Methyl (R)-2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

Toxicity to birds

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to birds: acute oral toxicity test

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

XRD 535
Lot #: RNN 88-7R
Purity: 99.3%

Dose method:

gavage

Analytical monitoring:

no

Vehicle:

yes

Remarks:

Corn oil

Test organisms (species):

Colinus virginianus

Details on test organisms:

TEST ORGANISM
- Common name: Bobwhite quail
- Source: Monkfield, Bourn, Cambridgeshire, England
- Age: Young adults over 16 weeks of age
- Sexes used: Male and Female

Limit test:

no

Remarks:

Single dose followed by a 14-day observation period

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

5

Control animals:

yes, concurrent vehicle

Nominal and measured doses / concentrations:

500, 1000, 2000 mg/kg

Details on test conditions:

ACCLIMATION
- Acclimation period: 14 days

FEED WITHHOLDING PERIOD BEFORE DOSING
- No. of hours: Overnight starvation

PEN SIZE AND CONSTRUCTION MATERIALS
- Description: Each cage was constructed from stainless steel wire and contained an automatic drinker and food hopper
- Compliant to good husbandry practices: Yes
- Caging: Group s of 5 (males and females separately)

NO. OF BIRDS PER STAGE OR REPLICATE
- For vehicle control: 5/sex
- For treated: 5 /sex/dose

TEST CONDITIONS (range, mean, SD as applicable)
- Temperature: 16-18°C
- Relative humidity (%): 67 ± 7.4
- Photoperiod: 7 hours light and 17 hours dark
- Ventilation: Ventilation fans were adjusted as necessary

RANGE FINDING STUDY
- Test concentrations: 500, 1000, 2000 mg/kg
- Test conditions: An initial range-finding study was conducting using 6 adult bobwhite quail (3 males and 3 females). The birds were starved overnight prior to dosing.
- Results used to determine the conditions for the definitive study: 1 male and 1 female birds were found dead at 2000 mg/kg. No deaths at 1000 and 500 mg/kg.

Details on examinations and observations:

MORTALITY / CLINICAL SIGNS
- Time schedule for examinations: Daily

BODY WEIGHT
- Time schedule for examinations: Days -14, -7, 0, 7, and 14

FOOD CONSUMPTION
- Time schedule for examinations: Weekly over the following periods: Days -14 to -8; -7 to -1; 1 to 7; 8 to 14

PATHOLOGY
- Dose groups that were examined: All birds that died during the study were examined post-mortem. At termincation of the study, post-mortem examination was carried out on ten birds from the highest surviving dose groups

Reference substance (positive control):

no

Key result

Dose descriptor:

LD50

Effect level:

1 159 mg/kg bw

Conc. / dose based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: 95% CL: 858-1554 mg/kg

Dose descriptor:

NOEC

Effect level:

< 500 mg/kg bw

Conc. / dose based on:

test mat.

Basis for effect:

body weight

Remarks on result:

other: 14 day observation

Mortality and sub-lethal effects:

MORTALITY:
- Results: 4/10 and 9/10 birds were found dead at 1000 and 2000 mg/kg, respectively. No mortality at 500 mg/kg and control groups.

CLINICAL SIGNS
- Results: In all test groups the faeces produced appeared dark and yellow stained.

ABNORMAL BEHAVIOUR
- Results: Subdued behaviour and unsteadiness of gait were observed within 2-4 days following dosing in all groups treated with the test substance. The effects were more frequent and more severe at the highest dose level. Birds dosed at 500 and 1000 mg/kg recovered on Days 9 and 10 respectively. The remaining bird dosed at 2000 mg/kg recovered on Day 13.

BODY WEIGHT
- Results: All groups exhibited similar bodyweights during the pre-treatment period. Over days 0-7 bodyweights in the test groups tended to decrease with increasing dose level. Compensatory increase in weight were observed over Days 7-14.

FOOD CONSUMPTION
- Results: Food consumption was similar in all groups during the pre-treatment period. During the first 7 days following dosing there was a progressive overall decrease in food consumption with increasing dose level, correlating with the bodyweight data. Food consumption over Days 8-14 showed no clear evidence of any treatment-related effect.

PATHOLOGY
- Results: Grey fluid was released from the beak of one bird at 2000 mg/kg upon examination. Several birds dosed at 1000 and 2000 mg/kg were found to be thin. No abnormalities were detected in any other birds examined.

