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EC number: 205-443-5 | CAS number: 140-93-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Effects on fertility
Link to relevant study records
- Endpoint:
- extended one-generation reproductive toxicity - with developmental neurotoxicity (Cohorts 1A, 1B without extension, 2A and 2B)
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Remarks:
- Carbon disulphide has been demonstrated to form during hydrolysis in gastric fluid. Any oral toxicity on the xanthate needs to consider oral effects of carbon disulphide and the corresponding alcohol
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Carbon disulphide has been demonstrated to form during hydrolysis in gastric fluid.
Any oral toxicity on the xanthate needs to consider oral effects of carbon disulphide and the corresponding alcohol
Data access has been requested, but this summary is extracted from disseminated information published by ECHA
Further animal testing on the xanthate cannot be justified - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- exposure-related information
- Remarks:
- Due to rapid hydrolysis in gastric fluid, oral ingestion of xanthates will result in formation of carbon disulphide
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- Once daily 7 days a week.
- Details on mating procedure:
- Cohabitation 1:1
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentrations of 91%, 95% and 89% were determined
Results are therefore expressed as nominal - Duration of treatment / exposure:
- F0-males minimum of 11 weeks, including 10 weeks prior to mating and during the mating period,
F0-females minimum of 16 weeks, including 10 weeks prior to mating, and at least 21 days after delivery, Females were not dosed during littering.
During lactation (up to PND 21), pups were not treated directly
From weaning onwards (PND 21), F1-animals of Cohorts 1A, 1B, 1C and 2A dosed - Frequency of treatment:
- Daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 1.2 mg/kg bw/day (nominal)
- Dose / conc.:
- 12 mg/kg bw/day (nominal)
- Dose / conc.:
- 120 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- At least daily observations
Weekly weight assessment
Food consumption assessed for each group
Blood chemistry assessed in parental animals - Oestrous cyclicity (parental animals):
- Yes
- Sperm parameters (parental animals):
- Checked on necropsy as part of post-mortum examinations
- Litter observations:
- Number and vigour
- Postmortem examinations (parental animals):
- Full necropsy and gross examination of organs at scheduled termination
- Postmortem examinations (offspring):
- Pups found dead and at scheduled termination
- Statistics:
- Statistical analysis was applied as needed
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Slight salivation in response to treatment, predominantly at highest dose.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 120 mg/kg/day, body weights / body weight gain of males and females were slightly decreased
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Minor changes in white blood cell count and reticulocyte count (males) but not considered significant
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Minor but statistically significant effects seen in the top dose.
The changes were not considered to be of toxicological significance. - Endocrine findings:
- not examined
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Effects seen at top dose, confirming maximum tolerated dose was used
Minor changes in spleen, thymus and eyes, with the effect on eyes considered adverse - Histopathological findings: neoplastic:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A small number of pairs in all treatment and control groups failed to reproduce.
This was in line with background observations and not treatment related - Dose descriptor:
- NOAEL
- Effect level:
- ca. 12 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- ophthalmological examination
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 120 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- ophthalmological examination
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 120 mg/kg bw/day (nominal)
- System:
- eye
- Organ:
- retina
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- Mortality across groups not considered to be significantly different to historical levels
No treatment related effects - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significantly decreased in males at 120 mg/kg/day from Day 8
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Sexual maturation:
- no effects observed
- Anogenital distance (AGD):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Minimal changes, perhaps based on actual size of pups in highest dose group
- Nipple retention in male pups:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Decrease in brain weight and spleen, male and female at higher dose level
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Effects seen in top dose group, including significant effect on eyes
Other findings not considered adverse - Behaviour (functional findings):
- no effects observed
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- ca. 12 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- Dose descriptor:
- LOAEL
- Generation:
- F1
- Effect level:
- ca. 120 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- Critical effects observed:
- yes
- System:
- central nervous system
- Organ:
- brain
- Reproductive effects observed:
- no
- Conclusions:
- Animals were treated at up to the maximum tolerated dose with some parental toxicity observed.
