Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to OECD guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
name: Cyanamide, (4,5-dihydroxy-2-thiazolyl)-
molecular formula: C4 H5 N3 S
molecular weight: 127.2
physical state: solid
analytical purity: 98 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Winkelmann, Borchen (Germany)
- Age at study initiation: 2 - 3 months
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet: e.g. ad libitum
- Water: e.g. ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): approximately 50 %
- Air changes (per hr): approximately 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h/12 h; artificial light from 6.00 a.m. to 6.00 p.m. Central European Time


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: modular chamber as published by Pauluhn (1994)
- Exposure chamber volume: about 3.8 I
- Method of holding animals in test chamber: tubing system
- Source and rate of air: Compressed air was supplied by Boge compressors and was conditioned (i.e. freed from water, dust, and oil) automatically
by a VIA compressed air dryer. Adequate control devices were employed to control supply pressure.
- System of generating particulates/aerosols: EXACTOMAT 4200 (TSE, 61348 Bad Homburg, Germany)
- Method of particle size determination: The particle-size distribution was analyzed using a BERNER-TYPE AERAS lowpressure
critical orifice cascade impactor (Hauke, Gmunden, Austria).
- Treatment of exhaust air: The exhaust air was purified via cotton-wool/activated charcoal and HEPA filters. These filters were disposed of.
- Temperature, humidity, pressure in air chamber: The temperature and humidity measurements were made using a computerized system (Leybold Heraeus).


TEST ATMOSPHERE
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see below
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 11.9 µm

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
No. of animals per sex per dose:
5 males and 5 females at each dose and at control.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The appearance and behavior of each rat were examined carefully several times on the day of exposure and at least once daily thereafter. Weekend assessments were made once a day (morning). Body weights were measured before exposure, on days 3 and 7, and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, rectal temperatures

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 508 mg/m³ air
Exp. duration:
4 h
Remarks on result:
other: hightest attainable concentration
Sex:
male/female
Dose descriptor:
other: NO(A)EL
Effect level:
< 503 mg/m³ air
Exp. duration:
4 h
Mortality:
The maximum technically attainable concentration was tolerated without mortality.
Clinical signs:
other: control group: All rats tolerated the exposure without specific signs. dose groups: Bradypnea, labored breathing pattern, piloerection, ungroomed haircoat.
Body weight:
Mildly and transiently decreased body weights observed in the male of the high dose group are considered to be the only ones of toxicological relevance.
Gross pathology:
In rats exposed to the test compound a conclusive, concentration-dependent increased incidence of macroscopical findings could not be observed. Therefore, the observed mild discolorations of lungs are considered to be spurious and of no biological significance (related to postmortal color changes and often observed in rats euthanized with an overdose of pentobarbital).
Other findings:
Statistically significantly decreased body temperature in the high dose group.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study the substance is not subject to classification.
Executive summary:

A study addressing the acute inhalation toxicity of 2-CYANIMINO-1,3-THIAZOLIDIN

(hereafter referred to as test substance) on rats has been conducted in accordance

with OECD Guideline No. 403. Groups of rats were nose-only exposed to an average

solid aerosol concentration (micronized dust) of 503 and 1508 mg/m3 air. Attempts

were made so that aerosol generated was respirable to rats. The results can be

summarized as follows:

LD50 inhalation (aerosol. 4 hr) NO(A)EL
Males & females: > 1508 mg/m3 Males & Females: 503 mg/m3 

Exposure to the technically maximum technically attainable dust concentration of

1508 mg/m3 air was tolerated without mortality. Following exposure, the rats

experienced a labored breathing pattern, piloerection, ungroomed hair-coat, hypothermia,

and mildly decreased body weights. All effects resolved within the first postexposure

week. With regard to the respirability of the solid aerosol generated,

internationally recognized recommendations such as of SOT (1992) were not

fulfilled, i.e. the MMAD was > 4 urn. Despite several technical measures were taken

to increase the respirability of particles as well as the maximum technically attainable

concentration, e.g., the test substance was micronized using a jet-mill or a mortar

mill, neither the respirability nor the maximum concentration could be increased.

In summary, the aerosolized test substance proved to have a low acute inhalation

toxicity to rats at an exposure concentrations in the range of the limit concentration

SOT (1992). The mild hypothermia is a common finding in rodents when exposed to

upper respiratory tract sensory irritants. The fact that the measures taken to increase

the respirability of particles were unsuccessful demonstrate convincingly that the

exposure potential to this substance is low.