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Lewisite rabbits

The Army s interim RfD of 1 x 10 " mg/kg per day for lewisite was based on two oral studies a two-generation reproductive study and a 90-day toxicity study in rats. In both studies, necrosis and hyperplasia of the forestomach were observed. After considering those studies and other potential studies, the subcommittee concludes that a 1987 teratogenicity study conducted in rabbits is more appropriate than the rat studies for deriving the RfD, because there is evidence that the rabbit might be more susceptible to lewisite than the rat. On the basis of the rabbit study, in which maternal mortality and gastric lesions were observed, the snbcommittee believes that the RfD for lewisite should be lowered from 1 x 10 mg/kg per day to 1 x 10 mg/kg per day. [Pg.24]

The major gaps in the available information on lewisite are the lack of information on the implications of administering lewisite directly to the stomach over a short time and the absence of chronic oral toxicity data from which to derive an RfD. Because of those deficiencies, the RfD for lewisite was estimated by extrapolating from a less-than-ideal animal study to humans. Confidence in the RfD can be increased if subchronic oral toxicity studies in rabbits and rats are conducted to compare the effects of chronic oral exposure to low concentrations of lewisite with the effects of short-term intragastric administration of small volumes of lewisite. Such studies will provide not only the data needed to better understand the implications of dosing techniques but also more pertinent information on whether the rabbit is more appropriate than the rat for deriving an RfD for lewisite. [Pg.24]

Hackett, P.L., R.L. Rommereim, F.G. Burton, R.L. Buschbom, and L.B. Sasser. 1987. Teratology Studies on Lewisite and Sulfur Mustard Agents Effects of Sulfur Mustard in Rats and Rabbits. Final Report. DTIC AD-A187495. Prepared by Pacific Northwest Laboratory, Richland, Wash., for the U.S. Army Medical Research and Development Command, Fort Detrick, Frederick, Md. [Pg.98]

ORNL also considered a teratogenicity study (Hackett et al. 1987) in which rabbits were administered lewisite by intragastric intubation on days 6-19 of gestation at doses of 0.07, 0.2, and 0.6 mg/kg per day. Increased mortality of 13% (in fact, 15% but reported incorrectly by... [Pg.102]

Because the subcommittee recommends the use of the teratogenicity study in rabbits (Hackett et al. 1987) as the basis for deriving the RfD for lewisite, it assigned values to the uncertainty factors and the modifying factor with respect to that study below. [Pg.105]

The approach used by ORNL to calculate the RfD for lewisite is consistent with the guidelines of the EPA. The subcommittee does not agree, however, with ORNL s proposed RfD of 1 x lO mg/kg per day, which is based on studies in the rat, and recommends deriving the RfD on the basis of a rabbit study. The RfD for lewisite recommended by the subcommittee is 1 x 10" mg/kg per day, which is an order of magnitude more conservative than the Army s interim RfD. [Pg.107]

This NOAEL is slightly lower than the NOAEL of 0.5 mg/kg/day from the Sasser et al. (1989a) study and, therefore, is being used as the basis for the RfD for lewisite. The selection of this NOAEL is supported by the available data set with the exception of the rabbit data, the vahdity of which uncertain. The RfD for lewisite is calculated as follows ... [Pg.307]

Snider, T.H., M.G. Wientjes, R.L. Joiner and G.L. Fisher. 1990. Arsenic distribution in rabbits after lewisite administration and treatment with British anti-lewisite (BAL). Fundam. Appl. Toxicol. 14 262—272. [Pg.311]

Multigeneration reproductive studies in rats (Sasser et al, 1989b) and teratology studies in rats and rabbits (Hackett et al, 1987) given lewisite by gastric intubation were negative or compromised by concurrent maternal toxicity. [Pg.103]

Human data concerning the toxicity of lewisite via the oral route of exposure are not available. However, there are limited toxicity data on lewisite ingestion from animal studies. In animals, ingestion of lewisite can produce acute inflammation of the mucous membrane of the stomach or intestine, which is characterized by hemorrhage, necrosis of the epithelium, and submucous edema. Developmental effects have been reported in pregnant rats and rabbits... [Pg.118]