No reproductive or developmental effects were seen, other than a slight reduction in size of the young in the highest treatment group. - Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on test type
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Well documented GLP study, that provides important information on reproductive and developmental toxic effects of the substance. However, only female animals of F0 (not male) were exposed to CS2 and examined for reproductive effects. Developmental effects were examined in F1.
- Justification for type of information:
- Read-across from key metabolite, carbon disulphide
Carbon disulphide has been demonstrated to form during hydrolysis in gastric fluid.
Any inhalation toxicity on the xanthate needs to consider inhalation effects of carbon disulphide and the corresponding alcohol
Further animal testing on the xanthate cannot be justified - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Female rats were exposed to CS2 by whole body inhalation for 6 h daily for 14 days prior mating, during mating and until gestation day 19. Potential adverse effects on gonadal function, estrous cycles, conception rates, perturition and lactation of the F0 maternal generation were examined. Viability, growth and development of the F1 litters were also assessed.
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River breeding Laboratories, Mischigan
- Age at study initiation: (P) 104 days
- Weight at study initiation: Females: 215-300 g
- Housing: individually, clean stainless stell wire-mesh cages suspended above cage-board till gaestation day 19; after mating the females were put to plastic maternity cages with nesting material, ground corn cob bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22.8
- Humidity (%): 28-76
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The test atmospheres was generated as vapors by introducing liquid carbon diaulfide into 1/4 J Air Atomizers (nebulizers) fitted with Model 1050 Fluid Caps and Model 84 Air Caps (Spraying Systems, Inc.). The air atomizer assemblies were located in the rear wall of the tangential turret head of each exposure chamber at a 90 degree angle to the direction of mass air flow. Liquid test material feed to the air atomizers was accomplished by use of Harvard Apparatus Co., Inc. Model 975 Compact Infmion Pumps. A positive flow of dried air was introduced to the air atomizers at a rate of approximately 6 liters per minute to aid in the complete vaporization of the test material.
- Temperature, humidity: 22 ± 2, 40-70%,
- Air flow rate: 12-15 changes/hour - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Proof of mating was confirmed by the presence of sperm on the vaginal smear or a vaginal copulatory plug, referred to as day 0 of gestation
- After 10 days of unsuccessful pairing replacement of first male by another male with proven fertility took place.
- Further matings after two unsuccessful attempts: no
- After successful mating each pregnant female was caged as described above - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 6 h
- Frequency of treatment:
- daily
- Details on study schedule:
- The parental animals were exposed for at least 14 days and thereafter, they were paired with unexposed males. Exposure continued throughout mating until the 19th day of gestation.
- Age at mating of the mated female animals in the study: 17 weeks - Remarks:
- Doses / Concentrations:
389, 777, 1554 mg/m3 (125, 250, 500 ppm)
Basis:
other: target concentrations - No. of animals per sex per dose:
- 15, 24 in the control group
- Control animals:
- yes
- Parental animals: Observations and examinations:
- CLINICAL OBSERVATIONS AND MORTALITY
- Time schedule: moratlity and moribundity were observed twice daily; detailed clinical observations were recorded daily during the treatment period (before and after exposure). After treatment period clinical observations were recorded weekly.
BODY WEIGHT: Yes
- Time schedule for examinations: weekly till mating; after mating on gestation days 0, 6, 9, 12, 15, and 20 and on lactation days 0, 3, 6, 9, 15 and 21.
FOOD CONSUMPTION :
- Food consumption for each animal determined: weekly, gestation or lactation body weights - Oestrous cyclicity (parental animals):
- Vaginal smears were evaluated 10 days before CS2 administration and throughout the 14 day pre-pairing exposure period. During mating smearing continued until evidence of copulation.
- Sperm parameters (parental animals):
- not examined
- Litter observations:
- STANDARDISATION OF LITTERS
- yes, maximum of 10 pups/litter, 5/sex when possible randomly selected; excess pups were killed and discarded on lactation day 4.
