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Toxicity to birds

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Endpoint:
short-term toxicity to birds: acute oral toxicity test
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 November 1993 to 14 November 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OPP 71-1 (Avian Acute Oral Toxicity Test)
Deviations:
no
GLP compliance:
yes
Dose method:
capsule
Analytical monitoring:
no
Vehicle:
no
Test organisms (species):
Colinus virginianus
Details on test organisms:
TEST ORGANISM
- Common name: Bobwhite Quail
- Age at test initiation (mean and range, SD): at least 16-18 weeks old
- Sexes used: male and female
- Disease free: yes (daily check performed during acclimation period)
Limit test:
no
Remarks:
One dosing
Post exposure observation period:
15 days
No. of animals per sex per dose and/or stage:
Five
Control animals:
yes
Nominal and measured doses / concentrations:
400, 800, 1086, 1474 and 2000 mg/kg bw
Details on test conditions:
ACCLIMATION
- Acclimation period: at least fifteen days
- Feeding: Avian Layer Diet, Special Diet Services, Witham, Essex, UK ad libitum
- Health (any disease or mortality observed): no

FEED WITHHOLDING PERIOD BEFORE DOSING
- No. of days: overnight before dosing

PEN SIZE AND CONSTRUCTION MATERIALS
- Description: stainless steel grid cages
- Caging: individual

NO. OF BIRDS PER REPLICATE
- For treated: five per sex

TEST CONDITIONS (range, mean, SD as applicable)
- Temperature: 18-25 ºC
- Relative humidity (%): 40-70 %
- Photoperiod: eight hours light/16 hours dark
- Ventilation: approximately fifteen air changes per hour

RANGE FINDING STUDY
- Test concentrations: 2000 ppm
- Test conditions: as main test
- Results used to determine the conditions for the definitive study: yes (one male and one female treated at 2000 ppm, both died within 7 days. 2000 ppm used as highest dose in main study).
Details on examinations and observations:
MORTALITY / CLINICAL SIGNS
- Time schedule for examinations: three times on day 1 and at least once daily from day 2 onwards

BODY WEIGHT
- Time schedule for examinations: day before dosing (day -1), days 1, 8 and 15.

FOOD CONSUMPTION (if feeding study)
- Time schedule for examinations: weekly

PATHOLOGY
- Dose groups that were examined: all
- Remarks: all body cavities were opened, larger organs were sectioned and the intestinal tract was opened at intervals for examination of mucosal surfaces.
Reference substance (positive control):
no
Key result
Dose descriptor:
LD50
Effect level:
683 mg/kg bw
Conc. / dose based on:
test mat.
Remarks on result:
other: 95 % CL 549-818 mg/kg bw
Key result
Dose descriptor:
LD50
Effect level:
698 mg/kg bw
Conc. / dose based on:
test mat.
Remarks on result:
other: males only
Key result
Dose descriptor:
LD50
Effect level:
727 mg/kg bw
Conc. / dose based on:
test mat.
Remarks on result:
other: females only
Mortality and sub-lethal effects:
Ante mortem signs comprised under-activity, resting on hocks, reluctance or inability to stand, staggering gait, unconsciousness, prone position, slow and deep respiration, closed eyes, thin body conformation, cold to touch, ungroomed appearance, plumo-erection, little diet eaten, few faeces and feather loss. Some birds treated at 2000 mg/kg also had pink staining in the under-trays. Signs of reaction to treatment in surviving birds comprised thin body conformation, plumo-erection, little diet eaten and few faeces. All of these birds were overtly normal on day 13.

The food consumption of birds treated at 400 mg/kg was considerably lower than that of control birds during the first week of the study. Thereafter, the food consumption of these birds was similar to that of the controls. Other surviving birds treated with the test material consumed little diet throughout the study.

Birds treated at 400 mg/kg lost considerable body weight during the first week of the study, but made substantial gains during the second week. The remaining surviving birds treated with the test substance lost body weight throughout the study. Necropsy findings were unremarkable.

