Triethylene glycol HO(CH2CH2O)3H.

TEG is a liquid higher glycol of very low vapor pressure with uses that are primarily industrial. It has a very low order of acute toxicity by i.v., i.p., peroral, percutaneous and inhalation (vapor and aerosol) routes of exposure. It does not produce primary skin irritation. Acute eye contact with the liquid causes mild local transient irritation (conjunctival hyperemia and slight chemosis) but does not induce corneal injury. Animal maximization and human volunteer repeated insult patch tests studies have shown that TEG does not cause skin sensitization. A study with Swiss-Webster mice demonstrated that TEG aerosol has properties of a peripheral chemosensory irritant material and caused a depression of breathing rate with an RD(50) of 5140 mg m(-3). Continuous subchronic peroral dosing of TEG in the diet of rats did not produce any systemic cumulative or long-term toxicity. The effects seen were dose-related increased relative kidney weight, increased urine volume and decreased urine pH, probably a result of the renal excretion of TEG and metabolites following the absorption of large doses of TEG. There was also decreased hemoglobin concentration, decreased hematocrit and increased mean corpuscular volume, probably due to hemodilution following absorption of TEG. The NOAEL was 20 000 ppm TEG in diet. Short-term repeated aerosol exposure studies in the rat demonstrated that, by nose-only exposure, the threshold for effects by respiratory tract exposure was 1036 mg m(-3). Neither high dosage acute nor repeated exposures to TEG produce hepatorenal injury characteristic of that caused by the lower glycol homologues. Elimination studies with acute peroral doses of TEG given to rats and rabbits showed high recoveries (91-98% over 5 days), with the major fraction appearing in urine (84-94%) and only 1% as CO(2). TEG in urine is present in unchanged and oxidized forms, but only negligible amounts as oxalic acid. Developmental toxicity studies with undiluted TEG given by gavage produced maternal toxicity in rats (body weight, food consumption, water consumption, and relative kidney weight) with a NOEL of 1126 mg kg(-1) day(-1), and mice (relative kidney weight) with a NOEL of 5630 mg kg(-1) day(-1). Developmental toxicity, expressed as fetotoxicity, had a NOEL of 5630 mg kg(-1) day(-1) with the rat and 563 mg kg(-1) day(-1) with mice. Neither species showed any evidence of embryotoxicity or teratogenicity. There was no evidence for reproductive toxicity with mice given up to 3% TEG in drinking water in a continuous breeding study. TEG did not produce mutagenic or clastogenic effects in the following in vitro genetic toxicology studies: Salmonella typhimurium reverse mutation test, SOS-chromotest in E. coli, CHO forward gene mutation test (HGPRT locus), CHO sister chromatid exchange test, and a chromosome aberration test with CHO cells. The use patterns suggest that exposure to TEG is mainly occupational, with limited exposures by consumers. Exposure is normally by skin and eye contact. Local and systemic adverse health effects by cutaneous exposure are likely not to occur, and eye contact will produce transient irritation without corneal injury. The very low vapor pressure of TEG makes it unlikely that significant vapor exposure will occur. Aerosol exposure is not a usual exposure mode, and acute aerosol exposures are unlikely to be harmful, although a peripheral sensory irritant effect may develop. However, repeated exposures to a TEG aerosol may result in respiratory tract irritation, with cough, shortness of breath and tightness of the chest. Recommended protective and precautionary measures include protective gloves, goggles or safety glasses and mechanical room ventilation. LC(50) data to various fish, aquatic invertebrates and algae, indicate that TEG is essentially nontoxic to aquatic organisms. Also, sustained exposure studies have demonstrated that TEG is of a low order of chronic aquatic toxicity. The bioconcentration potential, environmental hydrolysis, and photolysis rates are low, and soil mobility high. In the atmosphere TEG is degraded by reacting with photochemically produced hydroxyl radicals. These considerations indicate that the potential for ecotoxicological effects with TEG is low.

