1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

Toxicity to birds

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to birds: reproduction test

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-11-10 to 2001-07-17

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:

April 2000 draft

Deviations:

yes

Remarks:

see "Principles of method if other than guideline"

Principles of method if other than guideline:

PROTOCOL DEVIATIONS
Temperature and relative humidity in the room of the adults and in the cabins of the chicks deviated from the protocol. Deviations were mostly small and no changes in health and behaviour of the animals were noted. Therefore, these deviations were considered not to have affected the study integrity.

Temperature and relative humidity in the storage, incubator and hatcher deviated from the protocol. Deviations were mostly small and hatchability was good during the study. Therefore, these deviations were considered not to have affected the study integrity.

Body weight of males and females were higher at start of the pre-treatment. This was considered not to have affected the study integrity, because male group means were within the range and female group range deviated only 5 gram.

Light intensity was lower than 10 lux at start acclimatisation (8 lux). Deviation was only slight and was intended to reduce aggressiveness. Therefore, this was considered not to have affected the study integrity.

Necropsy was for practical reasons one day later (day 44) than six weeks after start of treatment (day 43). Therefore, body weights were also measured on day 44. Because this was only one day, and all measurements were finished on day 43 (after six weeks of treatment), this was considered not to have affected the study integrity.

GLP compliance:

yes

Specific details on test material used for the study:

The test material is a white powder.

Dose method:

homogenously mixed into feed (accounts for technical substances)

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

Acetone

Details on preparation and analysis of diet:

DIET PREPARATION
- Preparation of doses: Test diet was prepared in basal diet a few days in advance to study weeks 1 and 4 of treatment. The appropriate amount of test substance was weighed into a glass flask on an analytical balance and 200 ml acetone was added. The test substance was mixed with some diet (premix) and subsequently mixed with the bulk of the diet (15 kg in total). Immediately after preparation, the diets were stored for approximately 24 hours at room temperature to allow the acetone to evaporate. Hereafter, the diets were stored at -20°C until usage. Test diet for the control birds was not mixed with the test substance, but further treated in exactly the same way. Over the study period, the amount of test substance incorporated into the diet was constant in terms of mg a.s/kg diet.

HOMOGENEITY AND STABILITY OF TEST MATERIAL IN DIET
- How often was homogeneity and stability tested: Preceding the main study, a trial diet was prepared for chemical analyses. Because the chemical analyses showed that the diets were not homogeneously mixed, a second trial diet was prepared with acetone as a vehicle. Accuracy was determined in both trial diets at dietary concentrations of 100, 330 and 1000 mg a.s./kg. During the main study accuracy of preparation of all concentrations was determined in the prepared diets. Homogeneity of test substance in the diet was determined in both trial diets at concentrations of 100, 330 and 1000 mg a.s./kg. Stability analyses were performed in the second trial diet prepared at all concentrations. The 100 ppm, 330 ppm and 1000 ppm diets prepared on 08-02-2001 and 27-02-2001 were tested for homogeneity. The 100 ppm, 330 ppm and 1000 ppm diets prepared on 27-02-2001 were analysed on 02-03-2001 after 3 days of storage at -20°C (t=3), on 05-04-01 after 37 days of storage at -20°C and on 05-04-2001, after 30 days of storage at -20°C and 7 days under test conditions for stability.
- When and at what dose levels were samples of treated food analyzed for stability and concentration during the study: In the main study stability analysis were performed in diets prepared prior to week 1 at all test concentrations. The 100 ppm, 330 ppm and 1000 ppm diets prepared on 08-03-2001 were analysed on 14-03-2001 after 6 days of storage at -20°C (t=6) and on 05-04-2001, after 21 days of storage at -20°C and 7 days under test conditions.
- Nominal concentration (mg/kg feed): nominal concentrations of 100, 330 and 1000 mg a.s./kg

ANALYTICAL METHODS IN THE FEED
- Separation method: HPLC

Test organisms (species):

Coturnix coturnix japonica

Details on test organisms:

TEST ORGANISM
- Common name: Japanese quail (Coturnix coturnix iaponica)
- Age at test initiation: Approximately 12 weeks old
- Body weight at start of pre-treatment: males: 177-265 g; females: 204-319 g.
- Body weight at start of treatment: males: 165-237 g; females: 153-294 g.
- Sexes used / mixed or single sex: mixed
- Disease free: yes
- Kept according to standard practices: yes

Limit test:

no

Total exposure duration (if not single dose):

6 wk

Remarks:

The test period was divided into three different phases:
(i) Acclimatisation and stabilisation - 5 weeks
(ii) Pre-treatment period - 2 weeks
(iii) Treatment period - 6 weeks

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

20 pairs per dose group.

