Methomyl

Toxicity to birds

Link to relevant study record(s)

Reference

Reference 1

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 71-2 (Avian Dietary Toxicity Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Methomyl technical
X1179-512
Purity: 98.7%

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

acetone

Test organisms (species):

Anas platyrhynchos

Limit test:

no

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/group

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

Nominal: 0 (C1 and C2), 178 (T1), 316 (T2), 562 (T3), 1000 (T4), 1780 (T5), 3160 (T6), and 5620 (T7) mg a.i./kg diet
Measured: 0 (C1 and C2), 154 (T1), 258 (T2), 575 (T3), 963 (T4), 1680 (T5), 2870 (T6), and 5080 (T7) mg a.i./kg diet

Details on examinations and observations:

Daily observations to monitor mortality, moribundity, and clinical symptoms. Body weights and feed consumption were also measured. At completion of the test, four surviving birds were arbitrarily selected from each group and sacrificed for gross pathological examination. Examinations included digestive system, liver, kidneys, heart, bile duct, spleen, and muscle tissue.

Reference substance (positive control):

no

Key result

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

3 952 mg/kg diet

Basis for effect:

mortality

Key result

Duration (if not single dose):

5 d

Dose descriptor:

other: LLC

Remarks:

lowest lethal concentration

Effect level:

3 160 mg/kg diet

Basis for effect:

mortality

Key result

Duration (if not single dose):

5 d

Dose descriptor:

NOEC

Effect level:

1 780 mg/kg diet

Basis for effect:

mortality

Mortality and sub-lethal effects:

Clinical symptoms: Head Twitch T1-T7; Slightly Lethargic T2-T6; Slight Ataxia T2, T4-T7; Hyporeactive T6-T7; Salivating T6-T7; Labored Breathing T6; Moribund T6; Emaciated T7; Unbalanced T7; Ataxia T7; and Mortality T6-T7
Feed consumption: T4-T7 decreased feed consumption from the C groups days 0-5
Body weight: T2, T5-T7 significantly lower than C groups day 5; T1, T2, T5-T7 significantly lower than C groups day 8; T5-T7 significantly lower than C groups percent change days 0-5 and days 0-8
Gross pathology: Emaciation T6 and T7; Enlarged spleen T6

Validity criteria fulfilled:

yes

Conclusions:

5-day LC50 = 3952 mg/kg diet
5-day LLC = 3160 mg/kg diet
5-day NOEC for mortality = 1780 mg/kg diet
5-day NOEC for signs of toxicity was undetermined

Executive summary:

Methomyl technical was orally administered via the diet to 9-day old Mallard ducks at nominal concentrations 0 (C1 and C2), 178 (T1), 316 (T2), 562 (T3), 1000 (T4), 1780 (T5), 3160 (T6), and 5620 (T7) mg a.i./kg diet. Toxicological symptoms were noted in the T1-T7 groups, with mortality in the T6 and T7 groups. On day 5 there was a statistically significant (p=0.05) decrease in body weights in the T2, T5-T7 treatment groups when compared to the Control groups. On day 8 there was a statistically significant (p=0.05) decrease in body weights in the T1, T2, T5-T7 treatment groups when compared to the Control groups. The percent change in body weights from days 0-5 and days 0-8 showed a statistically significant (p=0.05) decrease in weight gain in the T5-T7 treatment groups when compared to the Control groups. For the feed consumption period days 0-5 there was a dietary concentration-response pattern of decreased feed consumption in the T4-T7 treatment groups when compared to the Control groups. The LC50was determined to be 3952 mg a.i./kg diet. The LLC was determined to be 3160 mg a.i./kg diet. The NOEC for signs of toxicity was undetermined in this study. The NOEC for mortality was determined to be 1780 mg a.i./kg diet.

Reference 2

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 71-2 (Avian Dietary Toxicity Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Methomyl technical
X1179-512
Purity: 98.7%

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

acetone

Test organisms (species):

Colinus virginianus

Limit test:

no

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/group

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

Nominal: 0 (C1 and C2), 178 (T1), 316 (T2), 562 (T3), 1000 (T4), 1780 (T5), 3160 (T6), and 5620 (T7) mg a.i./kg diet
Measured: 0 (C1 and C2), 154 (T1), 258 (T2), 575 (T3), 963 (T4), 1680 (T5), 2870 (T6), and 5080 (T7) mg a.i./kg diet

Details on examinations and observations:

Daily observations to monitor mortality, moribundity, and clinical symptoms. Body weights and feed consumption were also measured. At completion of the test, four surviving birds were arbitrarily selected from each group and sacrificed for gross pathological examination. Examinations included digestive system, liver, kidneys, heart, bile duct, spleen, and muscle tissue.

