clothianidin (ISO); (E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine

Toxicity to birds

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to birds: reproduction test

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 Jan - 29 Jul, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 206 (Avian Reproduction Test)

Version / remarks:

1984

Deviations:

yes

Remarks:

missing few observation records and temperature records

GLP compliance:

yes

Dose method:

homogenously mixed into feed (accounts for technical substances)

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

acetone

Details on preparation and analysis of diet:

Nominal preparation for premixes was as follows:
Control: 7938.0 g ration + 180 ml corn oil + 200 ml acetone
80 ppm: 17.8200 g TI-435 Technical + 7920.2 g ration + 180ml com oil + 200 ml acetone
200 ppm: 44.5500 g TI-435 Technical + 7893.5g ration + 180ml corn oil + 200 ml acetone
500 ppm: 111.3750 g TI-435 Technical + 7826.6 g ration + 180ml com oil + 200 ml acetone

As needed, the appropriate premix was incorporated into the final diet as follows:
0 ppm: 2000 g Premix + 50.25 kg ration + 2.750 kg limestone
80 ppm: 2000 g Premix + 50.25 kg ration + 2.750 kg limestone
200 ppm: 2000 g Premix + 50.25 kg ration + 2.750 kg limestone
500 ppm: 2000 g Premix + 50.25 kg ration + 2.750 kg limestone

Samples were extracted with acetone. Concentrations of TI-435 Technical in extracts of the samples were determined by liquid chromatography using a Hewlett-Packard Model 1090 High Performance Liquid Chromatograph (HPLC) equipped with a Jasco Model 975 UV/VIS Detector.
he calculated LOD was 6.25 mg a.i./L. The method limit of quantitation (LOQ) for these analyses was set at 40.0 ppm based upon the lowest matrix fortification level analyzed concurrently with the samples.

Test organisms (species):

Anas platyrhynchos

Details on test organisms:

Pen-reared mallards, apparently healthy and phenotypically indistinguishable from wild birds. All birds were from the same hatch and were 30 weeks of age at test initiation (first day of exposure to test diet). Birds ranged in weight from 838 to 1340 grams at test initiation. The birds were approaching their first breeding season and had not been used in previous testing. Sex of the birds was determined by a visual examination of the plumage.

Limit test:

no

Total exposure duration (if not single dose):

21 wk

No. of animals per sex per dose and/or stage:

Each dose contained 16 pairs of birds with one male and one female per pen.

Control animals:

yes, concurrent no treatment

Nominal and measured doses / concentrations:

nominal concentrations: 80, 200 and 500 ppm.
Mean measured concentrations: 77.5, 205 and 525 ppm (97 to 105% of the mean nominal)

Details on test conditions:

The adult birds were housed indoors in batteries of pens measuring approximately 75 x 90 x 45 cm high and equiped with a feeder. The floors, walls, and ceilings of the pens were constructed of vinyl-coated wire grid.
During the feeding period additional feed was weighed and added to the feeders as needed. Water was supplied by nipple-type waterers.
The average temperature in the adult mallard study room during the course of the test was 19.9° C ± 1.8° C with an average relative humidity of 43% ± 17% . The air handling system in the study room was designed to vent up to 15 room air volumes every hour and replace them with fresh air.
The photoperiod during acclimation and the first 10 weeks of the test was eight hours or less of light per day. The photoperiod was increased to 17 hours of light per day at the beginning of Week 11 and was maintained at that length until the adult birds were euthanized.

Hatchlings were placed in batteries of brooder pens which measured approximately 62 x 92 x 25.5cm high. The walls, floor and ceiling were constructed
of vinyl coated wire mesh. Each contained a feeder and a waterer. Thermostats in the brooding compartment of each pen maintained a temperature of approximately 38°C from hatching until the birds were 5 to 7 days of age. The average ambient room temperature was 24.9°C ± 1.7°C with an average relative humidity of 76% ± 19%. The photoperiod for the hatchlings was maintained by a time clock at 16 hours of light per day.

Details on examinations and observations:

All adults and offspring will be observedat least oncedaily for mortality, general condition, overt signs of toxicity and abnormal behavior. Individual body weights of the adults will be taken at the initiation of the test, at the end of test weeks 2, 4, 6, 8 and at adult termination. Feed consumption of the adults will be recorded by pen for a seven day period each week throughout the test with the exception of the last interval which will be determined by experimental termination.