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities, physical development: pinnal detachment, incisor eruption, palpebral seperation, testicular descent, vaginal patency
GROSS EXAMINATION OF DEAD PUPS: yes - Postmortem examinations (parental animals):
- SACRIFICE
- Maternal animals: All Fo female rats with viable pups were killed on lactation day 21. The females that failed to deliver were also sacrificed, on post coital day 25. Females with total litter loss were sacrificed within 24 h.
GROSS NECROPSY
- Complete gross necropsy performed including examinations of the abdominal, thoracic, and pelvic cavities
HISTOPATHOLOGY
Tissues were examined only when deemed necessary after the gross necropsy - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring were sacrificed on lactation day 42.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination)
Pinnal detachment: started on lactation day 4 and continued daily until the pup had both pinnae detached
Incisor eruption: incisors were xhecked on lactation day 9
Palpebral seperation: started on lactation day 13 and continued until both eyelids were seperated
Testicular descent: from lactation day 25, the day were the testis apperared in the scotrum was recorded
Vaginal patency: on day 30 (open vaginal lumen)
GROSS NECROPSY
- Gross necropsy performed
HISTOPATHOLOGY / ORGAN WEIGTHS
Tissues were examined only when deemed necessary after the gross necropsy - Statistics:
- Two-tailed tests (significance level of 5%): Chi-square test with Yates' correction factor and one-way ANOVA with Dunett's test
- Reproductive indices:
- Fertility index (%): No of females paired resulting in pregnancy/total No of females paired with males
- Offspring viability indices:
- Each litter was examined daily for survival and all deaths were recorded. Livebirth index (%): No of viable pups at birth/No of implantation sites
- Clinical signs:
- effects observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- not examined
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not examined
- Description (incidence and severity):
- female animals
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEC
- Effect level:
- 250 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEC
- Effect level:
- 500 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: reproductive function and performance
- Dose descriptor:
- NOAEC
- Effect level:
- 777 mg/m³ air
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEC
- Effect level:
- 1 554 mg/m³ air
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: reproductive function and performance
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings:
- not examined
- Dose descriptor:
- NOAEC
- Generation:
- F1
- Effect level:
- 250 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: overall effects
- Reproductive effects observed:
- not specified
- Conclusions:
- No effects were observed on the reproductive function and reproductive performance of the animals at all concentration levels. Signs of maternal (body weight loss, dystocia) and neonatal (mortality of the pups, decreased viability, decreased litter size) toxicity were exerted by exposure to CS2 in a concentration of 500 ppm.
Read-across from key metabolite, carbon disulphide
Carbon disulphide has been demonstrated to form during hydrolysis in gastric fluid.
Any inhalation toxicity on the xanthate needs to consider inhalation effects of carbon disulphide and the corresponding alcohol
Further animal testing on the xanthate cannot be justified - Executive summary:
In the present study carbon disulfide vapours were administered to 15 Sprague-Dawley female rats/dose via whole body inhalation at dose levels of 125, 250 and 500 ppm (389, 777, 1554 mg/m3) for 14 days before mating, 6 h/day. Twenty- four animals were used as controls and were exposed to clean filtered air. Thereafter, they were paired with unexposed males and exposure to CS2 continued throughout mating and until the 19th day of gestation. The animals were allowed to deliver normally and they were sacrificed on lactation day 21. The pups were sacrificed on lactation day 42. Inhalation of CS2 by Fo maternal animals at a level of 500 ppm elicited maternal toxicity (clinical signs, gestational body weight and food consumption decreases and indications of dystocia) as well as neonatal toxicity (increased pup mortality, decreased pup viability and decreased live litter size). No adverse effects were noted in Fo maternal animals or F1 pups at the 125 and 250 ppm levels. No effects were observed on the reproductive function and performance of the animals at all concentration levels. Based on these results, the NOAEC for maternal toxicity and neonatal toxicity was considered to be 250 ppm (777 mg/m3), while the NOAEC for reproduction toxicity was 500 ppm (1554 mg/m3).
