3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione;famoxadone (ISO)

Toxicity to birds

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to birds: reproduction test

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

February 9, 1995 - August 17, 1995

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

Qualifier:

according to guideline

Guideline:

EPA OPP 71-4 (Avian Reproduction Test)

Version / remarks:

1982

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 97.4%
Batch: DPX-JE874-221

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

vehicle (com oil) and solvent (acetone)

Details on preparation and analysis of diet:

Diet for the birds was formulated to Wildlife International Ltd. specifications by Agway Inc. The diet contained 27% protein minimum, 2.5% fat minimum and 5% fiber maximum. Five percent (w/w) limestone was added to the diet to provide a calcium source. Test diets were prepared weekly.

Homogeneity of the test substance in the diet was evaluated by collecting six samples each from the treatment groups on Day 0 of Week 1. Homogeneity samples were collected from the top, middle and bottom of the left and right sections of the mixing vessel. A control sample was also collected on Day 0 of Week 1. Test substance concentrations in the diets were verified by analyzing one sample collected from the control group and duplicate samples collected from each treatment group for Weeks 2, 3, 4, 8, 12, 16 and 20 of the test. Additionally, diet samples were collected from the feeders of each of the control (one sample) and treatment groups (two samples) on Day 7 of Week 1 to verify the presence of the test substance under actual test conditions. The diet samples were stored frozen and transferred on dry ice to Haskell Laboratory, P.O. Box 50, Elkton Road, Newark, Delaware 19714 for analysis.

Test organisms (species):

Anas platyrhynchos

Total exposure duration (if not single dose):

21 wk

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

16/sex/dose

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

Nominal: 0, 50, 250, 1250 ppm
Means and standard deviations for the three test concentrations were 44.1 ± 1.93 ppm a.i., 254 ± 11.5 ppm a.i. and 1250 ± 63.1 ppm a.i., respectively, while coefficients of variation were 4.38%, 4.53% and 5.05%, respectively. Control diet samples collected during the test showed no interferences. Diet samples collected during Weeks 1, 2, 3, 4, 8, 12, 16 and 20 following preparation of the 50, 250 and 1250 ppm a.i. test concentrations averaged 91%, 101% and 101% of the nominal concentrations, respectively. Analysis of diet samples collected on Day 7 of Week 1 averaged 98%, 94% and 99% of the Day 0 value for the 50, 250 and 1250 ppm a.i. test concentrations, respectively.

Details on examinations and observations:

MORTALITY / CLINICAL SIGNS
All adult birds were observed throughout the test for signs of toxicity or abnormal behavior.
A record was maintained of all mortalities and observations

BODY WEIGHT
Adult body weights were measured at test initiation, on Weeks 2, 4, 6, 8, and at adult termination. Body weights were not measured during egg laying because of the possible adverse effects handling may have on egg production

FOOD CONSUMPTION
Feed consumption was measured for each pen for a seven day period. Feed consumption was determined by weighing the freshly filled feeder on Day 0, recording the amount of any additional diet added during the week and weighing the feeder and remaining feed at the end of the feeding period. No attempt was made to quantify the amount of feed wasted by the birds, as the wasted feed is normally scattered and mixed with water and excreta. Therefore, feed consumption is presented as an estimate.

PATHOLOGY
At the conclusion of the exposure period all surviving adult birds were euthanized by cervical dislocation, necropsied and disposed of by incineration.

Details on reproductive parameters:

The following parameters were examined per parental pen per week:
- Eggs laid
- Eggs cracked; eggs broken
- Eggs set
- Eggshell thickness or eggshell strength
- Embryos viable
- Live 3-week embryos
- hatchlings
- body weight of hatchlings
- 14-day old surviving chicks
- Chick body weight at 14 days after hatching

Key result

Duration (if not single dose):

21 wk

Dose descriptor:

NOEC

Effect level:

1 250 other: ppm

Conc. / dose based on:

test mat.