Table 1: Mortality distribution

   Mortality
 Dose (mg/kg)  Males  Females
 0  0/5  0/5
 400  0/5  0/5
 800  5/5  4/5
 1086  3/5  5/5
 1474  5/5  5/5
 2000  5/5  5/5
Validity criteria fulfilled:
not specified
Conclusions:
Under the conditions of the test, the acute oral median LD50 of the test material was 683 mg/kg bw (95 % C.I. 549-818 mg/kg bw).
Executive summary:

In a GLP compliant acute oral toxicity to birds study conducted in line with standardised guideline EPA 71-1, the acute oral toxicity of the test material to bobwhite quail was determined. The test material was administered by capsule as a single dose, followed by a 15 day observation period, at 0, 400, 800, 1086, 1474 and 2000 mg/kg. Under the conditions of the test the LD50value was determined to be 683 mg/kg bw (95 % C.I. 549-818 mg/kg bw).

Endpoint:
short-term toxicity to birds: dietary toxicity test
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 June 1987 to 24 March 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OPP 71-2 (Avian Dietary Toxicity Test)
Deviations:
no
GLP compliance:
yes
Dose method:
feed
Analytical monitoring:
no
Vehicle:
no
Details on preparation and analysis of diet:
DIET PREPARATION
- Description and nutrient analysis of basal diet provided in study report: no
- Preparation of doses: weighed amount of test material was added to untreated diet to give a premix of 25000 ppm which was mixed by being shaken in a polythene bag for a minimum of three minutes. Aliquots of the premix were used to prepare the final inclusion levels.
Test organisms (species):
Anas platyrhynchos
Details on test organisms:
TEST ORGANISM
- Common name: Mallard duck
- Age at test initiation (mean and range, SD): 10 days old
- Weight at test initiation (mean and range, SD): mean 71 g
- Sexes used: not determined
Limit test:
no
Total exposure duration (if not bolus):
5 d
Post exposure observation period:
Three days
No. of animals per sex per dose and/or stage:
Ten animals per dose (sex not identified)
Control animals:
yes, plain diet
Nominal and measured doses / concentrations:
0, 650, 1300, 2600 and 5200 ppm
Details on test conditions:
PEN SIZE AND CONSTRUCTION MATERIALS
- Description: galvinzed steel tiered brooders

NO. OF BIRDS PER REPLICATE
- For treated: 10

TEST CONDITIONS (range, mean, SD as applicable)
- Room temperature: 26 ± 1 ºC - 29 ± 1 ºC
- Relative humidity: mean 65 ± 10 %
- Photoperiod: continuous illumination
- Ventilation: adjusted as required
Details on examinations and observations:
MORTALITY / CLINICAL SIGNS
- Time schedule for examinations: daily

BODY WEIGHT
- Time schedule for examinations: group-weighed on days -3, 0 (prior to introduction of diets), 5 and 8

FOOD CONSUMPTION (if feeding study)
- Time schedule for examinations: over the following days: -3 to -1, 1 to 5 (daily) and 6 to 8.

PATHOLOGY
- Dose groups that were examined: eight surviving birds treated at 5200 ppm and two surviving birds treated at 2600 ppm were examined macroscopically at the termination of the study.
Reference substance (positive control):
no
Key result
Duration (if not bolus):
5 d
Dose descriptor:
LC50
Effect level:
> 5 200 mg/kg diet
Conc. / dose based on:
test mat.
Basis for effect:
mortality
Mortality and sub-lethal effects:
Two mortalities occurred in the 5200 ppm treatment period. All birds were in good health during pre-treatment period. During the treatment period birds dosed at 2600 ppm and 5200 ppm became subdued and were huddled together. Birds in all other groups remained in good health throughout the treatment period. All birds appeared to be in good health during the post-treatment period. Body weight changes and an overview of the deaths occurring are given in Table 1.

Birds in the controls and the 650 ppm treatment group comparable body weight increase, birds in the 1300 ppm treatment group showed a reduced increase during the treatment period, birds in the 2600 ppm treatment group showed only a very small increase during the treatment period, while the surviving birds in the 5200 ppm treatment group showed an actual decrease during the treatment period. During pre- and post-treatment period body weights changes were similar in all groups.

There was a treatment related depression of food consumption in the three highest treatment groups during the treatment period, but it increased again during the post-treatment period. The two birds in the 5200 ppm treatment group, which died during the treatment period, were examined microscopically and both birds were found to be thin. At termination of the study a total number of ten birds (two from the 2600 ppm treatment group and eight from the 5200 ppm treatment group) were examined. No abnormalities were detected.

