RESUMEN
This study was conducted among U.S. Army soldiers to evaluate the association between exposure to o-chlorobenzylidene malononitrile (CS riot control agent) and urinary metabolite 2-chlorohippuric acid (CHA) detected in test subjects (n = 87) after completion of Mask Confidence Training. CS exposures ranged 0.086-4.9 mg/m³ ([Formula: see text] = 2.7 mg/m³). CHA levels (corrected for creatinine) at 2-, 8-, 24-, and 30-hr post-exposure resulted in ranges of 94.6-1120 µg/g-cr ([Formula: see text] = 389 µg/g-cr), 15.80-1170 µg/g-cr ([Formula: see text] = 341 µg/g-cr), 4.00-53.1 µg/g-cr ([Formula: see text] = 19.3 µg/g-cr), and 1.99-28.4 µg/g-cr ([Formula: see text] = 10.6 µg/g-cr), respectively. Spearman's correlation revealed CHA levels strongly correlated with time sampled (r = -0.748, p < 0.05) and weakly correlated with CS concentration (r = 0.270, p < 0.05). A linear relationship was observed between CHA, CS concentration, and time of urine sample according to the following regression equation: ln(CHA, µg/g-cr) = 5.423 + 0.316 (CS conc., mg/m³) - 0.002 (time sampled), (R = 0.910, R² = 0.827, p < 0.05). This relationship suggests that CHA has the potential to be an effective retrospective indicator of CS exposure in future biomarker developments.
Asunto(s)
Hipuratos/análisis , Sustancias para Control de Disturbios Civiles/metabolismo , o-Clorobencilidenomalonitrila/metabolismo , Adulto , Biomarcadores/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Personal Militar , Exposición Profesional/análisis , Dispositivos de Protección Respiratoria , Sustancias para Control de Disturbios Civiles/toxicidad , Factores de Tiempo , o-Clorobencilidenomalonitrila/toxicidadRESUMEN
The analysis of biomedical samples such as urine and blood can provide evidence of exposure to chemicals for a range of applications including occupational exposure monitoring, detection of drugs of abuse, performance enhancement in sport and investigations of poisoning and incapacitation. This paper reports the development of an analytical method for two suspected urinary metabolites of the riot control agent 2-chlorobenzylidene malononitrile (CS): 2-chlorohippuric acid and 2-chlorobenzyl-N-acetylcysteine. 2-Chlorohippuric acid was identified in all 2h post-exposure samples from a set of urine samples taken from army recruits exposed to low levels of thermally dispersed CS during training. 2-Chlorobenzyl-N-acetylcysteine, a metabolite known to be formed in the rat, was not identified in any of the samples. The lower limit of detection (LLOD) for 2-chlorohippuric acid and 2-chlorobenzyl-N-acetylcysteine was 1ng/ml and 0.5ng/ml in pooled urine from the pre-exposed subjects. 2-Chlorohippuric acid was rapidly excreted but was detectable in the urine of 17 of the 19 subjects tested 20h after exposure.
Asunto(s)
Cromatografía Liquida/métodos , Hipuratos/orina , Sustancias para Control de Disturbios Civiles/metabolismo , Sustancias para Control de Disturbios Civiles/orina , Espectrometría de Masas en Tándem/métodos , o-Clorobencilidenomalonitrila/metabolismo , o-Clorobencilidenomalonitrila/orina , Adolescente , Adulto , Animales , Humanos , Límite de Detección , Masculino , Ratas , Sustancias para Control de Disturbios Civiles/administración & dosificación , Adulto Joven , o-Clorobencilidenomalonitrila/administración & dosificaciónRESUMEN
A report of seven people who accidentally drank a juice contaminated with CS (o-chlorobenzylidene malononitrile) is given. Due to its mucosal irritating properties, CS (also known as "tear gas") is commonly used by policemen and soldiers in riot control. However, only a few reports of its ingestion by humans exist. Ingestion of CS may cause immediate irritation of the oral mucosa and gastrointestinal symptoms later on. Damage of internal organs, which has been shown in animals but only rarely in humans, is probably related to the dose ingested. The extensive use of CS gas merits recognition of the signs and symptoms of its exposure in order to reduce anxiety in both patients and medical staff and to facilitate fast and efficient management.
