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Endpoint:
mechanistic studies
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Well-documented publication and acceptable for assessment. Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study addresses the mechanism of neurotoxicity of CS2 in rats, dosed by intraperitoneal injection. Particularly, its ability to covalently cross-link to a cytoskeletal protein of the erythrocytes, spectrin , is examined.The authors assess whether cross-linking of spectrin after exposure to CS2, can be used as a biomarker for neurotoxicity.
GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
neurotoxicity
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12
Route of administration:
intraperitoneal
Vehicle:
corn oil
Details on exposure:
Rats were dosed once daily by intraperitoneal injection with corn oil or CS2 in corn oil at 2 or 5 mmol/kg (total volume 0.15-0.4 ml) for periods of 21 and 42 days.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
21 or 42 d
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0, 2, 5 nmol/kg
Basis:
nominal conc.
Control animals:
yes, concurrent vehicle
Examinations:
The ability of the rats to return their hind limbs under their body after forced extension to the rear was examined. Body weights of the animals were recorded each week. Within 24 hr of the last treatment rats were exsanguinated under chloral hydrate anesthesia and sections of the muscular branch of the posterior tibial nerve were fixed using 4% glutaraldehyde in 0.1 M sodium cacodylate buffer, pH 7.2. Nerve sections were postfixed in 2% osmium tetroxide, dehydrated in graded alcohols and propylene oxide, and embedded in Epon. Thick sections were stained using toluidine blue.
Details on results:
No evidence of hind limb paralysis was observed. No axonal swellings were observed in any exposed group.

The SDS-PAGE showed two major bands in the region of 200 -250 kDa in all groups, that correspond to alpha- and beta-spectrin, and represented the proteins with the highest molecular weight in the controls. In the CS2 exposed groups, additional eluting proteins appeared in the 410 kDa region, as two distinct bands, with a more diffuse, less intensely staining region between the major bands. Based on the following peptide mapping, these two extra bands represent the spectrin dimer that failed to separate due to cross-linking. The selective base hydrolysis, suggested the presence of both thiourea and dithiocarbamate ester cross-linking structures in spectrin dimers. No spectrin dimer was detected in any of the control samples.

Conclusions:
The study reveals that CS2 exposure results in covalent cross-linking of erythrocyte spectrin in vivo, after intraperitoneal injection of rats.
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX.
Executive summary:

What follows is the original abstract of the publication with slight modifications

Covalent cross-linking of proteins by CS2 has been demonstrated in vitro and represents a potential mechanism for the toxicity of this compound. In the present investigation the ability of CS2 to cross-link proteins covalently in vivo is demonstrated using denaturing polyacrylamide gel electrophoresis. Intraperitoneal injection of CS2 in rats at 2 or 5 mmoL/kg for 21 or 42 days produced several high-molecular-weight (~410 kDa) proteins eluted from erythrocyte membranes which were not present in control animals. Limited proteolysis of the high-molecular-weight protein bands, monomeric alpha-spectrin, and monomeric beta-spectrin using endoproteinase glu-C, followed by peptide mapping on denaturing polyacrylamide gels, showed the high-molecular-weight proteins to be alpha, beta heterodimers. The production of multiple heterodimers exhibiting different distances of migration was consistent with the existence of several preferred sites for cross-linking. Evidence for the presence of dithiocarbamate ester and thiourea cross-linking structures in spectrin dimers was obtained using selective base hydrolysis. No spectrin dimer was detected in control animals, and dimer formation demonstrated a cumulative dose response in CS2-treated rats. The longevity of red blood cells, the cumulative dose response, and the stability of the cross-linking structures endows spectrin cross-linking with the potential to serve as a biomarker of chronic low-level exposures to CS2 and may provide a means to correlate pathological changes with existing methods of CS2 exposure monitoring. The ability of CS2 to covalently cross-link erythrocyte spectrin suggests that CS2 may also cross-link other proteins in vivo and supports covalent cross-linking of proteins as a possible molecular mechanism through which CS2 manifests toxicity. If so, then spectrin cross-linking may parallel cross-linking reactions in the axon and provide a sensitive, pre-neurotoxic biomarker of this molecular event.

