Registration Dossier
Registration Dossier
Diss Factsheets
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EC number: 202-607-8 | CAS number: 97-77-8
- 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
Description of key information
Oral
WoE, 820053 (OECD 401) rat: LD50 = 4573 mg/kg bw (females) and >5200 mg/kg bw (males)
WoE, NIOSH (no Guideline), rat: LD50 = 500 mg/kg bw
WoE, PDT C-77-123 (OECD 401), rat: LD50 = 2090 mg/kg bw (females) and 1860 mg/kg bw (males)
Inhalation
Source, RA-A, CAS 137-26-8, key, 4730-87 (EPA OPP 81-3), rat: LC50 = >5.06 mg/L (males), 3.46 mg/L (females), 4.42 mg/L (combined)
Target, CAS 97 -77 -8, rat: LC50 = 5.44 mg/L (combined LC50 corrected for molecular weight differences (factor 1.23))
Dermal
Key, 820054 (OECD 402), rabbit: LD50 > 2000 mg/kg bw (males and females)
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- other: National Institute for Occupational Safety and Health - Publication
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Principles of method if other than guideline:
- Within a information sheet on disulfiram published from the U.S. Department of Health and Human Services, Public Health Service, information on acute toxicity of disulfiram in animals was summarized.
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Doses:
- No data
- No. of animals per sex per dose:
- No data
- Control animals:
- not specified
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 500 mg/kg bw
- Based on:
- test mat.
- Clinical signs:
- other: Major signs of acute toxicity are ataxia, hypothermia, and paralysis
- Interpretation of results:
- Category 4 based on GHS criteria
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 7 Nov - 19 Dec 1977
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Version / remarks:
- adopted in 1987
- Deviations:
- not specified
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Experimental Animals, Shizuoka
- Age at study initiation: 7 weeks
- Weight at study initiation: Male 240-270 g, Female 200-220 g
- Housing: 10 animals/ cage
- Diet: CE-2 Type (Nihon Clea Co., Osaka), ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 1°C
- Humidity (%): 60 ± 10% - Route of administration:
- oral: unspecified
- Vehicle:
- corn oil
- Doses:
- 500, 650, 845, 1000, 1300, 1700, 2200, 2860, 3850 and 5000 mg/kg bw
- No. of animals per sex per dose:
- 10 animals per sex per dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes - Statistics:
- No data
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 1 860 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- 1 510 - 2 290
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 2 090 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- 1 960 - 2 480
- Mortality:
- At 1000 and above: Death was found in 1-7 days post-treatment.
Mortalities were:
- 500 mg/kg bw: 0/10 males, 0/10 females
- 650 mg/kg bw: 0/10 males, 0/10 females
- 845 mg/kg bw: 0/10 males, 0/10 females
- 1000 mg/kg bw: 1/10 males, 1/10 females
- 1300 mg/kg bw: 2/10 males, 1/10 females
- 1700 mg/kg bw: 3/10 males, 2/10 females
- 2200 mg/kg bw: 8/10 males, 4/10 females
- 2860 mg/kg bw: 10/10 males, 10/10 females
- 3850 mg/kg bw: 10/10 males, 10/10 females
- 5000 mg/kg bw: 10/10 males, 10/10 females
Summarized results can be found in Attachment 1 in the attached background material. - Clinical signs:
- other: At 500 mg/kg: No toxic symptoms were seen. At 650 and 845 mg/kg: Only slight motor ataxia was observed. At 1000 and above: Decrease of spontaneous motor activity, piloelection, irregular respiration and dyspnea were developed 3-4 hours after administratio
- Body weight:
- other body weight observations
- Remarks:
- not examined
- Gross pathology:
- No remarkable changes were found in any animals of each group.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The study was conducted similar to OECD guideline 401. The LD50 for female rats was 2090 mg/kg bw, the LD50 for male rats was 1860 mg/kg bw. Based on the LD50 in males, the substance should be classified for acute oral toxicity category 4 (Acute Tox. 4, H302) according to the Regulation (EC) 1272/2008.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 22 - 29 Jun 1982
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Version / remarks:
- adopted in 1987
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Sasco, Inc., O’Failon, MO
- Age at study initiation: Young adult (Approximately 8 weeks)
- Weight at study initiation: 230 - 262 g (males) and 166 - 190 g (females)
- Fasting period before study: fasted overnight
- Housing: one per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported
IN-LIFE DATES: From: 28 Jul 1982 To: 11 Aug 1982 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Doses:
- 2500, 3606, 5200 and 7500 mg/kg bw
- No. of animals per sex per dose:
- 5 animals per sex per dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations: 3 times within the first 8 hours after dosing and twice daily therafter until sacrifice.