Lewisite does not cause damage to the bone marrow or immunosuppression (Sidell et al, 1997). Arrhythmias and renal dysfunction are due to hypovolemia from fluid loss. Lewisite was fetotoxic to rats and rabbits and is a suspected carcinogen (Goldman and Dacre, 1989 RTECS, 2008). [Pg.725]

A chelator should be given if there is dyspnea, pulmonary edema, or skin bums larger than pahn size (Goldfrank et al, 2002). BAL is the traditional arsenic chelator, but it has numerous side effects. The deep intramuscular injections are very painful and BAL can cause hypertension, tachycardia, and vomiting. 2,3-Dimercaptosuccinic acid (DMSA, Succimer ) can also be used to chelate arsenic (Graziano et al, 1978). 2,3-Dimercapto-l-propanesulfonic acid (DMPS) is used in Europe and has been effective in protecting rabbits from the lethal effects of lewisite (Aposhian et al, 1982). [Pg.726]

Precise data, i.e. a diffusion coefficient expressing the p.c. absorption of lewisite (amount absorbed per area and time), are not available. However, Inns and Rice (1993) conducted p.c. toxicity studies in rabbits and determined the LD50 at 5.3mg/kg (3.5-8.5 mg/kg, 95% confidence interval). The exposed area was 2 cm and exposure lasted for 6 h. [Pg.780]

Inns et al. (1990) had also determined the LD50 of i.v. lewisite administration at 1.8 mg/kg (1.6-2.1 mg/kg 95% confidence interval). Thus, it can be concluded that by exposing 2 cm of rabbit skin to a dose of 5.3 mg/kg for 6 h, a dose producing the equivalent effect of 1.8 mg/kg is absorbed. No further calculations that might exaggerate the reliabihty of available data shall be conducted here. [Pg.780]

Snider et al. (1990) determined the elimination of lewisite from rabbits after p.c. injection. Half-life was determined, ranging from 55 to 75 h. A clearance of 120ml/h/kg was found. However, these findings only describe the overall elimination of arsenic from the organism, following a lewisite exposure. [Pg.781]

In tests performed on rabbits. Lewisite caused almost immediate edema of the lids, conjunctiva, and cornea as well as, early and severe involvement of the iris and ciliary body followed by gradual depigmentation and shrinkage of the iris stroma (Mann et al., 1946). Miosis appeared early. In this same study, miosis was not noted after mustard exposure. No long-term effects of Lewisite were noted, such as the delayed keratitis seen after mustard. [Pg.308]

Mann I, Pirie A, PuUinger BD. A study of Lewisite lesions of the eyes of rabbits. Am. J. Ophthalmol. 1946 29 1215-1227. [Pg.310]

In another study, clipped rabbits were exposed to sulfur mustard, lewisite (L), thickened soman, and VX and were decontaminated between 30 s and 5 min postexposure. Eor the vesicants (sulfur mustard and L), lesion areas were compared. Decontaminating for 1 min resulted in the lesion areas being reduced 21-fold for sulfur mustard and 22-fold for L, relative to no decontamination. For the nerve agents (soman and VX), the inhibition of blood acetylcholinesterase (AChE) was used as a marker. Using a 2 min decontamination time, the dose of nerve agent required to produce 50% inhibition of AChE was increased 1.8-fold for thickened soman and 18-fold for VX (Hobson et al., 1993). [Pg.618]

In the studies of intravenously injected lewisite in the rabbit, changes in the lungs, including hemorrhage and edema, with lymphocytic infiltration, were seen (Inns et al, 1988,1990). Damage was found in the biliary tree, including epithelial necrosis in the gall bladder. Inns and Rice... [Pg.469]

Hackett PL, Sasser LB, Rommereim RL et al. (1987). Teratology studies on lewisite and sulphur mustard agents effects of lewisite in rats and rabbits, AD-A198423, Fort Detrick, Frederick, MD, USA US Army Research and Development Command. [Pg.474]


See other pages where Lewisite rabbits is mentioned: [Pg.103]    [Pg.104]    [Pg.104]    [Pg.106]    [Pg.108]    [Pg.301]    [Pg.302]    [Pg.305]    [Pg.308]    [Pg.119]    [Pg.119]    [Pg.467]    [Pg.470]    [Pg.473]    [Pg.196]    [Pg.104]    [Pg.105]    [Pg.109]   
See also in sourсe #XX -- [ Pg.796 ]




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