(3S,6S,7R,8R)-8-Benzyl-3-{[(3-hydroxy-4-methoxypyridin-2-yl)carbonyl]amino}-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropanoate

Toxicity to terrestrial arthropods

Administrative data

Endpoint:

toxicity to bees: acute oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 213 (Honeybees, Acute Oral Toxicity Test)

Deviations:

yes

Remarks:

A limit test was conducted in which 48% mortality occurred. The study was terminated and no further full dose-response test was carried out due to inconsistencies related to the solvent.

GLP compliance:

yes

Application method:

oral

Test material

Test material information

Constituent 1

Reference substance name:

(3S,6S,7R,8R)-8-benzyl-3-(3-hydroxy-4-methoxypyridine-2-amido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropanoate

Cas Number:

167173-85-5

Molecular formula:

C26H30N2O9

IUPAC Name:

(3S,6S,7R,8R)-8-benzyl-3-(3-hydroxy-4-methoxypyridine-2-amido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropanoate

Specific details on test material used for the study:

Substance name: X642188 (a metabolite of XDE-777)
Lot No.: SYN-FS08353-048 (TSN303567)
Purity: 99%

Sampling and analysis

Analytical monitoring:

no

Test substrate

Vehicle:

yes

Remarks:

Sucrose solution and DMSO

Test organisms

Test organisms (species):

Apis mellifera

Animal group:

Hymenoptera (honeybees)

Study design

Study type:

laboratory study

Limit test:

yes

Total exposure duration:

48 h

Test conditions

Test temperature:

25°С

Humidity:

40-63%

Photoperiod and lighting:

24 h darkness

Nominal and measured concentrations:

15.0 μg a.i./bee.

Reference substance (positive control):

yes

Remarks:

dimethoate

Results and discussion

Effect concentrations

Key result

Duration:

48 h

Dose descriptor:

LD50

Remarks:

Oral

Effect conc.:

> 15 µg per animal

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality

Results with reference substance (positive control):

The LD50 values obtained with the reference item (dimethoate), were within the required ranges. The oral LD50 (24 h) value of the reference item (dimethoate) was calculated to be 0.15 μg a.i./bee.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The LD50 (48 h) was >15.0 μg a.i./bee in the oral toxicity test.

Executive summary:

In the oral toxicity test the maximum nominal test level of the test substance (15.0 μg a.i./bee) corresponded to an actual intake of exact 15.0 μg a.i./bee. This dose level led to 48 % mortality after 48 hours. 6.0 % mortality occurred in the water control group (50 % w/v sucrose solution = 500 g sucrose/L tap water). 2.0 % mortality occurred in the solvent control group (2.5 % DMSO in 50 % w/v sucrose solution).

Test item induced behavioural effects of a few bees (bees were moribund or affected, apathetic) were observed at all assessments in the oral test.

This study was terminated after the limit test recorded unexpectedly high mortality at the functional solubility maximum. Another study conducted by IBACON (IBACON Project 73133035; DAS Project 120379; completion date: November 29, 2012) shows no mortality at a dose level of 101.9 μg/bee when acetone was used as the solvent (5% acetone, 45% water, 50% sugar). Taken together, this suggests that the enhanced toxicity was attributable to the DMSO.

The oral LD50 (24 h) value of the reference item (dimethoate) was calculated to be 0.15 μg a.i./bee.

The toxicity of the test substance was tested in an acute oral toxicity test on honeybees. The LD50 (48 h) was > 15.0 μg a.i./bee in the oral toxicity test.