Table 1: Avian dietary toxicity to the mallard duck (deaths and group mean body weight changes)

Dose units (mg/kg)   0  0  0  650  1300  2600  5200
Mortality  0/10  0/10  0/10  0/10  0/10  0/10  2/10
 Days of study  Group mean body weight change in g/bird
 -3 to 0  +36  +41  +44  +37  +41  +40  +36
 0 to 5  +102  +95  +99  +97  +64  +7  -15
 5 to 8  +44  +47  +49  +52  +47  +59  +53

Validity criteria fulfilled:
not specified
Conclusions:
Under the conditions of the test, it was not possible to determine a LC50 value since only two mortalities occurred at the highest dose level tested. The LC50 for the test material in the mallard duck is therefore >5200 mg/kg diet.
Executive summary:

In a GLP compliant short-term dietary toxicity to birds study conducted in line with standardised guideline EPA 71-2, the short-term dietary toxicity of the test material to mallard ducks was determined. The test material was administered by dietary inclusion at 650 1300, 2500 and 5200 ppm. Under the conditions of the test it was not possible to determine a LC50value because there were only two mortalities at the highest dose level tested. This value must therefore be in excess of 5200 mg/kg diet.

Endpoint:
long-term toxicity to birds: reproduction test
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 November 1999 to 07 September 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 206 (Avian Reproduction Test)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 71-4 (Avian Reproduction Test)
Deviations:
no
GLP compliance:
yes
Dose method:
feed
Analytical monitoring:
yes
Vehicle:
no
Details on preparation and analysis of diet:
DIET PREPARATION
- Description and nutrient analysis of basal diet provided in study report: yes
- Preparation of doses: test substance was mixed into a premix that was used for weekly preparation of the final diet.

HOMOGENEITY AND STABILITY OF TEST MATERIAL IN DIET
- How often was homogeneity and stability tested: on day 0 of week 1 and then during weeks 2, 3, 4, 8, 12, 16 and 20.
- When and at what dose levels were samples of treated food analysed for stability and concentration during the study: all dose levels.
- % of nominal: 91.0-98.7 %
Test organisms (species):
Colinus virginianus
Details on test organisms:
TEST ORGANISM
- Common name: Northern bobwhite quail
- Age at test initiation (mean and range, SD): 20 weeks
- Weight at test initiation (mean and range, SD): 180-223 g
- Sexes used: male/female
Limit test:
no
Total exposure duration (if not bolus):
22 wk
No. of animals per sex per dose and/or stage:
Sixteen
Control animals:
yes, plain diet
Nominal and measured doses / concentrations:
0, 150, 300 and 600 ppm (nominal)
Details on test conditions:
ACCLIMATION
- Acclimation period: 6 weeks

PEN SIZE AND CONSTRUCTION MATERIALS
- Description: 27 x 51 cm galvanised wire mesh/galvanised sheeting pens with ceiling height of 20-25 cm
- Compliant to good husbandry practices: yes
- Caging: one male and one female per pen

NO. OF BIRDS PER REPLICATE
- For treated: 16

TEST CONDITIONS (range, mean, SD as applicable)
- Room temperature: 19.4 ± 1.6 ºC
- Relative humidity (%): 37 ± 12 %
- Photoperiod: 8 hours light per day in the first seven weeks and then 17 hours per day to induce egg laying
- Ventilation: vent up to 15 room air volumes every hour and replace with fresh air
Details on examinations and observations:
MORTALITY / CLINICAL SIGNS
- Time schedule for examinations: daily

BODY WEIGHT
- Time schedule for examinations: at test initiation, weeks 2, 4, 6, 8 and at termination but not during egg laying to prevent adverse effects on egg production.

FOOD CONSUMPTION (if feeding study)
- Time schedule for examinations: weekly
- Remarks: presented as an estimate because it was not possible to measure wasted feed.

