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Diss Factsheets

Administrative data

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

Data source

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

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Thiram
EC Number:
205-286-2
EC Name:
Thiram
Cas Number:
137-26-8
Molecular formula:
C6H12N2S4
IUPAC Name:
thiram

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levelsopen allclose all
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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 4.42 mg/L (371 mg/kg bw) for males and females combined, 5.04 mg/L (424 mg/kg bw) for males and 3.46 mg/L (290 mg/kg bw) for females.
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.