2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-pyridine carboxylate; imazapyr (ISO)

Endpoint summary

Description of key information

AQUATIC TOXICITY

Short-term toxicity to fish

In two acute bioassays with bluegills and trout an LC50 >100 mg/L was observed for the test substance.

Long-term toxicity to fish

In an early-life stage test a NOAEC of 43.1 mg/L (based on mean measured concentrations) in rainbow trout (Oncorhynchus mykiss) was observed. In another early-life stage test with fathead minnow (Pimephales promelas) a NOEC of 118 mg/L (based mean measured concentrations) was observed. And a full life-cycle test with fathead minnows revealed a NOEC of 120 mg/L (based on mean measured concentrations).

Short-term toxicity to aquatic invertebrates

The toxic effects of the test substance was estimated in both, freshwater (Daphnia magna) and marine species (Penaeus duorarum, Crassostrea virginica). In all acute toxicity assays an EC50 value >100 mg/L was observed.

Long-term toxicity to aquatic invertebrates

In a 21-day flow-through toxicity test with daphnia magna exposed to the test subtance a NOEC of 97.1 mg/L (mean measured concentration) was determined.

Toxicity to aquatic algae and Cyanobacteria

In a 7-day algal growth inhibition test with Anabaena flos-aquae EC25 and EC50 values of 7.3 and 11.7 mg/L were determined, respectively. Anabaena flos-aquae was the most sensitive species tested.

Toxicity to aquatic plants other than algae

In a growth inhibition test, an EC25 of 0.013 mg/L and an EC50 of 0.024 mg/L was determined for Lemna gibba exposed to the test substance.

Toxicity to microorganisms

Two Activated Sludge Respiration Inhibition studies with two read-across substances are available. Read-across with CAS 081335-37-7 revealed an EC50 >100 mg/L. In the study with the read-across substance CAS 114311-32-9, the EC50 was estimated to be >1000 mg/L

TERRESTRIAL TOXICITY

Toxicity to terrestrial arthropods

The acute contact toxicity study with Apis mellifera revealed an LD50 > 99 µg/bee after 48 h.

Toxicity to terrestrial plants

The most sensitive species in a terrestrial phytotoxicity study was lettuce. The NOEC for dry weight was 408 g/ha. The calculated EC25 and EC50 values were 681 (95 % confidence interval; 378 to 983) and > 1670 g/ha, respectively.

Toxicity to birds

21-day oral toxicity studies in Mallard ducks and Bobwhite quail revealed an LD50 >2150 mg/kg bw.

8 -day dietary studies in Mallard ducks and Bobwhite quail revealed an LC50 >5000 mg/kg diet.

One-generation reproductive toxicity study in Mallard ducks and Bobwhite quail revealed an NOEC >2000 mg/kg diet.

Additional information

AQUATIC TOXICITY

Short-term toxicity to fish

Key study (American Cyanamid Company, 954-94-127, 1994)

The toxicity of the test substance to Oncorhynchus mykiss (rainbow trout) was determined in a 96-hour acute toxicity test under flow-through conditions equivalent to OECD guideline 203. Rainbow trout were exposed to nominal test item concentrations of 15.6, 25.9, 43.2, 72.0 and 120 mg/L, a formula blank and a negative control (well water). These nominal concentrations corresponds to the mean measured test item concentrations of 13, 29, 39, 68 and 110 mg/L. Under the conditions of this test, the 96-hour LC50 value for the rainbow trout exposed to the test item was > 100 mg/L, the highest concentration tested. The 96-hour NOEC, determined by an examination of mortality and clinical observation data, was 100 mg/L. 
 
Supporting study (American Cyanamid Company, 30096, 1983)

Additionally, an acute toxicity test with Lepomis macrochirus (bluegill sunfish), performed equivalent to OECD guideline 203, is available. The bluegills were exposed to the nominal test item concentrations (in acetone) of 10, 18, 32, 53 and 100 mg/L for a period of 96 hours under static conditions. An analytical verification of the nominal test substance concentrations was not performed. As a quality check, the bluegill sunfish were challenged with a reference compound, Antimycin A. The estimated 96 hour LC50 and 95% confidence limits were within the 95% confidence limits reported in the literature, indicating that the fish were in good condition. The NOEC based on mortality and abnormal effects was 100 mg/L after 96-hour. Therefore, the determined LC50 is >100 mg/L. 
 