Reference substance (positive control):

no

Key result

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 5 620 mg/kg diet

Basis for effect:

mortality

Key result

Duration (if not single dose):

5 d

Dose descriptor:

other: LLC

Remarks:

lowest lethal level

Effect level:

> 5 620 mg/kg diet

Key result

Duration (if not single dose):

5 d

Dose descriptor:

NOEC

Effect level:

5 620 mg/kg diet

Basis for effect:

mortality

Mortality and sub-lethal effects:

Clinical symptoms: Slight Ataxia T5-T7; Slightly Lethargic T5-T7; Fluffed Feathers T6; Hyporeactive T6-T7; Wing Drop T6-T7; Labored Breathing T7; and Ataxia T7
Feed consumption: T3-T7 decreased feed consumption from the C groups days 0-5
Body weight: T3-T7 significantly lower than C groups day 5; T3, T5-T7 significantly lower than C groups day 8; T2- T7 significantly lower than C groups percent change days 0-5; T3-T7 significantly lower than C1 and T6 and T7 significantly lower than C2 percent change days 0-8
Gross Pathology: None

Validity criteria fulfilled:

yes

Conclusions:

Acute LC50 > 5620 mg/kg diet
LLC (lowest lethal concentration) > 5620 mg/kg diet
NOEC for mortality: 5620 mg/kg diet
NOEC for signs of toxicity: 178 mg/kg diet

Executive summary:

The acute oral dietary toxicity to the Northern Bobwhite (Colinus virginianus) was determined according to OECD guideline 205. Nominal concentrations were 0 (C1 and C2), 178 (T1), 316 (T2), 562 (T3), 1000 (T4), 1780 (T5), 3160 (T6), and 5620 (T7) mg/kg diet. Measured concentrations were 0 (C1 and C2), 154 (T1), 258 (T2), 575 (T3), 963 (T4), 1680 (T5), 2870 (T6), and 5080 (T7) mg/kg diet. Ten birds per dose were evaluated. Mortality, moribundity, and clinical symptoms were monitored daily. Body weights and feed consumption were also measured. At completion of the test, four surviving birds were arbitrarily selected from each group and sacrificed for gross pathological examination. Examinations included digestive system, liver, kidneys, heart, bile duct, spleen, and muscle tissue.

 

On day 5 there was a statistically significant decrease in body weights in the T3-T7 treatment groups when compared to the control groups. On day 8 there was a statistically significant decrease in body weights in the T3, T5-T7 treatment groups when compared to the Control groups. The percent change in body weights from days 0-5 showed a statistically significant decrease in weight gain in the T2-T7 treatment groups when compared to the control groups. The percent change in body weights from days 0-8 showed a statistically significant difference in the T3-T7 treatment groups when compared to at least one of the Control groups. For the feed consumption period days 0-5 there was a dietary concentration-response pattern of decreased feed consumption in the T3-T7 treatment groups when compared to the Control groups.

 

The LC50 was determined to be >5620 mg/kg diet. The LLC was determined to be >5620 mg/kg diet. The NOEC for signs of toxicity was determined to be 178 mg/kg diet. The NOEC for mortality was determined to be 5620 mg/kg diet.

Reference 3

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:

EPA OPPTS 850.2100 (Avian Acute Oral Toxicity Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Methomyl technical
DPX-X1179-571
Purity: 99.4%

Dose method:

gavage

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

reverse osmosis and deionized water

Test organisms (species):

other: zebra finches (Taeniopygia guttata)

Limit test:

no

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: 0, 0.25, 0.5, 1, 2, and 4 mg/kg
Measured: 99%, 101%, 68%, 99% and 101% of nominal concentrations

Details on examinations and observations:

From test initiation until termination, all birds were observed cage-side at least twice daily. A record was maintained of all mortality, signs of toxicity, and abnormal behavior. Body weights and food consumption were recorded periodically. A gross necropsy was performed on all birds that died during the test. This included 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.