Medical management of the traumatic consequences of civil unrest incidents: causation, clinical approaches, needs and advanced planning criteria.

In the context of this review, civil unrest is defined as disharmony, expressive dissatisfaction and/or disagreement between members of a community, which leads to a situation of competitive aggression that may find expression as disruption of organisation, conflicts, damage to property and injuries. Such a breakdown of harmonious relationships, which may result in property damage and human injuries that may be threatening to life, varies in magnitude from participation of a very few individuals up to the involvement of large crowds of people, which may evolve into a full-scale riot. It is the latter situation often involving demonstrators, opposing groups and law enforcement personnel that can result in multiple casualties and present a very significant challenge to the resources of local healthcare institutions. The causation of civil unrest incidents is multifactorial and has generic, specific and potentiating elements. With the current national and international societal, political and discriminatory problems, it is likely that civil unrest incidents on both small and large scales will continue to occur at a high and possibly increasing rate on a worldwide basis, and for these not infrequent incidents, the medical community should be in a state of informed preparation. The circumstances of civil unrest incidents are very variable with respect to causation, overall magnitude, frequency, timing, geographical location, numbers of persons involved, demographics of participants, influence of extremists, confrontation with opposing groups and control measures used by law enforcement agencies. Methods used by police and security forces for the control of civil unrest incidents, if advanced negotiations with organisers and verbal warnings have failed, fall basically into two categories: physical and chemical measures. Physical methods include restraint holds, truncheons, batons, mounted horses, projectiles (such as bean bags, plastic and rubber bullets), water cannons, tasers and (rarely) live ammunition. All of these physical measures are associated with pain and immobilisation, and there is a high potential for soft tissue and bone injuries. Some of the more severe physical methods, including plastic and rubber bullets, may cause lethal injuries. The basis for using chemicals in civil unrest incidents is that they cause distraction, transient harassment and incapacitation, temporary impairment of the conduct of coordinated tasks and cause a desire to vacate the area of unrest. Although screening smokes and malodors have sometimes been employed, the major group of chemicals used are peripheral chemosensory irritants (PCSIs), which reversibly interact with sensory nerve receptors in exposed skin and mucosal surfaces, resulting in the production of local uncomfortable sensations and associated reflexes. Major effects are on the eye, respiratory tract and (to a lesser degree) skin. Thus, the induced transient pain and discomfort in the eye, respiratory tract and skin, together with associated lacrimation, blepharospasm, rhinorrhoea, sialorrhoea, cough and breathing difficulties, produce temporary incapacitation and interference with the conduct of coordinated tasks, and form the basis for harassment of malefactors. Currently used peripheral chemosensory irritants are 1-chloroacetophenone, 2-chlorobenzylidene malononitrile, dibenz(b.f)-1,4-oxazepine, oleoresin capsicum and pelargonic acid vanillylamide. Depending on operational circumstances, irritants may be dispersed as a smoke, powder cloud, aerosol, vapour, or in solution; the mode of generation and dispersion of irritant can influence hazard. Brief acute exposure to chemosensory irritants produces effects that generally resolve within an hour, leaving no long-term sequelae. However, sustained exposure to high concentrations may produce tissue injury, notably to the eye, respiratory tract and skin. With solutions of sensory irritants, other formulation constituents may enhance PCSI toxicity or introduce additional local and/or systemic toxicity. By the very circumstances of civil unrest incidents, injuries are inevitable, particularly when emotions are heightened and police and security forces have to resort to various chemical and/or physical means of control. Trauma may include slight to severe physical and/or chemical injuries, psychological problems and occasional deaths. Hospitals should be prepared for a wide range of casualties, and the fact that those seeking help will constitute a heterogeneous group, including wide age range, male, female, and individuals with pre-existing ill health. A major civil unrest incident necessitates that the local receiving hospital should be prepared and equipped for decontamination and triage processes. It is necessary to reassure patients who have been exposed to sensory irritants that the signs and symptoms are rapidly reversible, and do not result in long-term sequelae. With respect to chemical exposures, detailed evaluation should be given to possible ocular, cutaneous, respiratory and gastrointestinal effects. Also, exposure to chemosensory irritants results in transient increases in blood pressure, bradycardia and increased intraocular pressure. This indicates that those with cardiovascular diseases and glaucoma may be at increased risk for the development of complications. This article details the pharmacological, toxicological and clinical effects of chemicals used in civil disturbance control and discusses the management of contaminated individuals. Additionally, the potential for adverse effects from delivery systems and other physical restraint procedures is summarised. Due to the emergency and specialised circumstances and conditions of a civil unrest incident, there is a clear need for advanced planning by healthcare institutions in the event that such an incident occurs in their catchment area. This should include ensuring a good information base, preparations for medical and support staff readiness, and availability of required equipment and medications. Ideally, planning, administration and coordination should be undertaken at both local (regional) and central (governmental) centres. Regional centres should have responsibilities for education, training, ensuring facilities and staffing are appropriate, and that adequate equipment and medicines are available. There should be cooperative interactions and communications with local police and other emergency services. Centrally directed functions should include ensuring adequacy of the information base, coordinating activities and agreeing approaches between the regional centres, and periodic audits of regional centres with respect to the staffing, facility, equipment and training needs. Also, there is a need for most countries to introduce detailed guidelines and formal (regulatory) schemes for the assessment of the safety-in-use of chemicals and the delivery systems that are to be used against heterogeneous human populations for the control of civil unrest incidents. Such regulatory approval schemes should also cover advisory functions for safe use and any required restrictions.

