Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted prior to GLP similar to OECD guideline 403 on the registered substance itself. The method is to be considered scientifically reasonable with minor deficiencies in documentation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not applicable
GLP compliance:
no
Remarks:
test conducted prior to GLP implementation
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Substance type: pure substance
- Analytical purity: chemically pure

Test animals

Species:
other: mice, rats, hamsters, rabbits
Strain:
other: NMRI mice, Wistar-II rats, Syrian gold hamsters and albino rabbits
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann animal breeder (Kirchborchen, Paderborn district) and Gierlich animal breeder (Bochum)
- Weight at study initiation: 160-210g (rats), 25-31g (mice), 60-75g (hamsters), 3.5-4.3kg (rabbits)
- Housing: macrolon cages, Type III (rats, mice, hamsters), individually in standard rabbit cages (Manufacturer: E. Pluppins, Hamburg) (rabbits)
- Diet (e.g. ad libitum): Altromin R Standard diets (Altromin GmbH, Lage/Lippe) (mice, rats), sniff full diet feed for hamsters (Intermast GmbH, Bockum-Hövel) (hamsters), Höing rabbit feed (rabbits) ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:
other: dust or vapour
Type of inhalation exposure:
other: only through breathing (dust), whole body (vapour)
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dusting device (from JÖTTEN) (dust) / electrical heating pot (vapour)
- Exposure chamber volume: 20L cylinder (dust) / 0.4m³ chamber (vapour)

TEST ATMOSPHERE
- Brief description of analytical method used: analysis of the weight (dust) / gas chromatograph with the help of a nitrogen detector (vapour)
Analytical verification of test atmosphere concentrations:
yes
Remarks:
analysis of weight or gas chromatography
Duration of exposure:
4 h
Concentrations:
600 mg/m³ (dust); 137, 207, 24,725, 24,650 mg/m³ (vapour), see results for details
No. of animals per sex per dose:
10 rats/sex (dust)
in total 20 mice, 10 rats, 5 hamsters and 2 rabbits per dose, sex not stated (vapour)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 600 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: dust, rats
Sex:
male/female
Dose descriptor:
LC0
Effect level:
>= 600 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: dust, rats
Sex:
not specified
Dose descriptor:
LC0
Effect level:
>= 24 725 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: vapour, mice and rats, concentration calculated mathematically
Sex:
not specified
Dose descriptor:
LC0
Effect level:
>= 24 650 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: vapour, hamsters and rabbits, concentration calculated mathematically
Mortality:
no mortality occurred
Clinical signs:
other: Neither death nor symptoms of poisoning occurred immediately after the 4-hour exposure or in the following 14-day post-observation time with the rats. The vapours formed with the heating of the test item at 100°C and 200°C caused no appearance of poisonin

Any other information on results incl. tables

Table 1: Results of the acute toxicity study with vapour

Test item / g

Concentration of test item / mg/m³ air

Calculated mathematically

Vaporising temperature / °C

Test duration / h

Animals

Toxicol. Results after 14d*

Inserted

Vaporised

4.0

0.055

137

100

4

Mice

0/0/20

Rats

0/0/10

4.0

0.083

207

100

4

Hamsters

0/0/5

Rabbits

0/0/2

10.0

9.892

24725

200

4

Mice

0/0/20

Rats

0/0/10

10.0

9.863

24650

200

4

Hamsters

0/0/5

Rabbits

0/0/2

*1stNumber = Number of dead animals

2ndNumber = Number of animals with symptoms

3rdNumber = Number of animals used

Applicant's summary and conclusion

Interpretation of results:
other: EU-GHS criteria not met
Conclusions:
The study was conducted prior to GLP similar to OECD guideline 402 on the registered substance itself. The method is to be considered scientifically reasonable with minor deficiencies in documentation. Hence, the results can be considered as sufficiently reliable to assess the acute oral toxicity in rats. The LC0 for dust was determined as ≥ 600 mg/m³ air in rats, and the LC0 for vapour was determined as ≥ 24725 mg/m³ air (rats, mice) and ≥24650 mg/m³ air (hamsters, rabbits), respectively. The results for both sexes and all species are consistent and suitable to determine the classification of N-Methyl-2-thion-thiazolidine. According to Regulation (EC) No. 1272/2008, the substance does not need to be classified as acute toxic by inhalation.
Executive summary:

In an acute inhalation toxicity study (similar to OECD 403), groups of Wistar-II rats (10/sex) were exposed by inhalation route to dusts of N-Methyl-2-thion-thiazolidine for 4 hours (inhalation only) at a concentration of 600 mg/m³. Further, Wistar-II rats (20/group), NMRI mice (10/group), Syrian gold hamsters (5/group) and albino rabbits (2/group) were exposed by inhalation route to vapours of N-Methyl-2-thion-thiazolidine for 4 hours (whole body) at concentrations of 137 and 24,725 mg/m³ (rats, mice) and 207 and 24,650 mg/m³. Animals then were observed for 14 days.

 

LC50 > 600 mg/m³ (dust, rats, m/f)

LC0 ≥ 600 mg/m³ (dust, rats, m/f)

LC0 ≥ 24,725 mg/m³ (vapour, rats, mice)

LC0 ≥ 24,650 mg/m³ (vapour, hamsters, rabbits)

 

With the dynamic dusting of N-Methyl-2-thion-thiazolidine, an LC50 >600mg/m³ air resulted with a one-time four-hour exposure for male and female rats. With this concentration, no symptoms of poisoning appeared immediately after the exposure or in the following 14-day post-observation time.

When N-Methyl-2-thion-thiazolidine was vaporised (at 100 or 200°C), there were no injuries in the case of rats, mice, rabbits and hamsters through a four-hour exposure.

 

N-Methyl-2-thion-thiazolidine is classified as being of low toxicity based on the results above and does not trigger classification as acute toxic by inhalation.