(2S,3S)-2-benzhydryl-N-[(5-tert-butyl-2-methoxy-phenyl)methyl]quinuclidin-3-amine

Short-term toxicity to fish

Administrative data

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 850.1075 (Freshwater and Saltwater Fish Acute Toxicity Test)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

(2S,3S)-2-benzhydryl-N-[(5-tert-butyl-2-methoxyphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine;2-hydroxypropane-1,2,3-tricarboxylic acid;hydrate

Cas Number:

359875-09-5

Molecular formula:

C38H50N2O9

IUPAC Name:

(2S,3S)-2-benzhydryl-N-[(5-tert-butyl-2-methoxyphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine;2-hydroxypropane-1,2,3-tricarboxylic acid;hydrate

Test material form:

solid: particulate/powder

Details on test material:

Lot No 503881

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

Water samples were collected from freshly prepared batch (or pooled replicate samples as in
the Rainbow trout) of test solution for each treatment group and control at test initiation. All samples
were collected from mid-depth in the test solutions, placed in glass vials, and processed immediately
for analysis.

Test solutions

Vehicle:

yes

Details on test solutions:

A primary stock solution was prepared in well water at a nominal concentration of
5.0 mg/L. The stock was stirred with two top-down electric mixers for ~30 minutes to mix.
The primary stock solution appeared clear and colorless. Proportional aliquots of the primary
stock solution were diluted with U.V. sterilized well water to prepare the 0.063, 0.13, 0.25,
0.50, 1.0 and 2.0 mg/L test solutions. The test solutions appeared clear and colorless. All
organisms were transferred from old test solutions to freshly prepared test solutions at 48
hours.

For the rainbow trout study samples of freshwater were fortified at 0.600, 0.400 and 2.00
mg/L using a stock solution of Maropitant in methanol, and were analyzed concurrently with the test
samples. The measured concentrations for the matrix fortification samples ranged from 84.4 to 115%
of fortified concentrations.

Test organisms

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

Source: Thomas Fish Company, Anderson, California
Age at Test Initiation: Juveniles
Feeding: During holding, fed a commercially prepared diet supplied by Zeigler
Brothers, Inc., Gardners, Pennsylvania. No feeding during the test.

Study design

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Test conditions

Hardness:

135 mg/L as CaCO3

Test temperature:

20ºC, consistent within +/- 1ºC (20.2 – 20.9ºC)

pH:

8.2 – 8.5

Dissolved oxygen:

7.0 – 9.9 = >65% ASV

Conductivity:

301 µmhos/cm

Nominal and measured concentrations:

nominal concentrations: 0.063, 0.13, 0.25, 0.50, 1.0 and 2.0 mg/L
measured concentrations: 0.068, 0.13, 0.27, 0.57, 1.1, 1.8 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: 38 L at initiation and 54 L (all stainless steel aquaria) at 48-hour renewal
- Type (delete if not applicable): open / closed
- Material, size, headspace, fill volume:
- Aeration: yes
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 2


TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Water used for culturing and testing of the daphnids was obtained from a well located on the Wildlife International Ltd. site.
- Well water characteristics
(Mean of 4 weekly measurements taken prior to test initiation): Hardness
(135 mg/L as CaCO3,); Alkalinity (181 mg/L as CaCO3); Conductivity (301
µmhos/cm) and pH (8.2).
- Intervals of water quality measurement: DO at 0, 24, 48 (old and new solutions), 72 and 96 hours; Temperature and pH at test initiation, 48 hours (old and new solutions) and termination;

OTHER TEST CONDITIONS

- Photoperiod: 16-hrs light; 8-hrs dark


EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Observations of mortality and clinical signs of toxicity at 0-24, 24, 48, 72
and 96 hours. Mortality data at 24, 48, 72 and 96 hours were used to
determine LC50 values.

Reference substance (positive control):

no

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

24 h

Dose descriptor:

LC50

Effect conc.:

1.3 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Effect concentrations 2

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

1.3 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Effect concentrations 3

Duration:

72 h

Dose descriptor:

LC50

Effect conc.:

1 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Effect concentrations 4

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.83 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The calculated LC50 of Rainbow trout, Oncorhynchus mykiss, Exposed to Maropitant for 96-Hours under Static-Renewal Test Conditions was 0.83 mg/L