Asunto(s)
Sustancias para Control de Disturbios Civiles/envenenamiento , o-Clorobencilidenomalonitrila/envenenamiento , Adulto , Bebidas/envenenamiento , Femenino , Humanos , Masculino , Sustancias para Control de Disturbios Civiles/metabolismo , o-Clorobencilidenomalonitrila/metabolismoRESUMEN
The clastogenicity of the sensory irritant 2-chlorobenzylidene malonitrile (CS) to V79 Chinese hamster cells was investigated at various exposure conditions. CS efficiently induced chromatid-type aberrations in a dose-dependent manner provided the cells could run through at least one or two S-phases during a 20-h exposure over a 3-h exposure followed by a 20-h recovery period (cell cycle time 8-10 h). The induction of SCEs indicates an S-dependent mechanism. The hydrolysis products o-chlorobenzaldehyde and malonitrile were inactive in these experiments.
Asunto(s)
Mutágenos/toxicidad , o-Clorobencilidenomalonitrila/toxicidad , Animales , División Celular/efectos de los fármacos , Línea Celular , Cricetinae , Mutágenos/metabolismo , o-Clorobencilidenomalonitrila/metabolismoRESUMEN
The aneuploidy inducing capacity of 2-chlorobenzylidene malonitrile (CS), a chemical used as a riot control agent, and its hydrolysis products o-chlorobenzaldehyde and malonitrile was studied at various exposure conditions in V79 Chinese hamster cells. Chromosomes were counted in metaphase preparations with preserved cytoplasm. A significant increase in the number of aneuploid cells was found after CS and o-chlorobenzaldehyde exposure but not after malonitrile exposure. o-chlorobenzaldehyde, which also introduced high levels of polyploid cells, seems to be an important metabolite for the aneuploidogenic effectiveness of CS.
Asunto(s)
Aneuploidia , Benzaldehídos/toxicidad , Nitrilos/toxicidad , o-Clorobencilidenomalonitrila/toxicidad , Animales , Línea Celular , Cromosomas/efectos de los fármacos , Replicación del ADN , Dimetilsulfóxido/farmacología , Pruebas de Micronúcleos , o-Clorobencilidenomalonitrila/metabolismoRESUMEN
The genotoxicity of the sensory irritant 2-chlorobenzylidene malonitrile (CS) to V79 Chinese hamster cells was investigated using the induction of gene mutations, micronuclei and DNA repair synthesis as biological endpoints. CS efficiently induced micronuclei and mutants resistant to 6-thioguanine in these cells, but it did not elicit DNA repair synthesis. Induction of micronuclei and mutants showed very similar courses of concentration dependence, suggesting that both events were caused by the same mechanism. The hydrolysis products of CS, o-chlorobenzaldehyde and malononitrile dit not induce micronuclei and were much less cytotoxic than CS. The observation of heritable genetic changes in cells exposed to CS in the absence of detectable DNA damage suggests that the genetic effects of CS are not caused by an interaction of the compound or its hydrolysis products with DNA. It appears more likely that the mutagenic activity is the consequence of effects of CS on the mitotic apparatus of the cells causing chromosomal aneuploidy.