Body weights: recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes - Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 7 074 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- 4 962 - 420 000
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- > 5 200 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 4 573 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- 3 241 - 6 710
- Mortality:
- Female rats were more susceptible to lethal intoxication by the test material than were male rats. Most of the deaths occurred from the fourth through sixth days after dosing. Mortalities were:
- 2500 mg/kg bw: 1/5 males, 1/5 females
- 3606 mg/kg bw: 0/5 males, 0/5 females
- 5200 mg/kg bw: 0/4 males (1 rat died following a traumatic intubation), 3/5 females
- 7500 mg/kg bw: 0/3 males (2 rats died following traumatic intubation), 5/5 females
Summarized results can be found in Attachment 1 in the attached background material. - Clinical signs:
- other: Most clinical signs of toxicity were observed in more female than male animals. Notable signs of intoxication included ataxia, tremors, and an abnormal gait. Other commonly observed clinical abnormalities included lethargy, ptosis and lacrimation.
- Body weight:
- other body weight observations
- Remarks:
- Males: Body weight loss occurred during the first week after administration, but all surviving rats gained weight in the second week on the test. Females: Body weight loss occurred in 10/12 surviving females during the first week of the study. 8/10 females gained weight during the second half of the study. Summarized results can be found in Attachment 1 in the attached background material.
- Gross pathology:
- Effects like depletion of adipose tissue, congestion of the brain's vascular system, dark red pituitary, distended/hemorrhaged intestines and dark red lungs occurred sporadically and/or were considered to be secondary results of intoxication.
Summarized results can be found in Attachment 1 in the attached background material. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The study was conducted similar to OECD guideline 401 and under GLP conditions. The LD50 for female rats was 4573 mg/kg bw, the LD50 for both sexes combined was 7074 mg/kg bw. For male rats, no LD50 could be calculated as only 1 rat in the low dose group died and in high doses 3 males died of inturbation complications. The LD50 in males is considered to be at least 5200 mg/kg bw.
Referenceopen allclose all
Sex difference was not seen.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 500 mg/kg bw
- Quality of whole database:
- The available information comprises adequate and reliable studies, and is thus sufficient to fulfill the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- refer to analogue justification provided in IUCLID section 13.
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- > 5.04 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: source substance
- Key result
- Sex:
- female
- Dose descriptor:
- LC50
- Effect level:
- 3.464 mg/L air (analytical)
- Based on:
- test mat.
- 95% CL:
- >= 2.98 - <= 4.03
- Exp. duration:
- 4 h
- Remarks on result:
- other: source substance
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 4.42 mg/L air (analytical)
- Based on:
- test mat.
- 95% CL:
- >= 3.09 - <= 6.32
- Exp. duration:
- 4 h
- Remarks on result:
- other: source substance
- Key result
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- 6.2 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: target substance, after correction for molecular weight differences (factor 1.23).
- Key result
- Sex:
- female
- Dose descriptor:
- LC50
- Effect level:
- 4.26 mg/L air (analytical)
- Based on:
- test mat.
- 95% CL:
- >= 3.67 - <= 4.96
- Exp. duration:
- 4 h
- Remarks on result:
- other: target substance, after correction for molecular weight differences (factor 1.23).
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 5.44 mg/m³ air (analytical)
- Based on:
- test mat.
- 95% CL:
- >= 3.8 - <= 7.77
- Exp. duration:
- 4 h
- Remarks on result:
- other: target substance, after correction for molecular weight differences (factor 1.23).