Reference substance (positive control):

no

Key result

Dose descriptor:

LD50

Effect level:

1.95 mg/kg bw

Mortality and sub-lethal effects:

There were no mortalities in the 0.25, 0.5 and 1 mg/kg treatment groups. There was 20% (2 of 10) mortality at the 2 mg/kg dosage level and 100% (10 of 10) mortality at the 4 mg/kg dosage level. All control birds were normal in appearance and behavior for the duration of the study.

At the 0.25 mg/kg dosage level, no signs of toxicity were noted on the day of dosing. During the course of the test from Day 2 to Day 13 there were some birds that were noted with a ruffled appearance or a slight ruffled appearance. The ruffled appearance was intermittently seen in a total of four birds. One bird was noted with a wing droop on the afternoon of Day 7. All birds were normal in appearance and behavior on the afternoon of Day 13 and on Day 14 of the test. The observations noted from Day 2 to Day 13 are not uncommon for zebra finch, were not concentration responsive and are often seen during acclimation. They were considered to be incidental and not related to treatment. At the 0.5 mg/kg dosage level, two birds were noted with a slight ruffled appearance approximately 30 minutes following dosing. All birds were normal in appearance and behavior for all other observations during the test. At the 1 mg/kg dosage level, signs of toxicity were first noted eighteen minutes after dosing, when all birds were noted with a loss of coordination, ruffled appearance and lethargy. Approximately four hours following dosing all but one bird was normal in appearance and behavior. Signs of toxicity noted at the 1 mg/kg dosage level were ruffled appearance, wing droop, lethargy, loss of coordination, lower limb weakness and prostrate posture. From Day 1 to Day 5, a total of five birds were intermittently noted with a slight wing droop, slight ruffled appearance or a ruffled appearance. These observations are not uncommon for zebra finch and are often seen during acclimation. They are not considered to be treatment related. All birds were normal in appearance and behavior from Day 6 until test termination.

At the 2 mg/kg dosage level, signs of toxicity were first noted within fifteen minutes of dosing, when the first four birds dosed were noted with signs of toxicity. Twenty-five minutes following dosing all birds were noted with signs of toxicity. Signs of toxicity noted at the 2 mg/kg dosage level were ruffled appearance, lethargy, loss of coordination, lower limb weakness, prostrate posture, loss of righting reflex, depression and salivation. One mortality was noted approximately four hours after dosing and a second mortality was noted on the morning of Day 1. All surviving birds were normal in appearance and behavior from Day 1 until test termination. At the 4 mg/kg dosage level, all birds were found dead within twenty-two minutes of dosing, the time of the first recorded observation. Between the time of individual dosing of the birds and the recording of observations, the birds in the 4 mg/kg dosage level did display some signs of toxicity for a short amount of time prior to death. The signs were consistent with those seen at the 2 mg/kg dosage level (ruffled appearance, prostrate posture, loss of righting reflex, depression and salivation) but were more severe.

Validity criteria fulfilled:

yes

Conclusions:

oral LD50 = 1.95 mg/kg, with 95% confidence interval of 1.0 to 4.0 mg/kg, based on mean measured values.
The no mortality level was 1.0 mg/kg. The no-observed-adverse-effect level was 0.5 mg a.s./kg bw.

Executive summary:

The acute oral toxicity to the zebra finch was determined using methods based on EPA OCSPP 850.2100 guidelines. Nominal concentrations of 0, 0.25, 0.5, 1, 2, and 4 mg/kg were tested. Five birds per sex per dose were evaluated. From test initiation until termination, all birds were observed cage-side at least twice daily. A record was maintained of all mortality, signs of toxicity, and abnormal behavior. Body weights and food consumption were recorded periodically. A gross necropsy was performed on all birds that died during the test. This included 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.

 

The acute oral LD50 value for zebra finch exposed to Methomyl as a single oral dose was determined to be 1.95 mg/kg, with 95% confidence interval of 1.0 to 4.0 mg/kg, based on mean measured values. The no mortality level was 1.0 mg/kg. The no-observed-adverse-effect level was 0.5 mg/kg.