Conclusions:

LD50 (bobwhite quail): 1159 mg/kg

Executive summary:

Groups of five birds of each sex received doses of 0, 500, 1000 or 2000 mg/kg in corn oil by oral gavage and were observed for 14 days.

Nine birds in the top dose group and four from the intermediate group died during the course of the study. Subdued behaviour and unsteadiness of gait were observed within 2 to 4 days of dosing in all test dose groups, with increasing frequency and severity in the higher dose groups. Surviving birds in the low and intermediate groups recovered by days 9 and 10, respectively, and the remaining high dose bird on day 13. Faeces from all test groups was dark and yellow stained. Decreases in body weight and food consumption, more marked with increasing dose were observed in all test groups between days 0 and 7; this trend was reversed during the last week.

The acute oral LD50 of the test substance to bobwhite quail was calculated to be 1159 mg/kg and the no-effect level below 500 mg/kg.

Reference 2

Endpoint:

long-term toxicity to birds: reproduction test

Type of information:

experimental study

Adequacy of study:

key 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 206 (Avian Reproduction Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Haloxyfop (R)
Lot #: F0530-173
Purity: 98.7%

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

Feed

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 diets were prepared on each mixing day by mixing the test substance directly into the feed using a Hobart mixer. Fresh batches of the test diet were mixed every 21 days, beginning at day 0 and continuing for approximately 140 days. A base mix was not used. Instead, each batch was mixed from fresh feed.
- Type, identity and function of solvent: Acetone was used for rinsing

HOMOGENEITY AND STABILITY OF TEST MATERIAL IN DIET
- How often was homogeneity and stability tested: Homogeneity and stability of the test diet were determined for the low and high dietary concentrations during the definitive test. Samples for homogeneity verification were removed at the time of mixing of each batch from the low and high dietary treatment levels. Two samples were removed from each treatment at the top, middle and bottom of the mixing tub for each batch of food.
- Results of homogeneity analysis: Samples removed from the 100 and 800 mg a.i./kg dietary concentrations ranged from 83.8 to 126% of nominal, demonstrating homogeneity of the test substance in the diet throughout the reproductive study
- Nominal concentration: 0, 100, 200, 400 and 800 mg a.i./kg feed
- Concentration analysed: 96, 210, 410 and 850 mg a.i./kg feed
- % of nominal: The measured concentrations ranged from 78.4 to 128% of nominal concentrations and demonstrated that the appropriate dietary concentrations were administered to test birds during the reproductive study.
- Mixing procedure adequate and variance between nominal and actual dosage acceptable: Yes

Test organisms (species):

Colinus virginianus

Details on test organisms:

TEST ORGANISM
- Common name: Northern Bobwhite Quail
- Source: Sand Prairie Quail Farm, Maquoketa, Iowa
- Age at test initiation: 25 weeks at experimental start
- Weight at test initiation: 180 and 260 g
- Sexes used: male/female
- Kept according to standard practices: yes

Limit test:

no

Remarks:

10 weeks of exposure to treated feed prior to photostimulation, 4 weeks of pre-egg laying photostimulation period and 10 weeks of egg collection

Post exposure observation period:

approximately 6 weeks per set

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

18

Control animals:

yes, plain diet

Nominal and measured doses / concentrations:

- Nominal concentration: 0, 100, 200, 400 and 800 mg a.i./kg feed
- Measured concentration: 0, 96, 210, 410 and 850 mg a.i./kg feed

Details on test conditions:

ACCLIMATION
- Acclimation period: 15 days
- Acclimation conditions: Same as test
- Feeding: basal diet, ad libitum

PEN SIZE AND CONSTRUCTION MATERIALS
- Description: The reproduction toxicity test was conducted in cages with dimensions of 51 cm deep x 25 cm wide x 20½ to 25 cm in height, with slanted floors for egg collection (minimum height of 20.3 cm). The sides, floor and top of the cages were made of epoxy-coated wire mesh.

NO. OF BIRDS PER GROUP
- For vehicle control: 18 per sex
- For treated: 18 per sex


TEST CONDITIONS
- Brooder temperature: 35 to 38°C during the first week and 30 to 32 °C during the second week
- Room temperature: 15 to 30°C
- Relative humidity: Ambient
- Photoperiod: The initial photoperiod was 7 hours light and 17 hours of darkness. Beginning at the end of week 8 through week 9, the photoperiod was gradually increased to 17 hours light and 7 hours darkness to induce egg production.