Basis for effect:

other: no adverse effects observed at highest dose tested

Mortality and sub-lethal effects:

There were no treatment related mortalities, overt signs of toxicity or treatment related effects on body weight or feed consumption at any of the concentrations tested.
While no mortalities occurred in the control group or in the 250 and 1250 ppm a.i. treatment groups, one incidental mortality occurrea m the 50 ppm a.i. treatment group. The single mortality in the 50 ppm a.i. treatment group was a drake (Pen 232) that was found dead during Week 6. One day prior to death, the drake was noted with a swollen foot and leg and was unable to stand. At necropsy, the drake had a body weight of 949 grams. Externally, abrasions were noted on the edges of both wings. Internally, chalk-like deposits were noted in the heart, the lower margins of the lungs were congested and the spleen was enlarged. The kidneys were pale and the testes were developing. No other lesions were noted and necropsy of the drake's penmate was unremarkable. No other mortalities occurred during the course of the test. Due to the nature of the lesions observed at necropsy, the mortality that occurred was not considered to be treatment related.

Effects on reproduction:

There were no statistically significant differences in the reproductive parameters measured at the 50, 250 or 1250 ppm a.i. test concentrations.
Although when compared with the control group there were slight reductions in egg production at both the 50 and 1250 ppm a.i. test concentrations, the differences were not statistically significant and were the result of the presence of one unproductive hen in each of the two groups. When data from those two pens were eliminated, the numbers of eggs laid per hen (50 ± 14 and 51 ± 10, respectively) were found to be comparable to the control group (53 ± 15). Since it is not atypical to have one or more unproductive hens per group in reproduction studies with first year breeders, the presence of one unproductive hen in both the 50 and 1250 ppm a.i. treatment groups was considered to be neither treatment related nor biologically meaningful. The slight differences in the mean numbers of eggs laid per group were not considered to be treatment related.

While there was a slight reduction in embryo viability at both the 250 and 1250 ppm a.i. test concentrations, the observed differences from the control group not statistically significant. The reduction in mean embryo viability observed at the 250 ppm a.i. treatment group was exacerbated by one pen in which none of the eggs that were incubated contained viable embryos at the Day 14 candling. When data from that pen were eliminated, the mean percent viability was 87% ± 12%. All values were comparable to the current study control (94% ± 6%) and the historical control value for this parameter of 90% ± 5%.

Additionally, there appeared to be slight reductions in the numbers of hatchlings as a percentage of live З-week embryos at both the 250 and 1250 ppm a.i. test concentrations. The observed differences from the control group in both the 250 and 1250 ppm a.i. treatment groups were primarily the result of decreases in the numbers of pens with hatchability of greater than 70%. However, the differences observed were not statistically significant, and all values comparable to the mean value for this parameter, 46% ± 13%, observed in the ten closest contemporaneous mallard reproduction studies.

Validity criteria fulfilled:

yes

Conclusions:

21-week NOEC (Mallard duck) = 1250 ppm (the highest dose tested)

Executive summary:

A one-generation mallard reproduction study was conducted with DPX-JE874-221. This study was conducted in compliance with the FIFRA 71-4 and OECD guideime 206. DPX-JE874-221 was administered ad libitum in the diet to groups of 16 pairs of young adult mallards (21 weeks old at test initiation) approaching their first breeding season. Mature mallards received DPX-JE874-221 at nominal dietary concentrations of 50, 250, and 1250 ppm a.i. for 21 weeks. A control group was maintained concurrently with the treatment groups. The study was conducted with the highest concentration level at or above the maximum field residue level (i.e., the expected concentration on avian food items when treated at recommended label rates).

The mallards were observed daily for mortality, abnormal behavior, and signs of toxicity. Adult body weights were measured at test initiation, on Weeks 2, 4, 6, 8 and at adult termination. Feed consumption was measured weekly for each pen for a seven day period. Necropsies were performed on all adults surviving until adult termination and all adults that died during the test.

 

For the first 9 weeks of the test the birds were held under a photoperiod of 8 hours or less of light per day. The photoperiod was increased to 17 hours of light per day at the beginning of Week 10 to induce egg laying. The adults continued on a photoperiod of 17 hours of light per day until adult termination. Eggs were collected daily from the onset of egg production and set weekly for incubation. The first eggs were set during Week 11. Weekly throughout the laying period, eggs were collected from every other pen for egg shell thickness measurements. In addition, effects upon egg production and quality, and hatchling health and survivability examined.

 

There were no treatment related mortalities, overt signs of toxicity or treatment related effects on body weight or feed consumption at any of the concentrations tested. There were no statistically significant differences in the reproductive parameters measured at the 50, 250 or 1250 ppm a.i. test concentrations. Based upon statistical analysis of the data, the no observed effect concentration for mallards exposed to DPX-JE8 74-221 in the diet during this study was 1250 ppm a.i., the highest concentration tested.