Referenceopen allclose all
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): no significant effects detected on the mean weekly body weight or body weight gain and weekly food consumption (evaluated as g/animal/day and g/kg/day). The same was observed during the lactation period measuremnts. Throughout gestation body weights were significantly reduced at the highest concentration group, while food consumption appeared slightly affected at the same group during days 15-20.
REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS): variations occured in all study groups; the regularity and duration of estrous were not affected by CS2 exposure
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS): not affected by CS2 exposure. Female mating indices were 100% for the control group and the concentrations of 125 and 25 ppm, and 93.3% for the 500 ppm, while fertility indices were 87.5 %, 93.3%, 80% and 80%, respectively. The 80% was very common among the historical control data of the laboratory.
GESTATION: apparent signs of dystocia were observed in two females at the highest concentration group
GROSS PATHOLOGY (PARENTAL ANIMALS)
Females which failed to deliver: 3, 1, 3 and 2 animals in the control, 125, 250 and 500 ppm groups, respectively, were sacrificed on post-mating day 25 and one female of the last group on day 15. The animals were nongravid and internally normal.
Females with total litter loss: three females in the 500 ppm group, on lactation day 3. Two of them were internally normal, while one had pale eyes, kidneys and liver, as well as irregularly shaped white areas on all lobes of the liver.
Females that deliverd and killed on lactation day 21: no treatment-related findings
CLINICAL SIGNS (OFFSPRING): the general physical conditions in all F1 pups was similar to the controls.
BODY WEIGHT (OFFSPRING): a non statistically significant difference in mean size of live litters; still biologically significant according to the authors. No significant differences detected on mean body weights of the pups through lactation day 42.
PHYSICAL DEVELOPMENT: pinnal detachment, incisor eruption, palpebral seperation, testicular descent and vaginal patency were not affected in any of the pups, due to maternal exposure to CS2.
SEX RATIOS (OFFSPRING): not affected
GROSS PATHOLOGY (OFFSPRING): port mortem examinations of pups found dead were (in 2 pups of the 500 ppm group) dark red lungs, red foamy contents in the trachea, red fluid contents in the esophagus and red contents in the stomach.Dark red lungs and a reddened cortico-medullary junction in each kidney were noted for one pup each in the 250 and 500 pprn groups. One control pup died as a result of a water system malfunction; this pup was internally normal. With the exception of the presence or absence of milk in the stomach, all other remarkable post mortem findings involved malformations and variations. The abnormalities observed did not indicate any specific pattern of maldevelopment. Regarding the pups that were sacrificed on lactation day 42, no treatment related findings were observed.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 120 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 777 mg/m³
- Study duration:
- subchronic
- Experimental exposure time per week (hours/week):
- 42
- Species:
- rat
Effect on fertility: via dermal route
- Endpoint conclusion:
- no adverse effect observed
Effects on developmental toxicity
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Remarks:
- Read-across from key metabolite, carbon disulphide
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Carbon disulphide has been demonstrated to form during hydrolysis in gastric fluid.