PATHOLOGY
- Dose groups that were examined: all
- Remarks: all animals that died or euthanised during the course of study and all surviving animals at termination.
Details on reproductive parameters:
The following parameters were examined per parental pen per week:
- Eggs laid
- Eggs cracked; eggs broken
- Egg abnormalities
- Eggshell thickness or eggshell strength
- Eggs fertile
- Embryos viable
- Normal hatchlings
- 14-day old surviving chicks
- Chick body weight at hatching and 14 days after hatching
Reference substance (positive control):
no
Key result
Duration (if not bolus):
22 wk
Dose descriptor:
NOEC
Effect level:
150 other: ppm
Conc. / dose based on:
test mat.
Basis for effect:
reproductive parameters
Remarks:
egg production, hatchability and offspring survival
Mortality and sub-lethal effects:
No mortalities occurred in the 300 ppm treatment group, two incidental mortalities occurred in the control group and one incidental mortality occurred in both the 150 and 600 ppm treatment groups; none of these are considered to be treatment-related.

No overt signs of toxicity were observed at any of the concentrations tested. Except for incidental findings (including foot, leg, back, wing and head lesions, feather loss, bruising, lameness, lower limb weakness, reduced reaction to external stimuli, ruffled appearance), all birds appeared normal throughout the study.

All surviving adults were subjected to gross necropsy following adult termination (see Table 1). All findings were considered unrelated to treatment.

There were no apparent treatment-related effects upon adult body weight at any of the concentrations tested (see Table 2).

There were slight, but statistically significant, differences in the mean body weights of cocks in all treatment groups. They were primarily the result of the presence of two heavier males in the control group and very tight standard deviations for all groups. The slight differences observed were not considered biologically meaningful or related to treatment.

There were no apparent treatment-related effects upon feed consumption. No statistically significant differences were observed at any of the feed consumption intervals.
Effects on reproduction:
There were no treatment-related effects upon any of the reproductive parameters measured at the 150 ppm test concentration.

While not statistically significant, there were slight, but treatment-related, reductions in egg production and offspring survival in the 300 ppm treatment group. The reductions in egg production and offspring survival also were reflected as non-statistically significant reductions in 14-day old survivors as a percentage of eggs set, and hatchlings as a percentage of the maximum number of eggs set, and as a statistically significant (p <0.01) reduction in 14-day old survivors as a percentage of the maximum number of eggs set.

There were marked, treatment related, effects on reproductive performance at the 600 ppm test concentration. When compared to the control group, the observed reductions in egg production, hatchability and offspring survival were statistically significant at p <0.01. The reductions were further reflected as statistically significant (p <0.05 and p <0.01) reductions in hatchlings and 14-day old survivors as percentages of both eggs set and the maximum number of eggs set. Summaries of the reproductive data can be found in Table 3.

There were no apparent treatment related effects upon eggshell thickness. There were no apparent treatment related effects upon offspring body weights at the 150 or 300 ppm test concentrations and any differences from the control group were not statistically significant for either the hatchlings or the 14-day old survivors. However, there were treatment related reductions in the mean body weights of hatchlings and 14-day old survivors in the 600 ppm treatment group. Offspring body weight data can be found in Table 4.

Table 1: Gross pathological observations (adult birds euthanised at test termination)

   Males (ppm)  Females (ppm)
   0  150  300  600  0  150  300  600
 Number of birds  14  15  16  16  14  15  16  16
 Foot/leg lesions  0  1  2  0  0  0  1  0
 Feather loss  2  6  8  4  9  10  11  10
 Breast muscle - pale  0  0  0  0  0  0  1  0
 Spleen - pale  0  0  0  0  0  0  0  1
 Small intestines - areas of hyperemia  1  0  4  0  0  0  0  0
 Testes - small (one or both)  6  3  3  4  -  -  -  -
 Ovary - regressing  -  -  -  -  0  0  0  1
 Not remarkable  7  6  6  8  5  5  5  6

Table 2: Mean adult body weight (g) and weight change (g)