Control animals:

yes, plain diet

Nominal and measured doses / concentrations:

Nominal concentrations of 100, 330 and 1000 mg a.s./kg.
Mean measured concentrations of the main study: 83 mg a.s./kg (97.7%), 271 mg a.s./kg (81%) and 905 mg a.s./kg (94.0%) of nominal concentrations of 100, 330 and 1000 mg a.s./kg, respectively.

Details on test conditions:

ACCLIMATION
- Acclimation period: 5 weeks

PEN SIZE AND CONSTRUCTION MATERIALS
- Description: Adults were pair-housed (1 male/1 female) in wire mesh stainless steel battery-type cages with slanting floors and egg catchers (55 cm x 90 cm with a height of 30 cm). The paper sheet under the wire mesh floors was changed weekly. Several pairs were separated for the greater part of the day because of their aggressive behaviour, but housed together for at least 0.5 hrs per day. Chicks were group-housed in stainless steel, wire mesh cages (100 cm x 60 cm and a height of 25 cm).
- Compliant to good husbandry practices: yes
- Caging: group

NO. OF BIRDS PER STAGE OR REPLICATE
- For negative control: 20 pairs
- For treated: 20 pairs

TEST CONDITIONS
- Room temperature: 9-22.5°C
- Relative humidity (%): 35-75%Floor area (cm2/ bird) - Floor area (cm2/ bird): 2475
- Photoperiod: Adults: 17 hours artificial light/7 hours dark. Chicks: 14 hours artificial light/10 hours dark. Controlling day/night rhythm was by automatic timers. Lights emit a spectrum simulating that of daylight (TLD 50W; 84HF).
- Ventilation: Air-conditioned rooms with about 14 air changes per hour for adults and about 7 air changes per hour for chicks and controlled environment.
- Light intensity: 8-36 lux at the level of the feeders and recorded prior to start of the acclimatisation/stabilisation period, 10-34 lux at start of the pre-treatment and 11 -31 lux at start of the treatment.
- Feeding: Adults and chicks had free access to a standard commercial breeder diet. For adults, food troughs were covered with a wire grid in order to prevent spillage.
- Water: Free access to tap water

Details on examinations and observations:

MORTALITY
- Time schedule for examinations: Twice daily.
- Remarks: Animals showing pain, distress or discomfort and which was considered to be non-transient in nature or likely to become more severe was sacrificed for humane reasons.

CLINICAL SIGNS
- Time schedule for examinations: All birds were observed for clinical signs once daily. Signs were only reported once weekly unless major significant changes in health status are seen during daily observations.
- Remarks: The observations were coded and the degree of the condition, where appropriate, time of onset and duration were recorded in the computer system (TIS, Syseca, BASEL, SWITZERLAND). All symptoms were recorded and graded according to fixed scales: Maximum grade 3: grading slight (1) to severe (3). Maximum grade 1: presence was scored (1). Observations included changes in behavioural pattern, toe-picking, excessive aggression, tremors, convulsion, salivation, laboured respiration, leg weakness, ruffled feathers, diarrhoea, and lethargy.
BODY WEIGHT
- Time schedule for examinations: Measured at start of pre-treatment, at start of treatment and at the end of treatment (day 43).
- Remarks: Because necropsy was performed on day 44, body weights were also measured on day 44 (for organ/body weight ratio calculations). Body weights of animals that died or were killed in extremis were also recorded.

FOOD CONSUMPTION
- Time schedule for examinations: Food consumption per pen was measured during the pre-treatment and treatment period once a week and recorded.

PATHOLOGY
All moribund birds and birds surviving to the end of the observation period were sacrificed by carbon dioxide asphyxiation. Pen-mates of birds killed in extremis or found dead were sacrificed on the same day. All birds assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded. Gross necropsies included general inspection of the gastro-intestinal tract, liver, kidney, heart, spleen and reproductive organs. All moribund chicks were sacrificed by decapitation. All chicks surviving to the end of the test were sacrificed by carbon dioxide asphyxiation. No further examinations were performed.