Details on examinations and observations:

MORTALITY / CLINICAL SIGNS
- Time schedule for examinations: Daily

BODY WEIGHT
- Time schedule for examinations: at start of acclimation, just prior to the experimental start date, during week 8 at the start of photostimulation, and at post-egg collection upon adult euthanasia

FOOD CONSUMPTION
- Time schedule for examinations: During testing, adult bird feed consumption was measured by cage at the end of each 7-day period throughout the reproduction study

PATHOLOGY
- Dose groups that were examined: All adult birds remaining at the termination of egg laying

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
- Clinical signs of toxicity, abnormalities and mortality
- 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 single dose):

23 wk

Dose descriptor:

NOEC

Effect level:

210 mg/kg diet

Conc. / dose based on:

act. ingr.

Basis for effect:

reproductive parameters

Duration (if not single dose):

23 wk

Dose descriptor:

LOEC

Effect level:

410 mg/kg diet

Conc. / dose based on:

act. ingr.

Basis for effect:

reproductive parameters

Mortality and sub-lethal effects:

MORTALITY
There were ten mortalities.Five of the mortalities occurred from cage injury and/or pair aggression. The other five birds all died without any abnormal observations recorded prior to their death. Only one of these birds had any recorded notations that might be construed as being treatment-related. Liver and kidney abnormalities were recorded on the post-mortem form for this female bird. However, since no other birds were observed to have any treatment-related effects at post-mortem, it is not likely that this mortality is related to test substance exposure.

CLINICAL SIGNS
- There were numerous observations regarding cage injury and pair aggression resulting in foot injuries. Most of these notations were associated with female birds and the observations were among all groups. Five of these birds died. There were no observations that could be attributed to treatment-related effects.

BODY WEIGHT
- A significant adult body weight reduction was found in the 850 mg a.i./kg feed treatment group mean compared to the control mean for adult males and females recorded at the end of treated feed.

FOOD CONSUMPTION
- The 850 mg a.i./kg feed treatment group mean for feed consumption was significantly lower than the control group mean. There were no differences in feed consumption between the other treatment groups and the control group.

PATHOLOGY
- The majority of birds in the control group were observed to be sexually active at the end of the study. Three birds were observed to have gaseous intestines and one bird was observed to have numerous discolored growths with an irregular texture. There were eight observations of birds incurring some degree of pair aggression, all female.
The majority of birds in the 96 mg a.i./kg feed group were observed to be sexually active at the end of the study. There were seven observations of birds incurring some degree of pair aggression, one male and six female .
Every bird in the 210 mg a.i./kg feed group was observed to be sexually active at the end of the study., One female was observed to have gaseous intestines. There were seven observations of birds incurring some degree of pair aggression, two male and five female.
The majority of birds in the 410 mg a.i./kg feed group were observed to be sexually active at the end of the study. There were five observations of birds incurring some degree of pair aggression, two male and three female.
Every bird in the 850 mg a.i./kg feed group was observed to be sexually active at the end of the study. There were no observations indicating pair aggression. Ten males and eleven females were observed to have enlarged kidneys, some to only a slight degree and one female had a single kidney. Other observations included three males that were slightly or moderately emaciated. Two females were observed with dark colored intestines and one female was observed to have a milky liquid present around her eggs.

Effects on reproduction:

- Number of eggs laid per hen and per day: The 850 mg a.i./kg feed treatment group mean was significantly lower than the control group mean.
- Number of eggs set and the percentage eggs set related to eggs laid: The 850 mg a.i./kg feed treatment group mean for the Number of Eggs Set was significantly lower than the control group mean.
- Numbers of eggs cracked and the percentage eggs cracked related to eggs laid: No significant differences
- Number of broken eggs: No significant differences
- Eggshell thickness or eggshell strength measurements: No significant differences
- Number of fertile eggs and the percentage fertility related to eggs set: No significant differences
- Number of viable embryos and the percentage viability related to fertile eggs: No significant differences
- Number of normal hatchlings as percentage of viable embryos: The 850 mg a.i./kg feed treatment group mean was significantly lower than that of the control group in Number of Eggs Hatched/Number of viable embryos
- Other: The 850 mg a.i./kg feed treatment group mean was statistically lower than that of the control group for the Number of 14 Day survivors/Number of eggs hatched.
Both the 850 and 410 mg a.i./kg feed treatment group means were significantly lower (p≤0.05) than the control group mean for Hatch Weights.
Both the 850 and 410 mg a.i./kg feed treatment group means were significantly lower (p≤0.05) than the control group mean for 14-day survivor weights.