- Interpretation of results:
- other: CLP EU criteria not meet based on adaption for molecular weight of the dose descriptor
- Conclusions:
- The available study was peformed with the source substance and represents a guideline-conform study conducted under GLP conditions.
Under the conditions of this study, a combined LC50 value of 4.42 mg/L for 4-hour exposure was determined. After correcting the LC50 value according to molecular weight differences, a LC50 value > 5 mg/L is considered for the target substance.
In accordance with Regulation (EC) No 1272/2008, classification of the target substance is not warranted. - Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 8 Apr - 3 Sep 1987
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- not specified
- Deviations:
- yes
- Remarks:
- methodological deficiencies (whole body exposure)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 81-3 (Acute inhalation toxicity)
- Version / remarks:
- not specified
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- HSD:(SD) BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc. Houston, Texas, USA
- Age at study initiation: young adult
- Weight at study initiation: 242 - 350 g (male), 178 - 219 g (female)
- Housing: 1 - 3 per cage, males seperate from females, suspended wire bottom stainless steel cages
- Die: Purina Formulab Chow # 5008 ad libitum
- Water: tap water ad libitum
- Acclimation period: at least one week - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: dried filtered air
- Mass median aerodynamic diameter (MMAD):
- >= 3.9 - <= 4.5 µm
- Geometric standard deviation (GSD):
- >= 1.5 - <= 3
- Remark on MMAD/GSD:
- Please refer to "Any other information on materials and methods incl. tables"
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel dynamic flow inhalation chamber
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: not reported
- System of generating particulates/aerosols: A stream of dry, filtered air was passed through either two (for thee lower exposure concentration) or four (for the higher exposure concentration) glass flasks containing the test material. The concentrated aerosol was then diluted with dried and filtered air and drawn into the exposure chamber.
- Method of particle size determination: Andersen cascade impactor
- Treatment of exhaust air: not reported
- Temperature, humidity, pressure in air chamber: Temperature: 8.9 - 20 °C, Humidity: 67 - 71%
TEST ATMOSPHERE
- Brief description of analytical method and equipment used: particle size was determined gravimetrically twice per h
- Samples taken from breathing zone: yes - Analytical verification of test atmosphere concentrations:
- yes
- Remarks:
- The concentration of the test atmosphere was determined gravimetrically twice per h, the particle size determination was performed using an Andersen cascade impactor.
- Duration of exposure:
- 4 h
- Concentrations:
- Nominal concentrations: 6.90, 14.1, 32.03 mg/L
Analytical concentrations: 2.06, 3.36, 5.04 mg/L (gravimetric) - No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations: Observations for mortality and pharmacological and/or toxicological effects were made frequently on the day of exposure and at least once daily thereafter for 14 days on all animals. Due to chamber design, only four animals (two males, and two females) could be observed during the exposure period.
- Necropsy of survivors performed: yes
- Body weight: Individual body weights were recorded prior to dosing and on day 7 and 14 or at the time of discovery of death. - Key result
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- > 5.04 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: According to Litchfield and Wilcoxon
- Key result
- Sex:
- female
- Dose descriptor:
- LC50
- Effect level:
- 3.464 mg/L air (analytical)
- Based on:
- test mat.
- 95% CL:
- >= 2.98 - <= 4.03
- Exp. duration:
- 4 h
- Remarks on result:
- other: According to Litchfield and Wilcoxon
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 4.42 mg/L air (analytical)
- Based on:
- test mat.
- 95% CL:
- >= 3.09 - <= 6.32
- Exp. duration:
- 4 h
- Remarks on result:
- other: According to Litchfield and Wilcoxon
- Mortality:
- - 2.06 mg/L: 1/5 males (Day 1), 0/5 females
- 3.36 mg/L: 1/5 males (Day 2), 2/5 females (both Day 2)
- 5.04 mg/L: 1/5 males (Day 1), 5/5 females (Day 1, 2, 2 and 3) - Clinical signs:
- other: Please refer to "Any other informations incl. tables"
- Body weight:
- Reduced body weight was observed at Day 7 in all dose groups. However, body weight of the surviving animals recovered till the end of the observation period.
