An evaluation of possible effects on health following exposure to ethylene oxide.

A study was made of the effects of ethylene oxide (ETO) on the health of sterilizer workers and other personnel exposed while using ETO for sterilization of disposable medical devices. The only significant findings were obtained by chromosomal analysis of cultured lymphocytes harvested from the workers. There were significant differences in the numbers and types of chromosomal aberrations between the exposed workers and the nonexposed controls. Quadriradial and triradial chromosomal forms, which are rarely found in nonexposed populations, were increased in exposed workers. Increased numbers of sister chromatid exchanges (SCE) were found in the cultured lymphocytes of some, but not all, exposed persons during the 2 yr of study. Thirteen workers were removed from exposure in 1979 because of increased numbers of aberrant cells. Follow-up over 4 yr has not shown a significant improvement, except for a moderate reduction in SCE. Recommendations are given for a surveillance of persons working with or exposed to ethylene oxide.

Health effects of silicon tetrachloride. Report of an urban accident.

A spill of silicon tetrachloride (SiCl4) at a chemical plant caused the evacuation of several thousand people from an industrial park; 28 persons sought medical attention. Most of the affected individuals suffered only transient eye and upper airway irritation. Six of the plant employees were later referred for detailed evaluation of possible lung injury, but no definite evidence of SiCl4-induced pulmonary dysfunction was found. Five of these workers also experienced recurrent headaches, and two complained of pedal dysesthesias after the accident. Although the temporal relationship between the exposure and onset of these symptoms is notable, no definite etiologic relationship could be established.

Analysis of fatalities from acute narcotism in a major urban area.

The incidence of acute, fatal narcotism in San Francisco was determined to be 3.2% of all deaths (10 882) subject to medical examiner's inquiry in a five-year period. Heroin was responsible for the greatest number of these cases, usually accompanied by alcohol or other abused drugs. The median concentration of the heroin metabolite, morphine, in the blood in fatal cases was 20 microgram/dL. Death from propoxyphene, the second most frequently encountered narcotic, was generally determined to be suicidal, while death from heroin was judged to be accidental. The highest rate occurred in black males between the ages of 21 and 30 years. The three most consistent findings were positive identification of the drug in the body (100% of the cases), pulmonary edema (90.4% of the cases), and microscopic liver changes (71.1% of the cases).

Clinical pharmacology of dichlorvos.

Polyvinyl resin formulation pellets (V-3 and V-12) containing dichlorvos were administered to male volunteers in single doses up to 32 mg/kg and repeated doses up to 16 mg/kg/day for up to three weeks. The cholinesterase activity depressions following single doses were dose related. Following multiple doses, the plasma cholinesterase activity was maximally depressed at all dose levels and the RBC cholinesterase activity depression was dose related.

Mutagenicity of 2- and 3-carbon halogenated compounds in the Salmonella/mammalian-microsome test.

Short-chain, 2- and 3- carbon halogenated hydrocarbons were tested for mutagenicity for Salmonella typhimurium strain TA 100 both with and without the presence of S-9. Without exception, all brominated derivatives were more mutagenic than the chlorinated derivatives, usually by a substantial order of magnitude. 2-Fluoroethanol, the only fluorinated compound tested, showed little or no mutagenic activity up to 100 micromole per plate concentration. Two highly purified propane derivatives containing a halogen atom on each of the three carbons showed little or no direct mutagenic activity. A third trihalogenated compound with a halogen atom on each carbon atom showed some direct mutagenic activity, probably due to impurities. However, all three trihalogenated compounds were highly active mutagens following S-9 activation. The presence of a double bond in the case of 1, 2, 3-trichloropropene resulted in a higher level of direct mutagenic activity than 1, 2, 3-trichloropropane, but activation with S-9 resulted in a further increase in mutagenic activity with the former compound. On the other hand, S-9 caused a substantial decrease in mutagenic activity of most compounds containing a double bond. With the presence of an alcoholic group in a compound, the addition of S-9 caused variable responses, increasing the number of his+ revertant colonies due to 2, 3-dibromopropanol but had little or no effect with five other compounds containing an alcoholic group. Evidence is also presented that the position of a double bond in relation to the halogen atoms may influence mutagenic activity.

Mutagenicity of halogenated and oxygenated three-carbon compounds.

Four structurally related three-carbon compounds, known for their antifertility activity in the male, and the brominated derivatives of two of these compounds were tested for mutagenic activity by the Salmonella typhimurium test of Ames et al. In the presence of strain TA-100, a base-pair substituion detector strain, 1,2-dibromo-3-chloropropane (DBCP), was the most active compound tested but required enzymatic conversion by 59 microsomal preparation to an active mutagen. Three of these compounds containing an epoxide group-epichlorohydrin, epibromohydrin, and glycidol-were highly active direct mutagens, not requiring 59 for activation, alpha-Chlorohydrin was the least active compound tested; alpha-bromohydrin was 40 times more active than its chlorinated analog. Epibromohydrin was only slightly more active than epichlorohydrin, but both were highly active. With both of the halogenated epoxides, 59 preparation caused a substantial decrease in mutagenic activity at every concentration tested. All six compounds showed dose-related responsiveness for the base-pair substitution detector strains used. However, they were relatively inactive against the frameshift detector strain of S. typhimurium, TA-98. Glycerol, propylene glycol, and n-propanol, which are also three-carbon compounds containing one or more hydroxy groups, were inactive when trested at high concentrations with strain TA-100.

