Single Dermal Dose Research Articles

EVALUATION OF THE ACUTE TOXICITY OF SILAHYDROCARBON

Silahydrocarbon (SHC) is a base stock for a candidate high-temperature hydraulic fluid. Because United States Air Force personnel working with SHC may be exposed to potential health hazards, a complete battery of acute toxicity tests was performed with the fluid. A single neat dose of 0.1 mL SHC into New Zealand White (NZW) rabbit eyes resulted in slight conjunctival irritation 1 hr after treatment in all unflushed eyes and one of three flushed eyes. Conjunctival irritation persisted through 24 hr but dissipated by 48 hr. Rinsing the eyes after treatment was of questionable benefit. A single treatment of 0.5 mL neat SHC to rabbit skin produced negative results for all but a single animal, which had very slight erythema at the test site 48 hr after treatment. Guinea pigs failed to exhibit a sensitization response following repeated application of SHC. A single oral dose of 5 g SHC/kg body weight given to five male and five female F-344 rats and a single dermal dose of 2 g SHC/kg body weight applied to five male and five female NZW rabbits resulted in no deaths or signs of toxic stress. Five male and five female F-344 rats were exposed to 4.8 mg/L (near limit concentration) of aerosolized SHC for 4 hr. All male rats and four female rats survived. During exposure, the animals exhibited signs of eye and upper respiratory irritation.

Teratogenicity of 2-methoxyethanol applied as a single dermal dose to rats

2-Methoxyethanol (2-ME) was applied as a single dermal dose on the backs of collared, pregnant Sprague-Dawley rats on Gestation Days (GD) 10, 11, 12, 13, or 14 at doses of 0 and 2000 mg/kg, and at doses of 0,250, 500, and 1000 mg/kg on GD 12. Except for a transient loss in body weight observed the day after 2-ME administration, no signs of maternal toxicity were observed. On GD 20, dams were necropsied and the fetuses evaluated for normal development. Resorptions were significantly ( p < 0.05) increased in dams exposed to 2-ME on GD 10. Fetal body weights were reduced at dose levels of 1000 and 2000 mg/kg, but statistically significant differences were found only on GD 10 and 12. Significant increases in external, visceral, and skeletal malformations were observed in fetuses exposed to 2-ME at dose levels of 500 mg/kg or greater. Defects of the cardiovascular and urinary systems were the prominent visceral malformations observed. Limb defects (especially those pertaining to the digits) and vertebral column defects (primarily of the tail) were the most frequently observed skeletal defects. At the 2000 mg/kg dose level, 2-ME was teratogenic regardless of the GD of administration. Based on the results of this study, the no observed adverse effect level for developmental toxicity for a single dermal dose of 2-ME applied on GD 12 was determined to be 250 mg/kg.

Teratogenicity of 2-Methoxyethanol Applied as a Single Dermal Dose to Rats

Teratogenicity of 2-Methoxyethanol Applied as a Single Dermal Dose to Rats

Electromyographic, neuropathologic, and functional correlates in the cat as the result of tri- o-cresyl phosphate delayed neurotoxicity

To investigate the cat as a test animal for organophosphorous compound-induced delayed neurotoxicity, tri- o-cresyl phosphate (TOCP) was applied directly on the unprotected back of the neck of young adult cats. Single dermal doses, ranging from 250 to 2000 mg/kg TOCP, or subchronic daily administration of 1 to 100 mg/kg produced delayed neurotoxic effects in the cat. Severity of delayed neurotoxicity depended on the dose and duration. Clinical signs were characterized by hindlimb weakness, ataxia, and paresis. Electromyographic abnormalities resulting from acute denervation were observed in most cats that developed a neurologic deficit. No changes were seen in the motor nerve conduction, thus suggesting that the deficits were in the terminal branch rather than being diffuse lesions in the peripheral nerves. These results correlated well with histopathologic results showing lesions in the most distal portion of the longest tracts in both central and peripheral nervous systems. In the spinal cord, histopathologic studies showed that the ascending tracts of the upper cervical levels and descending tracts of the lumbosacral regions were affected most frequently. Although this study shows that the cat, like the chicken, is susceptible to TOCP-induced delayed neurotoxicity, it demonstrates two differences between the cat and the chicken: (1) greater sensitivity of the cat to the acute effect of TOCP, and (2) greater extent of recovery or improvement of the cat from delayed neurotoxicity. This recovery was demonstrated by: improvement of clinical signs, gain in body weight, disappearance of electromyographic abnormalities, and regeneration of peripheral nerves. Dermal administration of a single 100-mg/kg dose or subchronic 0.5-mg/kg doses of TOCP did not produce delayed neurotoxicity.