Any oral toxicity on the xanthate needs to consider oral effects of carbon disulphide and the corresponding alcohol
Data access has been requested, but this summary is extracted from disseminated information published by ECHA
Further animal testing on the xanthate cannot be justified - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- exposure-related information
- Remarks:
- Due to rapid hydrolysis in gastric fluid, oral ingestion of xanthates will result in formation of carbon disulphide
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Remarks:
- Pre-dates widespread introduction of GLP Data set considered valid
- Limit test:
- no
- Species:
- rat
- Strain:
- other: CD
- Details on test animals or test system and environmental conditions:
- Age 8 - 12 weeks at start of study
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY)
- Age at study initiation: 8-12 weeks
- Housing: solid bottoom polypropylene or polycarbonate cages with stainless steel wire lids
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 14 days quarantine period
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-20
- Humidity (%): 52-77
- Air changes (per hr): 12-14
- Photoperiod (hrs dark / hrs light): 12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: overnight
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- Gestation day 6 to 15
- Frequency of treatment:
- Daily
- Duration of test:
- From gestation day 6 to 15
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Dose / conc.:
- 400 mg/kg bw/day (nominal)
- Dose / conc.:
- 600 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 22-27 (in total; two replicates)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on a preliminary toxicity study performed. The doses applied were: 0, 10, 50, 100 and 200 mg/kg bw/day
- Maternal examinations:
- CLINICAL OBSERVATIONS: Yes
- Time schedule: before exposure, 0 and 4 h after exposure
BODY WEIGHT: Yes
- Time schedule for examinations: gestation day 0, 6 through 15 (prior to daily dosing) and 20 (immediately after sacrifice)
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organ weights measured: liver, gravide uterine
- Status of uterine implantation sites were examined (i.e. number of implants, resorptions, dead fetuses and live fetuses) - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Blood sampling:
- Not specified
- Fetal examinations:
- Yes; external, visceral, skeletal and head
The following observations were recorded: live litter size, individual body weight, sex and gross morphological abnormalities
- External examinations: Yes
- Visceral examinations: Yes, all live fetuses
- Skeletal examinations: Yes, all per litter
- Head examinations: Yes, half per litter - Statistics:
- Non-parametric statistics, Kruskal-Wallis test, ANOVA, Mann-Whitney U test, Jonckheere's test, one-tailed Fischer's exact test, two-way ANOVA design, William's test, Dunnett's test
- Historical control data:
- Not specified
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Lethargy, ataxia, abnormal posture and rough coat
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One female, mid dose
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Decrease in body weight for highest doses
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Endocrine findings:
- not examined
- Urinalysis findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased liver weights in higher dose groups
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not examined
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Substance-treated animals exerted clinical signs of toxicity: lehtargy, ataxia, abnormal posture, rigidity and/or paralysis of the hindlimbs, and rough or erect coat. No deaths were observed, except for 1 (1/25, 4%) animal at the 400 mg/kg bw dose level. After sacrifice pregnacy was confirmed in 92%, 82.8%, 81.5%, 92.3, and 100% of females in the control, 100, 200, 400 and 600 mg/kg bw/ day groups, respectively. Maternal body weights were depressed significantly on gestation days 11, 15 and 20 for the groups exposed to the last two doses, when compared to the controls. For the dose groups of 200, 400 and 600 mg/kg bw/day, a significant decrease in absolute body weight gain was observed during treatment. Gravid uterine weights showed a dose-consistent decreasing trend; still, not significant. Larger relative liver weights were measured in the two high dose groups. - Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- organ weights and organ / body weight ratios
- Remarks on result:
- other: Toxicological significance of maternal effects not specified
- Abnormalities:
- not specified
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Weight decrease in highest dose groups
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced weights of litters at higher doses, mirroring maternal effect
- Changes in postnatal survival:
- no effects observed
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Across various dose levels and within historical control
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Across various dose levels and within historical control
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Across various dose levels and within historical control
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes. Remark: fetal toxicity, but no teratogenic effects
Details on embryotoxic / teratogenic effects:
No statistically signifcant changes were observed in: implantation sites/litter, proportion of litters with resorbed, dead, nonlive or affected fettuses, number of live fetuses/live litter, % of males/live litter. Average fetal body weight/litter was decreased significantly in both sexes for the dose groups of 200, 400, and 600 mg/kg bw. The percent of fetuses malformed per litter (but not the proportion of litters with one or more malformed fetuses) and the percent of females malformed per litter was significantly different across the groups. However, a clear dose-related trend was not observed. The percent of of malformed fetuses declined at the high dose group (0.53%) in comparison to the control (~5%) and no individual group showed a significant difference when compared to the control. What follows is stated in the report, with some modifications: Four fetuses exhibited malformations which had not been previously observed in historical control fetuses. These anomalies included (1) branched rib observed in one fetus with multiple skeletal defects, edema and low body weight (2.32 g) in the 100 mg/kg/day CS2 group; (2) micromelia observed in one fetus (200 mg/kg/day CS2 group), with low body weight (2.58 g), edema and bilateral anophthalmia, (3) constricted tail in one fetus (200 mg/kg/day CS group) with low body weight (2.95 g), and (4) displaced ovaries, fused kidneys and missing adrenals in one fetus with low body weight (2.32 g) and multiple skeletal malformations in the 400 mg/kg/day CS2 group. - Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
- Abnormalities:
- effects observed, non-treatment-related
- Localisation:
- other: Various changes - no obvious significance
- Description (incidence and severity):
- Various effects observed but within historical levels.