Reference 4

Endpoint:

long-term toxicity to birds: reproduction 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:

EPA OPP 71-4 (Avian Reproduction Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

DPX-X1179-394
Purity: 98.35%

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

acetone and corn oil

Test organisms (species):

Colinus virginianus

Limit test:

no

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, 150, 500 ppm
Measured: 0, 49±5, 153±16, 459±42 ppm

Details on examinations and observations:

The birds were observed daily for mortality, abnormal behavior, and signs of toxicity. Body weights and feed consumption were periodically measured. All adult birds that died during the study were necropsied. In addition, necropsies were performed on all adults surviving until study termination.

Details on reproductive parameters:

Eggs were collected daily from all pens and stored in a cold room. At weekly intervals all eggs in the cold room were counted and eggshell thickness measured. Remaining eggs were placed in an incubator and then on day 21 were placed in a hatcher and allowed to hatch.

Reference substance (positive control):

no

Key result

Duration (if not single dose):

20 wk

Dose descriptor:

NOEC

Effect level:

150 other: ppm

Basis for effect:

reproductive parameters

Remarks:

egg production

Mortality and sub-lethal effects:

There were no treatment related mortalities, overt signs of toxicity or treatment related effects upon feed consumption. While there were no effects upon body weight at the 50 ppm or 150 ppm test concentrations, at the 500 ppm test concentration there may have been a slight decrease in body weight gain of cocks through Week 8 of the study.

Effects on reproduction:

There were no apparent treatment related effects upon reproductive parameters at test concentrations of 50 ppm or 150 ppm. While not statistically significant, at the 500 ppm test concentration there was a reduction in the number of eggs laid per hen, and a subsequent reduction in the number of offspring.

Validity criteria fulfilled:

yes

Conclusions:

20-week NOEC = 150 ppm based on egg production

Executive summary:

The Northern bobwhite were exposed to nominal dietary concentrations of 0, 50, 150 and 500 ppm for 20 weeks in a one-generation reproduction study. Test procedures were according to EPA OPP guideline 71-4.

These concentrations did not result in treatment related mortalities, overt signs of toxicity or treatment related effects upon feed consumption. While there were no effects upon body weight at the 50 ppm or 150 ppm test concentrations, at the 500 ppm test concentration there may have been a slight decrease in body weight gain of cocks through Week 8 of the study. There were no apparent treatment related effects upon reproductive parameters at test concentrations of 50 ppm or 150 ppm. While not statistically significant, at the 500 ppm test concentration there was a reduction in the number of eggs laid per hen, and a subsequent reduction in the number of offspring. Based upon the effect upon egg production at 500 ppm, the no observed effect concentration in this study for bobwhite was 150 ppm.

Reference 5

Endpoint:

long-term toxicity to birds: reproduction 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 206 (Avian Reproduction Test)

Version / remarks:

(draft)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 71-4 (Avian Reproduction Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

DPX-X1179-571
Purity: 99.4%

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

corn oil

Test organisms (species):

Anas platyrhynchos

Limit test:

no

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, 41, 122, 367, 1100 ppm
Measured: 37.1±1.20, 111±2.71, 347±9.09 and 1070±33.9 ppm

Details on examinations and observations:

All adult birds were observed daily throughout the test for signs of toxicity or abnormal behavior. Adult body weights were measured at test initiation, on Weeks 2, 4, 6, 8 and at adult termination. Feed consumption was measured weekly throughout the test. At the beginning of Week 9, the photoperiod was increased to induce egg production.

Details on reproductive parameters:

Following the start of egg production, eggs were set weekly for incubation. Weekly, eggs were selected by indiscriminate draw for egg shell thickness measurement and all remaining eggs were candled prior to incubation to detect egg shell cracks or abnormal eggs. Eggs were also candled twice during incubation to detect infertile eggs or embryo mortality. On Day 24 of incubation, the eggs were placed in a hatcher and allowed to hatch. Once hatching was completed, hatchlings were removed from the hatcher and the individual body weights of the hatchlings were determined. At 14 days of age, the body weights of all surviving offspring were determined.

Reference substance (positive control):

no

Key result

Duration (if not single dose):

21 wk

Dose descriptor:

NOEC

Effect level:

367 mg/kg bw/day

Mortality and sub-lethal effects:

There were no treatment-related mortalities, overt signs of toxicity or treatment-related effects upon adult body weight or feed consumption at the 41, 122 or 367 mg a.i./kg test concentrations. However, at the 1100 mg a.i./kg test concentration there were reductions in feed consumption and adult body weights and an increase in the number of hens with a regressing ovary at terminal necropsy that were considered to be related to treatment.