Respiratory peripheral chemosensory irritation, acute and repeated exposure toxicity studies with aerosols of triethylene glycol.

The potential for adverse effects from exposure to respirable aerosols of triethylene glycol (TEG: CAS Number 112-27-6) was investigated by a peripheral chemosensory irritation study, and by acute and repeated exposure toxicity studies. The sensory irritation study, conducted with male Swiss Webster mice, showed an exposure concentration-related depression of breathing rate that allowed the calculation of an RD50 of 5140 mg m(-3). In an acute study male and female Sprague Dawley rats were exposed whole body to aerosols of TEG up to 6730 mg m(-3) for 4 h. No mortalities occurred at this high concentration, but unexplained mortality occurred in female rats at 5230 mg m(-3) at 2-3 days postexposure. Two repeats of the 5230 mg m(-3) exposure did not cause mortality. Signs at 6730 and 5230 mg m(-3) were limited to those of irritancy. For a 9 day repeated exposure study rats were exposed whole body to 0, 494, 2011 and 4824 mg m(-3) TEG aerosols for 6 h day(-1). Mortalities occurred at 4824 mg m(-3) between exposure days 2 and 5. Nonspecific indications of toxicity at 2011 mg m(-3) were signs of irritation, decreased body weight and increased food and water consumption; evidence of hepatic dysfunction was indicated by increased serum alkaline phosphatase and alanine aminotransferase activities, but liver histology was normal. Fluid imbalance was suggested by increases in water consumption, blood urea nitrogen, relative kidney weight and urine volume, with decreased urine osmolality, pH and N-acetyl-beta-D-glucosaminidase activity. At 494 mg m(-3) there were minimal signs of irritation, increased water consumption and slightly increased alkaline phosphatase; histology of the kidney was normal. Thus, in this 9 day repeated aerosol whole body exposure study a No-Observed-Effect-Level (NOEL) could not be established. Since preening of the fur at these high aerosol concentrations exposures might have led to a confounding factor from the resultant oral intake, another 9 day repeated aerosol study was conducted, but by nose-only exposure of rats for 6 h day(-1) to TEG aerosol concentrations of 0, 102, 517 and 1036 mg m(-3). In this study there were no clinical signs, no effects on food and water consumption, and no biochemical or histological evidence of hepatorenal dysfunction. By the end of the exposure period, male and female rats of the 1036 mg m(-3) group had body weights lower than those of the controls, but not with statistical significance. Since there were no statistically significant effects on any monitors, 1036 mg m(-3) is considered to be a threshold for toxicity by nose-only exposure to TEG aerosol. The findings indicate that exposure to a respirable aerosol is not acutely harmful, but may cause sensory irritant effects. Repeated exposure to high concentrations of TEG aerosols may be harmful, particularly if there are contributions from additional routes of exposure.

