| Species, strain
(sex) Duration Reference | Route Dosing regimen, Animals/group at start | Incidence of tumours | Significance | Comments |
|---|---|---|---|---|
| Mouse C57 x IF F1 (M, F) 70 wk Clayson et al. (1967) | Oral–Gavage A group of 21 M and 28 F mice were dosed with 0.2 ml of a 25% 4-amino-biphenyl solution in arachis oil, twice/wk for 50 wk, and kept for an additional 20 wk. A group of 19 M and 31 F served as untreated controls | Hepatoma,
malignant: [hepatocellular carcinoma] M–0/19, 4/21; F–0/31, 13/28* Bladder carcinoma: M–0/19, 1/21; F–0/31, 0/28 | No
statistics *[P < 0.0001] | Also reported were four “probably
malignant” hepatomas in female mice. Purity of 4-aminobiphenyl NR |
| Mouse BALB/cStCrlfC3Hf/Nctr (M, F) 96 wk Schieferstein et al. (1985) | Oral–Drinking-water Groups of 120 M and 120 F mice were given 4-aminobiphenyl as the hydrochloride salt (> 99.5% pure) at doses of 0, 7, 14, 28, 55, 110, and 220 ppm (M) and 0, 7, 19, 38, 75, 150, and 300 ppm (F). Interim sacrifices were at 13, 26, 39, 52, and 96 wk | Angiosarcoma (all
sites): M–1/118, 1/117, 1/118, 2/119, 4/115, 5/119, 14/118* F–1/119, 4/120, 4/120, 2/120, 14/120, 26/118, 11/117* Bladder carcinoma: M–0/116, 1/117, 1/118, 0/118, 6/115, 15/118, 23/118* F–0/118, 0/118, 0/119, 1/118, 0/118, 5/117, 1/117 Hepatocellular carcinoma: M–2/118, 1/117, 0/118, 0/117, 0/114, 3/118, 2/117 F–0/117, 0/120, 2/120, 4/119, 10/119, 14/118, 7/117* | *P < 5x10−5, positive trend | |
| Dog Beagle (M) 33 mo Walpole et al. (1954) | Oral Two, 7 mo-old male dogs were given 4-aminobiphenyl in a gelatin capsule once daily, 6 × /wk until termination of the study. The dose level was lowered during the course of the experiment and dosing was also interrupted temporarily for 6 mo. The experiment was terminated after 33 mo; total dose for the two dogs was 2.9 and 3.3 g/kg bw, respectively | Bladder carcinomas occurred in both dogs | NR | No concurrent controls. Historical
data from this laboratory show that thirty Beagle dogs (age,
3–9 yrs) that died of various causes did not develop bladder
tumours. Purity of 4-aminobiphenyl NR |
| Dog Mongrel (F) Lifetime Deichmann et al. (1958) | Oral A group of four young adult female mongrel dogs were given 0.3 g of 4-aminobiphenyl admixed into the food on 5 d/wk for 1 yr. The dogs then received an oral dose (capsule) of 0.3 g of this compound 3 × /wk for the rest of the study. The total dose (range) at first appearance of tumours was 87.5–144.0 g per dog, corresponding to 8.2–14.1 g/kg bw | Bladder carcinomas occurred in all four dogs after 21–34 mo | NR | No concurrent
controls. Experimental design poorly described. Bladder is only tissue examined. |
| Dog Beagle (F) Up to 37 mo Deichmann et al. (1965) | Oral A group of six 6–12 mo-old female dogs were given an oral dose (capsule) of 4-aminobiphenyl at 1.0 mg/kg bw, 5 × / wk for up to 37 mo. The total dose range was 5.35–7.34 g per dog. | Bladder carcinomas (transitional cell type) were observed in three dogs, bladder papillomas in the three other dogs. | NR | No concurrent
controls. Bladder is only tissue examined. Purity of 4-aminobiphenyl NR |
| Dog Beagle (F) 42 mo Block et al. (1978) | Oral A group of 24 female dogs (age, 4 mo) were given 4-aminobiphenyl orally in a corn-oil suspension contained in a capsule on 5 d/wk for 36 mo. | Transitional cell urinary bladder
carcinomas 20/24 Grade-2 and -3 tumours 2/24 Grade-1 tumours 2/24 no detectable tumours | Authors indicate that twenty
matched littermates served as controls, but no other
information was provided for the control
animals. Purity of 4-aminobiphenyl NR | |
| Rabbit Strain NR (sex NR) Lifetime Bonser (1962) | Oral A group of 7 rabbits were treated with 4-aminobiphenyl to the limit of tolerance, which was continued until the onset of the final illness. Three animals were sacrificed in the first 2 yr and two each at 3–4 and 5–6 yr after the start of treatment. A group of 12 rabbits served as controls, 5 of which were sacrificed in the first two yr, one at 3–4 yr, and three each at 5–6 and > 7 yr after the start of treatment. | Bladder carcinoma: 0/12, 3/7 | NR [P < 0.036] | Experimental design very poorly
described. It appears bladder is the only tissue examined.