Asunto(s)
Pruebas de Mutagenicidad , Nitrilos/toxicidad , o-Clorobencilidenomalonitrila/toxicidad , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cricetinae , Cricetulus/genética , Daño del ADN , Reparación del ADN/efectos de los fármacos , Glutatión/metabolismo , Humanos , Ratones , Pruebas de Micronúcleos , Huso Acromático/efectos de los fármacos , Tioguanina/metabolismo , o-Clorobencilidenomalonitrila/metabolismoRESUMEN
The glutathione conjugation of 2-chloro-, 3-chloro-, 4-chloro- and 2,6-dichlorobenzylidene malononitrile (chloroBMNs) was investigated in vitro. In incubation mixtures containing rat liver cytosol (9000 g), the decrease in the initial amount of glutathione due to the various chloroBMNs ranged from 40 to 60% and occurred both enzymatically and spontaneously at physiological conditions (37 degrees C, pH 7.4). 2,6-DichloroBMN, however, depleted glutathione largely spontaneously (38 +/- 3%). The steric hindrance of the two chlorosubstituents probably plays an important role during the glutathione-S-transferase catalyzed reaction. The hydrolysis of the chloroBMNs to the corresponding chlorobenzaldehydes and malononitrile was studied in a mixture of buffer pH 7.4 and ethanol. The rate of hydrolysis of 2,6-dichloroBMN was slower than those of the related chloroBMNs. This means that 2,6-dichloroBMN will be the most stable compound in the presence of water. Only IP administration of 2-chloroBMN (CS) to adult male Wistar rats gave enhancement of urinary thioether excretion. A thioether could be isolated and was identified as the N-acetyl-S-[2-chlorobenzyl]-L-cysteine. The quantity of this benzylmercapturic acid in the urine of rats amounted to 4.4% dose (0.07 mmol/kg, n = 12). After IP administration of 2-chloro- and 3-chlorobenzaldehyde to rats benzylmercapturic acid excretion in the urine was found to be 7.6 and 1.1% of the dose, respectively. Administration of the related 4-chloro- and 2,6-dichlorobenzaldehyde, however, resulted in no urinary mercapturic acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Acetilcisteína/biosíntesis , Glutatión/metabolismo , Nitrilos/metabolismo , o-Clorobencilidenomalonitrila/metabolismo , Acetilcisteína/orina , Animales , Biotransformación , Hidrólisis , Técnicas In Vitro , Hígado/metabolismo , Masculino , Ratas , Ratas Endogámicas , o-Clorobencilidenomalonitrila/análogos & derivadosRESUMEN
Adult male Wistar rats administered i.p. with 2-chlorobenzylidene malononitrile (CS) excreted one mercapturic acid in urine. The amount of mercapturic acid determined gaschromatographically was about 4% of the dose (0.07 mmol/kg, n = 12). The structure of the mercapturic acid methylester was identified by t.l.c. and confirmed by synthesis and mass-spectrography. The acid appeared to be 2-chlorobenzylmercapturic acid [N-acetyl-S-(2-chlorobenzyl)-L-cysteine]. CS and some of its metabolites were also tested in the Ames Salmonella/microsome assay. Both mutagenic and toxic effects were measured with strain TA 100 as the indicator organism. No mutagenic effects were found with any of the tested substances. At dosages of CS, higher than 1,000 micrograms/plate a bacteriotoxicity was revealed.
Asunto(s)
Nitrilos/metabolismo , o-Clorobencilidenomalonitrila/metabolismo , Acetilcisteína/análogos & derivados , Acetilcisteína/toxicidad , Acetilcisteína/orina , Animales , Cromatografía de Gases , Masculino , Espectrometría de Masas , Pruebas de Mutagenicidad , Mutágenos , Ratas , Ratas Endogámicas , Salmonella/genética , o-Clorobencilidenomalonitrila/toxicidadRESUMEN
Lachrymators of varied structure are reduced either by hydrogen addition or halogen substitution using NADH model compounds as donors. Similar compounds without lachrymatory activity were reduced either very slowly or not at all. CS (o-Chlorobenzalmalonitril) is reduced by NADH, the reaction being catalyzed by an enzyme present in erythrocytes. Thus the lachrymatory action follows a general scheme for the activity of sensory transduction. This scheme consists of a reception in the nerve cell membrane and a fast or simultaneous chemical transformation in an enzymic reaction.