| Test | Materials and Methods | Results | Conclusions | References |
|---|---|---|---|---|
| Immunotoxicity in vivo studies | ||||
| T-cell-dependent antibody response study by s.c. injection | Female B6C3F1 mice (n = 8); daily s.c. injections containing 0 (com oil vehicle) or 40 mg/kg-d (160 μmol/kg-d) for 1 or 14 d; spleen IgM response was evaluated 4 d after injection with sRBCs (body weight, spleen weight, thymus weight, cellularity, and number of PFCs). | No change in the spleen IgM response to sRBCs. No change in spleen or thymus weight or spleen cellularity. A statistically significant increase (~34%) in body weight was reported after the 14-d exposure. | Perylene did not impair humoral immunity in mice under the conditions of this study. | White et al. (1985) |
| Immunotoxicity in vitro studies | ||||
| Cytokine release and cytotoxicity in human keratinocytes | Keratinocytes (Clonetics) were dosed at various concentrations (1, 2, 5, 10, or 15 μM) with perylene, methylpyrene, or both dissolved in sodium dodecyl sulfate for 24 h–9 d (depending on endpoint). Cells were assessed for viability, colony forming efficiency, scrape-wound healing assay, apoptosis/necrosis, and cytokine secretion. | At the lowest tested concentration (1 μM), perylene decreased keratinocyte adhesion and viability in a concentration-dependent manner. Perylene reduced keratinocyte colony formation, and increased apoptosis. Interleukin-1α and interleukin-6 levels were significantly increased with increasing exposure to perylene (>2 μM). Toxicity was enhanced when perylene and methylpyrene were assessed as a mixture. | Perylene induced dose-dependent increases in inflammatory cytokine secretion and exerted a cytotoxic effect on human keratinocytes. | Bahri et al. (2010) |
| Carcinogenicity in vivo studies | ||||
| Dermal complete carcinogenicity study | Male C3H mice (n = 20); 60 μL of a 0.15% perylene solution in decalin per application; 2 times/wk for up to 82 wk. An appropriate negative control group was not included. BaP (0.14%) was used as a positive control. |
Skin tumors Perylene: 0/16 (0%) Positive control (BaP): 15/21 (71%) (10 papillomas, 5 carcinomas) Note: Incidence is based on the number of mice alive at least 52 wk. | Perylene was not carcinogenic under the conditions of this study. | Horton and Christian (1974) |
| Dermal complete carcinogenicity study | Male Swiss mice (n = 20); 0.3% perylene in benzene every 4 d for up to 24 wk; a benzene-only vehicle control group was not included. BaP (0.3%) was used as a positive control. |
Skin tumors (unspecified) Perylene: 0/20 (0%) Positive control (BaP): 36/40 (90%) | Perylene was not carcinogenic under the conditions of this study. | Finzi et al. (1968) |
| Dermal complete carcinogenicity and initiation-promotion studies | Female CD-1 mice (number/group not specified); dermal application of 0 or 1% perylene 3 times/wk for 1 yr (vehicle not reported); a separate group of mice were initiated with a single 300 μg dermal dose of BaP followed by dermal application of 1% perylene 3 times/wk for 1 yr. | No increase in skin tumors in perylene or BaP + perylene treated mice, compared to vehicle control (incidence data not reported). | Perylene was not a complete carcinogen or tumor promotor under the conditions of this study. Data reporting is too limited for independent review (abstract only). | Anderson and Anderson (1987) |
| Dermal initiation-promotion study | Female Crl/CD-1(ICR)BR mice (n = 20); dermal application of 1 mg perylene in acetone applied in 10 doses (every other day), followed by 2.5 μg TPA in 0.1 mL acetone 3 times/wk for 25 wk; the vehicle control group was acetone with TPA promotion. BaP (0.05 mg) was used as a positive control. |
Skin tumors (“predominantly” papillomas) Acetone + TPA: 1/20 (5%) Perylene + TPA: 1/20 (5%) Positive control (BaP + TPA): 18/20 (90%) | Perylene was not a tumor initiator under the conditions of this study. | El-Bayoumy et al. (1982) |
| Dermal initiation-promotion study | Female ICR/Ha Swiss mice (n = 20); single dermal application of 800 μg perylene in benzene followed by 2.5 μg TPA in 0.1 mL acetone 3 times/wk for 58–60 wk; four control groups were used: untreated, acetone, perylene initiating dose only, and TPA-only (with no initiator). A benzene vehicle control was not included. DMBA (20 μg in acetone) was used as a positive control. |
Skin tumors Untreated control: 0/20 (0%) Acetone control: 0/20 (0%) Perylene only: 0/20 (0%) TPA only: 1/20 (5%) (1 papilloma) Perylene + TPA: 3/20 (15%) (3 papillomas) Positive control (DMBA + TPA): 19/20 (95%) (13 carcinomas, 6 papillomas) | Perylene was not a tumor initiator under the conditions of this study. Perylene may be a weak tumor initiator; papilloma incidence was slightly increased compared to controls but did not reach statistical significance. | Van Duuren et al. (1970) |
| Dermal cocarcinogenicity study | Male C3H mice (n = 20); 60 μL of a 0 or 0.15% perylene solution in a 50:50 decalin:dodecane (De:Do) vehicle per application; 2 times/wk for up to 82 wk. BaP (0.14%) was used as a positive control using 100:0, 80:20, or 60:40 De:Do vehicle. Dodecane was selected as the cocarcinogen because it had previously been shown to be a skin cocarcinogen with benz[a]anthracene but is not a skin carcinogen when administered alone. |
Skin tumors Vehicle control: 2/13 (15%) (2 papillomas) Perylene: 1/15 (7%) (1 papilloma) Positive control (BaP): 100% decalin: 15/21 (71%) (5 carcinomas, 10 papillomas) 80:20 De:Do: 13/15 (87%) (6 carcinomas; 7 papillomas) 60:40 De:Do: 15/15 (100%) (15 carcinomas) Note: Incidence is based on the number of mice alive at least 52 wk. | Perylene was not cocarcinogenic (with dodecane) under the conditions of this study. | Horton and Christian (1974) |
| Dermal tumor inhibition study | Male Swiss mice (n = 40); 0.3% BaP in benzene or 0.3% perylene and 0.3% BaP in benzene every 4 d for up to 24 wk. |
Skin papillomas BaP: 36/40 (90%) BaP + perylene: 13/40 (30%) | Perylene inhibited the tumorigenic response of BaP under the conditions of this study. Statistical analysis of results was not performed by the study authors. | Finzi et al. (1968) |
| Lung tumor study by i.p. injection | Strain A mice (sensitive model for lung tumor induction); i.p. injection of 0, 200, 500, or 1,000 mg/kg perylene 3 times/wk for 8 wk followed by a 16-wk observation period. | No increase in lung adenomas compared to control (vehicle not reported; incidence data not reported). | Perylene did not induce lung tumors under the conditions of this study. Data reporting is too limited for independent review (abstract only). | Anderson and Anderson (1987) |
BaP = benzo[a]pyrene; DMBA = 7,12-dimethylbenz[a]anthracene; IgM = immunoglobulin M; i.p. = intraperitoneal; n = number; s.c. = subcutaneous; sRBC = sheep red blood cell; PFC = plaque forming colony; TPA = 12-O-tetradecanoylphorbol acetate.
From: 2, REVIEW OF POTENTIALLY RELEVANT DATA (NONCANCER AND CANCER)
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