   Males (ppm)  Females (ppm)
   0  150  300  600  0  150  300  600
 Week 0  203  194*  196  192*  197  195  197  193
 Change week 0-2  2  1  2  0  0  1  2  1
 Week 2  205  195*  198  192**  198  196  199  194
 Change week 2-4  7  5  5  5  4  4  5  3
 Week 4  212  200**  203  197**  202  200  204  197
 Change week 4-6  5  4  4  5  2  3  4  3
 Week 6  216  203*  207  202**  204  203  209  200
 Change week 6-8  1  1  0  1  1  1  0  2
 Week 8  218  204**  207*  203**  204  205  208  202
 Change week 8-Term  8  3  7  0  42  44  36  34
 Term  225  206**  214  204**  245  249  244  236
 Total change  23  13  17  12  47  54  57  44

The means for body weights and body weight changes are calculated and rounded separately

*significantly different from control at p <0.05

**significantly different from the control at p <0.01

Table 3: Reproductive performance (normalised as percentage1)

   Experimental group (ppm)
 Reproductive parameter  0  150  300  600
 Number of replicates  14  15  16  16
 Total eggs laid2  765  734  669  419
 Eggs laid/Maximum laid (%)  76  68  58  36**
 Eggs cracked/Eggs laid (%)  0  2  1  0
 Viable embryos/Eggs set (%)  94  94  95  89
 Live 3 week embryos/Viable embryos (%)  100  100  100  100
 Hatchlings/Live 3 week embryos (%)  95  97  92  79**
 14 day old survivors/Hatchling (%)  97  93  89  73**
 Hatchlings/Eggs set (%)  89  90  87  71*
 14 day old survivors/Eggs set (%)  85  83  79  52**
 Hatchlings/Maximum set (%)  64  58  48  24**
 14 day old survivors/Maximum set (%)  62  54  45*  18**

*significantly different from the control p <0.05

**significantly different from the control p <0.01

1Values represent pen means for experimental group

2Represents the total number of eggs laid in each group

Table 4: Mean body weight (g) of hatchlings and 14 day old survivors

   0 ppm  150 ppm  300 ppm  600 ppm
 Hatchlings        
 Number  602  586  518  260
 Mean (± SD)  6 ± 0  6 ± 0  6 ± 0  5** ± 0
 14 day old survivors        
 Number  580  542  478  194
 Mean (± SD)  26 ± 3  25 ± 2  25 ± 2  19** ± 3

The total number of hatchlings weighed may differ from the total number of hatchlings since those found dead were not weighed.

**significantly different from the control p <0.01

Validity criteria fulfilled:
not specified
Conclusions:
Under the conditions of the test, the NOEC for Northern bobwhite exposed to the test material was determined to be 150 ppm based upon the effects seen in the 300 ppm treatment group.
Executive summary:

In a GLP compliant reproductive toxicity to birds study conducted in line with standardised guidelines OECD 206 and EPA 71-4, the reproductive toxicity of the test material to Northern bobwhite quail was determined. The test material was administered by dietary inclusion at 0, 150, 300 and 600 ppm. Under the conditions of the test the NOEC was determined to be 150 ppm based on the effects seen at the 300 ppm treatment level.

Endpoint:
long-term toxicity to birds: reproduction test
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 November 1999 to 25 September 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 206 (Avian Reproduction Test)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 71-4 (Avian Reproduction Test)
Deviations:
no
GLP compliance:
yes
Dose method:
feed
Analytical monitoring:
yes
Vehicle:
no
Details on preparation and analysis of diet:
DIET PREPARATION
- Description and nutrient analysis of basal diet provided in study report: yes
- Preparation of doses: test substance was mixed into a premix that was used for weekly preparation of the final diet.

HOMOGENEITY AND STABILITY OF TEST MATERIAL IN DIET
- How often was homogeneity and stability tested: on day 0 of week 1 and then during weeks 2, 3, 4, 8, 12, 16 and 20.
- When and at what dose levels were samples of treated food analysed for stability and concentration during the study: all dose levels.
- % of nominal: 91.0-98.7 %
Test organisms (species):
Anas platyrhynchos
Details on test organisms:
TEST ORGANISM
- Common name: Mallard
- Age at test initiation (mean and range, SD): 27 weeks
- Weight at test initiation (mean and range, SD): 905-1373 g
- Sexes used: male/female
Limit test:
no
Total exposure duration (if not bolus):
21 wk
No. of animals per sex per dose and/or stage:
Sixteen
Control animals:
yes, plain diet
Nominal and measured doses / concentrations:
0, 150, 300 and 600 ppm (nominal)
Details on test conditions:
ACCLIMATION
- Acclimation period: 13 weeks