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 200 mg/kg bw/day
- Treatment related:
- yes
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Conclusions:
- Oral treatment produced dose-related maternal and foetal toxicity at 200 mg/kg bw/day or higher.
There was no increase in the incidence of malformed foetuses.
Carbon disulfide oral gavage treatment produced dose-related maternal and fetal toxicity when administered in CD rats at doses including and above 200 mg/kg bw/daily, but did not increase the incidence of malformed fetuses. - Executive summary:
Carbon disulfide (CS2), was evaluated for teratogenic effects in timed-pregnant CD rats. The following doses were administered: 0, 100, 200, 400 and 600 mg/kg/day in corn oil by gavage, in a volume of 5 ml/kg bw, on gestational days (gd) 6 to 15. All animals were sacrificed on gestation day 20. The gravid uterus for each dam was weighed and the number of implantation sites, and live, dead or resorbed fetuses were recorded. All live fetuses were weighed and examined for external, visceral and skeletal malformations. For the dose groups of 200, 400 and 600 mg/kg bw/day, a significant decrease in absolute maternal body weight gain was observed during treatment. Gravid uterine weights showed a dose-consistent decreasing trend; still, not significant. Larger relative liver weights were measured in the two high dose groups. Fetal body weights were decreased in rats exposed to 200 mg/kg bw/day and above.
There was no compound-related increase in malformations of the offspring.
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Remarks:
- Read-across from key metabolite, carbon disulphide
- Adequacy of study:
- key study
- 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 has been demonstrated to form during hydrolysis in gastric fluid.
Any oral toxicity on the xanthate needs to consider oral effects of carbon disulphide and the corresponding alcohol
Data access has been requested, but this summary is extracted from disseminated information published by ECHA
Further animal testing on the xanthate cannot be justified - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- animals were not exposed to CS2 throught the whole gestation period, but only from gestation day 6 to 18.
- GLP compliance:
- not specified
- Limit test:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazleton, Research Animals, Denver, Pennsylvania
- Age at study initiation: 5.5 to 7 months
- Weight at study initiation:
- Diet (e.g. ad libitum): on a restricted basis to avoid enteritis (based on the advice of the supplier)
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature: 65 ±5 F
- Humidity (%): 55±15
- Photoperiod (hrs dark / hrs light): 12 - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Carbon disulfide atmospheres were generated by nebulization of liquid carbon disulfide into a 1.2 cubic meter stainless steel and glass plenum. The aerosol was allowed to evaporate, and the carbon disulfide vapor was delivered to the exposure chambers. The delivery apparatus for the inhalation chambers was set up to bypass the chambers until the target concentration was reached. The target concentration used to develop subsequent exposure levels was based on the highest exposure level, and subsequent exposure levels were produced by dilution with HEPA filtered air. Chamber concentrations were controlled by adjustment of the ratio of dilution air to carbon disulfide vapor. The target concentration was produced and maintained at a stable level for approximately 15 minutes prior to incorporation into the air flow entering the exposure chambers. Carbon disulfide vapor used to obtain the target concentration bypassed the exposure chambers until the appropriate concentration was reached at which time the air flow containing the carbon disulfide vapor was routed into one of the five exposure chambers. The 0 ppm control chamber received HEPA filtered air only.
