Product Information. Ref: V:\Waterfronts\BCDMHOS.doc December 1999

Transcription

1 BioLab Water Additives A Subsidiary of Great Lakes Chemical Corporation Tenax Road Trafford Park Manchester M17 1WT UK Water Additives Phone +(44) Fax +(44) Product Information 1-Bromo-3-Chloro-5,5-Dimethylhydantoin (Bromicide ) Summaries of Toxicity Data Background: 1-Bromo-3-chloro-5,5-dimethylhydantoin (BCDMH) is a biocide. When dissolved in water, BCDMH hydrolyzes immediately to hypobromous acid, hypochlorous acid (the active biocides), and 5,5-dimethylhydantoin (DMH). Toxicity data are available for either BCDMH or DMH, but not necessarily for both. Summaries of toxicity data which are from the Federal EPA registration files are so indicated. 1. Microbial Mutagenicity: BCDMH was tested for potential mutagenic effects using a series of in vitro microbial assays employing Salmonella and Saccharomyces indicator organisms in the absence and presence of liver microsomal enzyme preparations from Arochlor (S9) induced rats. The results of the tests were all negative. BCDMH was not mutagenic under the conditions tested. Ref: V:\Waterfronts\BCDMHOS.doc December Acute Toxicity: BCDMH was administered as a single oral dose via gastric intubation to groups of five male and five female rats at dose levels of 500, 570, 650, 741 and 845 mg/kg. The combined oral LD 50 in rats was calculated to be 578 mg/kg. The acute dermal toxicity of BCDMH was determined to be greater than 2.0 g/kg for both male and female rabbits. No signs of systemic toxicity were observed. Inhalation toxicity of BCDMH was evaluated in a 4-hour, single, nose-only, exposure in male and female rats. BCDMH was administered as an air-milled dust with the MMAD ranging from 1.5 to 1.7 microns. Airborne concentrations (gravimetrically determined) were 0.11, 0.16 and 0.29 mg/l. The combined LC 50 of BCDMH was calculated to be mg/l of air. DMH was tested for potential mutagenic effects using a series of in vitro microbial assays employing Salmonella and Saccharomyces indicator organisms in the absence and presence of liver microsomal enzyme preparations from Arochlor (S9) induced rats. The results of the tests were all negative. DMH was not mutagenic under the conditions tested. 2. Mammalian Cell Mutagenicity: DMH was evaluated in rats for the potential to induce chromosome aberrations in bone marrow cells when administered by oral gavage to male and female rats. Dose levels of 200, 660 or 2000 mg/kg resulted in no statistically significant increases in the frequency of chromosomal aberrations when compared to control values. DMH was evaluated for the potential to induce gene mutations in cultured L5178Y mouse lymphoma cells in the absence and presence of a metabolic activation system. Under the test conditions, DMH, at concentrations up to and including 1000 mg/ml, did not cause an increase in forward mutations in L5178Y mouse lymphoma cells. DMH at concentrations up to and including 1000 mg/ml was tested for the potential to transform cultured C 3 H 10T 1/2 cells in the absence and presence of a metabolic activation system. In the absence of a metabolic activation, no dose related cytotoxicity and no Type III foci (transformed cells) were produced. In the presence of a metabolic activation, no dose related cytotoxicity resulted, but one Type III focus was produced at each concentration of 10, 30 and 300 mg/ml. The results of the study indicated that DMH did not produce neoplastic cell transformations. In one study the acute oral LD 50 for DMH in rats was reported as being >4000 mg/kg. DMH was administered as a single oral dose via gastric intubation to groups of five male and five rats. On the day of dosing two females were observed to be slightly to moderately lethargic with slight lacrimation; they were normal for the remaining 14 days. The acute oral LD 50 was calculated to be >5000 mg/kg. The acute dermal toxicity of DMH was determined to be greater than 3 g/kg for both male and female rabbits. No signs of systemic toxicity were observed. 5,5-Dimethylhydantoin is practically non-toxic by the dermal route of exposure. 