A review of developmental and reproductive toxicity of CS2 and H2 S generated by the pesticide sodium tetrathiocarbonate.

BACKGROUND: Sodium tetrathiocarbonate (STTC) is an example of a pesticide that when prepared for use in aqueous solution releases two toxic products carbon disulfide (CS2 ) (active ingredient) and hydrogen sulfide (H2 S) in ambient air in equimolar concentrations resulting in potential exposure to workers and bystanders. CS2 and H2 S are pollutants that are generated from several pesticides as well as in industrial settings. METHODS: Registrant submitted reports and open literature studies for STTC, CS2 and H2 S were reviewed. Previous reports suggest that CS2 was a concern as a developmental and reproductive toxicant. H2 S was also examined since it is a neurotoxicant and potentially harmful to developing fetuses. RESULTS: STTC did not induce developmental or reproductive effects in animal studies. CS2 was a developmental neurobehavioral toxin in rat pups (inhalation no observed effect level [NOEL]=0.01 ppm). Reproductive effects occurred in male and female factory workers after CS2 exposure (NOEL=1 ppm). H2 S had developmental effects in rats at doses at or above those observed for nasal pathology (NOEL=10 ppm) but was not a reproductive or developmental toxin in humans. CONCLUSIONS: The database for CS2 indicates a strong potential for developmental neurotoxicity in animals at low doses but it is lacking in acceptable, well-performed studies. There is also a lack of studies performed with CS2 and H2 S as a mixture.

Biological monitoring of carbon disulphide and phthalate exposure in the contemporary rubber industry.

OBJECTIVES: We studied the range in urinary levels of 2-thiothiazolidine-4-carboxyl acid (TTCA), a metabolite of CS2 and phthalic acid (PA), a common metabolite of phthalates, across factories and departments in the contemporary rubber manufacturing industry. METHODS: Spot urine samples from 101 rubber workers employed in nine different factories were collected on Sunday and during the workweek on Tuesday, Wednesday and Thursday at approximately 4 pm. In total, 386 urine samples were successfully analyzed. RESULTS: Levels of both biomarkers increased significantly by a factor 2 (paired t-test P-value <0.05) during the working week as compared to the Sunday biomarker levels with absolute increases of approximately 70 microg/l and 5 micromol/mol creatinine for PA and TTCA, respectively. Levels in both biomarkers did not differ markedly between working days. Increases seemed to be restricted to specific factories and/or departments (e.g. molding and curing). CONCLUSIONS: The results of this study demonstrate that rubber workers in the contemporary rubber industry are exposed to phthalates and low levels of CS2 ( approximately 0.05 ppm) as measured by PA and TTCA, respectively. Exposures to both compounds are largely driven by specific circumstances in factories. Therefore, when estimating exposures to phthalates and CS2 detailed information should be collected on the type and amount of phthalate containing ester plasticizers, dithiocarbamates and thiurams used. Preferably, personal exposure data should be collected. In this case, biological monitoring seems a reasonable approach. However, in the case of PA attention should be given to individual background levels as this could lead to a substantial overestimation of the occupational contribution to total phthalate exposure.

Accumulation of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) among workers occupationally exposed to carbon disulfide for 1 week.

OBJECTIVES: To investigate if carbon disulfide (CS(2)) accumulates after a 1-week exposure period, and how the work-shift duration and exposure magnitude affects this accumulation for the workers in viscose rayon industry. METHODS: Six 8-h and seven 12-h workers in the spinning department historically known to be exposed to high air CS(2) were recruited as the exposed groups. Seven workers from other non-CS(2)-exposed departments were recruited as non-exposure controls. Exposure monitoring covered a full work shift with personal breathing zone monitoring. Urine was collected pre- and post-shift every day throughout the 5 consecutive days. 2-Thiothiazolidine-4-carboxylic acid levels in the urine (U-TTCA) were determined. RESULTS: No detectable values were found for airborne (<0.6 ppm) and urinary (<35 ng/ml) monitoring for the control groups. The exposure levels for a 12-h shift (11.3+/-1.47) (AM+/-S.D.) were significantly greater than for an 8-h shift (6.3+/-0.64). The linear accumulation trend for daily U-TTCA across the workdays was only significant for the 12-h shift at pre-shift. Statistical significance was found in the regression of the ratios for pre-shift U-TTCA to airborne CS(2) levels on the preceding day to the day of the exposure at pre-shift for a 12-h shift (r=0.98, P=0.02). CONCLUSIONS: The U-TTCA accumulation for occupational exposure to CS(2) was exposure-magnitude-dependent. The linear equations derived in this study indicated that the U-TTCA increment at pre-shift for each additional daily 12-h exposure, after an adjustment for the CS(2) exposure level, was 0.02 mg/g creatinine/ppm of CS(2). The long-term exposure response under such repeated and intermittent conditions should be noteworthy.

