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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed in a scientifically reasonable manner to examine the limited endpoints with some deficiencies in documentation, but the given data indicate that the results with regard to the examined endpoints can be considered reliable.

Data source

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

Materials and methods

Principles of method if other than guideline:
The animals were exposed to the vapours 5 times for 4 hours. After the exposure, the animals were observed 14 days long.
GLP compliance:
no
Remarks:
test conducted prior to GLP implementation
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), ssniff 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:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: electrical heating pot (vapour)
- Exposure chamber volume: 20L cylinder (dust) / 0.4m³ chamber (vapour)

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatograph with the help of a nitrogen detector (vapour)
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
gas chromatography
Duration of treatment / exposure:
The animals were exposed to the vapours 5 times for 4 hours.
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2108 mg / m³ air
Basis:
other: analytical conc. for mice, rats
Remarks:
Doses / Concentrations:
2613 mg / m³ air
Basis:
other: analytical conc. for hamsters, rabbits
No. of animals per sex per dose:
Total number for single dose: 20 mice, 10 rats, 5 hamsters, 2 rabbits
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, mucous membranes of eye and nose, cornea

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No symptoms of poisoning occurred on the 5th day of testing or during the 14-day post-observation time with the animals.
Mortality:
no mortality observed
Description (incidence):
No symptoms of poisoning occurred on the 5th day of testing or during the 14-day post-observation time with the animals.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
A slight reduction of body weight was to be reported after the 5-day exposure with rats and hamsters. Normal body weight increases occurred again during the 14-day post-observation time with these animals.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Description (incidence and severity):
no changes on the cornea
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
Changes also did not appear on the mucous membranes of the nose or eyes or on the cornea.
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
Concentrations of 2108 mg/m³ air were borne by male and female rats and mice with a 5 x 4hour exposure and concentrations of 2613 mg/m³ air by male and female hamsters and rabbits. No symptoms of poisoning occurred on the 5th day of testing or during the 14-day post-observation time with the animals. Changes also did not appear on the mucous membranes of the nose or eyes or on the cornea after a once-only four-hour exposure or after a 5x four-hour exposure. A slight reduction of body weight was to be reported after the 5-day exposure with rats and hamsters. Normal body weight increases occurred again during the 14-day post-observation time with these animals.

Effect levels

open allclose all
Dose descriptor:
NOAEC
Effect level:
>= 2 108 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: mortality; body weight (rats, mice)
Dose descriptor:
NOAEC
Effect level:
2 613 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: mortality (hamsters, rabbits)
Dose descriptor:
LOEC
Effect level:
2 613 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: slight reduction of body weight after day 5 of exposure in hamsters and rabbits

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table: Exposure conditions and results

N-Methyl-2-thion-thiazolidine / g

Concentration mg/m³ air /

measured

Vaporizing Temperature / °C

Test duration / hours

Type of animal

Toxicol. Results after 14 days*

Inserted

vaporized

10.0

9.895

2108

200

5x4

Mice

rats

0/0/20

0/0/10

10.0

9.880

2613

200

5x4

Hamsters

rabbits

0/0/5

0/0/2

*1stNumber = Number of dead animals

2ndNumber = Number of animals with symptoms

3rdNumber = Number of animals used

Applicant's summary and conclusion

Conclusions:
The study was performed in a scientifically reasonable manner to examine the limited endpoints with some deficiencies in documentation, but the given data indicate that the results with regard to the examined endpoints can be considered reliable. Hence, the results are considered sufficiently reliable to study the effect of N-Methyl-2-thion-thiazolidine by inhalative exposure on rats, mice, hamsters and rabbits with regard to signs of poisoning or mortality. There were no relevant effects on the animals at vapiur concentrations of 2108 resp. 2613 mg/m³ air. The result can be used to support the results derived from the available oral 90 day study.
Executive summary:

When rats, mice, hamsters and rabbits were exposed to N-Methyl-2-thion-thiazolidine vapours for 4 hours at a time on five successive days, a concentration of 2108 mg/m³ air was borne by male and female rats and mice, and 2613 mg/m³ by rabbits. Symptoms of poisoning did not occur with the test animals on the 5 test days or during the 14-day post-observation time.

Changes also did not occur in the mucous membranes of noses and eyes or on the cornea after inhalation of dust and vapours, so NOECs were determined as ≥ 2108 mg/m³ air (mice, rats) resp. ≥ 2613 mg/m³ (hamsters, rabbits).