Disulfiram

Endpoint summary

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

Reference

Reference 1

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

Reference 2

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.

Sex difference was not seen.

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.

Reference 3

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.

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

Reference

Reference 1

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.

Reference 2

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.

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

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.

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

Reference

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.

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.