Summarized results can be found in Attachment 1 in the attached background material. - Gross pathology:
- The gross macroscopic examination of animals found dead between Day 1 and Day 3 after exposure revealed nasal discharge , salivation, lacrimation, polyuria, mottled red lungs and stomachs filled with gas and green-yellow paste. Except one male that showed mottled red lungs, no gross pathological abnormalities were noted in the animals sacrificed at the end of the post exposure observation period.
Summarized results can be found in Attachment 1 in the attached background material. - Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The study was a guideline-conform study and conducted under GLP conditions.
Under the conditions of this study, the acute inhalation LC50 for 4-hour exposure was determined at 5.04 mg/L for males and 3.46 mg/L for females, resulting in a combined LC50 of 4.42 mg/L.
In accordance with Regulation (EC) No 1272/2008 the test substance should be classified as acute toxic category 4 and the hazard statement H332 “harmful if inhaled” should be assigned.
Referenceopen allclose all
Clinical signs of toxicity included decreased activity, constricted pupils, gasping, lacrimation, nasal discharge, piloerection, polyuria, ptosis and salivation during the exposure period and were further observed thereafter until Day 7 (2.06 mg/mL), Day 9 (3.36 mg/mL) and Day 10 (5.04 mg/mL) after treatment. No abnormalities were detected in surviving animals during the post exposure observation period from Day 11 onwards.
Summarized results can be found in Attachment 1 in the attached background material.
Summarized results (tabulated):
Dose [mg/L] |
Toxicological results* |
Duration of clinical signs |
Time of death |
Mortality (%) |
|
Males |
|||||
2.06 |
1/5/5 |
1/2h - day 7 |
day 1 |
20 |
|
3.36 |
1/5/5 |
1/2h - day 9 |
day 2 |
20 |
|
5.04 |
1/5/5 |
1/2h - day 10 |
day 1 |
20 |
|
LC50 < 5.04 mg/L |
|||||
Females |
|||||
2.06 |
0/5/5 |
1/2h - day 7 |
day 1 |
0 |
|
3.36 |
2/5/5 |
1/2h - day 8 |
day 2 |
40 |
|
5.04 |
5/5/5 |
1/2h - day 3 |
day 1, 2, 3 |
100 |
|
LC50 = 3.464 mg/L |
|||||
Combined |
|||||
2.06 |
1/10/10 |
-- |
-- |
10 |
|
3.36 |
3/10/10 |
-- |
-- |
30 |
|
5.04 |
6/10/10 |
-- |
-- |
60 |
|
combined LC50 = 4.42 mg/L |
* first number = number of dead animals, second number = number of animals with signs of toxicity, third number = number of animals used
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 5.4 mg/L air
- Physical form:
- inhalation: aerosol
- Quality of whole database:
- The available information comprises an adequate and reliable study with a structurally similar substance, and is thus sufficient to fulfill the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 4 Aug - 18 Aug 1982
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- adopted in 2017
- Deviations:
- yes
- Remarks:
- 1/ Clinical observation: On one day, observations were only recorded once, and on two other days, they were not recorded. 2/ Environmental conditions not reported. Both protocol deviations were not considered to adversely affect study results
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Isaacs’ Rabbitry, Litchfield, Illinois
- Age at study initiation: Young adult
- Weight at study initiation: 2.27 - 2.64 kg
- Housing: one per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days - Type of coverage:
- occlusive
- Vehicle:
- physiological saline
- Details on dermal exposure:
- TEST SITE
- Area of exposure: dorsal surface
- % coverage: 10 - 30% of total body surface
- Type of wrap if used: wrap of latex rubber
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the excess material was wiped from the animal
- Time after start of exposure: 24 hours - Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg
- No. of animals per sex per dose:
- one group of 5 males and 5 females
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made three times during the first eight hours following test material administration and routinely twice daily (morning and afternoon) thereafter until sacrifice. On one day, observations were only recorded once, and on two other days, they were not recorded. These protocol deviations were not considered to adversely affect study results.
Body weights were recorded on days 0 (day of exposure), 7, and 14.