4. Irritation (Skin and Eye): The primary skin irritation index for BCDMH was calculated to be 6.1 according to the method of Draize. Eschar and necrosis of the skin were observed through day 7. On day 14, the irritation score was zero and eschar and necrosis were no longer observed. BCDMH was considered corrosive to the skin. Prolonged or repeated skin contact with solid BCDMH resulted in minor reddening of the skin and superficial necrosis with the development of excessive exfoliation. Contact with dilute solutions of 0.1% or less (1000 ppm or less) was not irritating to the skin (Federal EPA registration files). Eye contact with the powdered BCDMH resulted in persistent severe conjunctival irritation and slow development of corneal damage in rabbits. Washing the eyes promptly (within 30 seconds) The information contained in this product sheet is based on data available to BioLab, Inc., BioLab Water Additives and is thought to be correct. Since BioLab, Inc. has no control over the use of this information by others, BioLab, Inc. does not guarantee the same results described herein will be obtained, and makes no warranty of merchantability or fitness for a particular purpose or any express or implied warranty. This information is intended for use by technically trained personnel at their discretion and risk. Rev. 3/00 Responsible Care A Public Commitment

2 resulted in a significant reduction of adverse effects. Dilute solutions of 0.1% (1000 ppm) or less were essentially nonirritating to the eyes (Federal EPA registration files). DMH was tested for skin irritation. Slight irritation and edema were observed at 24 hours in the majority of the rabbits for both intact and abraded sites. At 72 hours, two abraded sites showed slight erythema; there were no other reactions. The primary skin irritation index was calculated to be 0.8 according to the method of Draize. 5,5-Dimethylhydantoin is classified as minimally irritating to the skin. Eye contact with powdered DMH resulted in slight to moderate erythema and slight to marked chemosis and discharge at the 1-hour reading in all rinsed and unrinsed eyes. All irritations had completely subsided at the 7 day reading. The primary irritation index, according to the method of Draize, was calculated to be 12.8 for unrinsed and 10.0 for rinsed. DMH is classified as mildly irritating to eyes. Aqueous solutions of DMH (10% or less) were found to be essentially non-irritating to the eye. 5. Skin Sensitization: The Buehler method was used to determine if DMH induced delayed contact hypersensitivity in albino guinea pigs. No reactions were observed in the test or naive control groups following either the initial challenge or the re-challenge insults. Based on the data, DMH was found to be non-sensitizing in the albino guinea pigs. The Guinea Pig Maximization Test was used to determine if DMH induced contact hypersensitivity. DMH was termed to be a mild skin-sensitizer when three of twenty animals responded at challenge to the application of a 10% aqueous solution Week Oral: DMH was offered on a continuous basis in the diet to groups of five male and five female mice for a period of four weeks. Dosage levels of 0, 1000, 5000, 10,000 and 50,000 ppm were used. Systemic toxicity was not apparent at any dose level. The only potential effect of DMH when administered to mice for 28 days was increased serum alkaline phosphatase (50,000 ppm females). DMH, suspended in 0.5% aqueous methyl-cellulose, was administered daily for 4 weeks by oral gavage to groups of male and female rats at 0, 2.5, 5.0, 9.0, and 12.5 g/kg. Two females died at 12.5 g/kg. A low incidence of lethargy and salivation was noted at 9.0 and 12.5 g/kg. The No-Observable-Effect-Level (NOEL) was considered to be 5.0 g/kg. DMH in capsules was administered daily for 28 days to Beagle dogs (2 males and 2 females) at 0, 250, 500, 1000 and 2000 mg/kg/day. Males administered DMH at 2000 mg/kg/day had lower testes/epididymides weights. Potential treatment-related clinical signs were noted in one 2000 mg/kg/day group male. A dosage level of 1000 and 2000 mg/kg/day were considered the No-Observable-Effect-Level (NOEL) for systemic toxicity when administered orally to male and female dogs, respectively Week Feeding: Three 5-month old female rats were used in a 6-week feeding study. Dry DMH was admixed daily in the rats diet. One rat received 10 mg/day during the first week; 15 mg/day during the second week; 25 mg/day during weeks three through five; and 60 mg/day during the sixth week. The other two rats received 10 mg/day throughout the 6-week test period. Evidence of gross toxicity was not observed during the test. There was no apparent effect on blood parameters, and no evidence of intestinal disturbances. Autopsy examination, with particular attention given to