Alcohol and urinary 2-thiothiazolidine-4-carboxylic acid.

The aim of this work was to study the effect of alcohol on the excretion characteristics of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) in people exposed to carbon disulfide (CS(2)) and in non-exposed subjects. Ten male non-exposed volunteers consumed 150, or 250 ml, of liquor (38 degrees ) and the excretion dynamics of urinary TTCA were detected by HPLC. A questionnaire and urinary TTCA analyses were conducted in 152 male workers exposed to CS(2) and 60 male controls. CS(2) concentrations at the workplace were measured by GC. Results showed that urinary TTCA levels in non-exposed volunteers reached a high peak 3 h after drinking 150 ml liquor, which returned 12 h later to the levels before drinking; TTCA levels were in accordance with the quantity of alcohol consumed. There were increasing tendency of urine TTCA levels in workers exposed to different concentrations of CS(2) (10 ppm). TTCA levels in people with drinking habits seemed higher in the non-exposed group than in the exposed group, especially in those exposed over 10 ppm. The results suggest that the consumption of liquor in large quantities may interfere with the levels of urinary TTCA. Thus, in biomonitoring of CS(2) a suitable sampling time is important to avoid a biased estimation of CS(2) exposure.

Biological monitoring of carbon disulphide: kinetics of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) in exposed workers.

The objectives of this study was to establish the kinetics of urinary 2-thiothiazolidine-4-carboxylic acid (U-TTCA) for workers exposed to carbon disulphide (CS2) and to investigate the effects of volume and creatinine adjustment methods for urine measurement. Ten workers in the spinning department of a rayon factory were individually monitored for airborne CS2 concentrations, with consecutive urine samples collected for 24-38 hours after termination of exposure. The U-TTCA, urine volume and creatinine level were measured for each sample. First-order and biphasic kinetics were determined using the curve-fit method, for the measurement series. For the first-order kinetics linearity fit, statistically significant correlation coefficients of 0.74-0.98 and 0.86-0.99 were derived for the volume- and creatinine-adjusted methods, respectively. For the biphasic kinetics approach, the overall correlation coefficients were 0.544-0.999 and 0.171-0.999 for the first and second phases of the creatinine-adjusted method, respectively. A post-shift U-TTCA of 3.0 mg/g Cr. equivalent, 40% below the current BEI setting at nearly PEL exposed level, was found. In conclusion, first-order kinetic response was confirmed for U-ITCA. Both volume- and creatinine-based urine adjustment are satisfactory for TTCA assessment as a biomarker of individual CS2 exposure although the correlation for creatinine-based measurement was modestly superior to the volume-based analogue. Based on the results of this study,we recommend a re-evaluation of the current biological exposure index of 5 mg/g creatinine at a CS2 exposure level of 10 ppm.

The cross-sectional study of the health effects of occupational exposure to carbon disulfide in a Chinese viscose plant.

This article presents results of carbon disulfide exposure assessment in a Chinese viscose rayon factory and represents the cross-sectional study beginning phase of the occupational epidemiological project. The authors measured external exposure levels to carbon disulfide at a Chinese viscose rayon factory and monitored results as internal exposure indexes by testing urine samples of workers exposed to carbon disulfide levels. The rate at which carbon disulfide is metabolized by exposed subjects was demonstrated by 2-thio-thiazolidine-4-carboxylic acid (TTCA) concentrations in urine of exposed subjects, which was studied to determine best time points for internal exposure sampling. Carbon disulfide concentrations in the air of the workplace were analyzed with gas chromatography with flame photometric detector (GC-FPD); presence of TTCA in urine samples of subjects was determined using a modified high-performance liquid chromatography method. Kinetics of TTCA excretion was studied by analysis at different time points during and after exposure of workers to carbon disulfide. A total of 155 personal samples were obtained. Carbon disulfide concentration at staple viscose hall was found to be 13.72 +/- 1.12 mg/m3 in terms of geometric mean and geometric standard deviation. Carbon disulfide concentration at filament spinning hall was found to be 20.05 +/- 1.33 mg/m3. TTCA values of subjects at staple spinning hall were 1.18 +/- 0.43 and 1.07 +/- 0.38 mg/g creatinine for subjects working at filament spinning hall. The best time for TTCA sampling is at the end of the exposure-working shift.

Identification of a new urinary metabolite of carbon disulfide using an improved method for the determination of 2-thioxothiazolidine-4-carboxylic acid.