 

Endpoint:
biochemical or cellular interactions
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The effects of carbon disulfide on the liver microsomal drug-metabolizing enzyme system and other enzyme activities were studied 1 hr after the oral administration of 3-300 mg/kg of CSZ in mice.
GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
acute toxicity: oral
Species:
mouse
Strain:
other: ddY
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Laboratory Animals, Japan
- Age at study initiation: 5 w
- Diet: ad libitum
- Water: ad libitum
Route of administration:
other: oral per oz
Vehicle:
olive oil
Details on exposure:
CS2 was freshly dissolved in olive oil and was given to mice at a volume of 0.05 ml/10 g bw.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Remarks:
Doses / Concentrations:
3-300 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on results:
Oral administration of CS2 did not exert any hepatotoxic effects, in contrast to the i.p. route. Following the oral administration of CS2, the liver microsomal cytochrome P-450 content and drug-metabolizing enzyme activities decreased rapidly, reaching the lowest levels at 1 hr, staying at this level for several hours, and then gradually reaching again the control levels by 24 hr. A dose-response relationship was observed. Changes, though at a lower extent, were already detectable after treatment with 3 mg/kg. After the repeated exposure of 2 weeks, the gross appearance of the liver was normal. The only alterations detected were in the levels of P-450 and drug-metabolizing enzymes, that showed a slight dose-dependent decrease 24 h after the last treatment. An additional experiment was conducted so as to test whether such effects show a cumulative trend. Half of the animals in each group were again treated with 30 mg/kg of CS2. It was demonstrated that this effect of CS2 was reversible and cumulative.

Oral administration of CS2 did not exert any hepatotoxic effects, in contrast to the i.p. route. Following the oral administration of CS2, the liver microsomal cytochrome P-450 content and drug-metabolizing enzyme activities decreased rapidly, reaching the lowest levels at 1 hr, staying at this level for several hours, and then gradually reaching again the control levels by 24 hr. A dose-response relationship was observed. Changes, though at a lower extent, were already detectable after treatment with 3 mg/kg. After the repeated exposure of 2 weeks, the gross appearance of the liver was normal. The only alterations detected were in the levels of P-450 and drug-metabolizing enzymes, that showed a slight dose-dependent decrease 24 h after the last treatment. An additional experiment was conducted so as to test whether such effects show a cumulative trend. Half of the animals in each group were again treated with 30 mg/kg of CS2. It was demonstrated that this effect of CS2 was reversible and cumulative.

Conclusions:
In this investigation it was demonstrated that CS2 may impair the liver drug-metabolizing system in mice after acute or subacute oral treatment with 3, 30, or 300 mg/kg bw; the effect was dose-dependent and it was prominent prior to pathological manifestations in the liver. The findings suggest that P-450 might be a selective site for CS2 action.
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX.
Executive summary:

What follows is the original abstract of the publication

The effects of carbon disulfide (CS2) on the liver microsomal drug-metabolizing enzyme system and other enzyme activities were studied 1 hr after the oral administration of 3-300 mg/kg of CS2 in mice. Considerable decreases in drug-metabolizing enzyme activities (such as hydroxylation of aniline, O-dealkylation of p-nitroanisole, 7-ethoxycoumarin and 7-ethoxyresorufin, and N-demethylation of N,N-dimethylaniline), NADPH-cytochrome P-450 reductase (but not NADPH-cytochrome c reductase), and P-450-associated peroxidase activities were already observed at 3 and 30 mg/kg of CS2, dose dependently. At the same dosage levels, the magnitudes of microsomal spectral changes induced by aniline and nicotinamide (type 2 substrates), but not those induced by hexobarbital and SKF-525A (type 1 substrates), were also reduced to a considerable extent. The degrees of these alterations were all greater than that of the measurable loss of P-450 content, i.e. the loss of functional activity of P-450 was much greater than simply expected from the apparent decrease in the hemoprotein content. Cytochrome b5 content and NADH-ferricyanide reductase activity were unchanged at 30 and 300 mg/kg of CS2, although NADH-cytochrome c reductase activity was increased at the latter dose. The following enzyme activities did not change significantly at up to 300 mg/kg of CS2: flavin-containing monooxygenase, UDP-glucuronyl transferase, glucose-6-phosphatase and heme oxygenase in microsomes, and glutathione S-transferases in the soluble fraction. Microsomal conjugated diene levels and liver glutathione content were also unchanged. These observations support the theory that P-450 is a sensitive and selective site for CS2 action, where CS2 itself is bioactivated. It was also shown that the loss of P-450 was reversible after a single, or repeated, administration of CS2.