ORGAN WEIGHTS
The wet weight of liver, spleen and testes was recorded as soon as possible after death.

Details on reproductive parameters:

EGGS
- Eggshell thickness: During the pre-treatment and treatment periods one egg per pen was collected from odd numbered pens per odd numbered week and from even numbered pens per even numbered week for measurement of the mean eggshell thickness. Cracked eggs were not measured. Eggs were opened at the girth, washed, dried with membrane intact for 48 hours and measured at four points around the girth (micrometer Oditest).
- Eggs laid: Collected and registered daily during all phases of the study. Reported as number per pen per week.
- Eggs cracked or broken: Checked daily while collecting during all phases of the study. During the pre-treatment and treatment phase eggs were checked for fine cracks by candling prior to setting. Reported as number per pen per week.
- Egg weight: Measured during the pre-treatment phase and treatment phase prior to start of incubation of all eggs laid during previous week. Reported on a weekly basis as mean egg weight per pen.
- Fertility /embryo viability: Determined weekly during all phases of the study by candling on day 8 of incubation. Reported as number per pen per week.
- Hatchability: Determined weekly during pre-treatment and treatment phase and reported as number per pen per week.

CHICKS
- Mortality/clinical signs: Chicks were checked daily during the first 14 days after hatching. Signs were only recorded once weekly unless major significant changes in health status were seen during daily observations. Reported as number of dead/affected chicks per pen per week.
- Body weights: Individual weights of hatchlings after removal from the hatcher (day 1) and of 14-day old survivors (day 15) were measured and reported on a weekly basis as mean egg weight per pen.
- 14-day old survivors: Numbers were recorded 14 days after hatching (day 15) and reported as number per pen per week.

Key result

Duration (if not single dose):

6 wk

Dose descriptor:

NOEL

Effect level:

122.1 mg/kg bw/day

Conc. / dose based on:

test mat.

Basis for effect:

other: signs of toxicity and reproductive parameters

Remarks on result:

other: No effect observed

Duration (if not single dose):

6 wk

Dose descriptor:

NOEC

Effect level:

>= 1 000 mg/kg diet

Conc. / dose based on:

test mat.

Basis for effect:

other: signs of toxicity and reproductive parameters

Remarks on result:

other: No effect observed

Duration (if not single dose):

6 wk

Dose descriptor:

LOEC

Effect level:

1 000 mg/kg diet

Conc. / dose based on:

test mat.

Basis for effect:

other: signs of toxicity and reproductive parameters

Mortality and sub-lethal effects:

MORTALITY
The following mortalities were noted during the treatment period (pen-mates of the decedents were sacrificed on the same day):
0 mg a.s./kg diet: One pair and one female were killed in extremis in week 5 of treatment.
100 mg a.s./kg diet: One male and one female were killed in extremis in week 4 of treatment.
330 mg a.s./kg diet: One female died spontaneously in week 6 of treatment, one female died spontaneously and one male was killed in extremis, both in week 5 (same pair).
1000 mg a.s./kg diet: One male and one female died spontaneously in week 4 and 2 of treatment, respectively.
Since a dose-effect relationship was lacking, these deaths were considered incidental and of no toxicological significance.

CLINICAL SIGNS
No test substance-related signs were noted at clinical observations during the pre-treatment and treatment period.
Among animals of group 1, group 2 and/or group 3 (0,100 and 330 mg a.s./kg diet, respectively) hunched posture, lethargy, uncoordinated movements, emaciation, abnormal gait, ptosis and watery discharge from eye were found during the treatment phase (except hunched posture which was also observed in females of group 2 during the pre-treatment phase). These effects were noted among the control group birds and among the treated animals and were transient of nature. Further, no dose relationship was present and therefore, these effects were considered to be incidental and not to be related to treatment with the test substance.
Alopecia, scabs, wounds, swellings, nodules and ruffled plumage were noted among males and females of all test groups and the control group during both phases of the study. These findings were attributed to excessive aggression among cage-mates and were considered of no toxicological significance.