Conclusion:
Based on acute bioassays in both species, bluegills and trout, the test substance is practically non-toxic to fish.

Long-term toxicity to fish

Key study (American Cyanamid Company,971-87-155, 1989)

An early-life stage test was conducted equivalent to OECD guideline 210 to estimate the chronic effects of the test substance on the rainbow trout (Oncorhynchus mykiss). Embryos were exposed to nominal test substance concentrations of 0, 6.25, 12.5, 25.0, 50.0 and 100 mg/L, which corresponds to the mean measured concentrations of <5.0, 6.59, 12.1, 24.0, 43.1 and 92.4 mg/L. The criterion of effect in the early life stage test were hatching success of embryos and growth and survival of juveniles for 28 days post swim-up. Under the condition of this early life-stage study in rainbow trout, a concentration of 92.4 mg/L resulted in reduced hatch and reduced fry survival (LOAEC). No effects were noted at a concentration of 43.1 mg/L (NOAEC). The study did not meet all guideline requirements (feeding limited the growth of replicates with higher fish densities).

 

Supporting study (American Cyanamid Company, ECO 97-102, 1998)

An early-life stage flow-through test was conducted to estimate the chronic effects of the test substance on the fathead minnow (Pimephales promelas). Fathead minnows were exposed to the test substance at nominal concentrations of 0, 7.5, 15, 30, 60 and 120 mg/L (corresponding to measured concentrations: >0.1, 7.4, 15, 31, 62 and 118 mg/L). Viability and hatchability of the eggs, and survival and growth of the larvae were evaluated as toxic endpoints. The test substance produced no treatment-related effects on embryonic survival, time to hatch, alevin survival, terminal length, or wet and dry weight. The NOEC was determined to be 118 mg/L (mean measured; nominal: 120 mg/L).

Supporting study (American Cyanamid Company, 954-97-101, 1999)
Additionally, in a full life-cycle flow-through test the effects of the test substance in fathead minnows (Pimephales promelas) were evaluated. Fathead minnows were exposed to nominal test substance concentrations of 0, 7.5, 15, 30, 60 and 120 mg/L. The test concentrations remained extremely stable throughout the test. Mean measured concentrations in the parental exposure were <LOD, 7.2, 15, 29, 59 and 120 mg/L; whereas mean measured concentrations during the second generation exposure were <LOD, 7.5, 15, 30, 61 and 120 mg/L. The endpoints addressed for the parental generation were: hatching success, survival, growth and reproduction. The endpoints evaluated for the second generation were hatching success, survival and growth. The test substance produced no treatment-related effects on growth, embryo survival, time to hatch or larval and juvenile survival of the F0 and F1 generations. No treatment-related effects were observed on percent spawning frequency, mean number of eggs produced per female or mean percent fertilization success. Consequently the NOEC was 120 mg/L, the highest concentration tested.

 

Conclusion:

Although, the early life stage test with rainbow trout did not meet all guideline requirements, it is used as key study due to worst case considerations.

 

Short-term toxicity to aquatic invertebrates

Freshwater species
WoE (American Cyanamid Company, 30098, 1983)
An acute toxicity study with Daphnia magna under static conditions was performed equivalent to OECD guideline 202. Water fleas were exposed to nominal test item concentrations of 10, 18, 32, 56 and 100 mg/L for a period of 48 hours. No analytical verification of the nominal test concentrations was performed. Under the conditions of this study, the test item was determined to be practically non-toxic to daphnids with an EC50 value >100 mg/L. 
 
Marine species
WoE (American Cyanamid Company, 87384-0200-2130, 1988)
A flow-through saltwater toxicity test was conducted to determine the acute toxicity of the test item to Pink shrimp (Penaeus duorarum). The test organisms were exposed to nominal test item concentrations of 0, 26, 43, 72, 120 and 200 mg/L for a period of 96 hours. The corresponding determined mean measured concentrations were <10.1, 25.0, 38.1, 60.6, 111 and 189 mg/L. The criterion for effect was death. After 96 hours of exposure an LC50 >189 mg/L was determined. One shrimp died at the second highest concentration level (111 mg/L), but mortality did not appear to be related to the treatment. No other signs of toxicity were observed. Therefore, the NOAEC was determined to be 189 mg/L, the highest concentration tested.

