1,3,5-Triazine-2,4-diamine, N2-[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-yl]-6-(1-fluoroethyl)-

Toxicity to birds

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to birds: acute oral toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 223 (Avian Acute Oral Toxicity Test)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.2100 (Avian Acute Oral Toxicity Test)

Qualifier:

according to guideline

Guideline:

other: FIFRA 71-1

GLP compliance:

yes (incl. QA statement)

Dose method:

capsule

Analytical monitoring:

yes

Test organisms (species):

Colinus virginianus

Details on test organisms:

TEST ORGANISM
- Common name: Bobwhite quail
- Source: WW Quail Ranch of Oklahoma, located in Wardville, Oklahoma
- Age at test initiation: 16 weeks
- Sexes used: males and females

Limit test:

no

Total exposure duration (if not single dose):

14 d

Remarks:

Single dosing with 14-day post-dose monitoring period

Post exposure observation period:

14 days

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

Ten birds (5 males and 5 females) were randomly allocated to each of the four treatment levels (500, 1000, and 2000 mg ai/kg bw) and one control (non-exposed) group

Control animals:

yes

Duration (if not single dose):

14 d

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Conc. / dose based on:

act. ingr.

Basis for effect:

body weight

Remarks:

, Feed consumption, mortalities, Post-Mortem Examinations

Remarks on result:

other: Single dosing with 14-day post-dose monitoring period

Acute Oral Toxicity to Birds.

Acute Oral LD50WithNorthern BobwhiteQuail Exposed to AE 1170437 Technical
	mg ai/kg body weight
LD50=	>2000
Lowest lethal dose (LLD) =	>2000
Lowest observed adverse effect level (LOAEL) =	>2000
No observed adverse effect level (NOAEL) =	2000

Observations:

No clinical signs of toxicity or treatment-related mortalities were noted at any treatment level. There were no statistically significant reductions in body weight or growth at any treatment level. There was no treatment related reduction in feed consumption at any treatment level. Post-mortem examinations revealed no treatment related gross lesions or unusual observations.

Conclusion:

Based on the results of this study, the LD50 for technical AE 1170437 in northern bobwhite quail was >2000 mg ai/kg bw. Based on all parameters measured and observed, the NOAEL was 2000 mg ai/kg bw and the LOAEL was >2000 mg ai/kg bw technical AE 1170437.

Reference 2

Endpoint:

long-term toxicity to birds: reproduction test

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 206 (Avian Reproduction Test)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.2300 (Avian Reproduction Test)

Qualifier:

according to guideline

Guideline:

other: FIFRA Guideline 71-4

Qualifier:

according to guideline

Guideline:

other: OECD Draft Guideline (April 2000)

Principles of method if other than guideline:

Two separate studies were conducted and combined into one report. The mallard
reproduction study exposed adult mallard ducks (Anas platyrhynchos) to AE 1170437
technical for approximately 22 weeks and the mallard modified reproduction study exposed adult mallard ducks (Anas platyrhynchos)
to AE 1170437 technical for approximately 6 weeks.

GLP compliance:

yes (incl. QA statement)

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

no

Test organisms (species):

Anas platyrhynchos

Details on test organisms:

TEST ORGANISM
- Common name: mallard ducks
- Source: Whistling Wings, Hanover, Illinois
- Age at test initiation: 16 weeks
- Disease free: yes

Limit test:

no

Total exposure duration (if not single dose):

22 wk

Remarks:

second study with 6 weeks of exposure

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

70 males and 70 females

Control animals:

yes

Duration (if not single dose):

22 wk

Dose descriptor:

other: NOAEC

Effect level:

>= 1 015 mg/kg diet

Conc. / dose based on:

act. ingr.

Basis for effect:

reproductive parameters

Remarks:

and mortality

Duration (if not single dose):

22 wk

Dose descriptor:

other: NOAEC

Effect level:

>= 114 mg/kg bw/day

Conc. / dose based on:

act. ingr.

Basis for effect:

reproductive parameters

Results are confirmend in the 6-week modified reproduction study.

Conclusion:

The No Observed Adverse Effect Concentration (NOAEC) for both parental toxicity and

reproduction endpoints of mallard ducks exposed AE 1170437 in a 22-week reproduction

study and 6-week modified reproduction study was 1015 mg ai/kg feed or 114 mg ai/kg

bw/day. The Lowest Observed Adverse Effect Concentration (LOAEC) was >1015 mg ai/kg

food or >114 mg ai/kg bw/day.