Details on reproductive parameters:

The following reproductive parameters were measured and recorded:
1. eggs laid
2. eggs cracked
3. eggs incubated
4. infertile or clear eggs
5. dead embryos (to Day 13-15)
6. viable embryos
7. dead embryos (to Day 20-22)
8. live three weekembryos
9. unnatched eggs
10. hatchlings
11. 14-day old offspring survival
12. offspring bodyweights, day 0 and 14
13. egg shell thickness

Key result

Duration (if not single dose):

21 wk

Dose descriptor:

NOEC

Effect level:

ca. 500 mg/kg diet

Conc. / dose based on:

test mat.

Basis for effect:

reproductive parameters

Mortality and sub-lethal effects:

No mortalities occurred in the control group or in the 80, 200 and 500 ppm treatment groups during the course of the study and no overt signs of toxicity were observed at any of the concentrations tested. Incidental clinical signs such as eye lesions, foot lesions, lameness, and feather loss were observed during the test. Such incidental signs, generally, were associated with penwear and incidental injuries. One hen in the 200 ppm treatment group was noted with a prolapsed uterus during Week 17 of the study. However, the prolapse was reduced and the hen appeared normal in all subsequent observations. Except for these incidental clinical findings, all birds appeared normal throughout the study.

Effects on reproduction:

There were no treatment-related effects upon reproductive performance at any of the concentrations tested. Any differences between the control group and the 80, 200, and 500 ppm treatment groups were not statistically significant for any of the reproductive parameters measured.
There were no apparent treatment-related effects upon eggshell thickness at any of the concentrations tested.
There were no apparent treatment related effects upon offspring body weight at any of the concentrations tested.

Further details on results:

There were no treatment-related effects upon adult body weight at any of the concentrations tested.
There were no treatment-related effects upon feed consumption at any of the concentrations tested.

Please refer to "overall remark/ attached background material" field for result tables.

Table 1: Validity criteria for OECD 206 (1984)

Criterion	Outcome	Criterion fulfilled
Mortality in the control < 10% at the end of the test.	0%	Yes
The average number of 14-day-old survivors per hen in the controls should be at least 12 (bobwhite quail)	Mean number 30	Yes
The average egg shell thickness for the control should be at least 0.34 mm (mallard)	Mean 0.381	Yes
There must be evidence that the concentration of the substance being tested has been satisfactorily maintained in the diet (it should be at least 80% of the nominal concentration) throughout the test period.	The mean measured concentrations ranged from 97 to 105%	Yes

Validity criteria fulfilled:

yes

Remarks:

For further details please refer to “Any other information on results incl. tables”.

Conclusions:

The present guideline study was conducted in compliance with GLP. Under the test conditions used, the 21-week NOEC for A. Platyrhynchos was 500 mga.s./kg diet.

Description of key information

The overall NOEC reproduction (21 weeks) for birds was estimated to be 500 mg a.s./kg diet for Anas platyrhynchos.

Key value for chemical safety assessment

Short-term EC50 or LC50 for birds:

5 200 mg/kg food

Long-term EC10, LC10 or NOEC for birds:

500 mg/kg food

Additional information

Four GLP-studies are available for toxicity testing to birds and one of them was identified as key study.

 

A key study (2000) investigating the chronic effects of test substance on bird species following OECD 206 guideline, under GLP was available. The birds were exposed to the nominal dietary concentrations of 80, 200 and 500 mg a.s./kg feed, alongside with a control. Mean measured concentrations ranged from 97% to 105% of nominal concentrations. Based on the nominal concentrations, after 21 weeks, no effects on the reproductive performance of Anas platyrhynchos were reported up to the highest concentration tested (NOEC = 500 mg a.s./kg diet).

 

A supportive study (2000) was conducted for 21 weeks according to the OECD 206 guideline and GLP with Colinus virginianus resulting in NOEC of 500 mg a.s./kg diet (highest tested concentration).

 

The acute dietary toxicity of test substance on bird species has been investigated in two supportives studies. The studies were conducted with standard species (Anas platyrhynchos and Colinus virginianus) according to EPA OPP Guidelines 71-2 and OECD 205, under GLP conditions. The results from the 5 days-dietary tests both resulted in a LC₅₀ > 5200 mg a.s./kg diet.

 

Additionally, birds mortality was evaluated in five acute oral tests, resulting in a LD₅₀ ranging from 414 to > 2000 mg a.s./kg body weight according to EPA OPP 71-1, OPPTS 850.2100 and OECD 223 guidelines.