Effects on reproduction:

There were no treatment-related effects upon any of the reproductive parameters measured at the 41, 122, 367 or 1100 mg a.i./kg test concentrations.

Validity criteria fulfilled:

yes

Conclusions:

21-week NOEC = 367 mg/kg/d

Executive summary:

The objective of this study was to evaluate the effects upon the adult mallard (Anas platyrhynchos) of dietary exposure to methomyl over a period of 21 weeks. Effects on adult health, weight gain and feed consumption were evaluated. In addition, the effects of adult exposure to methomyl on the number of eggs laid, normal development of eggs, viability of the embryos, percent hatchability, offspring survival, and egg shell thickness were evaluated. The study was conducted according to OECD Guideline 206, Avian Reproduction Test; U.S. EPA Ecological Effects Test Guidelines, OPPTS 850.2300 (draft), Avian Reproduction Test; and U.S. EPA, Pesticide Assessment Guideline, Subdivision E, Hazard Evaluation: Wildlife and Aquatic Organisms, Subsection 71-4. Nominal dietary concentrations tested were 0, 41, 122, 367, and 1100 mg/kg/day.

There were no treatment-related mortalities, overt signs of toxicity or treatment-related effects upon adult body weight or feed consumption at the 41, 122 or 367 mg a.i./kg test concentrations. However, at the 1100 mg a.i./kg test concentration there were reductions in feed consumption and adult body weights and an increase in the number of hens with a regressing ovary at terminal necropsy that were considered to be related to treatment. There were no treatment-related effects upon any of the reproductive parameters measured at the 41, 122, 367 or 1100 mg a.i./kg test concentrations. The no-observed-effect concentration for mallard exposed to methomyl in the diet during the study was 367 mg a.i./kg (equivalent to 48.5 mg a.i./kg/day).

Reference 6

Endpoint:

long-term toxicity to birds: reproduction 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:

EPA OPP 71-4 (Avian Reproduction Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

DPX-X1179-394
Purity: 98.35%

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

acetone and corn oil

Test organisms (species):

Anas platyrhynchos

Limit test:

no

Total exposure duration (if not single dose):

18 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, 150, 500 ppm
Measured: 0, 50±5, 150±16, 458±45

Details on examinations and observations:

The mallards were observed daily for mortality, abnormal behavior, and signs of toxicity. Body weights and feed consumption were periodically measured. All adult birds that died during the study were necropsied. In addition, necropsies were performed on all adults surviving until study termination.

Details on reproductive parameters:

Eggs were collected daily from all pens and stored in a cold room. At weekly intervals all eggs in the cold room were counted and eggshell thickness measured. Remaining eggs were placed in an incubator and then on day 24 were placed in a hatcher and allowed to hatch.

Reference substance (positive control):

no

Key result

Duration (if not single dose):

18 wk

Dose descriptor:

NOEC

Effect level:

150 other: ppm

Basis for effect:

body weight

Mortality and sub-lethal effects:

There were no treatment related mortalities, overt signs of toxicity or treatment related effects on feed consumption. While there were no effects upon body weight at the 50 or 150 ppm test concentrations, at the 500 ppm test concentration there appeared to be a treatment related decrease in body weight gain of hens during the last 10 weeks of the study.

Effects on reproduction:

There were no apparent effects upon reproductive parameters at test concentrations of 50 or 150 ppm. While not statistically significant, at the 500 ppm test concentration there may have been a slight reduction in the percent of viable embryos.

Validity criteria fulfilled:

yes

Conclusions:

18-week NOEC = 150 ppm based on body weight effects in hens

Executive summary:

Mallards were exposed to nominal dietary concentrations of 0, 50, 150 and 500 ppm for 18 weeks in a one-generation reproduction study. Test procedures were according to EPA OPP guideline 71-4.

These concentrations did not result in treatment related mortalities, overt signs of toxicity or treatment related effects on feed consumption. While there were no effects upon body weight at the 50 or 150 ppm test concentrations, at the 500 ppm test concentration there appeared to be a treatment related decrease in body weight gain of hens during the last 10 weeks of the study. There were no apparent effects upon reproductive parameters at test concentrations of 50 or 150 ppm. While not statistically significant, at the 500 ppm test concentration there may have been a slight reduction in the percent of viable embryos. Based upon the effect on body weight of hens at 500 ppm, the no observed effect concentration was 150 ppm.