the heart, lungs, gastro-intestinal tract, and kidneys, showed no treatment-related lesions. Three adult guinea pigs were used in a 6-week feeding study. One male received 30 mg/day during the first week; 40 mg/day during the second week; 50 mg/day during the third week; 60 mg/day during the fourth week; 75 mg/day during the fifth week; and 90 mg/day during the sixth week. The other male and the female received 30 mg/day for the six week period. Evidence of gross toxicity was not observed. There was no apparent effect on blood parameters, and no evidence of intestinal disturbances. Autopsy examination, with particular attention given to the heart, lungs, gastro-intestinal tract, and kidneys, showed no treatmentrelated lesions Day Oral: DMH was administered orally by gavage to rats for at least 90 days at 2000, 5000 or 10,000 mg/kg. Four mortalities were noted: one male and one female at 10,000 mg/kg; one female at 5000; and one control female. Histopathologic changes were noted in the kidney of all male treated groups and in the 5000 and 10,000 mg/kg group females. These histopathologic changes were accompanied by a dose related increase in kidney weights in males and the mid and high dose females. Clinical changes consistent with the histopathology were noted. Clinical observations included a dose related incidence of white granular material in the urogenital area and/or urine stains which were related to the high dose levels of material and the kidney pathologic changes. There was a slight decrease (7-10%) in mean body weights in high dose males from week 7 throughout the study. Mean food consumption was increased in high dose females from week 5 through the end of the study with the exception of week 9. Food consumption was also sporadically increased in mid dose females throughout the study. A No- Observable-Effect-Level (NOEL) was not determined in this study. DMH was dissolved in water and administered by gavage to groups of 5 male and 5 female rats at 0, 250, 500, 1000 and 2000 mg/kg/day for 90 days. No effects were noted in the study that could be attributed to treatment. The No-Observable-Effect- Level (NOEL) was considered to be 2000 mg/kg/day in this study. DMH was offered on a continuous basis in the diet to groups of 20 male and 20 female mice for a period of 13 weeks. Dosage levels were 0, 5000, 20,000 and 50,000 ppm. The only potential effect of DMH, when administered for a minimum of 90 days to mice, was a microscopic change in the adrenal glands in the 50,000 ppm females. The No-Observable-Effect-Level (NOEL) for systemic toxicity was considered to be 20,000 ppm in this study.

3 DMH was evaluated for toxicity in a 13-week subchronic toxicity study in beagle dogs. Dosages of 250, 500 and 1000 mg/kg/day were administered by capsule to groups of six males and six females. There were no adverse effects on survival rate, clinical condition of the animals, body weight gain, food consumption data, clinical pathologic parameters or organ weight data. No macroscopic or microscopic examinations of selected tissues revealed lesions that could be attributed to the test material. The No-Observable-Effect-Level (NOEL) was considered to be 1000 mg/kg/day in this study. 9. Developmental Toxicity: DMH was evaluated for potential maternal and/or developmental toxicity in a range-finding study in rabbits. DMH suspended in 1% aqueous methyl-cellulose was administered orally to groups of seven inseminated does as a single daily dose from days 6 through 18 of gestation. Dose levels were 0, 250, 500, 1000, 2000 and 2500 mg/kg/day. No compound related deaths or abortions occurred. Clinical signs (decreased defecation and white to brownish crystalline-like material in the feces) were observed in the 2500 mg/kg/day group. Body weight loss and reductions in food consumption were dose-related in the 1000 mg/kg and above groups. No treatment-related gross necropsy findings were observed at any dose level. Post-implantation losses were increased and live litter size was decreased at dose levels of 2000 and 2500 mg/kg/day. A severe reduction in mean fetal body weight was observed in the 2500 mg/kg/day group. External fetal malformations, primarily involving defects of the digits (adactyly and brachydactyly), were noted at dose levels of 1000, 2000 and 2500 mg/kg/day in 1, 7 and 10 fetuses, respectively. No external fetal variations were observed in any dose group. The No-Observable-Adverse-Effect-Level (NOAEL) was