WoE (American Cyanamid Company, 87384-0400-2130, 1988; 954-97-139, 1997)

Two flow-through toxicity tests were conducted to determine the acute effect of the test substance on the Eastern oyster (Crassostrea virginica) after 96-hour of exposure. The criterion of effect was in both tests reduced shell growth of exposed oysters compared to shell growth of the control oysters. In the first study (American Cyanamid, 87384-0400-2130, 1988) Eastern oyster were exposed to nominal concentrations of 0, 25.9, 43, 72, 120 and 200 mg test item/L for 96 hours. These concentrations correspond to the following mean measured concentrations: <10.5, 21.5, 42.4, 65.5, 109 and 173 mg/L. After 96 hours of exposure an EC50 of >173 mg/L was determined. No mortalities were observed in either the treated or control groups. There was a statistically significant decrease in mean shell deposition at 173 mg/L when compared to the control group (p ≤0.05). The NOAEC was determined to be 109 mg/L based on measured concentrations.
In the second acute toxicity test (American Cyanamind, 954-97-139, 1997) Eastern oyster were exposed to nominal test substance concentrations of 0, 16, 26, 43, 72 and 120 mg/L, which corresponds to the mean measured concentrations of <LOQ, 16, 27, 46, 80 and 132 mg/L. Under the conditions of this test, the 96-hour EC50 value for eastern oysters exposed to the test substance was estimated as >132 mg/L, the highest concentration tested. The NOEC was 132 mg/L. No significant adverse effects were observed on shell deposition for any treated group.

Conclusion:

The test item was determined to be practically non-toxic to the freshwater species, Daphnia magna and mairne Pink shrimp and Eastern oyster. In all acute toxicity assays an EC50 value >100 mg/L was observed.

Long-term toxicity to aquatic invertebrates

Key study (American Cyanamid Company, 87384-0500-2130, 1988)

A 21-day flow through toxicity test equivalent to OECD guideline 211 was conducted to estimate the chronic effects of the test substance to the water flea (Daphnia magna). The criteria for effect in the life cycle test were reproduction, growth, and survival of water fleas. Daphnia magna was exposed to the nominal concentrations of 0, 6.26, 12.5, 25, 50 and 100 mg/L corresponding to the mean measured concentrations of <2.63, 5.73, 11.7, 23.8, 45.6 and 97.1 mg/L. Since exposure to mean measured test item concentrations of 97.1 mg/L did not significantly reduce the survival, reproductive success, or growth of Daphnia magna. The NOEC was 97.1 mg/L.

 

Toxicity to aquatic algae and Cyanobacteria

Freshwater

Key study (American Cyanamid Company, 981 -86 -175, 1987)

A 7-day static freshwater test with cyanobacteria Anabaena flos-aquae was conducted equivalent to OECD guideline 201. Cyanobacteria were exposed to the test substance at nominal concentrations of 0, 5.6, 10, 18, 32, 56 and 100 mg/L. These nominal concentrations corresponds to the following mean measured concentrations: <0.02, 5.26, 9.6, 17.6, 30.2, 55.1 and 103 mg/L. Biomass was determined by cell counts on day 2, 3, 4 and 7. Percent inhibition or stimulation, relative to the control, was calculated for each concentration based upon the mean standing crop in cells/mL at seven days. Effects ranged from 4.8% stimulation to 99.4% inhibition. The 7-day EC25 was 7.3 mg/L (95% CI <0.0001 - 51.4 mg/L) and the 7-day EC50 was 11.7 mg/L (95% CI <0.0001 - 105.5 mg/L), based on mean measured concentrations. 

Supporting study (American Cyanamid, Company, 981-86-173, 1987)

An additional 7-day freshwater test with freshwater diatom Navicula pelliculosa performed equivalent to OECD guideline 201 is available. The freshwater diatom Navicula pelliculosa was exposed to nominal test substance concentrations of 0, 10, 18, 32, 56, and 100 mg/L. These nominal concentrations corresponds to the mean measured concentrations of <0.5, 8.2, 10.5, 23.5, 55.8 and 41.0 mg/L (the mean measured concentration for the highest nominal concentration, 100 mg/L, was actually lower than the mean measured concentration for the 56 mg/L nominal concentration). Biomass was determined by cell counts on days 2, 3, 4 and 7. Percent inhibition or stimulation, relative to the control, was calculated for each test concentration based upon the standing crop in cells/mL at seven days. All test concentrations were somewhat stimulatory to pelliculosa. Therefore, EC values could not be determined from the data. The 7-day EC25 and the 7-day EC50 would be greater than the highest mean measured test concentration, 55.8 mg/L, of the test substance. 