BODY WEIGHT
No adverse effects of the test substance on body weight or body weight gain of males or females were noted during the 2 weeks pre-treatment and the 6 weeks treatment period.

FOOD CONSUMPTION
No test substance related effects were found on food consumption in the pre-treatment and treatment phase in males or females.
During the first week of the pre-treatment and the fifth week of the treatment phase, food consumption was statistically significantly increased at 100 mg a.s./kg diet. Because no effects were found in the higher dose groups, these increases were considered incidental and without toxicological relevance.

PATHOLOGY
Macroscopic examination post-mortem revealed the following abnormalities (incidence):
0 mg a.s./kg diet - Males: pale discoloration of liver (1), kidneys (1) and spleen (1), reduced spleen size (1). Females: pale discoloration of liver (1), kidneys (1) and spleen (1).
100 mg a.s./kg diet - Males: pale discoloration of liver (1), kidneys (1) and spleen (1), black/brown contents of stomach (1). Females: emaciation (1), yellowish foci on liver (1).
330 mg a.s./kg diet - Males: no abnormalities. Females: black discoloration of liver (2), kidneys (1) and spleen (2), pale discoloration of kidneys (1), black foci on liver (2) and spleen (1), black contents of stomach (1).
1000 mg a.s./kg diet - Males: pale discoloration of liver (1), kidneys (1) and spleen (1). Females: yellowish discoloration of liver (1).
These findings were considered not to be attributable to PENCYCURON TECHNICAL because they were noted as well in the control group as in the treated groups. No further abnormalities were noted in any of the birds.

ORGAN WEIGHTS
Comparable mean organ weights of liver, spleen and testes were obtained for treated birds and control birds.
The statistically significantly increased absolute male liver weight at 330 mg a.s./kg diet was considered incidental because of the lack of an effect at 1000 mg a.s./kg diet. Liver weight relative to body weight was statistically significantly increased at 330 and 1000 mg a.s./kg diet, but without a dose-relationship. Absolute and relative liver weights were found to be comparable with the historical control data of the NOTOX laboratory. Further, at the macroscopical examination no effects in these dose groups were noted when compared to the control group. Therefore, these increases were considered not to be attributable to treatment with PENCYCURON TECHNICAL.

Effects on reproduction:

REPRODUCTIVE PARAMETERS
EGG PRODUCTION/QUALITY
During the treatment period comparable values were obtained for the treated and control groups with regard to the number of eggs laid per hen and the percentage of eggs cracked or broken of eggs laid. Comparable values were obtained for these parameters for the pre-treatment and treatment period.
Statistically significant increased mean egg weight was recorded during the treatment phase at 100 mg a.s./kg diet when compared with the control group. In the absence of a dose effect relationship this effect was regarded to be without toxicological significance.

INCUBATION DATA
No parameter showed lexicologically significant differences between the treated birds and the control birds, which could be related to treatment with PENCYCURON TECHNICAL. Moreover, for each dose group comparable values were obtained for these parameters for the pre-treatment and treatment phase.
In the treatment phase, statistically significant increase of the percentage late embryonic death of fertile eggs was seen in the 100 mg a.s./kg group. No effects were seen in the other dose groups, and therefore this effect was considered incidental.

OBSERVATIONS CHICKS
MORTALITY
PENCYCURON TECHNICAL in the diet at concentrations up to and including 1000 mg a.s./kg diet did not have an effect on chick survival.

CLINICAL OBSERVATIONS
The most common clinical observations, crippled or weak chicks, were observed in the dose groups to a comparable degree as in the control group, and not related to treatment with the test substance. Observations recorded as 'other' were abnormal posture leg, abnormal posture head, abnormal posture neck and crossed beak. These findings were also found to a comparable degree in all groups and were considered to be incidental and of no toxicological significance.

BODY WEIGHTS
During the treatment the weights of 1-day old chicks of the group receiving 1000 mg a.s./kg diet were statistically significantly lowered when compared to the weights of the control group. After correction for the results of pre-treatment no statistically significant findings were found anymore. Further, no corroborative findings were found in mean egg weight, weight of 14-day old survivors or growth rate at 1000 mg a.s./kg diet. Therefore, this finding was considered to have occurred by chance and not to be attributable to treatment with the test substance.
Growth rate of chicks from the 1000 mg a.s./kg dose group was statistically significantly decreased during the pre-treatment. Effects in the pre-treatment group could only be incidental because no test substance was administered to these birds. Therefore, this effect was considered to be a consequence of the biological variation.