PEN SIZE AND CONSTRUCTION MATERIALS
- Description: 75 x 90 x 45 cm pens
- Compliant to good husbandry practices: yes
- Caging: one male and one female per pen

NO. OF BIRDS PER REPLICATE
- For treated: 16

TEST CONDITIONS (range, mean, SD as applicable)
- Room temperature: 19.3 ± 1.0 ºC
- Relative humidity (%): 40 ± 15 %
- Photoperiod: 8 hours light per day in the first ten weeks and then 17 hours per day to induce egg laying
- Ventilation: vent up to 15 room air volumes every hour and replace with fresh air
Details on examinations and observations:
MORTALITY / CLINICAL SIGNS
- Time schedule for examinations: daily

BODY WEIGHT
- Time schedule for examinations: at test initiation, weeks 2, 4, 6, 8 and at termination but not during egg laying to prevent adverse effects on egg production.

FOOD CONSUMPTION (if feeding study)
- Time schedule for examinations: weekly
- Remarks: presented as an estimate because it was not possible to measure wasted feed.

PATHOLOGY
- Dose groups that were examined: all
- Remarks: all animals that died or euthanised during the course of study and all surviving animals at termination.
Details on reproductive parameters:
The following parameters were examined per parental pen per week:
- Eggs laid
- Eggs cracked; eggs broken
- Egg abnormalities
- Eggshell thickness or eggshell strength
- Eggs fertile
- Embryos viable
- Normal hatchlings
- 14-day old surviving chicks
- Chick body weight at hatching and 14 days after hatching
Reference substance (positive control):
no
Key result
Duration (if not bolus):
21 wk
Dose descriptor:
NOEC
Effect level:
300 other: ppm
Conc. / dose based on:
test mat.
Basis for effect:
reproductive parameters
Mortality and sub-lethal effects:
No mortalities occurred in the study. Incidental clinical observations were noted, including foot and ankle lesions, feather loss, bill abrasions and lameness. Except for incidental findings, all birds were normal in appearance and behaviour throughout the study. All surviving adults were subjected to gross necropsy following adult termination, findings are reported in Table 1.

There were no apparent treatment-related effects upon adult body weight at any of the concentrations tested (see Table 2).

There were no statistically significant differences between the control group and any treatment group of drakes or between the control group and the 150 ppm and 600 ppm treatment groups of hens. However, the mean body weights of hens in the 300 ppm treatment group were slightly, but significantly greater than the control at week 4, 6 and 8. Since the differences were slight, not concentration responsive, and represented an increase in body weight, the observed differences were not considered biologically meaningful or related to treatment.

Mean food consumption measurements are presented in Table 3. There were no treatment-related effects upon feed consumption at the 150 or 300 ppm test concentrations. However, at the 600 ppm test concentration, there was an increase in feed consumption during the first ten weeks of the study that was statistically significant at each of the ten intervals. As an impact upon energy conversion could not be precluded, the observed increases may have been treatment related.
Effects on reproduction:
There were no treatment-related effects upon reproductive performance at the 150 or 300 ppm test concentrations. Although there were statistically significant reductions in cracked eggs as percentages of eggs laid at all test concentrations, the observed differences were slight. Since the reductions represented improvements in performance, and all treatment group values were comparable to the historical control, they were not considered related to treatment. For any of the other reproductive parameters measured no statistically significant differences between the control and either the 150 or 300 ppm treatment groups. At the 600 ppm test concentration, there were marked, treatment-related, effects upon reproductive performance, including effects upon egg production, fertility and hatchability. When compared to the control group, the observed reduction in egg production was statistically significant. While not statistically significant, there were slight, but treatment-related, reductions in viable embryos as a percentage of eggs set and hatchlings as a percentage of live 3-week embryos. The reductions were further reflected as reductions in both hatchlings and 14-day old survivors as percentages of both eggs set and as statistically significant reductions in both hatchlings as 14-day old survivors as percentages of the maximum number of eggs set (see Table 4).

There were no apparent treatment related effects upon eggshell thickness. There were no apparent treatment related effects upon offspring body weights at the 150, 300 or 600 ppm test concentrations and any differences from the control group were not statistically significant for either the hatchlings or the 14-day old survivors (see Table 5).