Effects of a single dermal dose of [formula omitted], [formula omitted], [formula omitted]-TRI- [formula omitted]-Butyl Phosphorotrithioate (DBF) on brain acetylcholinesterase (AChE), acid phosphatase (APase) and 2',3'-cyclic nucleotide-3'—phosphohydrolase (CNP) and plasma butyrylcholinesterase (BuChE) and apase in hens

Effects of a single dermal dose of [formula omitted], [formula omitted], [formula omitted]-TRI- [formula omitted]-Butyl Phosphorotrithioate (DBF) on brain acetylcholinesterase (AChE), acid phosphatase (APase) and 2',3'-cyclic nucleotide-3'—phosphohydrolase (CNP) and plasma butyrylcholinesterase (BuChE) and apase in hens

Sensitivity of the cat to delayed neurotoxicity induced by O-ethyl O-4-nitrophenyl phenylphosphonothioate

Delayed neurotoxicity was produced in cats following the administration of either a single dermal dose of 22.5 to 225 mg/kg (0.2 to 5.0 times the LD50) or subchronic (90 days) administration of 0.5 to 2.0 mg/kg of technical grade O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN). The study showed three differences from the condition produced in the chicken: difficulty to protect from acute poisoning, slower progression of delayed neurotoxicity, and propensity for improvement. These animals received atropine sulfate and pyridine-2-aldoxime methyl chloride (PAM) to protect them against acute poisoning, but most developed signs of acute cholinergic neurotoxicity, the degree of severity being dose dependent. Also cats given small single doses of EPN showed only leg weakness, while those treated with large doses progressed to severe ataxia and death. In cats treated with subchronic dermal daily doses of EPN, the extent and permanence of injury and progression or improvement of neurologic deficit also depended on the dose size and duration of exposure. Histopathologic changes were present in the most distal portion of the longest tracts in both the central and peripheral nervous system. Ascending tracts were most affected in the cervical spinal cord, while change in the descending tracts was concentrated in the lumbosacral spinal cord. Recovery to a varying degree from delayed neurotoxicity was seen in all surviving cats. The recovery was demonstrated as improvement in clinical signs, increase in body weight, and regeneration of peripheral nerves.

The toxicity of amitrole in the rat

A single oral dose of 4080 mg/kg and a single dermal dose of 2500 mg/kg of amitrole, the highest doses given, were not lethal to adult rats. Dietary levels of 0, 1000, 500, 100 and 25 ppm amitrole were fed to groups of 10 male and 10 or 12 female rats. The dietary levels of 1000 and 500 ppm were fed for 107–110 days, the dietary levels of 100 and 25 ppm for 240–247 days to the F 0 generation and for 141 days to the F 1b generation. At the dietary levels of 1000 and 500 ppm the pups that were born were smaller and had atropic thymuses and spleens indicative of runt disease. Most of them had died with-in a week after weaning. Reproduction was not affected at the lower dietary levels. Hyperplasia of the thyroid was seen in all rats fed dietary levels of 100 ppm or greater. In the 25 ppm group 4 10 F 0 and 4 10 F 1b females and 6 10 F 1b males, but none of the F 0 males developed hyperplasia of the thyroid.