Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From October 6, 2009 to March 24, 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
2009
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF in Japan, No 12 Nosan No 8147
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-(cyclopropanecarbonyloxy)-6,12-dihydroxy-4,6a,12btrimethyl-11-oxo-9-(pyridin-3-yl)-1,2,3,4,4a,5,6,6a,12a,12b-decahydro-11H,12Hbenzo[f]pyrano[4,3-b]chromen-4-yl]methylcyclopropanecarboxylate
Cas Number:
915972-17-7
Molecular formula:
C33H39NO9
IUPAC Name:
[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-(cyclopropanecarbonyloxy)-6,12-dihydroxy-4,6a,12btrimethyl-11-oxo-9-(pyridin-3-yl)-1,2,3,4,4a,5,6,6a,12a,12b-decahydro-11H,12Hbenzo[f]pyrano[4,3-b]chromen-4-yl]methylcyclopropanecarboxylate
Test material form:
solid
Details on test material:
- Analytical purity: >94 %
Specific details on test material used for the study:
Lot number: 080722
Description: Pale yellow green powder
Expiry: 29 July 2010

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Fuji (Shizuoka, Japan)
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 229-247 g (males) and 149-167 g (females)
- Housing: Housed by sex in groups of 5 in holding cages made of stainless steel sheet and wire mesh that was suspended on a moveable rack. (240 mm wide x 400 mm depth x 180 mm height)
- Diet: SDS rat and mouse diet (RM1(E) SQC expanded pellet)
- Water: Tap water supplied by Anglian Water, ad libitum
- Acclimation period: At least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 50 ± 20%
- Air changes (per hr): at least 100 changes
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (07.00 – 19.00 GMT) in each 24-hour period

IN-LIFE DATES: From: October 28, 2009 to: November 18, 2009

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
4.3 µm
Geometric standard deviation (GSD):
1.89
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Turn-table type dust feeder with compressed air
- Exposure chamber volume: 31.2 L
- Method of holding animals in test chamber: Snout-only exposure chamber
- Source and rate of air: Airflow, 20 L/min
- Method of particle size determination: Gravimetrically with an electronic balance
- Treatment of exhaust air: Chamber air was exhausted through an air filter system consisting of a bag filter and was emitted to the atmosphere using a blower.
- Temperature, humidity, pressure in air chamber: 22-23°C; 45-51%,- 20 and -5 mm H2O

TEST ATMOSPHERE
- Brief description of analytical method used: HPLC
- Samples taken from breathing zone: Yes, 6 L of chamber air was drawn from the chamber sampling port using an air sampler

TEST ATMOSPHERE
- Particle size distribution: Measured three times with an Andersen type personal sampler at 1, 2 and 3 hours after the initiation of exposure.

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.48 mg/L
No. of animals per sex per dose:
5
Control animals:
yes
Remarks:
a vehicle control group (1.31 mg/L for white carbon) was conducted with 5 males and 5 females.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: Shortly before exposure and on 1, 3, 7 and 14 days after exposure
- Necropsy of survivors performed: Yes
- Other examinations: All animals were checked at 2 hours during the exposure. Further clinical observations were made immediately post exposure as well as 1 and 4 hours post exposure and daily thereafter.
Statistics:
Statistical methods employed are not detailed in the final report.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.48 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None
Clinical signs:
other: In the test substance group, abnormal respiratory sound was noted in four males and one female. This sign began to appear immediately after the termination of exposure and disappeared by 4 hours after the termination of exposure. No signs were noted in an
Body weight:
Several males in test substance group and all animals in vehicle control group lost body weight on day 1 after exposure. On 3 days afer exposure, all animals in vehicle control group lost body weight. All animals gained body weight by 7 and 14 days after exposure.
Gross pathology:
No gross pathological abnormalities were detected in the animals that underwent necropsy at termination of the study.
Other findings:
No other findings were observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met