ANALYSIS OF THE DIET

Diets were prepared twice during the treatment phase, using acetone as a vehicle. Preceding the main study, a trial diet was prepared for chemical analysis. The mean measured test substance concentrations in the trial diet were 92 mg a.s./kg, 306 mg a.s./kg and 956 mg a.s./kg (varied between 92% and 96% of the nominal concentrations of 100, 330 and 1000 mg a.s./kg). The mean measured test substance concentrations in the two batches of diets prepared for the main study were 85 and 92 mg a.s./kg, 334 and 290 mg a.s./kg and 963 and 905 mg a.s./kg, respectively (varied between 82% and 101% of the nominal concentrations of 100,330 and 1000 mg a.s./kg). Based on chemical analyses in the trial diet all test diet preparations were homogeneously mixed. In the trial diet stability of the test substance in the diet was preserved over 27 days of storage at -20°C and 7 days under test conditions in the feeding troughs (varied between 84% and 93.9% of nominal concentrations of 100, 330 and 1000 mg a.s./kg, mean measured concentrations were 78 mg a.s./kg, 272 mg a.s./kg and 898 mg a.s./kg). After 34 days weeks storage at -20°C mean measured concentrations were 92 mg a.s./kg, 285 mg a.s./kg and 901 mg a.s./kg (varied between 93% and 99.6% of nominal concentrations of 100, 330 and 1000 mg a.s./kg). In the main study the test substance proved to be stable at 100, 330 and 1000 mg a.s./kg diet after 15 days storage at -20°C followed by 7 days at test conditions (mean measured concentrations: 83 mg a.s./kg (97.7%), 271 mg a.s./kg (81%) and 905 mg a.s./kg (94.0%) of nominal concentrations of 100, 330 and 1000 mg a.s./kg, respectively).

 

ACCEPTABILITY OF THE TEST

The main conditions for acceptability are defined as follows:

• The test substance concentration in the test diet should be satisfactorily maintained (at least 80% of the nominal concentration) throughout the exposure period.


• During the last two weeks of acclimatisation period, not more than 3% mortality or debilitation in either sex should be noted.


• At least 16 breeding pairs that have produced eggs must be available in the control group at the end the 6-week treatment period.


• Pairs must have laid at least one egg before start of pre-treatment.

The study fulfilled the main conditions as described above.

 

See "Attachments" in "Overall remarks, attachments" for tables.

Validity criteria fulfilled:

yes

Conclusions:

PENCYCURON TECHNICAL caused no signs of toxicity in the breeding pairs of Japanese quail receiving up to the highest dietary level of 1000 mg a.s./kg for 6 weeks. Evaluation of the reproductive data revealed no adverse effects of PENCYCURON TECHNICAL on egg production, egg weight, eggshell quality, fertility, embryo viability or hatchability. Moreover, offspring parameters (chick mortality, clinical signs, and body weights of 1-day old chicks and 14-day old survivors and growth rate of 14-day old survivors) were not affected by parental treatment with PENCYCURON TECHNICAL. Based on these findings, the Lowest Observed Effect Concentration (LOEC) for parent birds and for reproductive data was considered to exceed 1000 mg a.s./kg diet, whereas the No Observed Effect Concentration (NOEC) was then considered to be 1000 mg a.s./kg diet for both parent birds and reproductive data.

Executive summary:

In this avian reproduction toxicity study, Japanese quail were photo-stimulated to approach egg production for a period of 5 weeks. The study was continued with a 2-week pre-treatment period, followed by a treatment period in which PENCYCURON TECHNICAL was administered in the daily diet over a period of 6 weeks. The birds were approximately 12 weeks at start of treatment. The study was conducted according to the proposed draft OECD Guideline for Testing of Chemicals, Avian reproduction toxicity test in the Japanese Quail or Northern Bobwhite (April 2000 draft).