Endpoint:
specific investigations: other studies
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Well-documented publication, acceptable for assessment Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX.
Qualifier:
no guideline followed
Principles of method if other than guideline:
CS2 effects on the structure or hemodynamics of the cardiovascular system were examined in male rats, that were exposed to vapours at 700 mg/m3, 6 h/d for 14 w. After the 14 w animals were anesthetized and electrocardiographs (ECG) were recorded, followed by hemodynamic tests.
GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
repeated dose toxicity: inhalation
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SPF, Charles River Kft, Budapest)
- Weight at study initiation: 285-335 g
- Housing: plastic cages, on steam-sterilized, hardwood shavings
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 40-70
Administration / exposur
Route of administration:
inhalation: vapour
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
6h/d for 14 w
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
222 ppm (700 mg/m3)
Basis:
nominal conc.
Control animals:
yes
Details on study design:
After the 14 w animals were anesthetized and electrocardiographs (ECG) were recorded, followed by hemodynamic tests.
Positive control:
.
Details on results:
CS2 exposure did not influence the food and water consumption. The body weights were decreased, while the relative weights of the heart, liver and kidneys were increased. CS2 treatment increased the arterial blood pressure, cardiac index and it decreased the cardiac output and blood flow for the kidneys and the lungs. The vascular resistance of the brain, lungs and kidneys was elevated. The ECG analysis revealed that CS2 administration affected significantly the pace-making and impulse-conducting system of the heart of the animals. No pathologic changes were detected in the organs examined.

CS2 exposure did not influence the food and water consumption. The body weights were decreased, while the relative weights of the heart, liver and kidneys were increased. CS2 treatment increased the arterial blood pressure, cardiac index and it decreased the cardiac output and blood flow for the kidneys and the lungs. The vascular resistance of the brain, lungs and kidneys was elevated. The ECG analysis revealed that CS2 administration affected significantly the pace-making and impulse-conducting system of the heart of the animals. No pathologic changes were detected in the organs examined.

Conclusions:
Subchronic CS2 exposure at 222 ppm, exerted cardio-depressive effects and hypertension in rats, which were manifested before the appearance of any histologic lesions in the brain, heart, lung, liver and kidneys.
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX.
Executive summary:

Carbon disulfide effects on the structure or hemodynamics of the cardiovascular system were examined. Male Sprague-Dawley rats were exposed to CS2 vapours at 222 ppm (700 mg/m3), 6 h/d for 14 w. Carbon disulfide treatment did not affect the food and fluid consumption of the animals, while it decreased body weight gain. CS2 increased arterial blood pressure and cardiac index, decreased their cardiac output, the fraction of the cardiac output, and blood flow for the kidneys and the lungs, and increased the relative heart, liver, and kidneys mass and the vascular resistance of the brain, lungs, and kidneys. With histological examinations no pathologic alterations were found in the organs studied. It was concluded that the early hemodynamic changes produced by carbon disulfide may play a significant role in the pathomechanism of the effects of the substance (hypertension, damage to the myocardium)