considered to be 500 mg/kg/day for maternal and developmental toxicity. DMH was evaluated in rabbits for potential maternal and developmental toxicity. Dose levels of 0, 100, 500 and 1000 mg/kg/day in 1% aqueous methyl-cellulose were administered to groups of 20 inseminated rabbits as a single dose on days 6 through 18 of gestation. A dose level of 1000 mg/kg/day produced moderate maternal toxicity that was exhibited by reductions in body weight gain and food consumption, primarily during the initial six days of compound administration. Potential developmental toxicity was expressed by an increase of one specific skeletal variant at dose levels of 500 and 1000 mg/kg/day and digital defects (forepaw digit #1) at a dose level of 1000 mg/kd/day. The dose level of 500 mg/kg/day was considered the No-Observable-Adverse-Effect-Level(NOAEL) for maternal toxicity and a dose level of 100 mg/kg/day was considered the NOAEL for fetal developmental toxicity. 10. Teratology in Rats: In a range-finding study, DMH, suspended in 0.5% methylcellulose, was administered to groups of 5 bred female rats as a single daily dose at 0, 1000, 2500, 5000, 7500 and 10,000 mg/kg/day on days 6 through 19 of gestation. Signs of toxicity (e.g., ataxia, lethargy, decreased body weight gain, and the presence of dried orange and red matter around the mouth) were noted in the majority of the females in each group. One female in the 7500 mg/kg group and two in the 10,000 g/kg group died during treatment. A No-Observable-Effect-Level (NOEL) was not determined in the study. DMH, suspended in 0.5% aqueous methyl-cellulose was administered to groups of 25 bred female rats as a single dose at 0, 500, 2000 or 4500 mg/kg/day on days 6 through 19 of gestation. Toxicity was not apparent in the 500 mg/kg/day group. Maternal and fetal toxicity were noted in the 2000 and 4500 mg/kg/day groups. Reduced fetal ossification was associated with the reduced fetal body weight and was considered to be a secondary response resulting from maternal toxicity. There were no major malformations or increased developmental variants expressed in the 500 or 2000 mg/kg/day groups. No-Observable-Adverse- Effect-Level(NOAEL) for maternal toxicity and fetal developmental toxicity was considered to be 500 mg/kg/day in this study 11. Reproduction: DMH was evaluated for potential adverse effects on the reproductive capabilities of the F0 and F1 generations and neonatal viability and growth. DMH, in 1% aqueous methyl-cellulose, was administered orally by gavage at dose levels of 0, 250, 500 and 1000 mg/kg/day to the F0 and F1 animals. Reproductive performance of the F0 and F1 generations was not adversely affected at a dose of 1000 mg/kg/day. Neonatal body weight (F1 and F2 litters) and F1 male body weight and food consumption were suppressed by DMH administration at dose levels of 500 and 1000 mg/kg/day. Reduced F2 pup viability was also apparent at 1000 mg/kg/day. A dose level of 250 mg/kg/day did not produce any apparent adverse results. Therefore, 1000 mg/kg/day was considered the No-Observable-Adverse-Effect- Level (NOAEL) for reproductive toxicity and 500 mg/kg/day was considered the NOAEL for parental toxicity. A dose level of 250 mg/kg/day was considered the NOAEL for neonatal toxicity. 12. Metabolism: The absorption and elimination in rats was studied using C 14 - DMH. Rats were given a single oral dose of 20 or 100 mg/kg C14-DMH and observed for 7 days. DMH was absorbed rapidly and eliminated primarily in the urine. The average recovery of C 14 from rats was 95%. Male and female rats at both the high and low levels showed similar C 14 distribution. Dosing with unlabeled DMH daily for at least 14 days before dosing with radio-labeled DMH caused no change in the excretory pattern. An average of 91% was found to be excreted in the urine with 88% eliminated in the first 24 hours after dosing. Only one metabolite was detected, which amounted to 2.5% of the urinary C 14. No measurable level of C 14 -residues were observed in tissues of rats receiving the low dose indicating levels of less than 20 ppb. In rats receiving the high dose, low levels of C 14 were detected in kidney and bone. 13. Chronic (Mouse): The oncogenic potential of DMH was evaluated in an 18-month dietary study in mice. Doses levels of 0, 100, 320, and 1000 mg/kg/day were administered in diet to groups of 80 male and 80 female mice. Treatment with DMH resulted in slight decreases in mean body weights for the 320 and 1000 mg/kg/day group males and elevated mean food consumption values for the