 

Reference 2

Endpoint:

long-term toxicity to birds: reproduction test

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

February 9, 1995 - August 7, 1995

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

Qualifier:

according to guideline

Guideline:

EPA OPP 71-4 (Avian Reproduction Test)

Version / remarks:

1982

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 97.4%
Batch: DPX-JE874-221

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

vehicle (com oil) and solvent (acetone)

Details on preparation and analysis of diet:

Diet for the birds was formulated to Wildlife International Ltd. specifications by Agway Inc. The diet contained 27% protein minimum, 2.5% fat minimum and 5% fiber maximum. Five percent (w/w) limestone was added to the diet to provide a calcium source. Test diets were prepared weekly.

Homogeneity of the test substance in the diet was evaluated by collecting six samples each from the treatment groups on Day 0 of Week 1. Homogeneity samples were collected from the top, middle and bottom of the left and right sections of the mixing vessel. A control sample was also collected on Day 0 of Week 1. Test substance concentrations in the diets were verified by analyzing one sample collected from the control group and duplicate samples collected from each treatment group for Weeks 2, 3, 4, 8, 12, 16 and 20 of the test. Additionally, diet samples were collected from the feeders of each of the control (one sample) and treatment groups (two samples) on Day 7 of Week 1 to verify the presence of the test substance under actual test conditions. The diet samples were stored frozen and transferred on dry ice to Haskell Laboratory, P.O. Box 50, Elkton Road, Newark, Delaware 19714 for analysis.

Test organisms (species):

Colinus virginianus

Total exposure duration (if not single dose):

20 wk

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

16/sex/dose

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

Nominal: 0, 50, 250, 1250 ppm
Means and standard deviations for the three test concentrations were 44.1 ± 1.93 ppm a.i., 254 ± 11.5 ppm a.i. and 1250 ± 63.1 ppm a.i., respectively, while coefficients of variation were 4.38%, 4.53% and 5.05%, respectively. Control diet samples collected during the test showed no interferences. Diet samples collected during Weeks 1, 2, 3, 4, 8, 12, 16 and 20 following preparation of the 50, 250 and 1250 ppm a.i. test concentrations averaged 91%, 101% and 101% of the nominal concentrations, respectively. Analysis of diet samples collected on Day 7 of Week 1 averaged 98%, 94% and 99% of the Day 0 value for the 50, 250 and 1250 ppm a.i. test concentrations, respectively.

Details on examinations and observations:

MORTALITY / CLINICAL SIGNS
All adult birds were observed throughout the test for signs of toxicity or abnormal behavior.
A record was maintained of all mortalities and observations

BODY WEIGHT
Adult body weights were measured at test initiation, on Weeks 2, 4, 6, 8, and at adult termination. Body weights were not measured during egg laying because of the possible adverse effects handling may have on egg production

FOOD CONSUMPTION
Feed consumption was measured for each pen for a seven day period. Feed consumption was determined by weighing the freshly filled feeder on Day 0, recording the amount of any additional diet added during the week and weighing the feeder and remaining feed at the end of the feeding period. No attempt was made to quantify the amount of feed wasted by the birds, as the wasted feed is normally scattered and mixed with water and excreta. Therefore, feed consumption is presented as an estimate.

PATHOLOGY
At the conclusion of the exposure period all surviving adult birds were euthanized by cervical dislocation, necropsied and disposed of by incineration.

Details on reproductive parameters:

The following parameters were examined per parental pen per week:
- Eggs laid
- Eggs cracked; eggs broken
- Eggs set
- Eggshell thickness or eggshell strength
- Embryos viable
- Live 3-week embryos
- hatchlings
- body weight of hatchlings
- 14-day old surviving chicks
- Chick body weight at 14 days after hatching

Key result

Duration (if not single dose):

20 wk

Dose descriptor:

NOEC

Effect level:

1 250 other: ppm

Conc. / dose based on:

test mat.

Basis for effect:

other: no adverse effects observed at highest dose tested

Mortality and sub-lethal effects:

There were no treatment related mortalities, overt signs of toxicity or treatment related effects on body weight or feed consumption at any of the concentrations tested.
While no mortalities occurred in the 1250 ppm a.i. treatment group, one incidental mortality occurred in both the control group and in the 50 and 250 ppm a.i. treatment groups. The single mortality in the control group was a hen (Pen 209) that was found dead during Week 19 without having exhibited prior clinical signs. At necropsy, the hen was in good flesh with a body weight of 248 grams. Externally, feather loss was noted on the head. Internally, a subcutaneous hematoma was noted on the dorsal portion of the neck and the neck was broken in the approximate area of the fourth to fifth cervical vertebrae. No other lesions were noted and
necropsy of the hen’s penmate was unremarkable.