Marine water

Supporting study (American Cyanamid Company, 981-86-174, 1987)

In a 7-day study with the marine diatom Skeletonema costatum is available. Skeletonema costatum was exposed to the nominal test substance concentrations 0, 10, 18, 32, 56 and 100 mg/L, which corresponds to the mean measured concentrations of <1, 8.9, 15.9, 28.7, 47.4 and 90.5 mg/L. Biomass was determined by cell counts on day 2, 3, 4 and 7. Percent inhibition, relative to the control, was calculated for each concentration based upon the mean standing crop in cells/mL at seven days. Effects ranging from 0.7% to 54.0% inhibition were observed. The 7-day EC25 was 42.2 mg/L and the 7-day EC50 was 85.5 mg/L, based on mean measured test concentrations.

Conclusion:

Anabaena flos-aquae was the most sensitive species of the three tested algae species with an EC25 and EC50 of 7.3 and 11.7 mg/L, respectively.

 

Toxicity to aquatic plants other than algae

Key study (American Cyanamid Company, 981-86-176, 1987)

The toxicity of the test substance to Lemna gibba was determined in a growth inhibition test equivalent to OECD 221. The duckweeds were exposed over a 14-day period to five nominal test concentrations ranging from 0.01 to 0.1 mg/L of the test substance. Analysis of test substance was unsuccessful and the results are therefore based upon nominal concentrations. Biomass was determined by frond counts on day 2, 4, 7, 9, 11 and 14. Percent inhibition, relative to the control, was calculated for each concentration based upon the mean standing crop in number of fronds at fourteen days. Inhibition ranged from 15.1% to 95.0%. A 14-day EC25 and EC50 of 0.013 mg/L (95% confidence limits 0.009 - 0.019 mg/L) and 0.024 mg/L (95% confidence limits 0.016- 0.033 mg/L) were observed, respectively.

 

Toxicity to microorganisms

Read-across was applied using characteristically similar compounds: 2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH-imadazol-2-yl]-5-(methoxymethyl)-3-pyridinecarboxylic acid (CAS 114311-32-9) and 2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH-imidazol-2-yl]-3-quinolinecarboxylic acid (CAS 081335-37-7).

 

WoE (BASF, EXA 02-001, 2002; EXA 01-043, 2002)

Activated Sludge Respiration Inhibition studies, performed according to OECD guideline 209, with the read-across substances CAS 081335-37-7 and CAS 114311-32-9 are available. The study with CAS 081335-37-7 was performed with nominal test substance concentrations of 5, 10, 30, 60 and 100 mg/L. Respiration rate reduction was <50% in all test substance treatments. The EC50 value was estimated to be >100 mg/L, the highest concentration tested. In the Activated Sludge Respiration Inhibition study with CAS 114311-32-9, nominal concentrations of 100, 250, 500, 750 and 1000 mg/L were tested. Under the conditions of this test, an EC50 value >1000 mg/L was determined.

 

TERRESTRIAL TOXICITY

Toxicity to terrestrial arthropods

Key study (BASF,1910-AMC-430-07,2008)

An acute contact toxicity study with the test substance in honeybees (Apis mellifera) was conducted according to OECD guideline 214. Honeybees were exposed to the following five test substance concentrations (in acetone) plus two control groups: 6.14, 12.38, 24.75, 49.50 and 99.00 µg/bee. 1 µL of each dose of testing was applied over the thorax of each organism using a micropipette. The organisms were observed at 4, 24 and 48 hours after application to determine their death rate. The LD50 obtained after 48 hours was > 99 µg/bee.

 

Toxicity to terrestrial plants

Key study (BASF SE, 84495, 2002)

In a non-target terrestrial phytotoxicity study the effect of the test substance on seedling emergence and growth of selected non-target terrestrial plants was assessed according to EPA OPPTS 850.4100 and EPA OPPTS 850.4225 (Tier I and Tier II). The effect of the test material on seeding emergence and growth of monocot (corn - Zea mays, oat - Avena sativa, onion - Allium cepa, ryegrass - Lolium perenne) and dicot (cabbage - Brassica o/eracea, carrot - Daucus carota, cucumber - Cucumis sativus, lettuce - Lactuca sativa, soybean - Glycine max, tomato - Lycopersicon esculentum) crops was studied at nominal treatments rates of 1690 and 1720 grams per hectare (g/ha) for tier I testing. The nominal application rates for the lettuce and ryegrass tier II testing were 0.0 (control), 0.0 (vehicle control), 104, 208, 417, 834, and 1670 g per hectare. The nominal application rates for the carrot tier II testing were 0.0 (control), 0.0 (vehicle control), 107, 213, 427, 854, and 1710 g per hectare. The negative control and vehicle control plants were sprayed with an equivalent amount of deionized water or a 50 % methanol and water mixture.