Endpoint:
mechanistic studies
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Well-documented publication, acceptable for assessment; data lacking regarding the chemical identity of the test material (source, analytical purity) Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX.
Qualifier:
no guideline available
Principles of method if other than guideline:
The effects of CS2 on the tissue catecholamine levels were examined. In order to get some insight in the underlying mechanism, potential inhibition of dopamine- β-hydroxylase (DBH) by CS2, via the formation of dithiocarbamate metabolites, was examined in vitro.
GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
basic toxicokinetics
repeated dose toxicity: inhalation
neurotoxicity
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Blue Spruce Farms, Altmont, N.Y.
- Weight at study initiation: 200 g
- Diet: ad libitum
- Water: ad libitum
Route of administration:
inhalation: vapour
Vehicle:
unchanged (no vehicle)
Details on exposure:
As described by McKenna & Di Stefano (1977; Carbon disulfide. I. The metabolism of inhaled carbon disulfide in the rat).
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
4 or 8 h
Remarks:
Doses / Concentrations:
0, 2000 mg/m3
Basis:
nominal conc.
Control animals:
yes, sham-exposed
Positive control:
no
Details on results:
In vivo results: Norepinephrine levels in the brain, heart and adrenal glands declined in a time-dependent manner.This was similar for epinephrine concentration in the adrenal glands. Adrenal and brain DA levels increased after 4 h , and decreased to control levels at 8 h. Cardiac dopamine could not be measured accurately by the method used. Brain norepinephrine levels were reached almost control levels 16 h postexposure.
In the in vitro study, CS2 exerted an inhibitory effect on the copper-requiring DBH. The other in vitro results are only mentioned in the executive summary.

In vivo results: Norepinephrine levels in the brain, heart and adrenal glands declined in a time-dependent manner.This was similar for epinephrine concentration in the adrenal glands. Adrenal and brain DA levels increased after 4 h , and decreased to control levels at 8 h. Cardiac dopamine could not be measured accurately by the method used. Brain norepinephrine levels were reached almost control levels 16 h postexposure.

In the in vitro study, CS2 exerted an inhibitory effect on the copper-requiring DBH. The other in vitro results are only mentioned in the executive summary.

Conclusions:
In the present study it has been demonstrated that acute CS2 exposure of rats to 634 ppm may exert changes in catecholamine levels in the heart, brain and adrenals. The exhibited inhibitory effect of CS2 on the activity of the copper-requiring enzyme dopamine-β-hydroxylase was associated with the formation of dithiocarbamates, which can create complexes with copper.
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX.
Executive summary:

What follows is the original abstract of the publication

Rats were exposed to carbon disulfide (CS2) vapor to study its effects on tissue catecholamine concentrations. Inhalation of CS2 for several hours produced depletion of brain, adrenal and cardiac norepinephrine as well as adrenal epinephrine concentrations. This was accompanied by an increase in dopamine concentration in the adrenals and brain. The observed alterations in tissue catecholamine concentrations in CS2-treated rats suggested that a primary effect of CS2 exposure is the inhibition of dopamine-β-hydroxylase (DBH). The ability of CS2 to react with endogenous amines has led to the hypothesis that inhibition of DBH may occur via the formation of dithiocarbamate metabolites which bind to enzymic copper. This hypothesis was tested in vitro with purified DBH and catecholamine storage granules prepared from bovine adrenal glands. CS2 had no effect on purified DBH. However, preincubation of the enzyme with CS2 and an amine or amino acid resulted in a significant decrease in DBH, activity. Synthesized dithiocarbamate derivatives of several amino acids were effective inhibitors of purified DBH. The inhibition decreased progressively with increasing Cu++concentration, and equimolar concentrations of Cu++and inhibitor were without effect, suggesting that the inhibition occurred through the binding of enzymic copper. The effects of CS2 and the amino acid dithiocarbamates on DBH were also compared in the medullary granule preparations CS2 treatment inhibited DBH more effectively than did equivalent concentrations of the dithiocarbamates. This observation suggests that CS2 diffuses rapidly across the granule membrane and reacts with intragranular catecholamines to form dithiocarbamates. Analysis of the intragranular content of CS2-treated preparations by gas chromatography provided evidence in support of this mechanism of action. The evidence led to the conclusion that inhibition of DBH activity by CS2 may be mediated by the action of dithiocarba­mates formed from endogenous amino acids and/or intragranular catecholamines.

