These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Toxicology and Carcinogenesis Studies of 8-Methoxypsoralen (CAS No. 298-81-7) in F344/N Rats (Gavage Studies).
    Author: National Toxicology Program .
    Journal: Natl Toxicol Program Tech Rep Ser; 1989 Jul; 359():1-130. PubMed ID: 12695782.
    Abstract:
    Oral administration of 8-methoxypsoralen followed by exposure to longwave ultraviolet light (primarily ultraviolet A, 320-400 nm) is used in the treatment of vitiligo and psoriasis. 8-Methoxypsoralen also occurs naturally in a variety of vegetables. Toxicology and carcinogenesis studies of 8-methoxypsoralen without ultraviolet A were conducted by administering USP-grade 8-methoxypsoralen (99% pure) in corn oil by gavage to groups of F344/N rats once or for 16 days, 13 weeks, or 2 years. In vitro genetic toxicology tests were performed with bacteria and mammalian cells. Single-Administration, Sixteen-Day, and Thirteen-Week Studies: In the single-administration studies, the chemical was administered at doses of 0 and 63-1,000 mg/kg. Four of five male rats and 5/5 female rats that received 1,000 mg/kg 8-methoxypsoralen died within 2 days. In the 16-day studies, the chemical was administered at doses of 0 and 50-800 mg/kg. All rats receiving 800 mg/kg died within 5 days, and one male and one female at 400 mg/kg and one female at 200 mg/kg also died before the end of the studies. The final mean body weights of animals at 200 or 400 mg/kg were 14% or 30% lower than those of vehicle controls. No compound-related effects were observed at necropsy. In the 13-week studies, the chemical was administered at doses of 0 and 25-400 mg/kg. Six of 10 male rats and 8/10 female rats that received 400 mg/kg died before the end of the studies. The final mean body weight of male rats that received 100, 200, or 400 mg/kg was 12%, 22%, or 45% lower than that of vehicle controls. The final mean body weight of female rats that received 200 or 400 mg/kg was 15% or 35% lower than that of vehicle controls. The liver weight to body weight ratios for all dosed groups of rats except the lowest (25 mg/kg) were greater than those for vehicle controls. Compound-related effects included fatty change in the liver in males and females and atrophy of the testis, seminal vesicles, and prostate. Based on these results, 2-year studies were conducted by administering 0, 37.5 or 75 mg/kg 8-methoxypsoralen in corn oil by gavage, 5 days per week for 103 weeks, to groups of 50 F344/N rats of each sex. Body Weight and Survival in the Two-Year Studies: The mean body weights of dosed male rats were generally 3%-14% lower than those of vehicle controls, and the mean body weights of high dose female rats were 5%-17% lower. The survival of both the low and the high dose groups of male rats was lower than that of the vehicle controls (male: vehicle control, 30/50; low dose, 16/50; high dose, 16/50; female: 39/50; 33/50; 36/50), likely because of kidney toxicity and neoplasia. Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Mineralization of the renal papilla was observed in high dose male rats (vehicle control, 0/50; low dose, 0/50; high dose, 31/49). The severity of nephropathy was increased in dosed male rats. Focal hyperplasia of renal tubular cells was observed in dosed male rats (0/50; 8/50; 8/49). The incidences of tubular cell adenomas (1/50; 11/50; 8/49), adenocarcinomas (0/50; 1/50; 3/49), and adenomas or adenocarcinomas (combined) (1/50; 12/50; 11/49) were increased in dosed male rats. Hyperplasia of the parathyroid glands (2/49; 22/47; 18/48) and fibrous osteodystrophy (2/50; 10/50; 12/49) in male rats were secondary to chronic nephropathy. The incidences of carcinomas or squamous cell carcinomas (combined) of the Zymbal gland were increased in dosed male rats (1/50; 7/50; 4/49). The mean historical incidence for carcinomas or squamous cell carcinomas (combined) in corn oil vehicle control male F344/N rats is 0.8% (16/1,949); the highest incidence in any one group is 4% (2/49). Fibromas of the subcutaneous tissue in male rats occurred with a positive trend (1/50; 5/50; 7/49). An additional high dose male had a sarcoma. The mean historical incidence of fibromas or fibrosarcomas (combined) of subcutaneous tissue in corn oil vehicle control male F344/N rats is 9% (171/1,949). Alveolar/bronchiolar adenomas occurred with a positive trend in male rats (4ts is 9% (171/1,949). Alveolar/bronchiolar adenomas occurred with a positive trend in male rats (4/50; 9/50; 9/49). The mean historical incidence of alveolar/bronchiolar neoplasms in corn oil vehicle control male F344/N rats is 3% (68/1,944); the highest incidence is 10% (5/50). Chronic inflammation, ulcers, and epithelial hyperplasia of the forestomach were observed at increased incidences in dosed male rats (chronic inflammation: 1/50; 6/50; 5/49; ulcers: 5/50; 13/50; 11/49; epithelial hyperplasia: 4/50; 19/50; 20/49). Squamous cell papillomas were observed in two low dose male rats. Squamous cell papillomas were observed in the palate or tongue of one low dose and three high dose female rats; none were observed in vehicle controls. These papillomas were not considered to be related to chemical administration. Diffuse hypertrophy of the thyroid gland was observed at increased incidences in dosed male rats (2/50; 31/50; 39/49). Genetic Toxicology: 8-Methoxypsoralen was mutagenic in Salmonella typhimurium strain TA104 in the presence and absence of activation and in strains TA98, TA100, and TA102 when tests were conducted with exogenous metabolic activation; 8-methoxypsoralen was not mutagenic with or without activation in strain TA1535. Treatment with 8-methoxypsoralen induced both sister chromatid exchanges (SCEs) and chromosomal aberrations in Chinese hamster ovary (CHO) cells in the absence of exogenous metabolic activation; in the presence of activation, in the presence of activation, induction of SCEs occurred, but no significant increases in chromosomal aberrations was observed. Audit: The data, documents, and pathology materials from the 2-year studies of 8-methoxypsoralen have been audited at the NTP Archives. The audit findings show that the conduct of the studies is documented adequately and support the data and results given in this Technical Report. Conclusions: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of 8-methoxypsoralen (without ultraviolet radiation) for male F344/N rats, as shown by increased incidences of tubular cell hyperplasia, adenomas, and adenocarcinomas of the kidney and carcinomas of the Zymbal gland. Subcutaneous tissue fibromas and alveolar/bronchiolar adenomas of the lung in male F344/N rats may have been related to chemical administration. Dose-related nonneoplastic lesions in male F344/N rats included increased severity of nephropathy and mineralization of the kidney and forestomach lesions. There was no evidence of carcinogenic activity of 8-methoxypsoralen for female F344/N rats given the chemical at 37.5 or 75 mg/kg per day for 2 years. Synonyms: 9-methoxy-7H-furo[3,2-g]benzopyran-7-one; 6-hydroxy-7-methoxy-5-benzofuranacrylic acid d-lactone; 8-MP; 8-MOP; 8-methoxy-(furano-3',2':6,7-coumarin); 8-methoxy-4',5':6,7-furocoumarin; 9-methoxypsoralen; 8-methoxypsoralene; methoxsalen; oxypsoralen Trade Names: Ammoidin; Meladinin (VAN); Meladinine; Meladoxen; Meloxine; Methoxa-Dome; Mopsoralen; Oxsoralen; Soloxsalen; Trioxun; Xanthotoxin; Xanthotoxine
    [Abstract] [Full Text] [Related] [New Search]