The single mortality in the 50 ppm a.i. treatment group was a cock (Pen 220) that was found dead during Week 14. During Week 6, the cock was noted with ventral head curl that was ultimately considered normal for the cock. No clinical signs were observed immediately prior to death. At necropsy, the cock was in good flesh, with a body weight of 219 grams. Internally, subcutaneous bruising was noted on both shoulders. Hematomas were noted on the right shoulder and dorsal portion of the neck. The neck was broken in the approximate area of the second to third cervical vertebrae. No other lesions were noted and necropsy of the cock’s penmate was unremarkable.

The single mortality in the 250 ppm a.i. treatment group was a hen (Pen 239) that was found dead during Week 13. Prior to death, the hen was noted with foot and leg lesions and limping. Additionally, the hen exhibited wing droop, loss of coordination, a thin and ruffled appearance and lethargy. At necropsy, the hen was emaciated, with a body weight of 95 grams and exhibited a significant loss of muscle mass and a prominent keel. Externally, foot lesions were noted, while feather loss was noted on the left flank with areas of bruising and abrasions. Internally, the abdominal cavity showed evidence of yolk remnants and slight egg yolk peritonitis. The intestinal tract contents were greenish black and pasty and the ovary was regressing. No other lesions were noted. Necropsy of the hen’s penmate was unremarkable.

No other mortalities occurred during the course of the test. Due to the nature of the
lesions observed at necropsy, none of the mortalities that occurred were considered to be
treatment related.

Incidental clinical observations normally associated with penwear or interactions among penmates were observed and included head, eye, wing, hock, rump, leg or foot lesions, ventral head curl and feather loss. Clinical signs such as lameness, difficulty navigating, lethargy and a ruffled appearance occasionally were noted, and were often associated with the incidental injuries. One hen in the 250 ppm a.i. test concentration was noted exhibiting a reduced reaction to external stimuli (sound and movement), lethargy and a ruffled appearance with no apparent injury during Week 13. However, the hen was considered to appear normal during Week 14, and remained so until adult termination. Except for incidental clinical findings, all birds appeared normal throughout the study.

Effects on reproduction:

There were no statistically significant differences in the reproductive parameters measured at the 50, 250 or 1250 ppm a.i. test concentrations.

While not statistically significant, there appeared to be slight reductions in egg production, embryo viability, and hatchling survivability at the 250 ppm a.i. test concentration. Additionally, there was a slight, but statistically significant (p < 0.05) decrease in hatchlings as a percentage of live З-week embryos in the 250 ppm a.i. treatment group. The above reductions in the 250 ppm a.i. treatment group were further reflected as statistically significant (p < 0.05) reductions in hatchlings and 14-day old survivors as percentages of both eggs set and the maximum number of eggs set. However, in each case, the reductions observed were confined to only a few pens in the treatment group. Since the reductions were slight, confined to several pens and were not concentration dependent, the differences were not considered to be related to treatment or biologically meaningful.

At the 1250 ppm a.i. test concentration there appeared to be a slight reduction in egg production. However, the apparent reduction was primarily the result of data from one pen in which no eggs were laid. When data from that pen were eliminated, the number of eggs laid per hen (46 ± 9) was found to be comparable to the control group (49 ± 14). It is not atypical to have several unproductive hens in reproduction studies in which first year, unproven breeders are required. Therefore, the presence of one unproductive hen in the 1250 ppm a.i. treatment group was considered to be neither treatment related nor biologically meaningful.

Validity criteria fulfilled:

yes

Conclusions:

20-week NOEC (bobwhite quail) = 1250 ppm (the highest dose tested)

Executive summary:

A one-generation northern bobwhite reproduction study was conducted with DPX-JE874-221. This study was conducted in compliance with the FIFRA 71-4 and OECD guideime 206. DPX-JE874-221 was administered ad libitum in the diet to groups of 16 pairs of young adult mallards (18 weeks old at test initiation) approaching their first breeding season. Mature quails received DPX-JE874-221 at nominal dietary concentrations of 50, 250, and 1250 ppm a.i. for 20 weeks. A control group was maintained concurrently with the treatment groups. The study was conducted with the highest concentration level at or above the maximum field residue level (i.e., the expected concentration on avian food items when treated at recommended label rates).