Endpoint:
behavioural effects
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Ethanol/ Ethyl Alcohol is both reagents used in the manufacture of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
Qualifier:
no guideline followed
Principles of method if other than guideline:
Behavioral effects of ethanol inhalation were studied on two fixed-ratio (FR) liquid-reinforced schedules and a continuous reinforcement (CRF) schedule intracranial self-stimulation (SS) in rats. Exposure regimes ranged from short to long in one day then repeated short exposures for 5 days.
GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
acute toxicity: inhalation
Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 180-210g
- Housing: housed individually, stainless steel cages
- Food: controlled, see details of method.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 1°C
- Humidity: 55 ± 5%
- Photoperiod: 12hr light/12hr dark
Route of administration:
inhalation
Vehicle:
other: air in chamber
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation behavioural chamber ex Pradhan & Copeland. Glass chamber over a grid floor fitted with a metal plate accommodating a lever and liquid dipper. Individual animals exposed to multiple concentrations. Laboratory air was mixed with ethanol vapour generated from an evaporating flask then cooled back to ambient before entering the test chamber.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
15 minute sampling of chamber atmosphere. Samples analysed by gas chromatography.
Duration of treatment / exposure:
1x2 hour, 1x5 hour and 5x2 hour over 5 days. Not all tests were used for all exposure regimes.
Frequency of treatment:
one exposure per day
Remarks:
Doses / Concentrations:
2 hour exposures: 140, 161, 202 and 398ppm
Basis:
analytical conc.
used for FR liquid re-inforced behaviour study.
Remarks:
Doses / Concentrations:
five hour exposure: 140ppm
Basis:
analytical conc.
used for FR liquid re-inforced behaviour study.
Remarks:
Doses / Concentrations:
2 hrx5 exposure: 206ppm
Basis:
analytical conc.
used for FR liquid re-inforced behaviour study.
Remarks:
Doses / Concentrations:
2 hour exposures: 130, 373, 603, 1287ppm
Basis:
analytical conc.
used for self stimulationbehaviour study.
No. of animals per sex per dose:
6
Control animals:
other: animal response on previous day in air.
Details on study design:
See other information below.
Details on results:
FR behaviour: reinforcement behaviour dropped by a small but statistically significantly amount in the 15 minute exposure periods from 45mins onward and for exposures of 202ppm and above. There was no cumulative effect (exposure for 5 hours did not produce any effects not seen in the 2hr exposure.). In the daily repeat exposure, effects declined showing a developing tolerance to ethanol. SS: there was a decline in self stimulation behaviour at exposures of 600ppm and above but these were not statistically significant.
Blood ethanol concentrations following 2 hr exposure: 393ug/ml after 600ppm, 545ug/ml after 1200ppm. Data from the other exposures was presented graphically. The author of this summary fitted a curve to this data . Over this data range a polynomial of form BEC=-0.0002C^2 + 0.7335C fits with an correlation co-efficient R=0.9989 and where BEC is the blood ethanol concentration (mg/l) and C the inhalation concentration (ppm). A linear equation with slope 0.5237 fits with R=0.9816.
Conclusions:
Acute tolerance to ethanol was observed in these experiments, particularly in the FR-24 schedule. Ethanol inhalation can produce adequate blood concentrations in the rat so as to produce behavioral effects but these are transient.
Ethanol/ Ethyl Alcohol is both reagents used in the manufacture of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide

Executive summary:

Behavioral effects of ethanol vapour inhalation were studied on two fixed-ratio (FR) liquid feed-reinforced schedules and a continuous reinforcement schedule intracranial self-stimulation (SS) in rats. Exposure regimes were 2 and 5 hours and daily 2 hour exposures over 5 days. . In the FR-50 schedule , small but significant decreases of the rate (around 20% reduction) were observed at 202 ppm and above. However, these effects did not increase with increased exposure time and when repeated daily, they disappeared after 3 days showing a developing tolerance to ethanol. In the SS behavior study, there was a decline in self stimulation behaviour at exposures of 600ppm and above but these were not statistically significant. Blood ethanol concentrations were measured to be 393 micrograms/ml and 545 micrograms/ml after exposure to 600 ppm and 1200 ppm of ethanol respectively. Acute tolerance to ethanol was observed in these experiments, particularly in the FR-24 schedule, leading to the conclusion that inhalation can produce adequate blood concentrations in the rat so as to produce some behavioral effects but these are transient, even if exposure is continued.

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