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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance tetramethylthiuram disulfide (CAS No. 137-26-8). In accordance to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance. (For detailed information on the justification of read-across, please refer to the analogue justification document attached in IUCLID section 13).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Thiram Technical
- Physical state: fine white powder
- Analytical purity: 99.5 %
- Lot/batch No.: M.5.1841; G3380
- Stability under test conditions: not provided by the sponsor
- Storage condition of test material: room temperature
- Median particle size: 5.61 µm

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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
- Diet (ad libitum): Purina Formulab Chow # 5008 ad libitum
- Water (ad libitum): tap water ad libitum
- Acclimation period: at least one week

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: dried filtered air
Analytical verification of test atmosphere concentrations:
yes
Remarks:
determined gravimetrically twice per hour (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

Results and discussion

Effect levelsopen allclose all
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. After correction for the molecular weight the LC50 for disulfiram is considered to be 5.45 mg/m3.
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. After correction for the molecular weight the LC50 for disulfiram is considered to be 6.22 mg/m3.
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. After correction for the molecular weight the LC50 for disulfiram is considered to be 4.27 mg/m3.
Clinical signs:
Activity decrease, constricted pupils, gasping, lacrimation, nasal discharge, piloerection, polyuria, ptosis, and salivation.
Gross pathology:
Treatment-related gross necropsy findings: lacrimation, nasal discharge, polyuria, and salivation, discoloration of the contents of the stomach, stomach distended with gas, discoloration of the lungs, and variations thereof.

Any other information on results incl. tables

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

0

3.36

1/5/5

1/2h - day 9

day 2

0

5.04

1/5/5

1/2h - day 10

day 1

80

LD50 > 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

LD50 = 3.464 mg/L

combined LD50 = 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

Applicant's summary and conclusion