A new method is reported for the analysis of 2-thioxothiazolidine-4-carboxylic acid (TTCA) in urine that is amenable to automation and provides greatly simplified chromatograms. The method comprises the addition of tetrahydro-2-thioxo-2H-1,3-thiazine-4-carboxylic acid, which is chemically similar to TTCA, as internal standard, purification on an Oasis HLB solid-phase extraction column, and analysis by HPLC with UV detection. The limit of detection for TTCA was 40 pmol/mL of urine, recovery was 79.3 +/- 1.0%, and detection was linear over at least 3 orders of magnitude. In addition, during the analysis of urine samples from workers exposed to CS(2), a novel urinary metabolite of CS(2) was recognized. The new metabolite demonstrated a dose response, was present at approximately 30% the level of TTCA, and was charaterized to be 2-thioxothiazolidin-4-ylcarbonylglycine (TTCG). Administration of TTCG to rats resulted in excretion of TTCA suggesting that TTCG is a likely precursor of TTCA. Although urinary excretion of both TTCA and TTCG resulted from administration of captan, only TTCA was detected following administration of methyl isothiocyanate. The greater selectivity of TTCG suggests that co-analysis of TTCA and TTCG in urine may aid in differentiating exposures to CS(2), captan and isothiocyanates.

Carbon disulfide and hydrogen sulfide removal with a peat biofilter.

Simultaneous removal of H2S and CS2 was studied with a peat biofilter inoculated with a Thiobacillus strain that oxidizes both compounds in an acidic environment. Both sulfurous gases at concentrations below 600 mg S/m3 were efficiently removed, and the removal efficiencies were similar, 99%, with an empty bed retention time (EBRT) of more than 60 sec. Concentrations greater than 1300-5000 mg S/m3 caused overloading of the filter material, resulting in high H2SO4 production, accumulation of elemental sulfur, and reduced removal efficiency. The highest sulfur removal rate achieved was 4500 g-S/day/m3 filter material. These results indicate that peat is suitable as a biofilter material for the removal of a mixture of H2S and CS2 when concentrations of gases to be purified are low (less than 600 mg/m3), but it is still odorous and toxic to the environment and humans.

An analysis of a trickle-bed bioreactor: carbon disulfide removal.

An analysis of the local processes occurring in a trickle-bed bioreactor (TBB) with a first-order bioreaction shows that the identification of the TBB operating regime requires knowledge of the substrate concentration in the liquid phase. If the substrate liquid concentration is close to 0, the rate-controlling step is mass transfer at the gas-liquid interface; when it is close to the value in equilibrium with the gas phase, the controlling step is the phenomena occurring in the biofilm. CS2 removal rate data obtained in a TBB with a Thiobacilii consortia biofilm are analyzed to obtain the mass transfer and kinetic parameters, and to show that the bioreactor operates in a regime mainly controlled by mass transfer. A TBB model with two experimentally determined parameters is developed and used to show how the bioreactor size depends on the rate-limiting step, the absorption factor, the substrate fractional conversion, and on the gas and liquid contact pattern. Under certain conditions, the TBB size is independent of the flowing phases' contact pattern. The model effectively describes substrate gas and liquid concentration data for mass transfer and biodegradation rate controlled processes.

Carbon disulfide neurotoxicity in rats: II. Toxicokinetics.

Carbon disulfide (CS2) is an important industrial chemical widely used in the production of rayon, cellophane, fungicides and biocides. The uptake and elimination kinetics of CS2 was characterized for a single i.v. dose and for a single inhalation exposure. The uptake of CS2 into the blood was rapid with half times of 6 to 9 minutes. Elimination was relatively quick with terminal elimination half times of 41 to 77 minutes. The plateau CS2 blood concentration was lower in females than in males and lower in the male 50 ppm treatment group than would be predicted by linear dose proportionality compared to the 500 ppm and 800 ppm treatments. The CS2 blood concentration for the female 50 ppm group was below the limit of detection. The total and central compartment apparent volumes of distribution, 4.2 l/kg and .9 l/kg, were estimated from a single 50 mg/kg i.v. dose. The concentration of CS2 in blood resulting from repeated exposure, was investigated in a 13 week inhalation study. Blood samples were taken in rats previously exposed to 0, 50, 500, and 800 ppm CS2 for 2, 4, 8, or 13 weeks. The concentration of CS2 in the blood of male rats remained relatively constant throughout study. However the female 500 and 800 ppm groups showed a marked decrease over the course of the 13 week study. The concentration of CS2 in the blood from the 500 and 800 ppm groups of both sexes at all time points was higher compared to the 50 ppm group, than would be predicted by linear dose proportionality. The concentration of 2-thiothiazolidine-4-carboxylic acid in urine collected from the same animals lacked dose proportionality between the treatment groups at all time points. CS2 exposure caused dose-related decreases in body weight gain in both male and female rats.

Carbon disulphide absorption during xanthate reagent mixing in a gold mine concentrator.