4 1000 mg/kg/day group males and females. No treatment related effects were seen on any other parameter evaluated during the study, including clinical signs of toxicity and palpable mass data. Tumor incidence was similar between the control and treated groups and did not reveal any changes related to the administration of DMH. Based on the data obtained, the No- Observable-Adverse-Effect-Level (NOAEL) for oncogenicity of DMH when administered in the diet to mice was greater than 1000 mg/kg/day. 14. Chronic (Rat): The possible long term toxic and oncogenic effects of DMH when administered to rats for 24 months were evaluated. Dose levels of 0, 100, 320 and 1000 mg/kg/day were administered in the diet to 100 male and 100 female rats (20 males and 20 females were assigned to a chronic subgroup and 80 males and 80 females were assigned to an oncogenicity subgroup). The chronic subgroups were necropsied at 52 weeks and the oncogenicity subgroups were necropsied following a minimum of 104 weeks of dosing. Two treatment related effects were noted: change in the clinical conditions (yellow matting in the urogenital region) of the animals in the 320 and 1000 mg/kg/day groups, which was not considered of toxicologic significance; and elevated food consumption means, which were attributed to the increased concentration of DMH in the diets, which was noted occasionally in the 320 mg/kg/day animals and frequently in the 1000 mg/kg/day animals. No treatment-related effects were observed on any other parameter evaluated during the study. Tumor incidence was similar between the control and treated groups and did not reveal any changes related to the dietary administration of DMH. Based on the data obtained, the No- Observable-Effect-Level (NOEL) for systemic toxicity of DMH when administered in the diet to rats was considered to be 100 mg/kg/day. The NOEL for oncogenicity was considered to be greater than 1000 mg/kg/day. 15. Chronic (Dog): The toxicologic potential of DMH was evaluated in a 1-year oral study in beagle dogs. DMH was administered in capsules to groups of four males and four females at doses of 0, 250, 500 and 1000 mg/kg/day. All animals survived to the scheduled necropsy. No DMH related effects were observed on hematology, serum chemistry or urinalysis parameters. No ocular lesions indicative of a toxic effect were observed. No macroscopic or microscopic lesions related to test article administration were noted. Mean absolute and relative organ weights in the treated groups were unaffected. No systemic toxicity was observed at any dose level evaluated. The No-Observable-Effect-Level (NOEL) for chronic systemic toxicity in the beagle was 1000 mg/kg/day. 16. Aquatic Uptake, Depuration and Bioconcentration: A dynamic 42-day study evaluated the bioconcentration of 14C- DMH using Bluegill sunfish, Lepomis macrochirus. A flow-through proportional diluter system was used to maintain a measured water concentration of 4.4 (± 0.33) ppm 14C-5,5- dimethylhydantoin for a 28 day exposure period. Radio-analysis of fillet, whole fish and visceral portions were performed throughout the exposure period. Daily bioconcentration factors were all less than the minimum quantifiable limits (QML) for viscera, fillet and whole fish throughout the exposure period. Uptake tissue concentrations of 14C-DMH were less than the minimum quantifiable limits for fillet, whole fish and viscera. Therefore, 5,5-DMH basically did not bioconcentrate after 28 days of exposure. To measure the elimination of 14C-DMH, the test fish were placed in clean water for 14 days. Radio-analysis throughout the depuration period indicated less than minimum quantifiable limits for fillet, whole fish and viscera. Since neither an uptake rate constant (K1) nor a depuration rate constant (K2) could be calculated or observed, a non-linear two compartment kinetic modeling program (BIOFAAC) could not be used for the analysis of the uptake/depuration data Hour Static Aquatic Toxicity: [Test protocols for fish and crustacean bioassays were based on "Registration of Pesticides in the United States" in Federal Register Vol 43, No. 132, July 10, Toxicity tests and general guidelines for the American oyster were based on guidelines in "Methods for Acute Toxicity Tests with Fish, Macroinvertebrates and Amphibians" (EPA-600/ , April, 1975), "Bioassay Procedures for the Ocean Disposal