Three-month inhalation exposure study with methane sulfonylfluoride.

The effects of exposure to methane sulfonylfluoride at concentrations of 20 or 100 ppb for a total of 61 exposures of 7 hours each were studied in male and female rats. The control and exposed groups did not differ in appearance, behavior, weight gain or food consumption. There was no effect on plasma cholinesterase. RBC cholinesterase was significantly depressed in the high-level male and female exposure groups. There was no significant accumulation of fluoride in either the liver or blood at either exposure level.

Mutagenic action of a series of epoxides.

The mutagenicity of a series of 13 epoxide compounds was studied using a bacterial plate assay system. The histidine-dependent tester strains TA98 (for frameshift mutagens) and TA100 (for base-pair substitution mutagens) of Salmonella typhimurium were used. Mutagenicity was evaluated both with and without the additon of rat liver microsomal extract. Dieldrin, diglycidyl ether of bis phenol A and 3 of its homologues were not mutagenic. Allyl glycidyl ether, n-butyl glycidyl ether, vinly cyclohexene diepoxide, glycidol, glycidal-dehyde, diglycidyl ether, diepoxybutane and diglycidyl ether of substituted glycerine were mutagenic in the TA100 strain, causing reversion of the bacteria to histidine independence. Dose-reponse curves of the mutagenicity of the latter 4 compounds were obtained. On a molar basis, glycidaldehyde was about 20-50 times more potent in producing mutation that were the other 3 epoxides in the dose-response test. In general, the mutagenicity of the epoxides was not enhanced or diminished by the addition of microsomal extract.

Tolerance, dependence and lethality in morphine-dependent mice after repeated oral administration of methadone.

Mice were rendered tolerant to and dependent on morphine via a morphine pellet implantation. Three days later methadone hydrochloride was administered at a dose of 100mg/kg per os 3 hours after pellet removal and then daily for a total of 5--6 days. This dose of methadone was shown to exhibit a high efficacy for the blockade of morphine abrupt withdrawal jumping and only minimal toxicity. Under these conditions, the level of analgetic tolerance with respect to morphine and methadone and the level of dependence as measured by the naloxone ED50 were initially elevated by the morphine treatment. However, upon substitution with oral methadone these levels declined with time at a rate which did not differ from that of a group of mice receiving only water after morphine pellet removal. Despite these findings, the methadone treatment was associated with an increasing tolerance to methadone lethality during the administration of this narcotic which was nearly double that of a similarly treated water control group by the sixth day. This observation could not be explained by an elevation in the level of cellular tolerance rendered by the methadone treatment since the morphine LD50 was not elevated following identical treatment with morphine and then methadone. The significance of these results is discussed with respect to the role of methadone administration and its metabolism in the modification of tolerance and dependence.

Arsenical neuropathy: residual effects following acute industrial exposure.

A case report is presented describing a worker who was splashed with arsenic acid in an industrial accident and subsequently developed symptoms of systemic arsenicalism and peripheral neuropathy. This is the only report, to the authors' knowledge, of a single episode of cutaneous absorption of arsenic resulting in peripheral neuropathy. Previous reports of arsenical neuropathy and rationale for BAL therapy early in the treatment of systemic arsenicalism are discussed.

Manganese intoxication.

We have reported two cases of chronic manganese poisoning. Case 1 followed exposure to manganese fumes in cutting and burning manganese steel. Case 2 resulted from exposure to dusts of manganese dioxide, an ingredient used in glazing of ceramics. There were initial difficulties in establishing the correct diagnosis. Prominent clinical features were severe and persistent chronic depressive psychosis (Case 1), transient acute brain syndrome (Case 2) and the presence of various extrapyramidal symptoms in both cases. Manganese intoxication has not previously been reported as occurring in California. With increasing use of the metal, the disease should be considered in the differential diagnosis of neurologic and psychiatric disease. Our observations were made in the period 1964 through 1968. Recently the prognosis of victims of manganese poisoning has been improved dramatically by the introduction of levodopa as a therapeutic agent.

Blood codeine concentrations in fatalities associated with codeine.

The toxicologic findings in eight cases of death due primarily to codeine overdosage are presented. Blood codeine concentrations ranged from 1.4 to 5.6 mug/ml as determined by gas-liquid chromatography. Morphine was found in only two of the blood samples, at concentrations of 0.2 and 0.6 mug/ml, and may have resulted from heroin usage rather than codeine metabolism. A case of death of a codeine user by violent means is also presented in which the blood codeine concentration was 2.6 mug/ml.