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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 - 22 Sep 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted 1981
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
428-040-8
EC Name:
-
Cas Number:
138261-41-3
Molecular formula:
C9H10ClN5O2
IUPAC Name:
2-chloro-5-{[2-(nitroimino)imidazolidin-1-yl]methyl}pyridine

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: laboratory animal breeder Winkelmann, Borchen, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 160 - 210 g
- Fasting period before study: not reported
- Housing: animals were housed in groups of 5 in Makrolon cages type III with low-dust wood granulate type 8/15 (Ssniff Co, Soest, Germany) for bedding material.
- Diet: Altromin 1324 Diet for rats and mice (Altromin GmbH, Lange, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
- Method of randomisation in assigning animals to test and control groups: randomizing lists produced by a computer program were used

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): approximately 50
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 08 Sep 1987 To: 22 Sep 1987

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
> 10.6 - <= 20 µm
Geometric standard deviation (GSD):
> 1.82 - <= 2.15
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: PVC inhalation chamber
- Exposure chamber volume: approximately 20 L
- Method of holding animals in test chamber: animals were confined to plexiglass exposure tubes matching the animals sizes
- Source and rate of air (airflow): see 'any other information on materials and methods incl tables' section for further information
- Method of conditioning air: in-line VIA compressed air dryer type A110, i.e. water, dust and oil were removed
- System of generating particulates: Bayer Dust Generator (see 'any other information on materials and methods incl tables' for further description)
- Method of particle size determination: aerodynamic particle sizer with laser velocimeter (TSI-APS 3300)
- Treatment of exhaust air: purified using an absolute filter
- Temperature, humidity, pressure in air chamber: 22 - 25 °C, 5 - 34 %, not reported

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: gravimetrical evaluation of 10 - 50 L of air using filters (SM 11106, pore size 0.45 µm)
- Samples taken from breathing zone: yes
- Particle size distribution: number of particles < 5 µm: 71 % (1.22 mg/L air), 65 % (2.57 mg/L air), 70 % (5.32 mg/L air)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 10.6 µm, 1.82 µm (1.22 mg/L air), 14.2 µm, 1.92 µm (2.57 mg/m³ air), 20.0 µm, 2.15 µm (5.32 mg/L air)
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Remarks on duration:
1 x 4h (dust)
Concentrations:
1.22, 2.57, and 5.32 mg/L air (dust)
No. of animals per sex per dose:
5 for treatment groups and 10 for air control
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights were recorded before exposure and on day 3, 7 and 14 (1 x 4h). Appearance and behavior were assessed several times on the day of exposure, but not during exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology, gross pathological examination, organ weights
Statistics:
Please refer to 'any other information on materials and methods incl. tables' section.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.32 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: difficult breathing, reduced motility and piloerection, slight tremors.
Remarks:
Doses up to 1.22 mg/L air were tolerated without symptoms by both sexes. At 2.57 mg/L air difficult breathing, reduced motility and piloerection and additionally at 5.32 mg/L air slight tremors were observed.
Body weight:
No effect on body weight was noted during the course of the study
Gross pathology:
Gross pathological examination revealed no substance-related findings.
Other findings:
No obvious treatment-related effects on relative organ weight were noticed for liver and lung.

Histopathological examination of lung and liver exhibited no signs of treatment-related changes.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
The study is in accordance with OECD 403, was performed under GLP conditions and is considered to be valid and reliable. Under the conditions chosen, the acute inhalation LC50 was determined to be >5.32 mg/L air (dust; 1x4h) in male and female rats. According to criteria of the CLP Regulation (EU) No. 1272/2008, classification of the test item for acute inhalation toxicity is not required.