Reference 3

Endpoint:

long-term toxicity to birds: reproduction test

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 206 (Avian Reproduction Test)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.2300 (Avian Reproduction Test)

Qualifier:

according to guideline

Guideline:

other: FIFRA Guideline 71-4

GLP compliance:

yes (incl. QA statement)

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

no

Test organisms (species):

Colinus virginianus

Details on test organisms:

TEST ORGANISM
- Common name: northern bobwhite quail
- Source: WW Quail Ranch of Oklahoma, Wardville, Oklahoma
- Age at test initiation: approximately 16 weeks
- Disease free: yes
- Kept according to standard practices: yes

Limit test:

no

Total exposure duration (if not single dose):

23 wk

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

Seventy two pairs (i.e. one male & one female) were utilized for the study.

Control animals:

yes

Duration (if not single dose):

23 wk

Dose descriptor:

NOEC

Effect level:

>= 1 023 mg/kg diet

Conc. / dose based on:

act. ingr.

Basis for effect:

reproductive parameters

Remarks:

and mortality

Duration (if not single dose):

23 wk

Dose descriptor:

NOEC

Effect level:

>= 111 mg/kg bw/day

Conc. / dose based on:

act. ingr.

Basis for effect:

reproductive parameters

Remarks:

and mortality

Dietary Concentration:

The nominal amounts of AE 1170437 technical in the dietary feed were administered at levels of 0 (control), 250, 500, and 1000 mg/kg feed. The average measured amounts of AE 1170437 technical for Week’s 1, 5, 10, 15, and 20 were determined as 0, 252, 524, and 1023 mg ai/kg feed representing percent nominal values of 101%, 105%, and 102%, respectively. These values correspond to daily dietary dose levels of 0, 26, 54, and 111 mg ai/kg bw/day, respectively. A summary of the dietary concentrations are included in the following table.

Feed Analysis Summary of AE 1170437
Nominal Dietary Level	Measured Dietary Level	Percent of	Daily Dietary Dose
(mg ai/kg feed)	(mg ai/kg feed)	Nominal	(mg ai/kg bw/day)
0 (control)	0	-	-
250	252	101 %	26
500	524	105 %	54
1000	1023	102 %	111

Adult Quail Clinical observations of adult birds exhibited no treatment related signs of toxicity. Adult mortality for the study included one control female bird with no mortality occurring in the treatment birds. There were no treatment–related mortalities, overt signs of toxicity or treatment-related effects upon body weight or feed consumption with the exception of feather loss and minor injuries as a result of cage wear. There were no compound related symptoms of toxicity in the adults and offspring.

Reproductive Effects

There were no statistically significant adverse effects for any reproductive endpoint in the study. The table below presents the reproductive endpoints totals.

Reproductive Parameter	Nominal Dietary Concentration (mg ai/kgfeed)
	Control	250	500	1000
No. of Eggs Laid	862	1099	1021	1043
No. of Eggs Cracked	13	23	14	16
No. of Eggs Set	786	988	923	932
No. of Viable Embryos	751	953	877	891
No. of 3-Week Live Embryos	750	941	872	885
No. of Hatched	708	865	836	834
No. of 14-Day Survivors	703	859	826	827

Reference 4

Endpoint:

short-term toxicity to birds: acute oral toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 223 (Avian Acute Oral Toxicity Test)

GLP compliance:

yes (incl. QA statement)

Dose method:

gavage

Vehicle:

yes

Details on preparation and analysis of diet:

DIET PREPARATION
- Preparation of doses: The test substance was dispersed in corn oil. The dosage was adjusted to 100% active ingredient. Therefore, the test dosages and the LD50 value are reported as milligrams of active ingredient per kilogram of body weight. Nominal dosages used in this study were 0, and 2000 milligrams of active ingredient per kilogram of body weight (mg a.i./kg).

Test organisms (species):

Poephila guttata

Details on test organisms:

TEST ORGANISM
- Common name: zebra finches
- Source: The birds were obtained from Maryland Exotic Birds Pasadena, MD
- Age at test initiation (mean and range, SD):
- Sexes used: males and femals
- Disease free: yes
- Kept according to standard practices: yes

Limit test:

yes

Total exposure duration (if not single dose):

14 d

Remarks:

day of dosing (Day 0)

Post exposure observation period:

Post-dosing Observation – 14 days

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

5 males and five females

Control animals:

yes

Duration (if not single dose):

14 d

Dose descriptor:

LC50

Effect level:

> 2 000 mg/kg diet

Conc. / dose based on:

act. ingr.

Basis for effect:

mortality

The acute oral LD50 value for Zebra Finch exposed to BCS-AA10717 Technical as a single oral dose was determined to be greater than 2000 mg a.i./kg, the highest dosage tested. The no-treatment related mortality level was 2000 mg a.i./kg.

Reference 5

Endpoint:

short-term toxicity to birds: dietary toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 205 (Avian Dietary Toxicity Test)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.2200 (Avian Dietary Toxicity Test)

Qualifier:

according to guideline

Guideline:

other: FIFRA Guideline 71-2

GLP compliance:

yes (incl. QA statement)

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

no

Test organisms (species):

Colinus virginianus

Limit test:

no

Total exposure duration (if not single dose):

5 d

Post exposure observation period:

The exposure period was followed by a 3-day subsequent recovery phase on untreated feed.

