Propargite

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:

6th May 1988 to 20th October 1988

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

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 850.2300 (Avian Reproduction Test)

Deviations:

no

GLP compliance:

yes

Dose method:

feed

Analytical monitoring:

no

Vehicle:

yes

Details on preparation and analysis of diet:

DIET PREPARATION
- Description and nutrient analysis of basal diet provided in study report: yes
- Preparation of doses: Omite® was mixed into a premix which was used for the weekly preparation of the final diet.
- Type and function of solvent/vehicle: acetone/corn oil

HOMOGENEITY AND STABILITY OF TEST MATERIAL IN DIET
- How often was homogeneity and stability tested: weekly after mixing

Test organisms (species):

Anas platyrhynchos

Details on test organisms:

TEST ORGANISM
- Common name: mallard
- Source: Whistling Wings, Box 1, 113 Washington Street, Hanover, Illinois 61041, USA
- Age at test initiation (mean and range, SD): 28 weeks
- Sexes used: male and female

Limit test:

no

Total exposure duration (if not single dose):

18 wk

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

Sixteen

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

0, 30, 100 and 300 ppm (nominal)

<2.0, , 43.2, 84.7 and 288.7 ppm (actual)

Details on test conditions:

ACCLIMATION
- Acclimation period: 10 weeks

PEN SIZE AND CONSTRUCTION MATERIALS
- Description: 75 x 90 x 45 cm (adults) constructed with galvanised wire grid and galvanised sheeting; 72 x 90 x 24 cm high (hatchlings) constructed with galvanised wire mesh and galvanised sheeting
- Compliant to good husbandry practices: yes
- Caging: one male / one female

NO. OF BIRDS PER REPLICATE
- For vehicle control: 2
- For treated: 2

NO. OF REPLICATES PER GROUP
- For vehicle control: 16
- For treated: 16

TEST CONDITIONS (range, mean, SD as applicable)
- Temperature: 23.0 ± 1.9 ºC (adults); >26 ºC (hatchlings)
- Brooder temperature: approximately 38 ºC
- Relative humidity: 73 ± 12 %
- Photoperiod: less than eight hours per day until week ten when it was increased to seventeen hours per day (adults); 17 hours per day (hatchlings)
- Ventilation: up to fifteen air changes per hour

Details on examinations and observations:

MORTALITY / CLINICAL SIGNS
- Time schedule for examinations: at least once daily

BODY WEIGHT
- Time schedule for examinations: study initiation, weeks 2, 4, 6, 8 and terminal sacrifice

FOOD CONSUMPTION (if feeding study)
- Time schedule for examinations: for each pen for each week throughout the study

PATHOLOGY
- Dose groups that were examined: all
- Remarks: all birds that died during the study were necropsied; birds that did not die were necropsied at the end of the study.

Details on reproductive parameters:

The following parameters were examined daily per parental pen:
- Eggs laid
- Eggs cracked
- Eggs set
- Eggshell thickness or eggshell strength
- Embryos viable
- Embryo survival
- Hatchlings
- Body weight of hatchlings
- 14 day old survivors
- Body weight of 14 day old survivors

Reference substance (positive control):

no

Key result

Duration (if not single dose):

18 wk

Dose descriptor:

NOEC

Effect level:

13.5 mg/kg bw/day

Conc. / dose based on:

test mat.

Basis for effect:

other: mortality, overt toxicity, effects on body weight, feed consumption and reproductive parameters

Mortality and sub-lethal effects:

There were four adult mortalities during the exposure phase; one in the control, one at 30 ppm and two at 300 ppm. The mortalities in the control and 30 ppm groups were not considered to be treatment-related as indicated by findings of a gross necropsy (egg yolk, visceral and intestinal lesions). The same was true for one of the 300 ppm mortalities (egg yolk, air sacculities, body cavity lesions and regressing ovary). However, in the second 300 ppm mortality, necropsy indicated the absence of body fat, inactive ovary, small liver, distended gall bladder, bile stained gizzard and haemorrhagic intestinal lining/contents. This single mortality appeared to be treatment-related. There were no overt signs of toxicity observed in any surviving adults at any concentration. A general observations of some birds appearing thin was made at week 16 in the 300 ppm group. Other non treatment-related signs associated with pen wear and interaction with pen mates included high wing carriage, lower limb weakness and lethargy noted at various concentrations. At necropsy, there was a treatment-related increase in the number of hens exhibiting a regressed ovary at 300 ppm. Also in the 300 ppm group, all females and 11/14 males had atrophied pancreases. Since this lesion was not observed in any of the control birds, this was attributed to treatment. There was no effect on body weight in the 300 ppm group or on the males in the 100 ppm group. There was a statistically significant reduction in body weight of 100 ppm females during week 6 and at study termination. There was also a statistically significant reduction in body weight of 300 ppm females at termination (body weight was also reduced by three-fold in 300 ppm males although this was not statistically significant). There were no treatment-related effects on food consumption.

Effects on reproduction:

There were no apparent treatment-related effects on reproductive parameters in the 30 and 100 ppm groups. At 100 ppm, there may have been a slight reduction in the number of hatchlings as a percentage of live three week embryos. The effect was minor and not statistically significant. At 300 ppm there was a marked effect on reproductive performance. Only 53 eggs were laid compared to 626 eggs in the control group. Only 8/14 hens in this group laid and of those eight, only three laid more than ten eggs. Of the 53 eggs laid, two were cracked and the remainder were either soft shelled or abnormal resulting in no eggs being available to set for this group. There were no effects on body weight of hatchlings or 14 day old offspring in the 30 and 100 ppm groups. There were no offspring from the 300 ppm group.

Reported statistics and error estimates:

Dunnett's method was used to determine statistically significant differences between the control group and each of the treatment groups. Percentage data were examined using Dunnett's method following arcsine transformation.

Validity criteria fulfilled:

not specified

Conclusions:

Under the conditions of the test, a dietary concentration of 30 ppm did not result in treatment-related mortality, overt toxicity, effects on body weight, feed consumption or reproductive performance of adult mallards. In the 100 ppm group, there was a treatment-related effect on female body weight which was considered to be minimal and isolated. Reproductive performance was not affected at 30 and 100 ppm. However, at 300 ppm there was a decrease in adult body weight and a very marked effect on reproductive performance. The NOEC was determined to be 10 ppm (equivalent to 13.5 mg/kg bw/day).

Executive summary:

A one-generation mallard reproduction study was conducted on Omite^® in compliance with EPA OPP 71-4. The test material was administered ad libitum in the diet of young adult mallards (28 weeks old at test initiation) approaching their first breeding season. Diets containing the test material at nominal concentrations of 0, 30, 100 or 300 ppm were fed to the adults for 18 weeks. The mallards were observed daily for mortality, abnormal behaviour and signs of toxicity. All adult birds found dead during the study were necropsied. In addition, necropsies were performed on all adults surviving until study termination.

For the first nine weeks of the test, the birds were held under a photoperiod of eight hours or less of light per day. The photoperiod was increased to 17 hours of light per day during week ten to induce egg laying. The adults continued on a photoperiod of 17 hours of light per day until sacrifice. Eggs were collected daily and set weekly for incubation beginning at week 12. Weekly throughout the laying period, eggs were collected from every other pen for egg shell thickness measurement. In addition, effects upon egg production and quality and hatchling health and survivability were also examined.

The dietary concentrations at 30 ppm did not result in treatment-related mortality, overt signs of toxicity or effects upon adult body weight or feed consumption during the 18 week exposure period. There were no apparent treatment-related effects upon the reproductive parameters at 30 ppm. In the 100 ppm treatment group, there were treatment-related effects upon the body weight of hens, which was considered to be minimal and isolated, and possibly an effect upon hatchability. In the 300 ppm group, there were effects upon the body weights of both hens and drakes and there was a profound effect upon reproductive performance. The NOEC was determined to be 100 ppm (equivalent to 13.5 mg/kg bw/day).