Permit Program" (EPA-600/ , March, 1978), "Methods for Measuring the Acute Toxicity of Effluents to Aquatic Organisms" (EPA-600/ , Revised July, 1978), and "Standard Methods, 14th Ed." (APHA, 1975).] Solutions were prepared in either synthetic saltwater medium or in freshwater and were not renewed during the tests. Six aquatic species were tested, including three freshwater species: the Rainbow trout, Salmo gairdneri; the Fathead minnow, Pimephases promelas; and the water flea, Daphnia magna. The three saltwater species were Sheepshead minnow, Cyprinodon variegatus; grass shrimp, Palaemonetes pugio; and the American oyster, Crassostrea virginica. BCDMH: The 96 hour static LC 50, except where otherwise indicated, for 1-Bromo-3-chloro-5,5-dimethylhydantoin were: Organism LC 50 (mg/l) NOEC (mg/l) Water flea (48 Hr.) Rainbow trout Fathead minnow Grass shrimp Sheepshead minnow American oyster > DMH: The 96 hour static LC 50 or EC 50 data, except where otherwise indicated, for 5,5-dimethylhydantoin (DMH), were: Organism LC 50 (mg/l) NOEC(mg/L) EC50(mg/L) Water flea (48 Hr) > Rainbow trout > Fathead minnow > Mysid shrimp > @24 hr. --- Sheepshead minnow > Eastern oyster (dynamic) >125 Bluegill sunfish >

5 18. Aquatic Reproduction Toxicity (Daphnia magna): Based on the effect of BCDMH on daphnid reproduction, the No- Observed-Effect Concentration (NOEC) was considered to be mg/l (nominal concentration). No statistically significant differences were determined between this test group concentration and the control group in terms of the number of young produced per adult over a period of 21 days. 19. Octanol/Water Partition Coefficient: For DMH, the average value of P from four replications at 25 o C was Chemical Oxygen Demand (COD): The COD for DMH at the nominal concentration of 50 mg/l was determined to be 60 mg O 2 per liter Day Biochemical Oxygen Demand (BOD5): The BOD5 for DMH at the nominal concentration of 50 mg/l was determined to be 6.25 mg O 2 per liter. 22. Hydrolysis: The half-life of DMH in water, using radio-labeled techniques was found to be: ph Half-life in Days (Tris buffer) (Phosphate buffer) Photolysis: The photolysis study was conducted with radio-labeled DMH in water at ph 7. The half-life for DMH in the sensitized exposed system was 2295 days. For the non-sensitized system, the halflife was 2100 days. The half-lives calculated represent the degradation rate based on little or no degradation. 24. Biodegradation: The biodegradation of DMH, the dehalogenated by-product of 1-bromo-3-chloro-5,5-dimethylhydantoin, was investigated using aerated mixed cultures of microorganisms found in activated sludge. Sludge was acclimated to 25 ppm unlabeled DMH over a 2-week period. Radio-labeled DMH was added and levels of DMH and radioactivity were monitored. Within 24 hours the level of DMH in the incubation mixture (measured by HPLC) decreased from about 20 ppm to an average of 5 ppm; a 75% loss. In the same period, however, radioactivity in the mixture showed only a 19% loss; this is explained by the release of metabolites into solution and subsequent absorption by the particulate matter. After 3 days, DMH concentration in the mixture was <1ppm, and radioactivity had decreased to 48% of its original level, showing that metabolites were ultimately leaving the system as carbon dioxide. By 19 days, 94% of the radioactivity had been recovered as carbon dioxide. Only tract amounts of radioactivity were found to be volatile other than carbon dioxide, and these appeared to be due to aerosols from the incubation mixture. When the results were corrected for known leakage of carbon dioxide in the apparatus, a carbon balance was maintained. Under the test conditions, DMH degrades rapidly without obvious toxic effects upon the organisms. 25. Avian Acute Oral LD 50 (Bobwhite quail): Sixty 27-week-old Bobwhite quail were administered a single oral dose of DMH at dose levels of 0, 464, 681, 1000, 1470 or 2150 mg/kg of body weight. The No-Observed-Effect-Level (NOEL) was considered to be greater than 2150 mg/kg of body weight. The acute oral LD 50 of DMH in Bobwhite quail was determined to be greater than 2150 mg/kg of body weight. 