Control animals:

yes

Nominal and measured doses / concentrations:

Measured dietary concentrations of 324, 572, 1234, 2545, and 5007 mg ai/kg feed. were used.

Duration (if not single dose):

5 d

Dose descriptor:

NOEC

Effect level:

5 007 mg/kg diet

Conc. / dose based on:

act. ingr.

Basis for effect:

signs of toxicity

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 5 007 mg/kg diet

Conc. / dose based on:

act. ingr.

Basis for effect:

mortality

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 787 mg/kg bw

Conc. / dose based on:

act. ingr.

Basis for effect:

mortality

Short-term dietary toxicity to birds

Subacute Dietary LC50 WithNorthern BobwhiteQuail Exposed to AE 1170437 Technical
	mg ai/kg feed	mg ai/kg bodyweight
LC50=	>5007	>787
Lowest lethal concentration (LLC) =	>5007	>787
Lowest observed effect concentration (LOEC) =	>5007	>787
No Observed Effect Concentration (NOEC) =	5007	787

Observations:

No clinical signs of toxicity or treatment-related mortalities were noted at any treatment level. There were no statistically significant reductions in body weight or growth during the exposure period at any treatment level. There was no treatment related reduction in feed consumption at any treatment level. Postmortem examinations revealed no treatment related gross lesions or unusual observations.

Conclusion:

The sub-acute dietary LC50 of technical AE 1170437 in Northern Bobwhite was >5007 mg ai/kg feed or >787 mg ai/kg bodyweight. Based on all parameters measured, the NOEC was 5007 mg ai/kg feed (787 mg ai/kg bodyweight) and the LOEC was >5007 mg ai/kg feed (>787 mg ai/kg bodyweight).

Reference 6

Endpoint:

short-term toxicity to birds: dietary toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 205 (Avian Dietary Toxicity Test)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.2200 (Avian Dietary Toxicity Test)

Qualifier:

according to guideline

Guideline:

other: FIFRA Guideline 71-2

GLP compliance:

yes (incl. QA statement)

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

no

Test organisms (species):

Anas platyrhynchos

Limit test:

no

Total exposure duration (if not single dose):

5 d

Post exposure observation period:

The exposure period was followed by a 3-day subsequent recovery phase on untreated feed.

Control animals:

yes

Nominal and measured doses / concentrations:

Measured dietary concentrations of 0 (control), 329, 647, 1320, 2518, and 5215 mg ai/kg feed were used.

Duration (if not single dose):

5 d

Dose descriptor:

NOEC

Effect level:

2 518 mg/kg diet

Conc. / dose based on:

act. ingr.

Basis for effect:

signs of toxicity

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 5 215 mg/kg diet

Conc. / dose based on:

act. ingr.

Basis for effect:

mortality

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 1 126 mg/kg bw

Conc. / dose based on:

act. ingr.

Basis for effect:

mortality

Conclusion: The sub-acute dietary LC50 of technical AE 1170437 in Mallards was >5215 mg ai/kg feed or >1126 mg ai/kg bodyweight. Based on all parameters measured, the NOEC was 2518 mg ai/kg feed (577 mg ai/kg bodyweight) and the LOEC was 5215 mg ai/kg feed (1126 mg ai/kg bodyweight).

Sub-acute Dietary LC50 With Mallards Exposed to AE 1170437 technical
	mg ai/kg feed	mg ai/kg bodyweight
LC50=	>5215	>1126
Lowest lethal concentration (LLC) =	>5215	>1126
Lowest observed effect concentration (LOEC) =	5215	1126
No Observed Effect Concentration (NOEC) =	2518	577

Description of key information

No biologically effects could be observed in birds up to the highest test concentration of the test substance. Therefore, based on the available information, there is no indication for bioaccumulation of the substance or secondary poisoning.

Additional information

After single oral application LD50 values of >2000 mg /kg diet were obtained in studies with northern bobwhite quails and zebra finch. Neither mortality nor clinical signs of toxicity occurred in any study. Short-term (5 -day) feeding resulted in LC50 values of > 5000 ppm (diet) in the northern bobwhite quail and the mallard duck. Neither mortality nor clinical signs of intoxication attributable to the test substance were observed in any study. In two reproduction studies, one with northern bobwhite quail and the other with mallard ducks, the NOAEL for systemic and reproductive toxicity was considered to be > 1000 ppm (diet), which is the limit dose according to the OECD testing guideline. The substance showed a very low acute, short- and long-term hazard potential to birds as evidenced by endpoint data being above or equal the limit doses as specified in the corresponding testing guidelines. All studies referred to herein have been conducted according to the prevailing OECD or US EPA testing guidelines and GLP.