Description of key information

NOEC 13.5 mg/kg bw/day (mallard); study conducted in accordance with EPA OPP 71-4; Beavers et al, 1998b

Key value for chemical safety assessment

Long-term EC10, LC10 or NOEC for birds:

13.5 mg/kg food

Additional information

The toxicity of propargite to birds was determined in two reproduction studies in the bobwhite quail and the mallard. Both studies were performed to standardised guidelines and GLP and were assigned a reliability score of 1. However, the mallard study had a more worst-case NOEC and so this was determined to be the key study. An acute and dietary toxicity study was also performed in the mallard. Both studies were performed to sound scientific principles but not to GLP and both assigned a reliability score of 2 and were considered to be supporting studies.

The key study, a one-generation mallard reproduction study, was conducted in line with EPA OPP 71-4. The test material was administered ad libitum in the diet of young adult mallards (28 weeks old at test initiation) approaching their first breeding season. Diets containing the test material at nominal concentrations of 0, 30, 100 or 300 ppm were fed to the adults for 18 weeks. The mallards was observed daily for mortality, abnormal behaviour and signs of toxicity. Eggs were collected daily and set weekly for incubation beginning at week 12. Weekly throughout the laying period, eggs were collected from every other pen for egg shell thickness measurement. In addition, effects upon egg production and quality and hatchling health and survivability were also examined. The dietary concentrations at 30 ppm did not result in treatment-related mortality, overt signs of toxicity or effects upon adult body weight or feed consumption during the 18 week exposure period. There were no apparent treatment-related effects upon the reproductive parameters at 30 ppm. In the 100 ppm treatment group, there were treatment-related effects upon the body weight of hens, which was considered to be minimal and isolated) and possibly an effect upon hatchability. In the 300 ppm group, there were effects upon the body weights of both hens and drakes and there was a profound effect upon reproductive performance. The NOEC was determined to be 100 ppm (equivalent to 13.5 mg/kg bw/day).

The main supporting study, was a one-generation bobwhite reproduction study conducted in line with EPA OPP 71-4. The test material was administered ad libitum in the diet of young adult bobwhite (18 weeks old at test initiation) approaching their first breeding season. Diets containing the test material at nominal concentrations of 0, 100, 300 or 1000 ppm were fed to the adults for 20 weeks. The bobwhite was observed daily for mortality, abnormal behaviour and signs of toxicity. Eggs were collected daily from the onset of egg production and set weekly for incubation beginning at week 13. Weekly throughout the laying period, eggs were collected from every other pen for egg shell thickness measurement. In addition, effects upon egg production and quality and hatchling health and survivability were also examined. Dietary concentrations at 100, 300 and 1000 ppm did not result in treatment-related mortality, overt signs of toxicity or effects upon body weight or feed consumption among adult bobwhite during the 20 week exposure period. No treatment-related effects upon reproductive performance were noted at 100 or 300 ppm concentrations. However, in the 1000 ppm treatment group, there was a slight decrease in the survivability of offspring and a possible reduction in both offspring body weight and egg shell thickness. There also did appear to be a slight treatment-related reduction in body weight among hens at 1000 ppm although no effects upon feed consumption were noted. The NOEC was determined to be 300 ppm (equivalent to 142 mg/kg bw/day).

In the first of the additional supporting studies, the acute toxicity of the test material to mallard ducks was determined in a non-GLP study conducted in line with sound scientific principles. Birds were treated with one dose of propargite, by gavage, at 215, 464, 1000, 2150 and 4640 mg/kg and then observed for eight days. Under the conditions of the test, the LD50 and NOEL of the substance were determined to be > 4640 and 2150 mg/kg bw, respectively.

In a non-GLP short-term dietary toxicity study conducted in accordance with sound scientific principles, the short-term toxicity of the test material to mallard ducks was determined. Birds were exposed to diet containing propargite at 215, 464, 1000, 2150 and 4640 ppm for five days and then observed for a further three days. Under the conditions of the test, the LC50 and NOEC of the substance were determined to be > 4640 and 2150 ppm diet, respectively.