Reference 7

Endpoint:

long-term toxicity to birds

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of Coturnix Quail were administered 0, 70, 140 or 210 ppm of the test substance for 30 days. The quail in each group were fed the test diet for one day followed by the control diet for 2 days. The cycle was repeated 10 times, resulting in a 30-day feeding period. Mortality, toxic effects, body weights and food consumption were recorded.

GLP compliance:

no

Specific details on test material used for the study:

INX-1179
Purity: 90%

Dose method:

feed

Analytical monitoring:

no

Test organisms (species):

other: Coturnix quail

Limit test:

no

Total exposure duration (if not single dose):

30 d

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

20/dose

Control animals:

yes

Nominal and measured doses / concentrations:

Nominal: 0, 70, 140, 210 ppm

Details on examinations and observations:

Mortality, toxic effects, body weights and food consumption were recorded.

Reference substance (positive control):

no

Key result

Duration (if not single dose):

30 d

Dose descriptor:

NOEC

Effect level:

210 other: ppm

Remarks on result:

other: highest dose tested

Mortality and sub-lethal effects:

The low incidence of mortality was attributable to incidental laboratory disease and was not considered to be compound related. No signs of compound effect were noted in any of the animals.

Validity criteria fulfilled:

yes

Conclusions:

30-day NOEC = 210 ppm (the highest dose tested)

Executive summary:

Groups of Coturnix Quail were administered 0, 70, 140 or 210 ppm of the test substance for 30 days. The quail in each group were fed the test diet for one day followed by the control diet for 2 days. The cycle was repeated 10 times, resulting in a 30-day feeding period. Mortality, toxic effects, body weights and food consumption were recorded. 

 

The low incidence of mortality was attributable to incidental laboratory disease and was not considered to be compound related. No signs of compound effect were noted in any of the animals.

Reference 8

Endpoint:

short-term toxicity to birds: acute oral toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: 1964 USDI fish and wildlife services "procedure for evaluation of acute toxicity to fish and wildlife"

GLP compliance:

no

Specific details on test material used for the study:

Insecticide 1179
Purity: 100%

Dose method:

feed

Analytical monitoring:

not specified

Vehicle:

no

Test organisms (species):

Colinus virginianus

Limit test:

no

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

Control animals:

yes, plain diet

Details on test conditions:

31.6 - 5620 ppm

Details on examinations and observations:

Birds were observed for appearance, behavior and toxic effects. Body weights were recorded initially, on Day 5 and at termination on Day 8. The average food and compound adminstration over the 8-day period was also recorded.

Reference substance (positive control):

yes

Remarks:

p,p'-DDT

Key result

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

3 680 other: ppm

Mortality and sub-lethal effects:

No toxic effects were noted in the birds that received the test substance. Birds that received the positive control exhibited tremors and convulsions.

Results with reference substance (positive control):

5-day LD50 for p,p'-DDT = 1340 ppm with 95% confidence limits of 1040-1730 ppm

Reported statistics and error estimates:

5-day LD50 for test substance = 3680 ppm with 95% confidence limits of 2300-5890 ppm

Validity criteria fulfilled:

not specified

Conclusions:

5-day LD50 for test substance = 3680 ppm with 95% confidence limits of 2300-5890 ppm

Executive summary:

The acute toxicity to pekin duck was tested in a 5-day test at nominal dose levels of 31.6 - 5620 ppm. The 5-day LC50 was 3680 ppm. 

Reference 9

Endpoint:

short-term toxicity to birds: acute oral toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: 1964 USDI fish and wildlife services "procedure for evaluation of acute toxicity to fish and wildlife"

GLP compliance:

no

Specific details on test material used for the study:

Insecticide 1179
Purity: 100%

Dose method:

feed

Analytical monitoring:

not specified

Vehicle:

no

Test organisms (species):

Anas platyrhynchos

Limit test:

no

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

Control animals:

yes, plain diet

Details on test conditions:

31.6 - 5620 ppm

Details on examinations and observations:

Birds were observed for appearance, behavior and toxic effects. Body weights were recorded initially, on Day 5 and at termination on Day 8. The average food and compound adminstration over the 8-day period was also recorded.