26. Avian Dietary LC 50 : DMH was administered in the diet to 5-day-old Mallard ducklings at dose levels of 0, 312, 625, 1250, 2500 or 5000 ppm for five consecutive days followed by a three day recovery period. The dietary levels employed in this study did not produce any signs of toxicity, mortality, decreased body weight, decreased diet consumption or gross pathological findings. The No-Observed- Effect- Level (NOEL) was considered to be in excess of 5000 ppm. The 8-day acute dietary LC 50 of DMH in Mallard ducklings was determined to be in excess of 5000 ppm. DMH was administered in the diet to 11-day-old Bobwhite quail at dose levels of 0, 312, 625, 1250, 2500 or 5000 ppm for 5 consecutive days followed by a 3-day recovery period. The dietary levels employed in this study did not produce any signs of toxicity, mortality, decreased body weight, decreased diet consumption, or gross pathological findings. The No-Observed- Effect-Level (NOEL) was considered to be in excess of 5000 ppm. The 8-day acute dietary LC 50 of DMH in Bobwhite quail was determined to be in excess of 5000 ppm. 27. Aerobic Aquatic Metabolism: The study was conducted under dark conditions using sandy loam soil at a DMH concentration of 10 ppm at 25 o C. Extractable residues and test water residues accounted for 12.3 and 87.4% of total residues, respectively. Bound and volatile residues remained low over the course of the study. DMH represented a mean of 96.2 and 96.4% of water and extractable residues, respectively. No degradation products were found in either the water or extracts. The stability of radio-labeled DMH precluded the estimation of a half-life. 28. Anaerobic Aquatic Metabolism: A 1-year anaerobic aquatic metabolism study was conducted with radio-labeled DMH. The study was conducted under dark conditions using sandy loam soil at 25 o C. The DMH concentration was 10 ppm. No significant changes were observed in the distribution of radio-labeled residues from day 0 through 12 months. The highest levels of activity were water soluble and accounted for 82.4% of the total residue at 12 months. Extractable residues in soil accounted for 17.2% of the total at 12 months. Non-extractable and volatile residues each accounted for less than 1% of the total residues at 12 months. After 12 months of anaerobic aquatic incubation, radio-labeled DMH was stable and accounted for 87.1% of the water soluble residues and 93.5% of the radio-labeled residues extractable from the sediment. No degradation of the DMH was observed. Due to the stability of DMH under anaerobic conditions, a half-life could not be estimated.

6 29. Aquatic Organism Accumulation: A 28-day study was conducted to evaluate the bioconcentration of radio-labeled DMH by Bluegill sunfish. Daily bioconcentration factors were all less than the minimum quantifiable limits. Uptake tissue concentrations of radio-labeled DMH were also less than the minimum quantifiable limits. To measure the elimination of radio-labeled DMH the test fish were placed in clean water for 14 days. Radio-analysis throughout the depuration period indicated less than minimum quantifiable limits. Neither an uptake rate constant (K1) nor a depuration rate constant (K2) could be calculated or observed. 30. Aerobic Soil Metabolism: A year long aerobic soil metabolism study was conducted with radio-labeled DMH. The study was conducted under dark conditions on sandy loam soil under microbial active conditions at 25 o C. The DMH concentration was 10 ppm. After 12 months of aerobic incubation, 97.4% of the extractable residues were parent compound. No degradation products were observed in the extracts. The persistence of radio-labeled DMH on soil under aerobic conditions precluded the estimation of a half-life. 31. Leaching: Radio-labeled DMH was used in a laboratory leaching study. The radio-labeled DMH recovered from the replicate columns of four types of soil (sandy loam, silt loam, loam and clay loam) were determined to be 90.1%, 104.2%, 100.7%, and 95.2% of the total applied DMH, respectively. 32. Adsorption/Desorption: Aqueous solutions of radio-labeled DMH were equilibrated with four soil types. Analysis demonstrated that 90 to 95% of the radio-labeled DMH was accounted for in the aqueous phase. No significant adsorption of DMH onto any of the soil types was observed. The soil adsorption coefficient, Kd and Koc are as follows: Soil Kd Koc Sandy loam Silt loam Loam Clay loam The information supplied above is presented in good faith and has been derived from sources believed to be reliable. However, no warranty, express or implied is extended regarding its accuracy or the results to be obtained from its use. Since conditions of use are beyond our control all risks are assumed by the user. JAB