Chemical meningism after lumbar facet joint block with local anaesthetic and steroids

A case is reported in which chemical meningism occurred after lumbar facet joint block with methylprednisolone acetate and bupivacaine. This complication was probably due to inadvertent dural puncture. The use of steroids in facet joint injections is questioned.     

Methylene Chloride: Two-Generation Inhalation Reproductive Study in Rats

Methylene Chloride: Two-Generation Inhalation Reproductive Studyin Rats. Nitschke, K. D., Eisenbrandt, D. L., Lomax, L. G.,and Rao, K. S. (1988). Fundam Appl Toxicol. 11, 60–67.Reproductive parameters in Fischer 344 rats were evaluated followinginhalation of methylene chloride (MeCl₂) for two successivegenerations. Thirty male and female rats were exposed to 0,100, 500, or 1500 ppm MeCl₂ for 6 hr/day, 5 days/week for 14weeks and then mated to produce f, litters. After weaning, 30randomly selected f, pups/sex/group were exposed to MeCl₂ for17 weeks and subsequently mated to produce f2 litters. Reproductiveparameters examined included fertility, litter size and neonatalgrowth, and survival. All adults and selected weanlings wereexamined for grossly visible lesions. Tissues from selectedweanlings were examined histopathologically. No adverse effectson reproductive parameters, neonatal survival, or neonatal growthwere noted in animals exposed to methylene chloride in eitherthe f₀ or fE generations. Similarly, there were no treatment-relatedgross pathologic observations in fo or f, adults or f, and f²weanlings. Histopathologic examination of tissues from f, andf² weanlings did not reveal any lesions attributed to methylenechloride. Thus, exposure of rats to concentrations as high as1500 ppm methylene chloride, which has been shown in a 2-yearstudy to produce treatment-related effects, did not affect anyreproductive parameters.     

Chronic Inhalation Toxicity and Carcinogenicity Study of Respirable Polymeric Methylene Diphenyl Diisocyanate (Polymeric MDI) Aerosol in Rats

Four groups of 60 Wistar rats of each sex were exposed by inhalationto 0, 0.2, 1.0, or 6.0 mg/m³ respirable polymeric methylenediphenyl diisocyanate (polymeric MDI) aerosol (93.5% < 4.2µm)for 6 hr a day, 5 days a week for up to 24 months. In addition,satellite groups of 10 rats/sex/group received the same treatmentfor 12 months. There was no adverse effect on general health,survival, body weight, or hematological or clinical chemistryparameters. Lung weights were increased in both males and femalesexposed to 6.0 mg polymeric MDI/m³ for 12 or 24 months. Grossexamination at autopsy of males exposed to 6.0 mg polymericMDI/m³ for 24 months revealed an increased incidence of spottedand discolored lungs. Increased incidences of degeneration andbasal cell hyperplasia of the nasal olfactory epithelium, oftenaccompanied by hyperplasia of Bowman's glands, were found inthe 1.0 and 6.0 mg/m³ groups. Light and electron microscopicstudies of the lungs revealed accumulations of alveolar macrophagescontaining polymeric MDI-associated refractile yellowish materialat the level of the alveolar duct in all exposed groups. Alveolarduct epithelialization as well as fibrosis of tissues surroundingthe macro phage accumulations occurred at the 1.0 and 6.0 mg/m³exposure levels. In addition, increased incidences of calcareousdeposits and localized alveolar bronchiolization were seen inthe 6.0 mg/m³ group. Moreover, eight pulmonary adenomas (sixin males and two in females) and one pulmonary adenocarcinoma(in a male) were observed in the 6.0 mg/m³ exposure group. Thetime sequence of the spectrum of pulmonary changes indicatesthat recurrent alveolar wall damage by polymeric MDI and/orpolymeric MDI-containing alveolar macrophages leads to alveolarbronchiolization and ultimately to bronchioloalveolar tumors.No lung tumors were found in the lower concentration groupsand in the control group. The incidence and distribution ofother types of tumors were not influenced by polymeric MDI.It was concluded that in the present study, the "no-observed-adverse-effectlevel" of polymeric MDI was 0.2 mg/m³ and that chronic exposureto polymeric MDI at a level of 6.0 mg/m³ was related to theoccurrence of pulmonary tumors. It was also concluded that exposureto polymeric MDI at concentrations not leading to recurrentlung tissue damage will not produce pulmonary tumors.     

Chlorpyrifos: A 13-Week Nose-Only Vapor Inhalation Study in Fischer 344 Rats

Fischer 344 rats were exposed by the nose-only inhalation routeto chlorpyrifos vapors at concentrations of 0, 5.2, 10.3, or20.6 ppb, 6 hr/day, 5 days/week for 13 weeks. The exposure concentrationswere limited by the low vapor pressure of chlorpyrifos (theoreticalmaximum vapor concentration of 25 ppb at 25?C). No treatment-relatedsigns of toxicity or changes in body weights were detected duringthe course of the study. Unnalysis, hematology, clinical chemistry,organ weights, gross pathologic, and histopathologic evaluationswere performed at the end of the study with no treatment-relatedeffects observed. In addition, no differences from controlswere noted in plasma, red blood cell, or brain cholinesteraseactivities. The results of this study indicate that the no-observed-effectlevel for chlorpyrifos vapor was the highest attainable concentration,20.6 ppb, in male and female Fischer 344 rats.     

