Rabbit, dermal toxicity

Toxicology. The acute oral and dermal toxicity of naphthalene is low with LD q values for rats from 1780—2500 mg/kg orally (41) and greater than 2000 mg/kg dermally. The inhalation of naphthalene vapors may cause headache, nausea, confusion, and profuse perspiration, and if exposure is severe, vomiting, optic neuritis, and hematuria may occur (28). Chronic exposure studies conducted by the NTP ia mice for two years showed that naphthalene caused irritation to the nasal passages, but no other overt toxicity was noted. Rabbits that received 1—2 g/d of naphthalene either orally or hypodermically developed changes ia the lens of the eye after a few days, foUowed by definite opacity of the lens after several days (41). Rare cases of such corneal epithelium damage ia humans have been reported (28). Naphthalene can be irritating to the skin, and hypersensitivity does occur. 

Dermal Toxicity. Fatty alkylamines are not considered especially toxic with regard to skin penetration and systemic absorption into the body certain polyamines may be absorbed through the skin to a much greater degree. The acute dermal LD q of decylamine in rabbits has been reported to be... 

Respiratory effects have been observed in one dermal toxicity study. Of six rabbits exposed to an unspecified amount of Cellulube 220 for an intermediate duration, one died on day 36 of weakness and dyspnea of 48-hour duration (Carpenter et al. 1959). Respiratory effects were not observed in rabbits dermally exposed to 1,000 mg/kg of cyclotriphosphazene for an intermediate duration (Kinkead et al. 1989c, 1990). No acute- or chronic-duration animal studies examining respiratory tract effects were located. 

Mineral Oil Hydraulic Fluids. No human studies examining dermal end points were located. In animals, no information on dermal effects following inhalation or oral exposure were located. A number of mineral oil hydraulic fluids have been tested for acute dermal toxicity in rabbits. Signs of skin irritation have been observed following application of a naphthenic petroleum-based hydraulic fluid designated as MIL-H-5606... 

Only a few in vivo dermal toxicity studies have been reported so far. Huczko and Lange [50] evaluated the potential of raw CNTs to induce skin irritation by conducting two routine dermatological tests (patch test on 40 volunteers with allergy susceptibilities and Draize rabbit eye test on four albino rabbits). Koyama etal. [51] showed the biological responses to four different types of carbon nanotubes (SWNTs, two types of MWNTs with different diameters, and cup-stacked carbon nanotubes) after their subcutaneous implantation in mice. Both tests [50, 51] showed no or poor irritation effects. However, the in vitro studies in epidermal cell lines exposed to CNTs, and also a more recent report on the toxic outcomes of topical exposure of mice to SWNTs [46], have raised concerns over these assessments. Clearly, this is an area requiring further scientific evaluation. 

Hexachloroethane caused reversible corneal injury in rabbits following ocular contact, but contact with the skin for 24 hours resulted in no dermal effects (Weeks et al. 1979). The physical properties of hexachloroethane suggest that absorption across human skin would be limited (Fiserova-Bergerova et al. 1990). Therefore, unless dermal absorption studies indicate that this prediction is incorrect, there is no need for additional studies of acute dermal toxicity. 

Flucke W. 1986. S 276 Technical - Study of subacute dermal toxicity to rabbits. Unpublished Report 14747 from Bayer AG, Institute of Toxicology, Wuppertal-Elberfeld, Germany. 

Acute toxicity tests are reported for the Cyanamid reagent Cyanex 272, showing values of 4.9gkg and >2.0gkg respectively, for rats (oral) and rabbits (dermal) [73]. The 96 hr tests for bluegill sunfish and rainbow trout gave values of 45 and 22 ppm, respectively. 

Ethylene chlorohydrin is highly irritating to mucous membranes but produces little reaction on contact with rabbit skin. Toxic amounts can be absorbed through the skin without causing dermal irritation the dermal LDso for rabbits is 68 mg/l. This value extrapolated to humans suggests that a volume slightly more than a teaspoon could be lethal with prolonged contact. ... 

In rabbits, dermal LD50 values for cresols were 890, 300, 2,830, and 2,000 mg/kg for o-, p-, m-, and mixed cresols, respectively (Vernot et al. 1977). These values are recorded in Table 2-2. Based on these LD50 values, p-cresol appears to be more toxic dermally than o-cresol, with m-cresol being the least toxic of the three isomers. 

