Neoplastic response in Japanese medaka and channel catfish exposed to N-methyl-N'-nitro-N-nitrosoguanidine.

Japanese medaka (Oryzias latipes) and channel catfish (Ictalurus punctatus) were investigated for carcinogenic response following a 28-day, 3 x/wk pulse exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Five-wk-old medaka were exposed at concentrations of 0, 0.5, and 1.0 mg/L, and 5-mo-old catfish at concentrations of 0, 0.1, and 0.5 mg/L. In medaka, a total of 19 tumors including 2 branchioblastomas, 6 thyroid follicular adenomas and 1 adenocarcinoma, and 11 subcutaneous fibrosarcomas were observed in 16 of 96 MNNG-exposed fish. In catfish, a total of 37 tumors including 4 squamous cell carcinomas and 16 papillomas, 3 lipomas, 1 fibroma, 1 osteosarcoma, 4 branchioblastomas, 6 thymic epithelial tumors, and 2 generalized lymphosarcomas were observed in 34 of 172 MNNG-exposed fish. The induction of neoplasms in medaka was primarily in the gill, thyroid, and subcutis of the cervical and trunk regions, whereas in catfish skin, thymus, oro-pharynx, and hemopoietic tissues were also commonly affected. In both species, the neoplastic response was considered to be related to direct exposure of the tissues to MNNG. Some of these tumors have not been reported in the literature in either natural or experimental fish. The results also suggest species-specific differences in carcinogenic response following MNNG exposure.

Inhalation toxicity of ammonium perfluorooctanoate.

Ammonium perfluorooctanoate (CAS Registry No. 3825-26-1) is a fine white powder which can become airborne; hence its inhalation toxicity was studied in the male rat. The compound was found to be moderately toxic following single 4-hr exposures, with an LC50 of 980 mg/m3. This concentration produced both an increase in liver size and corneal opacity. Both findings diminished with increasing time after exposure. Subchronic head-only inhalation exposures (6 hr/day on 5 days/wk for 2 wk to 0, 1, 8 or 84 mg/m3) suppressed body-weight gain at 84 mg/m3. Reversible liver-weight increases, reversible increases in serum enzyme activities, and microscopic liver pathology, including necrosis, occurred at exposure of 8 and 84 mg/m3. No ocular changes were produced. Concentrations of organofluoride in the blood showed a dose relationship with initial levels of 108 ppm in rats treated at 84 mg/m3 falling to 0.84 ppm after 84 days with a blood half-life of 5-7 days. The no-observed-effect level was 1 mg/m3 and a mean organofluoride blood level of 13 ppm was detected in rats immediately after the tenth exposure to an atmospheric level of 1 mg ammonium perfluorooctanoate/m3.

Induction of branchial (gill) neoplasms in the medaka fish (Oryzias latipes) by N-methyl-N'-nitro-N-nitrosoguanidine.

Juvenile medaka were exposed to N-methyl-N'-nitro-N-nitrosoguanidine in water under static renewal conditions for 28 days. Two groups of 134 fish each were pulsed 3 times weekly at nominal concentrations of 1.0 and 0.5 mg/liter with N-methyl-N'-nitro-N-nitrosoguanidine dissolved in dimethylformamide. A third group of 134 fish was exposed to the solvent control, 0.01% dimethylformamide in water. Following the 28-day exposure, and during the recovery period, fish were sampled at intervals of approximately 0, 3, 6, and 9 months and examined grossly. Selected tissues were evaluated microscopically. Many tumor types developed in both N-methyl-N'-nitro-N-nitrosoguanidine exposure groups, but only the gill lesions will be discussed. Approximately 50% of the fish in both treatment groups died from gill damage in the second to third month of the recovery period. More than 90% of the surviving treated fish displayed gill lesions, which progressed from mild epithelial hyperplasia of gill filaments at 0-months recovery to epitheliomatous hyperplasia at 3 months and advanced to a more focal nodular appearance of gill filaments at 6 months. Eight to 9 months after the treatment period, at least four fish displayed branchial blastomas. The control fish had no gill lesions. Chemically induced gill tumors have not been previously observed in fish. Even gill tumors of unknown origin are very rare.

Two cases of lymphosarcoma in channel catfish exposed to N-methyl-N'-nitro-N-nitrosoguanidine.

Of 158 channel catfish (Ictalurus punctatus) exposed to N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS:70-25-7] in water for 28 days, 2 developed disseminated lymphosarcoma. One fish was necropsied at 12 months and another at 18 months following exposure. Both fish had a massive neoplastic infiltration of the bilateral pairs of head and trunk kidneys from which the neoplastic cells appeared to originate. The neoplastic infiltration was also observed in the following: thymus, gills, oral mucosa, liver, skin, skeletal muscle of head-neck region, and to a lesser extent spleen and bone marrow. This is probably the first report of lymphosarcoma in channel catfish. Although the occurrence of lymphosarcoma in these 2 catfish appeared to be related to exposure to MNNG, the exact role MNNG played in the tumor formation was not determined.