 

The quails were observed daily for mortality, abnormal behavior, and signs of toxicity. Adult body weights were measured at test initiation, on Weeks 2, 4, 6, 8 and at adult termination. Feed consumption was measured weekly for each pen for a seven day period. Necropsies were performed on all adults surviving until adult termination and all adults that died during the test.

 

For the first 7 weeks of the test the birds were held under a photoperiod of 7 hours or less of light per day. The photoperiod was increased to 17 hours of light per day at the beginning of Week 8 to induce egg laying. The adults continued on a photoperiod of 17 hours of light per day until adult termination. Eggs were collected daily from the onset of egg production and set weekly for incubation. The first eggs were set during Week 11. Weekly throughout the laying period, eggs were collected from every other pen for egg shell thickness measurements. In addition, effects upon egg production and quality, and hatchling health and survivability examined.

 

There were no treatment related mortalities, overt signs of toxicity or treatment related effects on body weight or feed consumption at any of the concentrations tested. There were no statistically significant differences in the reproductive parameters measured at the 50, 250 or 1250 ppm a.i. test concentrations. Based upon statistical analysis of the data, the no observed effect concentration for bobwhite quails exposed to DPX-JE874-221 in the diet during this study was 1250 ppm a.i., the highest concentration tested.

 

Reference 3

Endpoint:

short-term toxicity to birds: dietary toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

April 14, 1994 - April 22, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 205 (Avian Dietary Toxicity Test)

Version / remarks:

1984

Qualifier:

according to guideline

Guideline:

EPA OPP 71-2 (Avian Dietary Toxicity Test)

Version / remarks:

1982

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 97.4%
Batch: DPX-JE874-221

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

vehicle (com oil) and solvent (acetone)

Details on preparation and analysis of diet:

Test diets were prepared by first dissolving the test substance in acetone, corn oil and then blending the solution into the diet in a Hobart (Model Number AS200T) mixer. The concentration of corn oil in the treated and control diets was 2%. Acetone was allowed to volatilize from the diets during the mixing procedure. An amount of diet sufficient to last the five day exposure period was prepared on the day of test initiation for each treatment and control group. Diets were presented to the birds at initiation of the test, and added to the feeders as needed during the five day exposure period. The dietary concentrations were not adjusted for purity of the test substance. Therefore all dietary concentrations and the LC50 value are reported as parts per million of the test substance as received.
Samples of the test diets were taken to verify the test concentrations administered and to confirm the stability and homogeneity of the test substance in the diets.

Test organisms (species):

Colinus virginianus

Details on test organisms:

10 days of age at test initiation

Total exposure duration (if not single dose):

5 d

Post exposure observation period:

3 days

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

10/sex/dose

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

Nominal dietary test concentrations used in this study were 562, 1000, 1780, 3160 and 5620 ppm.

Details on examinations and observations:

All birds were observed at least twice daily. A record was maintained of all mortality, signs of
toxicity and abnormal behavior.


Body weights by group were measured at the initiation of the test, on Day 5, and at termination of the test on Day 8. Average feed consumption values during the exposure period (Days 0-5) and the post-exposure observation period (Days 6-8) were determined for each treatment and control group. Feed consumption was determined by measuring the change in the weight of the feed presented to the birds over a given period of time. The accuracy of feed consumption values may have been affected by the unavoidable wastage of feed by the birds.

Key result

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 5 620 other: ppm

Conc. / dose based on:

test mat.

Basis for effect:

other: no effects at the highest dose tested

Mortality and sub-lethal effects:

There were no mortalіties in the control groups. All birds in the control groups were normal in appearance and behavior throughout the test period. Additionally, there were no mortalities or overt signs of toxicity noted at any of the test concentrations. At the 562 ppm test concentration, there was one mortality noted on Day 7 of the test, which was attributed to an impacted vent. This was apparently the result of vent picking, which is a form of cagemate aggression. No other mortalіties occurred in any treatment group, and the other birds were normal in appearance and behavior during the course of the study.
When compared to the controls, there did not appear to be an effect upon body weight or feed consumption at any of the concentrations tested.