A xanthate reagent mixer at a gold mine concentrator was exposed to carbon disulphide by extensive skin contamination with xanthate powder and solution during the reagent mixing process. Absorption of carbon disulphide was confirmed by the detection of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA). Drager colorimetric tube testing during subsequent mixing recorded a maximum concentration of at least 60 ppm carbon disulphide. An illness consisting of predominantly gastrointestinal symptoms began 20 h after the exposure. Although this may have been due to carbon disulphide toxicity this is by no means certain. The need for engineering controls, impervious protective clothing and full-face respirators with particulate and organic vapour cartridges is discussed. This episode occurred at another mine site, unrelated to Mount Isa Mines Limited.

Urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) as the major urinary marker of carbon disulfide vapor exposure in rats.

Male Sprague-Dawley rats (200-250 g; 60 per exposure group) were exposed to carbon disulfide (CS2) air concentrations of 0, 50, 150, and 500 ppm(v/v) for 6 hr/day, 5 days/week over six months. Following the exposures, nine rats from each exposure group had four sets of cumulated urines collected (between 0-8, 8-16, 16-24, and 24-48 hr). The urinary parameters measured were: 2-thiothiazolidine-4-carboxylic acid (TTCA), total thioethers (TE), and the compounds responsive to the iodine-azide (IA) test. Urinary TTCA elimination obeyed pseudo-first-order, one-compartment model kinetics of half-time (t0.5) 5.2 +/- 0.3 hr up to 16 hr of collection. The elimination of TE within 16 hr had a t0.5 of 8.5 +/- 0.6 hr. TTCA, IA, and TE were correlated highly in the first 16 hr. After 16 hr, the t0.5 for TE lengthened to 13.1 hr. At CS2 concentrations of 50, 150, and 500 ppm, the respective t0.5 for IA-responsive compounds were 12.6, 6.1, and 4.4 hr. TTCA had the highest correlation coefficient and p-value relative to CS2 exposure concentration, and also was the most sensitive, precise, and selective urinary marker.

Carbon disulphide. II. Investigations on the uptake of CS2 and the excretion of its metabolite 2-thiothiazolidine-4-carboxylic acid after occupational exposure.

The reported investigations on the uptake of carbon disulphide (CS2) and the excretion of its metabolite 2-thiothiazolidine-4-carboxylic acid (TTCA) were based on results from 403 personal air samples (352 passive and 51 active samples) and 362 TTCA determinations in biological material measured during a field study on the adverse effects due to CS2 exposure. The external exposure ranged from below the detection limit (0.2 ppm) to 66 ppm and the urinary TTCA excretion from below the detection limit (0.16 mg./l) to 33.4 mg/l. The excretion of TTCA in postshift urine related to creatinine and volume showed a linear correlation to the CS2 air concentration. On the basis of these results the influence on the internal exposure of physical work load, dermal exposure and individual parameters (age, Brocaindex, disturbed skin barrier) was evaluated. Correlations between the TTCA values in the postshift urine and the individually measured CS2 concentrations were carried out separately for individual departments and persons with and without indications of a disturbed skin barrier. In order to be able to judge the individual internal exposure related to external exposure, a personal quotient was formed from the TTCA level in the urine and the CS2 air concentration measured on the same day (relative internal exposure RIE index = TTCA mg/g creatinine/CS2 in ppm). On investigating interindividual differences, higher relative internal exposures were found in persons with a heavy physical work load and more intensive skin contact. It could be shown for a large group of persons exposed to CS2 that a pathological skin condition leads to an increase in the dermal penetration rate of hazardous substances.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of the biological exposure test "CS2 in urine"]. / Zu Problemen bei der Bewertung des biologischen Expositionstests "CS2 im Urin".

The necessity of integration of biological exposure tests, for example the BET "CS2 in urine", is shown in connection with the activities of the works doctor in order to evaluate the individual health risk of the exposed workers. The possibilities on principle for the tests are discussed Topical biological threshold limit values for CS2 in urine on the base of validity studies are presented. In addition a special intervention regime.

[Inhalation of carbon disulfide--studies of carbon disulfide uptake in dynamic dose administration lasting 4 hours]. / Zur inhalativen Aufnahme von Schwefelkohlenstoff--Untersuchungen zur Schwefelkohlenstoffaufnahme bei dynamischem Dosisangebot über 4 Stunden.

Experiments of CS2 inhalation were accomplished with both constant loads at the ergometer combined with constant concentration of inhalation and discontinuous offered doses combined with various physical loads during 240 minutes. The conditions of the experiment were approximated to the real conditions of exposure at a viscose rayon fibres production. The intake of CS2 increased by 20 percent in case of various conditions. The cause of this finding is a different adaptation during the intake phase in opposition to the breath off phase. The profile of the exposure affected by changed CS2 concentrations and various physical activities is decisive for the intake dosage and thus for the health risk.