The occupational toxicologist: professionalism, morality and ethical standards in the context of legal and non-litigation issues.

By its very nature, practice and intended applications, the profession of occupational toxicology has individual and collective responsibilities related to the design, conduct, interpretation and extrapolation of laboratory and controlled human clinical studies in order to determine the potential for industrial xenobiotics to produce adverse effects. The implications for health-related adverse effects in the workplace, and in the domestic and general environment carries many and various responsibilities for the toxicologist which are related to multiple and wide-ranging ethical issues. This review presents and discusses some of the major areas where the occupational toxicologist may experience potential ethical problems related to the conduct of routine professional activities. Emphasis is placed on the design, conduct, interpretation and reporting of laboratory studies; animal welfare; regulatory activities; human clinical volunteer studies; roles and responsibilities in defining workplace safety and protective measures; malpractices in various disciplines and work practices; misconduct in publication; and codes of ethical behavior.

Developmental toxicity study with triethylene glycol given by gavage to CD rats and CD-1 mice.

Triethylene glycol (TEG) is a liquid industrial chemical with a potential for human exposure. The likelihood for developmental toxicity was investigated in two species. Timed-pregnant CD rats and CD-1 mice were dosed daily by gavage with undiluted TEG over gestational days (gd) 5-15 at 0.0 (water control), 1126, 5630 or 11,260 mg kg(-1) day(-1) with rats and 0.0, 563, 5630 or 11,260 mg kg(-1) day(-1) with mice. They were examined daily, and gestational body weights and food and water consumption measured throughout gestation. At necropsy on gd 21 (rats) or gd 18 (mice) dams were examined for body, gravid uterine, liver and kidney weights, and implantation sites. Maternal kidneys were examined histologically. Fetuses were weighed, sex determined, and examined for external, soft tissue and skeletal variations and malformations. Rat dams had reduced body weights, body weight gains, and food consumption, and increased water consumption and relative kidney weights at 11,260 mg kg(-1) day(-1). They also had reduced body weight and increased water consumption at 5630 mg kg(-1) day(-1). Mice had clinical signs and increased relative kidney weight at 11,260 mg kg(-1) day(-1). Renal histology was normal in both species. Neither species had treatment-related effects on corpora lutea or implantations. Fetal body weights were reduced at 11,260 mg kg(-1) day(-1) (both species) and 5630 mg kg(-1) day(-1) (mice). In rat fetuses there was a pattern of delayed ossification in the thoracic region at 11,260 mg kg(-1) day(-1). Mouse fetuses had delayed ossification in the frontal and supraoccipital bones, cervical region, hindlimb proximal phalanges and reduced caudal segments at 11,260 mg kg(-1) day(-1), and in the skull bones at 5630 mg kg(-1) day(-1). These patterns of delayed ossification are consistent with reduced fetal body weights. No biologically significant embryotoxicity or teratogenicity was observed at any dosage in either species. The NOEL for TEG given by gavage over the period of organogenesis was 1126 mg kg(-1) day(-1) in the rat and 5630 mg kg(-1) day(-1) in the mouse for maternal toxicity, and 5630 mg kg(-1) day(-1) (rat) and 563 mg kg(-1) day(-1) (mouse) for developmental toxicology.

Developmental toxicity study with diethylene glycol dosed by gavage to CD rats and CD-1 mice.