The exhaust from the exposure chambers was delivered to an activated charcoal collection system, which removed carbon disulfide vapor from the exhaust chamber air prior to venting the air to the outside. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Monitored by infrared spectrophotometry. The mean chamber concentration for each exposure level was within the required 10% relative standard deviation for both the pre-exposure and exposure periods.
- Details on mating procedure:
- - Impregnation procedure: natural insemination (gestation day 0) at the vendor's facility
- Duration of treatment / exposure:
- 6 h/day for 12 days (gestation days 6-18)
- Frequency of treatment:
- daily
- Dose / conc.:
- 100 ppm
- Dose / conc.:
- 300 ppm
- Dose / conc.:
- 1 000 ppm
- Dose / conc.:
- 3 000 ppm
- No. of animals per sex per dose:
- 24
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: based on dose range finding study were 100, 300, 1000 or 3000 ppm were tested. Exposure to 3000 ppm was lethal to rabbits. Surviving animals in the remaining exposure levels were euthanitized on gestation day 29, cesarean sections were performed, and uterine contents were evaluated. Exposure to 1000 ppm of carbon disulfide did not produce overt maternal toxicity, and only a transient exposure-related anoxia was suggested. However, it produced significant embryo and fetal toxicity. From these data, concentrations of carbon disulfide were selected for the main study.
- Maternal examinations:
- CLINICAL OBSERVATIONS: Yes
- Time schedule: at least twice a day; prior to, during and following exposure period to gestation day 29
BODY WEIGHT: Yes
- Time schedule for examinations: on gestation day 0, 5, 6, 9, 12, 15, 18, 19 and 29
HEMATOLOGY: 10 animals per group; blood was collected on gestation days 6, 8, 11 and 19; the following parameters were examined: reciculocyte count, total hematology count, white blood cell differential, methemoglobin, hematocrit, and packed cell volume (PCV).
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29; cesarian sections were performed - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: yes
- Number of late resorptions: yes - Fetal examinations:
- All fetuses were examined for gross visceral , skeletal and cephalic malformations. Enhanced fetal evaluations included a double stain to evaluate skeletal and cartilaginous malformations. In addition, cephalic evaluations were conducted on all viable fetuses based on results from the dosage range-finding study.
- Statistics:
- ANOVA, Dunett's test, Fischer's exact test, Chi-Square test, Kruskal- Wallis test
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
see below in section 'any other information on results incl. tables' - Dose descriptor:
- NOAEC
- Effect level:
- 300 ppm
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEC
- Effect level:
- 600 ppm
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEC
- Effect level:
- 948 mg/m³ air
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEC
- Effect level:
- 1 896 mg/m³ air
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Abnormalities:
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Mean corpora lutea, mean crown-rump measurements, and mean number of implantations were not statistically different from the controls. Preimplantation losses were statistically different when compared to the 0 ppm control exposure level for the 100 ppm and 1200 ppm exposure groups. Because the animals were not exposed during the preimplantation period (Gestation Days 0-5), these data were not considered biologically significant. The fetal sex ratio was comparable among all treatment groups.
Postimplantation losses (resorptions and dead fetuses) in the 600 and 1200 ppm exposure groups were statistically different from the 0 ppm control exposure group. Postimplantation losses in the 600 ppm exposure group of 0.64 ± 1.00 were significantly higher when compared to the control 0 ppm exposure group. Accordingly, the number of live fetuses observed in this exposure group was statistically reduced when compared to the control group. Postimplantation loss in the 1200 ppm exposure group was 7.00 ± 3.94 as compared to the 0 ppm group loss of 0.30 ± 0.63.
Dead fetuses were observed in the 0, 100, and 600 ppm exposure groups; yet this was not considered a treatment-related finding because dead fetuses were observed in the control group, and none was observed in the 60, 300, or 1200 ppm exposure groups.