Hemolytic Activity of Ethylene Glycol Phenyl Ether (EGPE) in Rabbits

Hemolytic Activity of Ethylene Glycol Phenyl Ether (EGPE) inRabbits. BRESLIN. W. J., PHILIPS, J. E., LOMAX, L. G., BARTELS,M. J., DITTENBER, D. A., CALHOUN, L. L., AND MILLER, R. R. (1991).Fundam. Appl. Toxicol. 17, 466–481. Studies were conductedto characterize the hemolytic effects of EGPE in rabbits followingoral and dermal exposure, and to evaluate the in vitro hemolyticpotential of EGPE and its major metabolite using rabbit redblood cells (RBC). Gavage administration of EGPE to female NewZealand White rabbits at 100, 300, 600, or 1000 mg/kg/day forup to 10 consecutive days (one dose/day) resulted in a dose-relatedintravascular hemolytic anemia. The hemolytic anemia was characterizedby decreased RBC count, hemoglobin concentration, packed cellvolume, hemoglobinuria, splenic congestion, renal tubule damage,and a regenerative erythroid response in the bone marrow. Thehemolytic anemia was observed without alterations in RBC glutathioneor methemoglobin. Phenoxyacetic acid (PAA) was identified asa major blood metabolite of EGPE. In Vitro exposure of femalerabbit erythrocytes indicated EGPE to be considerably more hemolyticthan PAA. In a 90-day dermal study in which EGPE was appliedto the skin of male and female New Zealand White rabbits 6 hr/day,5 days/week, at doses up to 500 mg/kg/day, there was no indicationof a hemolytic response. The only treatment-related effectswere sporadic occurrences of slight erythema and scaling ofskin at the site of test material application in high dose groupmale and female rabbits. However, erythema and scaling werenot associated with gross or histopathologic changes and werenot considered toxicologically significant.     

Teratologic Evaluation of Orally Administered Nitrapyrin in Rats and Rabbits3 1

Teratologic Evaluation of Orally Administered Nitrapynn in Ratsand Rabbits.BERDASCO, 2N.M., LOMAX, L.G., ZIMMER, M. A., ANDHANLEY, T. R., JR. (1988). Fundam Appl Toxicol 11, 464—471.Pregnant Fischer 344 rats and New Zealand White rabbits wereorally administered 0, 5, 15, or 50 mg nitrapyrin/kg/day onGestation Days 6 through 15 (rats) or 0, 3, 10, or 30 mg/kg/dayon Gestation Days 6 through 18 (rabbits). In rats, 50 mg/kg/dayproduced slight histopathologic changes in the livers of pregnantfemales. Fetal examination revealed no evidence of fetotoxicityor teratogenicity among rats at dose levels up to 50 mg/kg/day.Among rabbits, a significant depression in maternal weight gainand increased absolute and relative liver weights were observedat 30 mg/kg/day. An increased incidence of crooked hyoid boneamong fetal rabbits in the 30 mg/kg/day dose group was consideredindicative of fetotoxicity but not 3 teratogenicity. Thus, administrationof nitrapyrin was not teratogenic at dose levels up to 50 mg/kg/dayin rats and 30 mg/kg/day in rabbits     

The Chronic Toxicity and Oncogenicity of Inhaled Technical-Grade 1,3-Dichloropropene in Rats and Mice

The Chronic Toxicity and Oncogenicity of Inhaled Technical-Grade1,3-Dichloropropene in Rats and Mice. LOMAX, L, G., STOTT, W.T., JOHNSON, K. A., CALHOUN, L. L., YANO, B. L., AND QUAST,J. F. (1989). Fundam. Appl. Toxicol. 12, 418–431. Maleand female Fischer 344 rats and B6C3F1 mice were exposed byinhalation to target concentrations of 0, 5, 20, or 60 ppm (0,22.7, 90.8, or 272 mg/m³) technical-grade 1,3-dichloropropene(DCPT) 6 hr/day, 5 days/week, for upto 2 years. Ancillary groupsof rats and mice were exposed for 6- and 12- month periods.Significant treatment-related nonneoplastic changes followingexposure for 2 years were morphological alterations in the nasaltissues of rats exposed to 60 ppm and mice exposed to 20 or60 ppm DCPT. In addition, mice exposed to 20 or 60 ppm had hyperplasiaof the transitional epithelium lining the urinary bladder. Survivalof male and female rats and mice exposed to DCPT was similarto that of the corresponding controls. No statistically increasedtumor incidence was observed in treated rats. The only neoplasticresponse observed in mice was an increased incidence of benignlung tumors (bronchioloalveolar adenomas) in male mice exposedto 60 ppm DCPT (22/50 versus 9/50 in controls).