Cabbage, carrot, corn, cucumber, oat, onion, soybean, and tomato did not display detrimental effects ≥25% for any of the test parameters (i.e., % emergence, mean shoot length, or mean dry weight) when exposed to calculated application rates of 1650 to 1690 gram per hectare. In the tier I testing, ryegrass seedlings treated with 1690 g/ha displayed a -44 % difference in dry weight versus the vehicle control value, however, during the tier II testing ryegrass did not display detrimental effects ≥25 % for any of test parameters. The most sensitive species was lettuce. In the tier I lettuce test, there was a 30 % decrease in treatment dry weight as compared to the vehicle control. Dry weight was also the most sensitive parameter during the tier II lettuce testing. The NOEC for this parameter was 408 g/ha. The calculated EC25 and EC50 values were 681 (95 % confidence interval; 378 to 983) and > 1670 g/ha, respectively.

 

Supporting study (American Cyanamid Company, 0450, IZ-549-001, 1988)

In a seedling emergence and vegetative vigor test comparable to OPPTS 850.4100, the effect of the test item was tested upon following plants: corn, wheat, sugarbeets, sunflower, tomato, cucumber, oats, onions, soybeans and green peas. The test item has a detrimental effect on all species tested. Seedling emergence was least affected of all parameters. The test item usually inhibited the growth in a rate responsive manner, as herbicide rates increased, crop injury also increased. The test item was more injurious to oats and wheat than to any of the other crops tested.

Supporting study (American Cyanamid Company, 0450, IZ-549-002, 1988)

In a vegetative vigor study comparable to OPPTS 850.4150, the effect of the test item was test upon following plants: corn, wheat, sugarbeets, sunflower, tomato, cucumber, oats, onions, soybeans and green peas. The test item is a broad spectrum non-selective herbicide that has the potential to kill seedlings of many species when applied post-emergence to the foliage. Green peas were by far the most tolerant crop species to post-emergence applications of the test item. All other crop species tested showed higher sensitivity to the test item. Sugarbeets were by far the most sensitive crop species (affected at rates of 0.548 g/ha). Larger seedlings were able to tolerate higher levels of the test item than smaller seedlings. In general, the monocot species could withstand up to 8.75 g/ha of the test item without noticeable crop injury. Dicot species were more variable in the amount of the material they could tolerate.  Larger seeded species were able to tolerate higher levels of the test item.

 

Toxicity to birds

Weight of evidence

Oral gavage studies (American Cyanamid Company, 716-743-4557, 716-743-4667, 1983)

Two 21-day oral gavage studies with the test substance in birds were conducted. Mallard ducks (Anas platyrhynchos) and Bobwhite quail (Colinus virginianus) were exposed to test substance concentrations of 1470 and 2150 mg/kg bw (in corn oil) and a solvent control group. The test substance was determined to be practically non-toxic to Bobwhite quail and Mallard ducks with LD50 of >2150 mg/kg for both species.

Dietary studies (American Cyanamid Company, 715-743-4557, 1983)

Two 8-day dietary studies with the test substance in birds were conducted. Mallard ducks (Anas platyrhynchos) and Bobwhite quail (Colinus virginianus) were exposed to test substance concentrations of 312, 625, 1250 and 5000 mg/kg diet and a control group. The test substance was determined to be practically non-toxic to Bobwhite quail and Mallard ducks with LC50 of >5000 mg/kg diet for both species.

One generation study (Cyanamid Company, 715 -743 -4557, 1987)

Two one-generation studies with the test substance in birds were conducted. Mallard ducks (Anas platyrhynchos) and Bobwhite quail (Colinus virginianus) were exposed to test substance concentrations of 500, 1000 and 2000 mg/kg diet and a control group. In both studies, the test substance produced no evidence of treatment-related adverse effects on adult or reproductive parameters with an NOAEC of 2000 mg/kg diet.