Mean fetal body weights were statistically lower in groups of 600 and 1200 ppm. Two litters of 22 in the 600 ppm group and 14 litters of 21 in the 1200 ppm group consisted of implantation sites with no live fetuses, i.e., the litters consisted exclusively of resorptions. Therefore, only 20 litters from the 600 ppm group and 7 litters from the 1200 ppm group had viable fetuses examined for visceral, skeletal, and cephalic malformations.
Visceral, skeletal and external examinations are summarized in Tables 7, 9 and 11, respectively. The total incidence of visceral and skeletal malformations was statistically higher in the 1200 ppm group (hydrocephaly, right-sided esophagus, absent right subclavian artery, swollen sublingual salivary glands, malformed stomach, small thyroid and parathyroid, abnormal caudal vertebrae, fused sternebrae, and split sternebrae). However, the incidence of any specific skeletal or visceral malformation was not significant. - Dose descriptor:
- NOAEC
- Effect level:
- 300 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: carbon disulfide was embryotoxic, developmentally toxic at exposure levels of 300 ppm (948 mg/m3) and above,
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- In the study of PAI (Pathology Associates, Inc.). 1991, carbon disulfide was embryotoxic, developmentally toxic at exposure levels of 300 ppm (948 mg/m3) and above, while overt maternal toxicity was observed only at the 1200 ppm exposure level.
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates.Sodium Isopropyl Xanthate (SIPX) 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 Sodium Isopropyl Xanthate (SIPX) - Executive summary:
In this developmental toxicity study, pregnant rabbits in groups of 24 were exposed to 0, 60, 100, 300, 600, 1200 ppm carbon disulfide 6 hours per day on days 6-18 of gestation. In dams exposed to 1200 ppm, statistically significant decreases in maternal weight gain and clinical signs of toxicity including ataxia, low food consumption, labored respiration, wheezing, tremors, and abortion with bloody excretion involving the death of two animals, were observed. No exposure-related signs of maternal toxicity were observed in the other dose groups. Post implantation loss had a significantly higher incidence in exposure groups of 600 or 1200 ppm. Total resorption was observed in 2/22 and 14/21 litters of the 600 ppm and 1200 ppm exposure groups, respectively. Mean fetal body weight was significantly reduced in the 600 and 1200 ppm exposure groups. In the 1200 ppm group, the total incidence of skeletal and visceral malformations was significantly increased; however, no single malformation accounted for this increase. In the lower dose groups, significant increases in skeletal malformations were observed in the incidences of rudimentary 13th ribs, extra ribs, extrathoracic vertebrae, or hypoplastic pubis. The malformations in the lower dose groups did not appear to be dose-related by the authors.
Referenceopen allclose all
Maternal toxicity
CLINICAL OBSERVATIONS: Ataxia, labored respiration, wheezing, and tremors were observed in the 1200 ppm exposure level, as well as scant feces and low food consumption, that were clearly associated with CS2 treatment. Three animal deaths at 1200 ppm were considered treatment related.
BODY WEIGHT (Fig.1, attachment): the group mean body weight for animals at 1200 ppm was statistically lower when compared to the control. Two statistically significant reductions in cumulative weight gain for the 100 and 600 ppm exposure groups on gestation day 29, were not considered to be dose-related.
HEMATOLOGY: statistically significant changes in groups exposed to 600 & 1200 ppm, on gestation day 19, in hemoglobin and hematocrit levels. Mean corpuscular volume (on gest.day 29), mean corpuscular hemoglobin concentration (on gest. day 8), segmented neutrophils (on gest. day 19), lymphocytes (on gesta. day 29) were significantly altered in the 1200 ppm exposure level, when compared to the control. Although there some evidence of toxicity on the 600 ppm level it does not seem to be treatment related.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 100 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 948 mg/m³
- Study duration:
- subacute
- Species:
- rat
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Additional information
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