Reference substance (positive control):

yes

Remarks:

p,p'-DDT

Key result

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

1 890 other: ppm

Mortality and sub-lethal effects:

No toxic effects were noted in the birds that received the test substance. Birds that received the positive control exhibited tremors and convulsions.

Results with reference substance (positive control):

5-day LD50 for p,p'-DDT = 1100 ppm with 95% confidence limits of 940-1290 ppm

Reported statistics and error estimates:

5-day LD50 for test substance = 1890 ppm with 95% confidence limits of 1350-2650 ppm

Validity criteria fulfilled:

not specified

Conclusions:

5-day LD50 for test substance = 1890 ppm with 95% confidence limits of 1350-2650 ppm

Executive summary:

The acute toxicity to pekin duck was tested in a 5-day test at nominal dose levels of 31.6 - 5620 ppm. The 5-day LC50 was 1890 ppm. 

Reference 10

Endpoint:

short-term toxicity to birds: acute oral toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 71-2 (Avian Dietary Toxicity Test)

Deviations:

no

GLP compliance:

not specified

Specific details on test material used for the study:

Purity: 98.7%

Dose method:

gavage

Analytical monitoring:

no

Vehicle:

yes

Remarks:

corn oil

Test organisms (species):

Colinus virginianus

Limit test:

no

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

10/sex/dose

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

Nominal: 0, 5.62, 10.0, 17.8 and 31.6 mg/kg

Details on examinations and observations:

All birds were observed daily throughout the study for mortality and/or signs of toxicity and abnormal behavior. The LD50 was determined by probit analysis using the SAS system. Body weights and food consumption were also periodically recorded during the 14 day post exposure period.

Reference substance (positive control):

no

Key result

Dose descriptor:

LD50

Effect level:

24.2 mg/kg bw

Basis for effect:

mortality

Mortality and sub-lethal effects:

No mortality occurred at the 5.62 mg/kg or 10.0 mg/kg dosage levels. Mortality was 30% at the 17.8 mg/kg dosage and 70% at the 31.6 mg/kg dosage.

Symptoms of toxicity occurred at the 5.62 mg/kg dosage group and above. At 5.62 dosage group, lethargy, reduced reaction to external stimuli, loss of coordination, and lower limb weakness were evident within one-half hour of dosing. The birds were asymptomatic within 2 hours of dosing and appear normal until study termination. Therefore, the NOEL during this study was < 5.62 mg/kg.

Validity criteria fulfilled:

yes

Conclusions:

LD50 = 24.2 mg/kg (95% confidence limits of 18.5 to 36.2 mg/kg)

Executive summary:

The acute oral toxicity to the bobwhite quail was determined using methods based on EPA OPP 71-2 guidelines. Nominal concentrations of 0, 5.62, 10.0, 17.8 and 31.6 mg/kg were tested. Ten birds per sex per dose were evaluated. All birds were observed daily throughout the study for mortality and/or signs of toxicity and abnormal behavior. The LD50 was determined by probit analysis using the SAS system. Body weights and food consumption were also periodically recorded during the 14-day post exposure period.

 

No mortality occurred at the 5.62 mg/kg or 10.0 mg/kg dosage levels. Mortality was 30% at the 17.8 mg/kg dosage and 70% at the 31.6 mg/kg dosage.

 

Symptoms of toxicity occurred at the 5.62 mg/kg dosage group and above. At 5.62 dosage group, lethargy, reduced reaction to external stimuli, loss of coordination, and lower limb weakness were evident within one-half hour of dosing. The birds were asymptomatic within 2 hours of dosing and appear normal until study termination. Therefore, the NOEL during this study was < 5.62 mg/kg.

Reference 11

Endpoint:

short-term toxicity to birds: acute oral toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

The compound was administered to six groups of Coturnix Quail by oral intubation. Nominal concentrations were 0, 4.64, 10.0, 21.5, 46.4, 100, and 215 mg/kg. Observations for mortality and clinical signs of effects were made immediately after dosing; at one, four, and 24 hours; and once daily thereafter for a total of 7 days. Gross necropsy was performed on all animals which died during the study and on those sacrificed at termination.

