| Abstract |
The effect of (methyl-14C) 2,4-toluenediamine was examined in a macromolecular binding assay. Male Fischer 344 rats were sacrificed 0.5, 1.5 and 4.5 hours after receiving 1, 10 or 100 mg/kg test article in distilled water by intraperitoneal injection. Dose dependent binding of radioactive label was observed in DNA, RNA and protein fractions derived from the liver; additionally, binding to all 3 components was observed in muscle, and binding to DNA and protein was observed in the testis at the 100 mg/kg dose level. The tissue distribution and excretion of 2,4-diaminotoluene-14C (DAT) were evaluated in groups of male B6C3F1 mice exposed to DAT by a single intraperitoneal injection of 0.667 mg/kg (1uCi). Groups of 5 animals were sacrificed at 0.5, 1, 2, 6, 16, and 24 hrs following dosing. By the 24 hr sacrifice, 52% of the administered radioactivity had been excreted in the urine (nearly 50% was excreted by 1 hr) and 22% had been excreted in the feces. In 24 hrs, 1.25% of the administered radioactivity had been trapped from the expired air of the animals. The highest concentration of radioactivity in most tissues was greatest at 1 hr (in all tissues within 2 hrs). The highest organ concentrations were observed in the liver (6.63% of dose/g at 1.0 hr) and kidneys (3.13% of dose/g at 0.5 hr). High concentrations (highs ranging from 5.70-2.09% of dose) were also observed in the adrenals, stomach, pituitary, lymph nodes, eyes and lungs. Elimination of radioactivity from the liver, kidneys and blood was biphasic with fast (alpha) phase half-lives of 0.89, 0.43 and 1.51 hr, respectively, and slow (beta) phase half-lives of 11.68, 9.09 and 12.55 hr, respectively. The dominant route of excretion was via the kidneys. The fate of 2,4-diaminotoluene-14C (2,4-DAT-14C) was studied in male B6C3F1 mice (5/group) intraperitoneally injected with 0.667 mg 2,4-DAT-14C/kg following pretreatment 3 times weekly for 16 weeks by intraperitoneal injection of distilled water (0.3 ml), 2,4-diaminotoluene (2,4-DAT, 30 mg/kg) or 2,6-diaminotoluene (2,6-DAT, 30 mg/kg). High concentrations (radioactivity as 5 dose/g tissue, 2,4-DAT and 2,6-DAT pretreated, respectively) were observed in all treated animals in the large intestine (10.2, 11.8, 7.5), bladder (1.9, 4.0, 2.6), and stomach (1.8, 0.3, 1.0). High levels (1.7-0.3% dose/g tissue) were also observed in the small intestine, liver, eyes, lymph nodes, kidneys, blood, and lungs. The only significant differences observed in the concentration of radioactivity in any of the tissues of water pretreated animals and un-pretreated animals from a previous experiment (exposed i.p. to 2,4-DAT-14C in exactly the same manner) were observed in the muscles (decrease of 31% after water pretreatment). Compared to water-pretreated mice, mice pretreated with 2,4-TDA exhibited statistically significant increases of 79, 31, 68, and 34% in the concentration of radioactivity in the small intestine, salivary glands, lungs, and muscle, respectively. Compared to water-pretreated mice, mice pretreated with 2,6-TDA exhibited statistically significant increases of 29 and 67% in the liver and pancreas, respectively. Tissue Distribution and Excretion of 2,4-toluene Diamine-14c in the Mouse. Toxicity Test on Meta Phenylene Diamine Distilled Flakes Bc34020. Tests for Eye Irritants Perpared by Allied Chem Corp with Attachments. Primary Dermal Irritation Test with Attachments. Guinea Pig Skin Hypersensitization Test with Attachments. Toluene Diamine Lethality-50-acute Toxicity Study with Cover Memos. Effects of Subchronic Pretreatment with 2,4-and 2 |