Validity criteria fulfilled:

yes

Conclusions:

5-day LC50 (bobwhite quail) > 5620 ppm (the highest dose tested)

Executive summary:

The objective of this study was to evaluate the toxicity of DPX-JE874- 221 when administered to juvenile bobwhite quails in the diet for five days. The methods used in the study were based upon procedures in FIFRA 71-2 and OECD guideline 205. Ten quail ducklings were assigned to each of the treatment and control groups by indiscriminate draw. Birds were acclimated from the day they were received until test initiation. The test consisted of a geometric series of five test concentrations and four control groups, dietary concentrations used in this study were 562, 1000, 1780, 3160 and 5620 parts per million (ppm). Each group was fed the appropriate test control diet for five days. During the exposure period the control group received an amount of the vehicle (corn oil) in their diet equivalent to the amount used in the treated diets. Following the five day exposure period all groups were given untreated feed for three days.

 

The dietary LC50 value for bobwhite quails exposed to DPX-JE874-221 was determined to be > 5620 ppm, the highest concentration tested. The no mortality and no observed effect concentrations were 5620 ppm.

 

Reference 4

Endpoint:

short-term toxicity to birds: dietary toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

April 14, 1994 - April 22, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 205 (Avian Dietary Toxicity Test)

Version / remarks:

1984

Qualifier:

according to guideline

Guideline:

EPA OPP 71-2 (Avian Dietary Toxicity Test)

Version / remarks:

1982

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 97.4%
Batch: DPX-JE874-221

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

vehicle (com oil) and solvent (acetone)

Details on preparation and analysis of diet:

Test diets were prepared by first dissolving the test substance in acetone, corn oil and then blending the solution into the diet in a Hobart (Model Number AS200T) mixer. The concentration of corn oil in the treated and control diets was 2%. Acetone was allowed to volatilize from the diets during the mixing procedure. An amount of diet sufficient to last the five day exposure period was prepared on the day of test initiation for each treatment and control group. Diets were presented to the birds at initiation of the test, and added to the feeders as needed during the five day exposure period. The dietary concentrations were not adjusted for purity of the test substance. Therefore all dietary concentrations and the LC50 value are reported as parts per million of the test substance as received.
Samples of the test diets were taken to verify the test concentrations administered and to confirm the stability and homogeneity of the test substance in the diets.

Test organisms (species):

Anas platyrhynchos

Details on test organisms:

10 days of age at test initiation

Total exposure duration (if not single dose):

5 d

Post exposure observation period:

3 days

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

10/sex/dose

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

Nominal dietary test concentrations used in this study were 562, 1000, 1780, 3160 and 5620 ppm.

Details on examinations and observations:

All birds were observed at least twice daily. A record was maintained of all mortality, signs of
toxicity and abnormal behavior.


Body weights by group were measured at the initiation of the test, on Day 5, and at termination of the test on Day 8. Average feed consumption values during the exposure period (Days 0-5) and the post-exposure observation period (Days 6-8) were determined for each treatment and control group. Feed consumption was determined by measuring the change in the weight of the feed presented to the birds over a given period of time. The accuracy of feed consumption values may have been affected by the unavoidable wastage of feed by the birds.

Key result

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 5 620 other: ppm

Conc. / dose based on:

test mat.

Basis for effect:

other: no effects at the highest dose tested

Mortality and sub-lethal effects:

There were no mortalіties in the control groups. All birds in the control groups were normal in appearance and behavior throughout the test period. Additionally, there were no mortalities or overt signs of toxicity noted at any of the test concentrations. All birds in all treatment groups were normal in appearance and behavior throughout the test period.
When compared to the controls, there did not appear to be an effect upon body weight or feed consumption at any of the concentrations tested.

Validity criteria fulfilled:

yes

Conclusions:

5-day LC50 (mallard duck) > 5620 ppm (the highest dose tested)

Executive summary:

The objective of this study was to evaluate the toxicity of DPX-JE874- 221 when administered to juvenile mallards in the diet for five days. The methods used in the study were based upon procedures in FIFRA 71-2 and OECD guideline 205. Ten mal lard ducklings were assigned to each of the treatment and control groups by indiscriminate draw. Birds were acclimated from the day they were received until test initiation. The test consisted of a geometric series of five test concentrations and four control groups, dietary concentrations used in this study were 562, 1000, 1780, 3160 and 5620 parts per million (ppm). Each group was fed the appropriate test control diet for five days. During the exposure period the control group received an amount of the vehicle (corn oil) in their diet equivalent to the amount used in the treated diets. Following the five day exposure period all groups were given untreated feed for three days.