Diethylene glycol (DEG; CAS Number 111-46-6) is a widely used industrial liquid chemical with a potential for human exposure. In view of the established teratogenic effects caused by ethylene glycol in laboratory animals, the developmental toxicity of DEG was investigated in mice and rats, species known to be sensitive to the developmental toxicity of ethylene glycol. Timed-pregnant CD-1 mice and CD rats were dosed daily by gavage with undiluted DEG over gestational days (gd) 6-15. Based on probe studies, mouse dosages were 0 (distilled water), 559, 2795 and 11,180 mg/kg/day, and those for rats 0, 1118, 4472 and 8944 mg/kg/day. They were examined daily for clinical signs of toxicity, and body weights, food consumption and water consumption measured periodically throughout gestation. At necropsy, on gd 18 (mice) or gd 21 (rats), dams were examined for gross pathology and body, gravid uterus, liver and kidney weights were measured. Maternal rat kidneys were examined histologically. Fetuses were weighed, sex determined, and examined for external, visceral and skeletal variations and malformations. With mice there was maternal toxicity at 11,180 mg/kg/day (mortality, signs, increased water consumption) and at 2795 mg/kg/day (increased water consumption). Implantations were comparable across all groups. Fetal body weights were significantly reduced at 11,180 mg/kg/day. There were no increases in variations or malformations, either total, by category, or individually. With rats, maternal toxicity was present at 8944 mg/kg/day (mortality, signs, reduced body weight gain, reduced food consumption, increased water consumption, increased liver weight, increased kidney weight, and renal histopathology), and 4472 mg/kg/day (increased water consumption). There were no treatment-related effects on corpora lutea or implantations. Fetal body weights were reduced at 8944 mg/kg/day. There were no significant effects with respect to total or individual external or visceral variations. Individual skeletal variations were significantly increased at 8944 mg/kg/day (poorly ossified interparietal, poorly ossified thoracic centra number 10 and number 13, and bilobed thoracic centrum number 10) and 4472 mg/kg/day (split anterior arch of atlas and bilobed thoracic centrum number 10). This pattern of delayed ossification is consistent with reduced fetal body weight. Malformations, total, by category, or individually, were similar between the control and DEG groups. Thus, under the conditions of these studies, the no-observed-effect-level (NOEL) for DEG given by gavage over gd 6-15 was 559 mg/kg/day with the mouse and 1118 mg/kg/day with the rat for maternal toxicity, and 2795 mg/kg/day with mice and 1118 mg/kg/day with rats for developmental toxicity (fetotoxicity). There were no indications of embryotoxicity or teratogenic effects at any dosage in either species.

Developmental toxicity study with 3-(methylthio)propionaldehyde vapor by whole-body exposure of Sprague-Dawley rats.

Time-mated Sprague-Dawley rats were exposed whole body to analytically measured 3-(methylthio) propionaldehyde (3-MTP) vapor concentrations of 0 (air controls), 9.87, 58.3 and 127.8 ppm over gestational days (gd) 6-15 for 6 h day(-1). There was an exposure concentration-related maternal toxicity (clinical signs, body weight change and food consumption) that was marginal at 9.87 ppm. No effects on gestational parameters, fetal numbers and sex ratio or fetal body weights were noted. There was no increase in the incidence of either malformations or variations (total, external, visceral or skeletal). Thus, the no-observed-adverse-effect level (NOAEL) for development toxicity for exposure to 3-MTP vapor was 127.8 ppm.

Glaucopsia: an occupational ophthalmic hazard.

