Gorzinski S J, Kociba R J, Campbell R A, Smith F A, Nolan R J, Eisenbrandt D L
Mammalian and Environmental Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674.
Fundam Appl Toxicol. 1987 Oct;9(3):423-35. doi: 10.1016/0272-0590(87)90025-x.
The single-dose oral LD50 values in Fischer 344 rats for technical-grade, 2,4-dichlorophenoxyacetic acid (2,4-D), esters, and salts ranged from 553 mg/kg (isobutyl ester in females) to 1090 mg/kg (dimethylamine salt in males). The LD50 values for the acid, esters, or salts, when expressed as acid equivalents, were consistent which suggests that the acute toxicity was due to 2,4-D per se. Acute dermal LD50 values in rabbits for the acid, esters, and salts were greater than 2000 mg/kg. Overall, these results indicate that the acute oral and dermal toxicity of 2,4-D are low. Pharmacokinetics were evaluated in male Fischer 344 rats given single oral doses of 10, 25, 50, 100, or 150 mg 2,4-[14C]D/kg. The amount of 2,4-D in the plasma, kidney, and urine 6 hr postdosing indicated that the urinary elimination of 2,4-D was saturated in male rats given oral doses in excess of 50 mg/kg. Subchronic dietary studies in male and female Fischer 344 rats used dose levels of 0, 15, 60, 100, or 150 mg/kg/day of purified or technical-grade 2,4-D acid for 13 weeks. Body weight gains were decreased for both sexes at the higher dose levels of purified and technical-grade 2,4-D acid. Kidney weights were increased in all treated male rats and in females given the higher three dose levels of purified 2,4-D. Treatment-related cytoplasmic alterations were present in the renal proximal tubules of most rats given 60 mg/kg/day and higher of purified or technical-grade 2,4-D; a few females given 15 mg/kg/day also had slight alterations in the cytoplasm of the proximal tubules. A dose-related degenerative change was identified in the descending proximal renal tubules of all male rats given the highest three dose levels of either test material and some given 15 mg/kg/day. Dose levels of 100 or 150 mg/kg/day of either compound for both sexes produced minimal swelling and increased staining homogeneity in the liver cells and were associated with a slight elevation of liver weight and serum glutamic pyruvic transaminase activity. Higher dose levels of technical-grade and purified 2,4-D decreased total serum tetraiodothyronine levels in female rats, however, the morphology of the thyroid gland was normal. The no-observed-effect level (NOEL) was less than 15 mg/kg/day for both purified and technical-grade 2,4-D acid.
在Fischer 344大鼠中，技术级2,4-二氯苯氧基乙酸（2,4-D）、其酯类和盐类的单剂量口服半数致死量（LD50）值范围为553毫克/千克（雌性异丁酯）至1090毫克/千克（雄性二甲胺盐）。以酸当量表示时，酸、酯或盐的LD50值是一致的，这表明急性毒性是由2,4-D本身引起的。兔经皮给予酸、酯和盐的急性LD50值大于2000毫克/千克。总体而言，这些结果表明2,4-D的急性口服和经皮毒性较低。对雄性Fischer 344大鼠单次口服给予10、25、50、100或150毫克2,4-[14C]D/千克后评估了药代动力学。给药后6小时血浆、肾脏和尿液中的2,4-D含量表明，口服剂量超过50毫克/千克的雄性大鼠中，2,4-D的尿排泄已饱和。对雄性和雌性Fischer 344大鼠进行的亚慢性饮食研究中，使用了0、15、60、100或150毫克/千克/天的纯化或技术级2,4-D酸剂量，持续13周。在纯化和技术级2,4-D酸的较高剂量水平下，两性的体重增加均减少。所有接受治疗的雄性大鼠以及接受较高三个剂量水平纯化2,4-D的雌性大鼠肾脏重量增加。给予60毫克/千克/天及更高剂量纯化或技术级2,4-D的大多数大鼠近端肾小管中出现与治疗相关的细胞质改变；少数给予15毫克/千克/天的雌性大鼠近端肾小管细胞质也有轻微改变。在给予两种受试物质最高三个剂量水平的所有雄性大鼠以及给予15毫克/千克/天的部分雄性大鼠的近端肾小管降支中发现了剂量相关的退行性变化。两种化合物给予两性100或150毫克/千克/天的剂量水平会使肝细胞出现最小程度的肿胀和染色均匀性增加，并伴有肝脏重量和血清谷丙转氨酶活性略有升高。技术级和纯化2,4-D的较高剂量水平降低了雌性大鼠血清总甲状腺素水平，然而，甲状腺形态正常。纯化和技术级2,4-D酸的未观察到有害作用水平（NOEL）均小于15毫克/千克/天。