- Necropsy of survivors performed: yes - Preliminary study:
- None
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality was observed
- Clinical signs:
- other: Erythema in the exposed area was observed in one female and two male animals on the day after dosing and in the same female rabbit on the following day. No other clinical abnormalities were observed.
- Body weight:
- other body weight observations
- Remarks:
- All animals gained weight as would be expected for this strain and age. Summarized results can be found in Attahcment 1 in the attached background material.
- Gross pathology:
- At necropsy, one male and two female animals had off-white fibrous tissue in and/or a marbled appearance of all hepatic lobes. Two of these same animals had numerous hard, yellow foci on all lobes of the liver, and one also had an area of green, necrotic hepatic tissue. All three of these animals also had tapeworm cysts in the mesentery. Pale renal coloration was observed in each of two animals, one of which also had kidneys with pitted exteriors. No abnormalities were observed in the remaining five rabbits.
Summarized results can be found in Attahcment 1 in the attached background material. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The study was conducted similar to OECD guideline 402 The acute dermal LD50 of the test substance was > 2000 mg/kg bw in male and in female animals.
According to Regulation (EC) No 1272/2008 the test substance does not require classification for dermal toxicity.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- > 2 000 mg/kg bw
- Quality of whole database:
- The available information comprises an adequate and reliable study, and is thus sufficient to fulfill the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.
Additional information
To assess acute toxicity of the test substance, data after oral and dermal exposure to the test substance are considered. For inhalation exposure, read across to a source substance is applied (for details please refer to the analogue justification provided in the technical dossier in section 13). Moreover, for acute oral toxicity, available literature and authority publications are considered. Most studies were GLP-compliant, and performed in accordance with appropriate guidelines (OECD 401, EPA OPP 81-3, OECD 402).
Oral exposure
In a weight of evidence approach, the acute oral toxicity of the test substance was assessed. Two study reports were available and a publication by the National Institute for Occupational Safety and Health (NIOSH). The studies (Rep. No. 820053 and PDT C-77-123) investigated the acute oral toxicity in rats. Signs of toxicity were decrease of spontaneous motor activity, ataxia, tremors, piloelection, irregular respiration and dyspnea. LD 50 ranged from 1860 mg/kg bw to > 5200 mg/kg bw. The NIOSH publication stated an LD50 in rats of 500 mg/kg bw.
A further study was disregarded due to methodological reasons. Brielfy, rabbits were exposed to the test substance in combination with alcohol, so that no clear relation to treatment could be drawn. In this study, the oral LD50 for the test substance in rabbits was found to be 650 mg/kg bw when combined with administration of 1.5 g alcohol/kg bw 20 -24 hours after disulfiram administration (Barnes and Fox, 1955).
Dermal exposure
By dermal application the test substance showed only very low toxicity (Rep. No. 820054). No mortality was observed. The acute dermal LD50 of the test substance was > 2000 mg/kg bw in male and in female animals. The clinical signs were limited to erythema in 3 animals.
Inhalation exposure
No data on acute toxicity following inhalation exposure are available for disulfiram. However, reliable data on the structural similar substance xxx are available. In summary, whole body inhalation exposure to the read across source substance, observed toxicological effects consisted of activity decrease, constricted pupils, gasping, lacrimation, nasal discharge, piloerection, polyuria, ptosis, and salivation (Rep. No. 4730-87). The median lethal concentration (LC50) for the test substance in the rat was > 5.04 mg/L in male rats and 3.46 mg/L in female rats, resulting in a combined LC50 of 4.42 mg/L. After correction for molecular weight differences (factor 1.23), the combined LC50 was 5.44 mg/kg bw/day, warranting no classification for acute inhalation toxicity.
Justification for classification or non-classification
The available data on acute oral toxicity and acute inhalation toxicity meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore sufficient for classification of the test substance for acute oral toxicity category 4 (Acute Tox. 4, H302).
The substance is listed in Annex VI of Regulation (EC) 1272/2008 (006-079-00-8). Harmonised classification in regard to minimum classification was adopted according to the available experimental data if appropriate.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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