hepatocellular and biliary proliferation | one dose level only | Hickling et al. (2010b) |
| Fischer 344 male rat (3–5) | 0.1, 0.5, 2 | 28 days, 5 days a week | Increased DNA synthesis, increased subcapsular mitosis, apoptosis and inflammation | (0.1) | Mally et al. (2010) |
| Wistar juvenile male rat (8) | 2, 4 and 8 | 90 days, 7 days a week | Increased hepatic TNF‐α | (2) | Selmanoglu et al. (2012) |
| Fischer 344 male and female rat (12) | 0.03, 0.12, 0.5, 2 and 8 | 90 days, 5 days a week | Increase in serum T4 in males c | 0.03 | Gill et al. (2010) |
| B6C3F1 male and female mouse (16) | 0.03, 0.12, 0.5, 2 and 8 | 90 days, 5 days a week | Distinct histopathological changes, changes in clinical blood parameters (BUN and phosphorous in serum) c | 0.12 | Gill et al. (2011) |
| Wistar male rat (8) | 2, 4 and 8 | 90 days, 7 days a week | Islet of Langerhans congestion | 4 | Karacaoglu et al. (2012) |
| Wistar juvenile male rat (8) | 2, 4 and 8 | 90 days, 7 days a week | Decrease in relative thymus weight, histological changes in the thymus | 2 | Kockaya et al. (2012) |
| Sprague–Dawley male (10) | 16 | 30 daysd | Changes in blood cells, blood cell phagocytic activity, serum immune parameters, oxidative stress in the spleen, changes in splenic lymphoid cells | One dose level only | Alam et al. (2017) |
ALP: alkaline phosphatase; ALT: alanine aminotransaminase; BUN: blood urea nitrogen; LDL: low‐density lipoprotein; LI: labelling index; LOAEL: lowest‐observed‐adverse‐effect level; NOAEL: no‐observed‐adverse‐effect level; SDH: sorbitol dehydrogenase; TNF: tumour necrosis factor.
Most sensitive endpoint given in bold.
LOAEL (in italics) or NOAEL (in bold) for the most sensitive endpoint affected schedule.
See comments under ‘Summary’.
Information on dose regimen not available.