Glaucopsia is a transient disturbance of vision that results from the development of corneal epithelial oedema and associated microcysts produced by exposure to the vapour of certain industrial chemicals, notably aliphatic, alicyclic and heterocyclic amines. After a latent period of a few hours of exposure, there is typically a blurring of vision, objects take on a blue-grey appearance and halos develop around bright objects. Corneal changes can be seen on biomicroscopy and corneal thickness increase is measurable by pachymetry. At concentrations higher than threshold values, visual acuity may be decreased, but contrast sensitivity is a better measure of visual effects. On vacating the causative vapour, vision returns to normal in a few hours without leaving permanent ocular sequelae. Vapour concentration of the causative amine is a major factor in the development of glaucopsia, and a concentration-effect relationship is usually evident. A correlation exists between the vapour concentration, degree of corneal oedema, corneal thickness and subjective symptoms, which permits no-effect and threshold-effect concentrations to be determined. The disturbance of vision is a nuisance factor and this may impair work efficiency, predispose to physical accidents and hinder the performance of coordinated tasks (e.g. driving). As a consequence, development of glaucopsia is considered a hazard and is thus an important consideration in assessing workplace safety. From a knowledge of threshold and no-effect concentrations, a workplace permissible vapour exposure concentration can be developed along with industrial hygiene precautionary measures.

Percutaneous toxicokinetic and repeated cutaneous contact studies with ethylene glycol monohexyl ether.

Ethylene glycol monohexyl ether (EGHE; CAS no. 112-54-4) is a liquid industrial chemical with a potential for skin contact. The toxicokinetics of EGHE was investigated in Fischer 344 rats and New Zealand White rabbits by intravenous (i.v.) and 48-h occluded epicutaneous dosing. Given i.v. to male rats (2.5-25 mg kg(-1)) [(14)C]EGHE demonstrated fi rst-order kinetics. Carbon-14 was eliminated mainly in urine (68-74%) as metabolites, with no free EGHE. The plasma free EGHE concentration declined rapidly post-dosing and was not detectable by 8 h. Similar results were obtained for [(14)C]EGHE given i.v. to male rabbits in the dosage range 1-10 mg kg(-1), except that the metabolism of EGHE was more rapid, with no free EGHE being detectable in plasma by 1 h post-dosing. After cutaneous dosing of male and female rats with 25 mg kg(-1), there was rapid percutaneous absorption, with >95% of the radiochemical dose being recovered. Percutaneous bioavailability was >75%. Carbon-14 was excreted in urine (21-33%) to a lesser extent than by the i.v. route, and (14)CO(2) and volatiles accounted for 15-18%. Carbon-14 recovery was low from tissues and organs (0.39-0.46%), with no preferential accumulation. Extensive metabolism was indicated by the rapid decline in plasma free EGHE, with none being detectable by 48 h. Free EGHE was not present in urine, and urinary radioactivity was associated with up to seven metabolites. After cutaneous dosing of male and female rabbits (10 mg kg(-1)) ca. 75% of the dose was recovered, most (14)C being in urine (58-60%). Urine radioactivity was associated with up to nine metabolite peaks, but no free EGHE. The toxicokinetic findings indicate a significant percutaneous absorption of EGHE across both rat and rabbit skin, which is rapidly and extensively metabolized, with renal excretion being the principal route of elimination of metabolites. A 9-day repeated skin contact study in the male and female New Zealand White rabbit, using a dosage range of 44-444 mg kg(-1) day(-1), did not show any evidence for percutaneous systemic toxicity.

Chronic toxicity and oncogenicity study with glutaraldehyde dosed in the drinking water of Fischer 344 rats.