GLP compliance:

no

Specific details on test material used for the study:

INX-1179
Purity: assumed to be 100%

Dose method:

gavage

Analytical monitoring:

no

Vehicle:

not specified

Test organisms (species):

other: Coturnix quail

Limit test:

no

Post exposure observation period:

7 days

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

10/group

Control animals:

yes

Nominal and measured doses / concentrations:

Nominal: 0, 4.64, 10.0, 21.5, 46.4, 100, and 215 mg/kg

Details on examinations and observations:

Observations for mortality and clinical signs of effects were made immediately after dosing; at one, four, and 24 hours; and once daily thereafter for a total of 7 days. Gross necropsy was performed on all animals which died during the study and on those sacrificed at termination.

Reference substance (positive control):

no

Key result

Dose descriptor:

LC50

Effect level:

34 mg/kg bw

Basis for effect:

mortality

Mortality and sub-lethal effects:

At the 4.64 mg/kg level, the one bird which died caught his foot in the feeder. There were no toxic signs observed in the two lower levels. Depression and tremors were observed prior to partial mortality at the 21.5 and 46.4 mg/kg levels with recovery in the survivors by 24 hours. Prostration was also noted at the 100 mg/kg level followed by total mortality. No gross pathology was observed.

Validity criteria fulfilled:

yes

Conclusions:

LD50 = 34 mg/kg with 95% confidence limits of 19.48 to 59.33 mg/kg

Executive summary:

The compound was administered to six groups of Coturnix Quail by oral intubation. Nominal concentrations were 0, 4.64, 10.0, 21.5, 46.4, 100, and 215 mg/kg. Observations for mortality and clinical signs of effects were made immediately after dosing; at one, four, and 24 hours; and once daily thereafter for a total of 7 days. Gross necropsy was performed on all animals which died during the study and on those sacrificed at termination. 

 

At the 4.64 mg/kg level, the one bird which died caught his foot in the feeder. There were no toxic signs observed in the two lower levels. Depression and tremors were observed prior to partial mortality at the 21.5 and 46.4 mg/kg levels with recovery in the survivors by 24 hours. Prostration was also noted at the 100 mg/kg level followed by total mortality. No gross pathology was observed. The LD50 was calculated to be 34 mg/kg with 95% confidence limits of 19.48 to 59.33 mg/kg.

Description of key information

Duration/Value Type	Species	Value	Guideline	Reliability
5-day Oral LD50	Colinus virginianus	3680 ppm	1964 USDI fish and wildlife services "procedure for evaluation of acute toxicity to fish and wildlife"	2
5-day Oral LD50	Anas platyrhynchos	1890 ppm	1964 USDI fish and wildlife services "procedure for evaluation of acute toxicity to fish and wildlife"	2
Oral LD50	Colinus virginianus	24.2 mg/kg	EPA OPP 71-2	2
Oral LD50	zebra finches (Taeniopygia guttata)	1.95 mg/kg	EPA OPPTS 850.2100	1
Acute Diet LC50	Colinus virginianus	> 5620 mg/kg	OECD 205, EPS OPP 71-2	1
NOEC for mortality	Colinus virginianus	5620 mg/kg	OECD 205, EPS OPP 71-2	1
NOEC for signs of toxicity	Colinus virginianus	178 mg/kg	OECD 205, EPS OPP 71-2	1
5-day Diet LC50	Anas platyrhynchos	3952 mg/kg	OECD 205, EPS OPP 71-2	1
5-day NOEC for mortality	Anas platyrhynchos	1780 mg/kg	OECD 205, EPS OPP 71-2	1
5-day NOEC for signs of toxicity	Anas platyrhynchos	undetermined	OECD 205, EPS OPP 71-2	1
18-week NOEC	Anas platyrhynchos	150 ppm	EPA OPP 71-4	1
20-week NOEC	Colinus virginianus	150 ppm	EPA OPP 71-4	1
21-week NOEC	Anas platyrhynchos	367 mg/kg/d	OECD 206, EPA OPP 71-4	1
30-day feeding NOEC	Coturnix quail	210 ppm	no guideline followed	2
Oral LD50	Coturnix quail	34 mg/kg	no guideline followed	2

Key value for chemical safety assessment

Short-term EC50 or LC50 for birds:

1.95 mg/kg food

Long-term EC10, LC10 or NOEC for birds:

150 mg/kg food