 

The dietary LC50 value for mallards exposed to DPX-JE874-221 was determined to be > 5620 ppm, the highest concentration tested. The no mortality and no observed effect concentrations were 5620 ppm.

 

Reference 5

Endpoint:

short-term toxicity to birds: acute oral toxicity test (LD50-only)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

May 24, 1994 - June 7, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 71-1 (Avian Acute Oral Toxicity Test)

Version / remarks:

1982

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 97.4%
Batch: DPX-JE874-221

Dose method:

gavage

Analytical monitoring:

no

Vehicle:

yes

Remarks:

vehicle (com oil)

Test organisms (species):

Colinus virginianus

Details on test organisms:

21 weeks of age at test initiation

Total exposure duration (if not single dose):

1 d

Post exposure observation period:

14 days

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

5/sex/dose

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

Nominal dosages used in this study. were 292, 486, 810, 1350 and 2250 milligrams of DPX-JE874-221 per kilogram of body weight.

Details on examinations and observations:

All birds were observed at least twice daily. A record was maintained of all mortality, signs of
toxicity and abnormal behavior.

Body weights were measured individually at the initiation of the test and on Days 3, 7, and 14. Average feed consumption was determined for each dosage group and the controls for Days 0-3, 4-7, and 8-14. Feed consumption was determined by measuring the change in the weight of the feed presented to the birds over a given period of time. The accuracy of feed consumption values may have been affected by the unavoidable wastage of feed by the birds.

Key result

Duration (if not single dose):

1 d

Dose descriptor:

LD50

Effect level:

> 2 250 mg/kg bw

Conc. / dose based on:

test mat.

Basis for effect:

other: no effects at the highest dose tested

Mortality and sub-lethal effects:

There were no mortalities in the control group. All birds in the control group were normal in appearance and behavior throughout the test period. Additionally, there were no mortalities or overt signs of toxicity noted at any of the test dosages. One female at the 1350 mg/kg test dosage was noted with an eye injury on Day 6. The hen kept the injured eye closed through the remainder of the study. This injury was apparently the result of cagemate aggression, and was not considered to be treatment related. Otherwise, all other birds at all dosages were normal in appearance and behavior throughout the test period.

When compared to the controls, there did not appear to be an effect upon body weight or feed consumption at any of the dosages tested

Validity criteria fulfilled:

yes

Conclusions:

Oral LD50 (bobwhite quail) > 2250 mg/kg (the highest dose tested)

Executive summary:

The objective of this study was to evaluate the acute toxicity of DPX-JE874-221 administered to the northern bobwhite as a single oral dose. The methods used in conducting this study were based FIFRA Section 71-1. Ten northern bobwhite, five males and five females, were assigned to each of the treatment groups and the control group by indiscriminate draw. The test consisted of a geometric series of five dosage groups and a control group. Nominal dosages used in this study. were 292, 486, 810, 1350 and 2250 milligrams of DPX-JE874-221 per kilogram of body weight. The control group was dosed with diluent only. At initiation of the test, a single dose of the test substance in diluent was orally intubated directly into the crop of proventriculus of each bird using a stainless steel cannula.

The acute oral LD50 value for northern bobwhite exposed to DPXJE874- 221 as a single oral dosage was determined to be > 2250 mg/kg, the highest dosage tested. The no mortality and no observed effect dosage was 2250 mg/kg.

 

Reference 6

Endpoint:

short-term toxicity to birds: acute oral toxicity test (LD50-only)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

August 18, 2016 - August 23, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.2100 (Avian Acute Oral Toxicity Test)

Version / remarks:

2012

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 978.2%
Batch: DPX-JE874-496

Dose method:

gavage

Analytical monitoring:

no

Vehicle:

no

Test organisms (species):

other: Taeniopygia guttata

Details on test organisms:

Approximately 7-8 months of age at initiation

Total exposure duration (if not single dose):

1 d

Post exposure observation period:

14 days

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

5/sex/dose

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

Nominal dosages used in this study were 0 and 2250 mg/kg of body weight.

Details on examinations and observations:

Following dosing, multiple cage-side observations were performed on Day 0 of the test, with particular attention being paid for signs of regurgitation. From test initiation until termination, all birds were observed twice daily. A record was maintained of all mortality, signs of toxicity, and abnormal behavior..