Table 1: The reproductive performance for those variables expressed as direct counts

Reproductive Parameter	Control	96 mg a.i./kg feed	210 mg a.i./kg feed	410 mg a.i./kg feed	850 mg a.i./kg feed
Number of replicates	16	18	18	17	15
Total eggs laid^a	807	939	931	714	430
Eggs cracked	18	16	24	17	9
Eggs set in incubator	722	840	820	625	361
Fertile eggs	683	792	778	595	314
Viable embryos	662	777	764	574	299
Hatchlings	641	744	735	541	274
14-day old survivors	618	721	704	497	218

^aTotal egg laying days=70 days.

 

Table 2: The reproductive performance for those variables expressed a ratios

Reproductive Parameter	Control	96 mg a.i./kg feed	210 mg a.i./kg feed	410 mg a.i./kg feed	850 mg a.i./kg feed
Number eggs laid per day per hen^a	45	52	52	40	24^b
Number eggs set per day per hen	45	47	46	40	27^b
Eggs cracked / eggs laid	0.022	0.017	0.027	0.019	0.017
Fertile eggs / eggs incubated	0.95	0.94	0.94	0.95	0.84
Viable embryos / fertile eggs	0.97	0.98	0.97	0.97	0.93
Hatchlings / viable embryos	0.97	0.95	0.96	0.94	0.86^b
14-day old survivors /hatchlings	0.96	0.96	0.95	0.92	0.69^b
Hatchlings / eggs incubated	0.89	0.89	0.90	0.87	0.76^b
14-day old survivors eggs incubated	0.86	0.86	0.86	0.80	0.60^b

^aTotal egg laying days = 70 days.

^bStatistically different (p =0.05) as compared to the controls.

Conclusions:

Reproductive NOEC (bobwhite quail): 210 mg a.i./kg feed
Reproductive LOEC (bobwhite quail): 410 mg a.i./kg feed

Executive summary:

The study was conducted according to the guidelines USEPA 71-4 and OECD 206 to evaluate the effects of the test substance administered via the diet to Northern Bobwhite Quail (Colinus virginianus) over a 23-week exposure period with the nominal concentrations of 0, 100, 200, 400 and 800 mg a.i./kg feed. Adult effects included health, body weight, and feed consumption. In addition, the reproductive effects (i.e., number of eggs laid, eggshell integrity and thickness, egg fertility, embryo viability, hatch rates, offspring survival and offspring weight) were evaluated.

A significant adult body weight reduction was found in the 850 mg a.i./kg feed treatment group mean compared to the control mean for adult males and females recorded at the end of treated feed. A significant difference was detected between the 850 mg a.i./kg feed treatment group mean and the control mean for the following reproductive parameters, eggs laid, eggs set, number of eggs hatched/number of eggs viable, and number of chicks survived/number of chicks hatched. A significant difference was detected in the 850 mg a.i./kg feed treatment group means compared to the control group mean for hatch weights and survivor weights.

A significant difference was detected in the 410 mg a.i./kg feed treatment group means compared to the control group mean for hatch weights and 14-day survivor weights.

The reproductive No-Observable-Effect Concentration (NOEC) observed during this study, was 210 mg a.i./kg feed, and the Lowest-Observable-Effect Concentration (LOEC) was 410 mg a.i./kg.

Description of key information

Acute LD50 (Bobwhite quail): 1159 mg/kg, EPA OPP 71 -1, Reliability = 1

23 week Reproductive NOEC (Bobwhite quail): 210 mg/kg, EPA OPP 71 - 4, OECD 206; Reliability = 1

Key value for chemical safety assessment

Short-term EC50 or LC50 for birds:

1 159 mg/kg food

Long-term EC10, LC10 or NOEC for birds:

210 mg/kg food