 

Diets were prepared twice during the treatment phase, using acetone as a vehicle. Preceding the main study, a trial diet was prepared for chemical analysis. The mean measured test substance concentrations in the trial diet were 92 mg a.s./kg, 306 mg a.s./kg and 956 mg a.s./kg (varied between 92% and 96% of the nominal concentrations of 100, 330 and 1000 mg a.s./kg). The mean measured test substance concentrations in the two batches of diets prepared for the main study were 85 and 92 mg a.s./kg, 334 and 290 mg a.s./kg and 963 and 905 mg a.s./kg, respectively (varied between 82% and 101% of the nominal concentrations of 100,330 and 1000 mg a.s./kg). Based on chemical analyses in the trial diet all test diet preparations were homogeneously mixed. In the trial diet stability of the test substance in the diet was preserved over 27 days of storage at -20°C and 7 days under test conditions in the feeding troughs (varied between 84% and 93.9% of nominal concentrations of 100, 330 and 1000 mg a.s./kg, mean measured concentrations were 78 mg a.s./kg, 272 mg a.s./kg and 898 mg a.s./kg). After 34 days weeks storage at -20°C mean measured concentrations were 92 mg a.s./kg, 285 mg a.s./kg and 901 mg a.s./kg (varied between 93% and 99.6% of nominal concentrations of 100, 330 and 1000 mg a.s./kg). In the main study the test substance proved to be stable at 100, 330 and 1000 mg a.s./kg diet after 15 days storage at -20°C followed by 7 days at test conditions (mean measured concentrations: 83 mg a.s./kg (97.7%), 271 mg a.s./kg (81%) and 905 mg a.s./kg (94.0%) of nominal concentrations of 100, 330 and 1000 mg a.s./kg, respectively).

 

No test substance-related mortality or clinical signs were recorded during the treatment period in the adult birds. Body weights (gain) at the end of treatment and weekly food consumption were similar for treated groups and the control group. Comparable values for mean organ weights were obtained for treated and control birds. No treatment-related abnormalities were recorded at macroscopic examination post-mortem.

 

When comparing data between the treatment groups and the control group, no toxicological significant effects of PENCYCURON TECHNICAL on egg production, egg weight, eggshell quality, fertility, embryo viability, hatchability or chick data were found. Even so, no toxicological significant differences were noted when comparing for each dose group the values obtained during the treatment period with the pre-treatment period.

 

PENCYCURON TECHNICAL caused no signs of toxicity in the breeding pairs of Japanese quail receiving up to the highest dietary level of 1000 mg a.s./kg for 6 weeks. Evaluation of the reproductive data revealed no adverse effects of PENCYCURON TECHNICAL on egg production, egg weight, eggshell quality, fertility, embryo viability or hatchability. Moreover, offspring parameters (chick mortality, clinical signs, and body weights of 1-day old chicks and 14-day old survivors and growth rate of 14-day old survivors) were not affected by parental treatment with PENCYCURON TECHNICAL. Based on these findings, the Lowest Observed Effect Concentration (LOEC) for parent birds and for reproductive data was considered to exceed 1000 mg a.s./kg diet, whereas the No Observed Effect Concentration (NOEC) was then considered to be 1000 mg a.s./kg diet for both parent birds and reproductive data.

Description of key information

The objective of the study was to investigate the effect of dietary exposure of Pencycuron on Japanese quail's reproduction. The 6-wk NOEL was determined to be 122.1 mg/kg bw/d.

 

Test species	Result	Assessment	Reference
Coturnix japonica (Japanese quail)	6-wk NOEC = 122.1 mg a.s./kg bw/d (corresponding to the reported 1000 mg a.s./diet)	Key study	Teunissen (2001)
Bobwhite quail	8-d LC50 >1750 mg a.s./kg bw/d (corresponding to the reported 5000 mg a.s./kg)	This study is an acute oral toxicity study. Such studies are not a data requirement.	Carlisle & Carsel (1983)
Colinus virginianus (Bobwhite quail)	14-d LC50 2000 mg a.s./kg bw	This study is an acute oral toxicity study. Such studies are not a data requirement.	Carlisle & Toll (1983)
Mallard ducks	8-d LC50 >1750 mg a.s./kg bw/d (corresponding to the reported 5000 mg a.s./kg)	This study is an acute oral toxicity study. Such studies are not a data requirement.	Carlisle & Toll (1983)

Key value for chemical safety assessment

Long-term EC10, LC10 or NOEC for birds:

122.1 mg/kg bw/day