Glutaraldehyde (GA) has a wide spectrum of industrial, scientific and biomedical applications. Its potential to produce chronic toxic and/or oncogenic effects was investigated in Fischer 344 rats (100/sex/group) given GA in drinking water for a maximum of 104 weeks. GA concentrations were 0 (control), 50,250 and 1000 ppm, resulting in average daily GA consumptions, respectively, of 0, 4, 17 and 64 mg/kg for males and 0, 6, 25 and 86 mg/kg for females. Interim euthanasia (10/sex/group) was performed at 52 and 78 weeks. Parameters evaluated were clinical signs, body weight, food and water consumption, hematology, serum chemistry, urinalysis, organ weights, gross and microscopic pathology. There were no treatment-related effects on mortality. Absolute body weights and body weight gains of the 250 and 1000 ppm males and females were reduced over the study in a dosage-related manner. Food and water consumption by the 250 and 1000 ppm groups were decreased in a statistically significant dose-related manner over the study, and mean water consumption by the 50 ppm animals was slightly reduced but not with statistical significance. The 250 and 1000 ppm groups had a dose-related decrease in urine volume with increased osmolality, and pH was slightly reduced. Absolute kidney weights were increased in the 250 and 1000 ppm groups at the 52 and 78 week sacrifices, and decreased at 104 weeks. Relative kidney weights were increased at all sacrifice times for the 1000 ppm group, at 52 weeks for the 250 ppm group, and at 72 weeks for the 50 ppm group. The urinalysis and renal weight changes are compatible with a physiological compensatory adaptation to reduced water consumption. Gross and histological evidence for gastric irritation was observed principally in the 1000 ppm rats euthanized at 104 weeks and in animals that died during the study. Bone marrow hyperplasia and renal tubular pigmentation, seen in rats that died and the 104 week euthanasia animals, may have been secondary to a low grade hemolytic anemia in animals with large granular lymphocytic leukemia (LGLL). The only neoplasm that showed a statistically significant increase was LGLL, which occurred at a high incidence in both sexes and all groups, including the controls, for both animals that died and at the 104 week euthanasia. A few instances of LGLL were observed at 78 weeks. The overall incidence of LGLL in the spleen for the 0, 50, 250 and 1000 ppm groups was, respectively, 43, 51, 40 and 46% for males, and 24, 41, 41 and 53% for females. Statistical analyses indicated that the severity of LGLL was associated with the higher dosages of GA in female, but not male, rats. Due to the background and variable incidence of LGLL in the Fischer 344 rat, the finding of a statistical significance only for female rats, and because, there was no clear dose-response relationship, the biological significance of the LGLL findings is unclear. There is the possibility that the significance was a statistical artifact due to the low incidence of LGLL in the female control animals as a result of biological variability within the study. It is also considered to be possible that the chronic dosage of GA in the drinking water resulted in a modification of one or more of the factors responsible for the expression of this common and spontaneously occurring neoplasm in the Fischer 344 rat.

Genetic toxicology studies with glutaraldehyde.

Glutaraldehyde (GA; CAS no. 111-30-8) has a wide spectrum of industrial, scientific and biomedical applications, with a potential for human exposure particularly in its biocidal applications. The likelihood for genotoxic effects was investigated in vitro and in vivo. A Salmonella typhimurium reverse mutation assay showed no evidence for mutagenic activity with strains TA98, TA1535, TA1537 and TA1538, with or without metabolic activation. However, there was a weak mutagenic response (1.9-2.3-fold at the highest non-toxic concentration) with TA100 in the presence of metabolic activation. In a Chinese hamster ovary (CHO) forward gene mutation assay (HGPRT locus) there were no consistent, statistically significant, reproducible or dosage-related increases in the frequency of 6-thioguanine resistant cells. There were no reproducible or dosage-related increases in sister chromatid exchanges in an in vitro test in CHO cells. An in vitro cytogenetics study in CHO cells showed no evidence for an increase in chromosomal aberrations on treatment with GA, either in the presence or absence of metabolic activation. In vivo, a mouse peripheral blood micronucleus test showed no increase in micronucleated polychromatophils at sampling times of 30, 48 and 72 h after acute gavage dosing with GA at 40, 80 and 125 mg kg(-1) (corresponding to 25, 50 and 85% of the LD(50)). The absence of an in vivo clastogenic potential was confirmed by no increase in chromosomal aberrations in a rat bone marrow cytogenetics study with sampling at 12, 24 and 48 h after acute gavage dosing with GA (12.5, 30 or 60 mg kg(-1) with males, and 7.5, 20 or 40 mg kg(-1) with females). Thus, in this series of tests, GA produced genotoxic effects in vitro only in a bacterial reverse mutation assay with no evidence for in vivo genotoxicity.