Table 1: Gross pathological observations (adult birds euthanised at test termination)

   Males (ppm)  Females (ppm)
   0  150  300  600  0  150  300  600
 Number of birds  16  16  16  16  16  16  16  16
 Foot/leg lesions  5  11  10  7  14  14  16  12
 Air sacculitis  0  0  0  0  0  0  0  1
 Spleen - enlarged  1  0  0  0  0  1  0  1
 Spleen - mottled  0  0  0  0  1  0  0  1
 Small intestines - areas of hyperemia  0  1  0  0  0  2  0  0
 Testes - small (one or both)  2  0  1  1  -  -  -  -
 Abdominal cavity - egg remnants  -  -  -  -  0  0  0  1
 Abdominal cavity - slight egg yolk peritonitis  -  -  -  -  1  1  1  1
 Abdominal cavity - egg yolk peritonitis  -  -  -  -  1  1  1  3
 Abdominal cavity - slight old egg yolk peritonitis  -  -  -  -  0  1  0  0
 Ovary - regressing  -  -  -  -  1  2  1  3
 Ovary - cystic follicles  -  -  -  -  1  0  0  2
 Ovary - cyst  -  -  -  -  1  0  0  0
 Not remarkable  10  4  6  9  2  2  0  3

Table 2: Mean adult body weight (g) and weight change (g)

   Males (ppm)  Females (ppm)
   0  150  300  600  0  150  300  600
 Week 0  1163  1204  1129  1202  1033  1060  1074  1018
 Change week 0-2  -42  -48  -7  -120  -57  -34  -31  -12
 Week 2  1121  1156  1121  1190  976  1027  1043  1006
 Change week 2-4  5  27  9  8  3  3  14  16
 Week 4  1126  1183  1130  1198  979  1030  1057*  1023
 Change week 4-6  22  -7  39  18  24  -1  -3  17
 Week 6  1149  1176  1169  1216  1003  1028  1091**  1043
 Change week 6-8  -11  -3  1  4  4  -1  -3  -17
 Week 8  1138  1174  1171  1221  1006  1027  1088*  1060
 Change week 8-Term  17  12  33  -3  126  151  95  32
 Term  1155  1185  1204  1218  1132  1178  1182  1092
 Total change  -9  -19  75  16  99  118  108  73

The means for body weights and body weight changes are calculated and rounded separately

*significantly different from control at p <0.05

**significantly different from the control at p <0.01

Table 3: Mean feed consumption (g/bird/day)

 Weeks  0 ppm  150 ppm  300 ppm  600 ppm
 1  60  65  71  83**
 2  96  102  99  120**
 3  96  112  104  122**
 4  101  113  103  128**
 5  108  115  114  134**
 6  105  126  117  142**
 7  105  123  111  143**
 8  122  132  121  160**
 9  112  127  114  152**
 10  120  135  115  152**
 11  118  130  113  140
 12  151  163  158  166
 13  168  187  163  176
 14  146  166  140  163
 15  166  175  172  173
 16  172  177  158  191
 17  171  189  172  192
 18  188  200  190  203
 19  190  199  183  204
 20  184  191  189  204
 21  189  191  198  201

**significantly different from the control p <0.01

Table 4: Reproductive performance (normalised as percentage1)

   Experimental group (ppm)
 Reproductive parameter  0  150  300  600
 Number of replicates  16  16  16  16
 Total eggs laid2  852  750  745  561
 Eggs laid/Maximum laid (%)  73  64  64  48**
 Eggs cracked/Eggs laid (%)  4  2*  1**  1**
 Viable embryos/Eggs set (%)  88  87  81  76
 Live 3 week embryos/Viable embryos (%)  99  100  97  98
 Hatchlings/Live 3 week embryos (%)  90  92  92  81
 14 day old survivors/Hatchling (%)  99  100  99  100
 Hatchlings/Eggs set (%)  78  80  72  59
 14 day old survivors/Eggs set (%)  77  80  72  59
 Hatchlings/Maximum set (%)  53  50  46  24**
 14 day old survivors/Maximum set (%)  53  50  46  24**