Body weights were measured individually one day prior to dosing (Day -1) to allow time for capsule preparation and on Days 3, 7 and 14 of the test. Average estimated feed consumption was determined by bird for each dosage group and the control group for approximately 24-hour intervals from Days 0 to 1, Days 1 to 2, and Days 2 to 3. Average estimated feed consumption was then measured by pen from Days 3 to 7, Days 7 to 10 and Days 10 to 14. Feed consumption was determined by measuring the change in the weight of the feed presented to the birds over a given period of time. The accuracy of feed consumption values may have been affected by the unavoidable wastage of feed by the birds.

A gross necropsy was performed on the carcasses of three of the ten surviving birds from each level at test termination. A gross necropsy included, but was not limited to, a general examination of the exterior of the bird and an examination of the thoracic and abdominal cavities, including cardiovascular and respiratory systems, liver, spleen, gastro-intestinal tract, and urogenital system.

Key result

Duration (if not single dose):

1 d

Dose descriptor:

LD50

Effect level:

> 2 250 mg/kg bw

Conc. / dose based on:

test mat.

Basis for effect:

other: no effects at the highest dose tested

Mortality and sub-lethal effects:

There were no incidents of regurgitation noted among the control birds or among any of the treatment birds. There were no mortalities in the control or 2250 mg a.s./kg treatment group. All control birds were normal in appearance and behavior throughout the test. One bird in the 2250 mg a.s./kg treatment level was noted as having a ruffled appearance in the PM observations on Day 4. The bird was otherwise normal in appearance during all other observations. Due to the isolated nature of this incident, it is not considered to be a toxicological response. All other birds at the 2250 mg a.s./kg bw level were normal in appearance and behavior for the duration of the test.
When compared to the control group, there were no apparent treatment-related effects upon body weight change at the 2250 mg a.s./kg bw dosage level.
When compared to the control group there were no apparent treatment-related effects on feed consumption for the 2250 mg a.s./kg treatment group.
A gross necropsy was performed on three birds from the control group and three birds from the 2250 mg a.s./kg bw treatment group at test termination. There were no remarkable findings for any of the three birds from the control group or the 2250 mg a.s./kg bw dosage level that were examined.

Validity criteria fulfilled:

yes

Conclusions:

Oral LD50 (Zebra finch) > 2250 mg/kg (the highest dose tested)

Executive summary:

The objective of this study was to evaluate the acute toxicity of DPX-JE874 administered to Zebrafinch as a single oral dose. The methods used in conducting this study were based on OCSPP 850.2100. Ten Zebrafinch, five males and five females, were assigned to each of the treatment groups and the control group. Nominal dosages used in this study. were 0 and 2250 milligrams of DPX-JE874-221 per kilogram of body weight. At study initiation, a single encapsulated dose of the test substance was orally inserted directly into the crop of each bird.

The acute oral LD50 value for Zebrafinch exposed to DPXJE874 as a single oral dosage was determined to be > 2250 mg/kg, the highest dosage tested. The no mortality and no observed effect dosage was 2250 mg/kg.

 

Description of key information

5-day dietary LC50 (mallard duck) > 5620 ppm (the highest dose tested), OECD 205 and OPP 71-2, Reliability = 1

5-day dietary LC50 (bobwhite quail) > 5620 ppm (the highest dose tested), OECD 205 and OPP 71-2, Reliability = 1

Oral LD50 (bobwhite quail) > 2250 mg/kg (the highest dose tested), OPP 71-1, Reliability = 1

Oral LD50 (Zebra finch) > 2250 mg/kg (the highest dose tested), OPPTS 850.2100, Reliability = 1

21-week Reproduction NOEC (Mallard duck) = 1250 ppm (the highest dose tested), OECD 206 and OPP 71-4, Reliability = 1

20-week Reproduction NOEC (bobwhite quail) = 1250 ppm (the highest dose tested), OECD 206 and OPP 71-4, Reliability = 1

Key value for chemical safety assessment

Short-term EC50 or LC50 for birds:

2 250 g/kg food

Additional information

Famoxadone was tested in 2 guideline dietary LC50 studies (mallard duck and bobwhite quail) with resultant 5-day LC50s > 5620 ppm (the highest dose tested) in both studies.  In two guideline oral LD50 studies (bobwhite quail and zebra finch) the resultant LD50s were > 2250 mg/kg (the highest dose tested) in both studies.  In two guideline reproduction studies, the 20/21 week reproduction NOEC was 1250 ppm (the highest dose tested) for both studies.