N-cyclohexylcyclohexanamine 2-[1-[[[(1R)-1-[3-[(1E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanyl]methyl]cyclopropyl]acetate

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 16 to 18, 2003

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-[1-[[1-[3-[2-[(7-Chloro-2-quinolyl)]vinyl]phenyl]-3-[2-(1-hydroxy-1-methyl-ethyl)phenyl]-propyl]sulfanylmethyl]cyclopropyl]acetic acid sodium salt

EC Number:

604-813-7

Cas Number:

151767-02-1

IUPAC Name:

2-[1-[[1-[3-[2-[(7-Chloro-2-quinolyl)]vinyl]phenyl]-3-[2-(1-hydroxy-1-methyl-ethyl)phenyl]-propyl]sulfanylmethyl]cyclopropyl]acetic acid sodium salt

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Montelukast sodium; Purity as is 98.8%, fine white powder
Received in Amber glass bottles, dessicated, stored at room temperature and was stored in the dark at room temperature

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

Test substance concentrations were determined in the control and test treatments at test initiation and termination. On test day 0, 100-mL samples were pipetted from the composite treatments before distribution to the test chambers. At test termination, all replicate chambers for each test concentration were pooled and 100-mL samples were pipetted from each composite.

Test solutions

Vehicle:

yes

Remarks:

DMF

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

Daphnia magna used for testing were obtained from Toxikon cultures, which originated from animals received from Aquatic Research Organisms, Hampton, New Hampshire in July 2002. A subculture of adults was isolated from these cultures and maintained prior to testing. Test organisms were taken from lot number DM 03-9-16 for the definitive test. The cultures were fed the green alga, Selenastrum capricornutum, and a solution leaves (Cerophyll®) and trout chow daily.
Less than 24 hours prior to tet initiation the adults were re-isolated in food-free dilution water. Neonates {<24 hours old) were collected for test initiation on September 16, 2003. Daphnia magna were cultured and isolated in moderately hard freshwater (dilution water). No ephippia were produced during culture and the organisms appeared in good physical condition at test initiation.

Study design

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Test conditions

Test temperature:

20.l to 20.5°C

pH:

ranged from 7.5 to 7.8 for the duration of the 48-hour exposure

Dissolved oxygen:

Inital range were 8.9 to 9. 0, ranged from 8.3 to 8.5 mg/L (92 to 94 percent of saturation} at termination

Nominal and measured concentrations:

Nominal concentrations (µg/L) : 6.25, 12.5, 25, 50, 100
Mean Measured (µg/L): 5.03, 7.31, 15, 31.3, 67.5

Results and discussion

Effect concentrations

Key result

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

> 0.068 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: NOEC was the maximium dissolved concentration

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The 48-hour EC50 could not be calculated due to lack of significant mortality at the specified time and can be stated to be greater than the highest concentration tested or > 67.5µg Montelukast sodium Salt . The 48- hour no observable-effect concentration (NOEC) was therefore the maximum dissolved concentration or 67.5 µg Montelukast sodium Salt /L.

Executive summary:

A static freshwater toxicity test was conducted at Toxikon Corporation, Jupiter, Florida, to determine the acute toxicity of (Montelukast sodium Salt) to the water flea, Daphnia magna. The criterion for effect was death or immobilization (i.e., animals unable to swim within 15 seconds after gentle agitation of the test chamber). Results of the test are expressed .as a 48- hour median effective concentration (EC50), the concentration of Montelukast sodium Salt estimated to result in immobilization or death to 50 percent of the test population at the specified time.

The 48-hour EC50 could not be calculated due to lack of significant mortality at the specified time and can be stated to be greater than the highest concentration tested  or>  67.5  µg  Montelukast sodium Salt . The 48- hour no observable-effect concentration (NOEC) was therefore the maximum dissolved concentration or 67.5 µg Montelukast sodium Salt /L.