Sex NR. Purity of 4-aminobiphenyl NR Dose and dose regimen NR |
| Mouse
Swiss (M, F) 52 wk Gorrod et al. (1968) | Subcutaneous
injection A group of 52 newborn mice were injected s.c. with 200 μg of 4-amino-biphenyl on each of the first three d of life, separated at weaning into a group of 24 M and 27 F, and kept for up to 52 wk. Groups of 41 M and 41 F newborn mice served as vehicle controls. | Male | NR | Purity of 4-aminobiphenyl NR |
| Hepatomas: | ||||
| M–5/41, 19/20 | [P < 0.0001] | |||
| F–2/41, 4/23 | [NR] | |||
| Rat Albino (M, F) Lifetime (animals kept for up to 582 d) Walpole et al. (1952) | Subcutaneous
injection Groups of 11 M and 12 F rats were each divided in two groups and given 4-aminobiphenyl in arachis oil 5 × /wk for a mean duration of 250–376 dosing d, to a total mean dose per animal of 3.6–5.8 g/kg bw. A control group of 12 M and 11 F rats received arachis oil only. | Intestinal tumours | Experimental design,
especially exposure durations, poorly
described. Small numbers of animals make study results difficult to interpret. | |
| M–0/12, 3/6 (4.4 g/kg bw), 1/5 (5.8 g/kg bw) | [P < 0.05], [NR] | |||
| F–1/11, 1/6 (3.6 g/kg bw), 2/6 (4.2 g/kg bw) | [NR], [NR] | |||
| Mouse B6C3F1/nctr (M) 12 mo Dooley et al. (1992) | Intraperitoneal
injection Newborn male mice were given 4-aminobiphenyl (> 98%). The amounts administered were 0, 0.625 and 1.25 μmol dissolved in 35 μl DMSO, injected in portions of 5, 10 and 20 μl on d 1, 8 and 15 after birth, respectively. Surviving pups were weaned on d 21 and designated for necropsy at 8 or 12 mo of age. | At 12 mo: Hepatocellular adenomas: 5/44, 19/19*, 15/15* Hepatocellular carcinomas: 0/44, 5/19*$, 5/15* | *P < 0.001, Fisher exact test), $[P < 0.005] | Initial number of animals NR |
| At
8 mo: Hepatocellular adenomas: 1/44, 22/24*, 8/11* No carcinomas | ||||
| Mouse B6C3F1 (M) 12 mo Parsons et al. (2005) | Intraperitoneal
injection Newborn male mice were given 0.3 μmol 4-aminobiphenyl dissolved in DMSO, by a series of injections: 1/7th of the dose on postnatal Day 1, 2/7th on Day 8, and 4/7th on Day 15. Control mice received DMSO only. | Hepatocellular adenoma: 4/18,
19/24 Hepatocellular carcinoma: 0/18, 2/24 | [P < 0.001] [NR] | Liver is the only tissue
examined. Initial number of animals NR |
| Mouse CD1 (M) 12 mo Von Tungeln et al. (1996) | Intraperitoneal
injection Newborn male mice were given a total dose of 625 nmol 4-amino-biphenyl (> 99% pure) in 35 μl dimethyl sulfoxide, given in portions of 5, 10 and 20 μl on Days 1, 8, and 15 after birth, respectively. At weaning, the animals were divided over two groups, which were fed ad libitum until the age of 14 wk. Thereafter, one group received 90% of the calories of the ad libitum feeding regimen during one wk, followed by 75% of the calories during one wk, and then 60% of the calories in the diet until sacrifice at 12 mo. | Ad-libitum
group: Hepatocellular carcinoma: 6/22 Hepatocellular adenoma: 12/22 Caloric restriction group: Liver tumours: 0/19 | P < 0.02 P < 0.001 Between ad libitum and caloric restriction groups | No tumours in calorie-restricted
group No untreated controls Initial number of animals NR |
| Mouse CYP1A2 −/− and CYP1A2+/+ (M, F) 16 mo Kimura et al. (1999) | Intraperitoneal
injection Groups of male and female mice were injected a total dose 600 or 1200 nmol of 4-aminobiphenyl in DMSO. Control animals were injected with DMSO only. | Hepatocellular
carcinoma: -/- M–0/12, 5/27, 8/42 +/+ M–0/12, 6/30, 4/26 -/- F–0/25, 0/25, 0/27 +/+ F–0/25, 1/23, 0/33 Hepatocellular adenoma: -/- M–2/12, 13/27**, 29/42* +/+ M–2/12, 21/30*, 18/26* -/- F–2/25, 2/25, 3/27 +/+ F–2/25, 4/23, 1/33 | *P < 0.01 **P < 0.05 | Liver was the only tissue
examined. Initial number of animals NR Mice derived from a mixed background of 129/Sv and C57BL/6 strains |
bw, body weight; d, day or days; DMSO, dimethyl sulfoxide; F, female; M, male; mo, month or months; NR, not reported; wk, week or weeks; yr, year or years
From: 4-AMINOBIPHENYL
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.