Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 4 DEC 1989 to 18 DEC 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990
Reference Type:
publication
Title:
Investigation of possible metabolism of Pigment Yellow 17, a 3,3'-dichlorobenzidine-based pigment, after inhalation exposure in rats
Author:
Hofmann T, Schmidt D
Year:
1993
Bibliographic source:
Arch. Toxicol. 67: 141-144
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF breeding colony
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: males mean: 227 g; females mean: 195 g
- Housing: macrolon cages (type 4) groups of 5 respectively 2 (= control animal and animal killed 1 day post application)
- Diet: rat diet Altromin 1324 ( Altromin-GmbH, Lage/Lippe, Germany); ad libitum
- Water: Tap water; ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12/12


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: cylindrical plastic cage
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: each animal was in a plastic tube
- Source and rate of air: laminar air stream of 1000 L/hour at 4 bar from above
- System of generating particulates/aerosols: dustgenerator "Wright Dust Feed" of L. Adams Ltd., London, UK
- Method of particle size determination: "Anderson-Kaskadenimpaktor Mark III" of Anderson Samples Inc, Atlanta, USA
- Treatment of exhaust air: exhaust device at the basement of the exposure chamber in line with a diverse system of filters

TEST ATMOSPHERE ANALYSIS
- Brief description of analytical method used: gravimetric measurement: The test atmosphere was sucked through filters ("Experimentiertrommelgasfilter", Elster AG, Mainz-Kastel, Germany; as well as a fibre glass and a membrane filter (diameter of pores 0.65 µm) Satorius Membranfilter GmbH, Göttingen, Germany) by means of vacuum. The exhaust quantity was 3 L/min, which resulted in an air flow of 1.25 m/sec. The filters were positioned in an exsiccator 24 h before use. The filters were weighed before and after each measurement by means of electrical scales.

TEST ATMOSPHERE
- Particle size distribution: < 0.6 µm to > 10.3 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.0 - 1.1/ 2.3 - 2.8
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric measurement
Duration of exposure:
4 h
Concentrations:
230 mg/m³ air
No. of animals per sex per dose:
6/sex/treatment group
1/sex/control group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: twice a day
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes

- Control urine and blood samples were collected from control animals.
- On day 1, 2 and 7 one male and one female were sacrificed to obtain blood samples. Final sacrifice of the remaining 3 animals/sex was on day 14 of the observation period.
- Urin samples were collected starting on the day of exposure till day 7 of the observation period and the last night before sacrifice.
- To collect urine the rats were placed in metabolism cages overnight without witdrawal of food and water. For technical reasons urine was collected continously on day 6 and 7.
- Blood was collected via puncture of the retro-orbital plexus.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 230 mg/m³ air
Exp. duration:
4 h
Remarks on result:
other: no animals died within the 14 day observation period
Mortality:
- no deaths occurred
Clinical signs:
- during the exposition: irregular breathing, narrowed palpebral fissures and female animals showed additional stilted gate
- no more clinical signs were observed in males 330 minutes p.a. and in females 450 minutes p.a.
Body weight:
- Body weight development was impaired in the first week, probably due to the frequent placement in metabolism cages.
- But all animals except for one female did excess their initial body weight at the end of the test period.
Gross pathology:
- no macroscopically visible changes were found

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Exposure of male and female Wistar rats to 230 mg/m³ test item for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 230 mg/m³.
Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Wistar rats. They were exposed to 230 mg test substance per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 230 mg/m³ for the inhalation of dust.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008 .