Abdel-Rahman MS, Skowronski GA, Turkall RM, et al. 1987b. Subchronic dermal toxicity studies of Alcide Allay gel and liquid in rabbits. J Appl Toxicol 7(5) 327-333. 

IPEC-US (intended clinical route)a Acute oral and dermal toxicity, skin and eye irritation, and skin sensitization. Bacterial gene mutation and chromosome damage. ADME (intended route). 28-day toxicity (2 species by intended clinical route) Short-term use studies. 90-day toxicity (most appropriate species). Teratology (rat and/or rabbit). Genotoxicity assays. Additional assays (conditional) 1 Short-/midterm studies. One-generation reproduction. Chronic toxicity (rodent and nonrodent) and carcinogenicity (conditional)... 

Acute dermal toxicity-LDso-uses rabbits... 

There is a listing of dermal LDso values in animals for a number of organotin compounds (Smith 1978). A dermal LDso in rabbits was reported to be 11,700 mg/kg bis(tributyltin)oxide (Elsea and Paynter 1958). For rats, an LDso of 605 mg/kg is given (Smith 1978). Despite variations in values for other compounds such as benzoates, naphthenates, and fluorides, the acute dermal toxicity of organotin compounds is generally less than by the oral route. The LDso values for representative species in the acute- and intermediate-duration category are recorded in Table 2-4. Doses are expressed as mg/kg/day compound rather than as doses of tin. 

Dermal toxicity is evaluated by applying the chemical to the skin for 6h a day for 21 days in rat studies, or 28 days in rabbit studies. Feeding studies are used to evaluate the toxicological effects of the chemical when a known dose is administered orally. 

Toxicity The acute oral toxicity of atrazine in rats is 2,850 mg/kg, and the acute dermal toxicity in rabbits is 7,550 mg/kg. The acute inhalation LC50 (1 hour) in rats is greater 167 mg/L. Atrazine did not cause any primary irritation in rabbits, although it caused eye irritation in rabbits.17 A carcinogenicity study of mice exposed to atrazine through diet (82 ppm) for 18 months is sketchy and requires more confirmatory data.23,24... 

For evaluation of the dermal toxicity of a chemical or drug, the adult rat, rabbit, or guinea pig have been considered useful species. However, use of other species requires a justification. Animals with the following weight ranges are useful and facilitate the toxicity test rat 200 to 300 g rabbits 2 to 3 kg guinea pig 350 to 450 g. Equal numbers of each gender with healthy intact skin are... 

Monsanto. 1983b. Acute dermal toxicity of p-nitrophenol to rabbits. NTIS/OTS0518153. 

The toxicity of aliphatic diisocyanates also warrants monitoring exposure to its vapors. HDI has a moderate potential for acute systemic dermal toxicity rabbit dermal LD50 is 570 ml/Kg (57). However, HDI is severely irritating to the skin and eyes. Irritation, lacrimation, rhinitis, burning sensation to throat and chest, and coughing have all been reported in humans following acute inhalation exposure to HDI. HMDI has a low eye and dermal irritation potential, as well as a low potential for acute toxicity. Exposure to HMDI aerosol can cause dermal sensitization of laboratory animals. IPDI can cause skin sensitization reactions as well as eye irritation. The acute toxicity of diisocyanates in rats is shown in Table 12. 

Acute dermal toxicity tests are an important method employed in assessing the safety of insecticides to workers. For dermal toxicity tests, typically, an albino rabbit weighing 2-3 kg is shaved around the abdomen and back, and the chemical in question is painted (dry power is moistened with isotonic saline to prepare a paste) over the area, which is then covered with either a rubber sleeve or cotton gauze held in place with a wire screen for up to 24 hr. The mortality is recorded and the median lethal dose obtained is referred to as dermal LD3(). 

Acute oral toxicity was determined in fasted male and female albino rats to be greater than 5000 mg/kg body weight for both methyl and ethyl esters of canola oil (25). Dermal toxicity was tested on albino rabbits. Applying levels of up to 2000 mg/kg body weight was found to have no observable effect for systemic toxicity (25). The treatment produced only slight and temporary erythrema (redness) and edema (swelling). 

Acute oral toxicity Acute dermal toxicity Primary skin irritation Primary eye irritation Skin sensitization Ames assay (gene mutation) Rat and/or in vitro method Rat and/or in vitro method Rabbit and/or in vitro method Rabbit and/or in vitro method Guinea pig or LLNA Bacteria... 

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