*significantly different from the control p <0.05

**significantly different from the control p <0.01

1Values represent pen means for experimental group

2Represents the total number of eggs laid in each group

Table 5: Mean body weight (g) of hatchlings and 14 day old survivors

   0 ppm  150 ppm  300 ppm  600 ppm
 Hatchlings        
 Number  572  538  495  263
 Mean (± SD)  37 ± 3  38 ± 2  37 ± 3  38 ± 2
 14 day old survivors        
 Number  568  533  482  261
 Mean (± SD)  260 ± 19  278 ± 20  276 ± 20  256 ± 21

The total number of hatchlings weighed may differ from the total number of hatchlings since those found dead were not weighed.

Validity criteria fulfilled:
not specified
Conclusions:
Under the conditions of the test, the NOEC for mallard ducks exposed to the test material was determined to be 300 ppm based upon the effects seen in the 600 ppm treatment group.
Executive summary:

In a GLP compliant reproductive toxicity to birds study conducted in line with standardised guidelines OECD 206 and EPA 71-4, the reproductive toxicity of the test material to mallard ducks was determined. The test material was administered by dietary inclusion at 0, 150, 300 and 600 ppm. Under the conditions of the test the NOEC was determined to be 300 ppm based on the effects seen at the 600 ppm treatment level.

Description of key information

Acute oral toxicity study in the Bobwhite Quail conducted in line with GLP and standardised guideline EPA 71-1; the LD50 value was determined to be 683 mg/kg bw (95 % C.I. 549-818 mg/kg bw).

The dietary toxicity (LC50) of the test material to the mallard duck conducted in line with GLP and standardised guideline EPA 71-2; the LC50 was determined to be >5200 mg/kg diet.

A reproduction study with the Northern bobwhite conducted in line with GLP and standardised guidelines OECD 206 and EPA 71-4; the NOEC was determined to be 150 ppm.

A reproduction study with the Mallard conducted in line with GLP and standardised guidelines OECD 206 and EPA 71-4; the NOEC was determined to be 300 ppm.

Key value for chemical safety assessment

Short-term EC50 or LC50 for birds:
5 200 mg/kg food
Long-term EC10, LC10 or NOEC for birds:
150 mg/kg food

Additional information

In the key GLP compliant acute oral toxicity to birds study conducted in line with standardised guideline EPA 71-1, the acute oral toxicity of the test material to bobwhite quail was determined. The test material was administered by capsule as a single dose, followed by a 15 day observation period, at 0, 400, 800, 1086, 1474 and 2000 mg/kg. Under the conditions of the test the LD50 value was determined to be 683 mg/kg bw (95 % C.I. 549-818 mg/kg bw).

In a supporting GLP compliant acute oral toxicity to birds study conducted in line with standardised guideline EPA 71-1, the acute oral toxicity of the test material to mallard ducks was determined. Under the conditions of the test it was not possible to determine a LD50value because there were no mortalities; the value must be in excess of 50 mg/kg bw, the maximum dose-level at which there were no emetic effects.

In the key GLP compliant short-term dietary toxicity to birds study conducted in line with standardised guideline EPA 71-2, the short-term dietary toxicity of the test material to mallard ducks was determined. The test material was administered by dietary inclusion at 650 1300, 2500 and 5200 ppm. Under the conditions of the test it was not possible to determine a LC50 value because there were only two mortalities at the highest dose level tested. This value must therefore be in excess of 5200 mg/kg diet.

In a supporting GLP compliant short-term dietary toxicity to birds study conducted in line with standardised guideline EPA 71-2, the short-term dietary toxicity of the test material to bobwhite quail was determined. Under the conditions of the test it was not possible to determine a LC50value because of the distribution of the mortalities that occurred; the value appears to be in the region of 5200 ppm, the maximum dose used.

In key GLP compliant reproductive toxicity studies conducted in line with standardised guidelines OECD 206 and EPA 71-4, the reproductive toxicity of the test material to Northern bobwhite quail and mallard duck was determined. The test material was administered by dietary inclusion at 0, 150, 300 and 600 ppm. Under the conditions of the tests the NOEC was determined to be 150 ppm (Northern bobwhite quail) and 300 ppm (mallard).