Adverse Effects
Hydramethylnon
CAS No.
67485-29-4
 
 

Return to Hydramethylnon Index Page

Activity: Insecticide (unclassified)
Structure:


Adverse Effects:
Amyloidosis - Kidney
Blood
Body Weight Decrease (including cachexia and anorexia)
Bone
Cancer: Possible Human Carcinogen - LUNG
Endocrine: Adrenal
Endocrine: Suspected Endocrine Disruptor
Endocrine: Testicular
Endocrine: Thymus
Endocrine: Uterus
Kidney
Lung
Reproductive/Developmental
Environmental

• US: As of February 15, 2005, this herbicide is permitted in or on 3 food commodities in the United States - see list at bottom of page.

• European Commission: Not allowed to be used after July 25, 2003


Amyloidosis (click on for all fluorinated pesticides)

-- In a carcinogenicity study, MRID 00101563, groups of 50 male and 50 female Charles River CD-1 mice received diets containing hydramethylnon at dose levels of 0, 25, 50, 100, or 200 ppm (0, 3.57, 6.93, 14.2, or 28.6 mg/kg/day in males, and 0, 4.45, 6.87, 17.3, or 33.1 mg/kg/day in females, based on food consumption) for 18 months. The 200 ppm males and females were sacrificed after 55 weeks because of high mortality. Survival after 18 months at the 50 and 100 ppm doses was 72% and 46% in males, and 66% and 46% in females (compared to control survival of 86% in males and 76% in females)... Dose-related amyloidosis was seen in the kidneys of the 50 and 100 ppm females.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

18-Month Feeding (oncogenic) - mouse: Systemic NOEL=25 ppm (2.75 mg/kg/day); Systemic LEL=50 ppm (3.75 mg/kg/day) (increased testicular lesions, decreased body weight gain, increased renal amyloidosis); core grade minimum (American Cyanamid, 1982d).
Ref: US EPA IRIS for Amdro (CASRN
67485-29-4).
http://www.epa.gov/iris/subst/0207.htm

Chronic toxicity... In an 18-month cancer assay, hydramethylnon at about 3.8 mg/kg/day was associated with amyloidosis, a syndrome in which abnormal protein deposition in the kidney fitration unit (glomerulus) results in damage [13].
Ref: E X T O X N E T Extension Toxicology Network Pesticide Information Profiles for Hydramethylnon.
http://ace.ace.orst.edu/info/extoxnet/pips/hydramet.htm

Blood (click on for all fluorinated pesticides)

PubMed abstract: Holstein calves (3 to 5 months of age) were used to develop an animal model sensitive to environmental toxicants. In the present study, the fire ant toxicant AMDRO was fed (113.5 g/day/calf) to weanling castrated calves (9 test and 9 controls) for 7 weeks. As early as 14 days after the start of the AMDRO feeding, leukopenia was observed. Differential counts revealed significant non-transient decreases in lymphocytes and eosinophils. Eosinopenia was observed from days 21 to 49 of AMDRO treatment. Variability in hematocrit and hemoglobin values in treated and control calves precluded making a determination of trends due to toxicant exposure...
Ref: Am J Vet Res 1984 May;45(5):1023-7;
Hematologic and immunologic responses of Holstein calves to a fire ant toxicant, by Evans DL, Jacobsen KL, Miller DM.

In a 21-day dermal toxicity study in rabbits, MRID 00101559, groups of 10 male and 10 female New Zealand White rabbits received a total of 15 repeated dermal applications of hydramethylnon at doses of 0 (control), 10, 50, or 250 mg/kg/day, 6 hours/day, 5 days/week over a three week period... Toxicity observed at the highest dose tested (250 mg/kg/day) included decreased food consumption in males and females as well as thrombocytopenia (a persistent decrease in the number of blood platelets that is usually associated with hemorrhagic conditions) in females. Although thrombocytopenia was observed at this dose (250 mg/kg/day), it was not considered to be an adverse, or biologically significant effect because it was seen in the presence of skin irritation in animals having abraded skins. In addition, alterations in hematological parameters are often seen in dermal toxicity studies in the presence of skin irritation. Therefore, the 250 mg/kg/day (the highest dose tested), in spite of the presence of this effect, is considered to be the NOAEL for dermal and systemic toxicity; a LOAEL was not established. MRID 00101559 is classified as acceptable and satisfies guideline requirement 82-2 for a 21-dermal toxicity study in rats.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Body Weight Decrease (click on for all fluorinated pesticides)

-- In a subchronic toxicity study, MRID 00061794, groups of 4 male and 4 female beagles received gelatin capsules containing hydramethylnon at doses of 0, 3.0, 6.0, or 12.0 mg/kg/day for 91 days. None of the control or low-dose dogs died, but 3 males and 3 females in the mid-dose died or were sacrificed moribund between days 27 and 75, and all high-dose dogs were sacrificed moribund between days 27 and 53. .. Body weights in the low, mid, and high-dose groups were decreased as much as 11%, 51%, and 34% in males; and 9%, 42%, and 37% in the females (body weight decreases were greatest in the mid-dose dogs because they survived longer than the high-dose dogs)... All mid and high-dose dogs were cachectic at necropsy... The 6 mg/kg/day dose caused lethality, as well as decreased food consumption and body weight gain, increased SGPT, cachexia, wasting of muscle and subcutaneous fat, and testicular atrophy. The LOAEL was 3 mg/kg/day (the lowest does tested) based on decreased food consumption and body weight gain; a NOAEL was not established.
--
In a 21-day dermal toxicity study in rabbits, MRID 00101559, groups of 10 male and 10 female New Zealand White rabbits received a total of 15 repeated dermal applications of hydramethylnon at doses of 0 (control), 10, 50, or 250 mg/kg/day, 6 hours/day, 5 days/week over a three week period... Food consumption was depressed as much as 38% and 45% in the high-dose males and females, compared to controls. The high-dose males and females weighed as much as 8% and 9% less than the controls... Toxicity observed at the highest dose tested (250 mg/kg/day) included decreased food consumption in males and females as well as thrombocytopenia (a persistent decrease in the number of blood platelets that is usually associated with hemorrhagic conditions) in females...
--
Chronic Toxicity and Carcinogenicity In a 6-month study, MRID 00035529, groups of 4 male and 4 female beagles dogs received gelatin capsules containing hydramethylnon at doses of 0, 0.33, 1.0, or 3.0 mg/kg/day for 26 weeks. The control group received 120 mg/kg/day of lactose. No dogs died... A high-dose male was removed from the study due to anorexia between study days 42 and 98, and day 120 to termination.
-- In a chronic toxicity/carcinogenicity study, MRID 00101565, groups of 50 male and 50 female Charles River CD rats were fed diets containing hydramethylnon at dose levels of 0, 25, 50, 100, or 200 ppm (0, 1.2, 2.4, 4.9, or 10.0 mg/kg/day in males, and 0, 1.5, 3.0, 6.2, or 12.1 mg/kg/day in females, respectively based on food consumption) for two years... Body weights in the males were as much as 17% less than the controls at 200 ppm, and 5% at 100 ppm. Body weights in the females were as much as 42% less than the controls at 200 ppm, and 22% at 100 ppm. Body weights were comparable in the other groups. Food consumption was reduced an average of 7% in the 200 ppm males, and 16% in the 200 ppm females. The other groups were comparable...
-- On May 28, 1998, the Agency's Cancer Peer Review Committee concluded that the dose levels of 100 ppm in males, and 50 ppm in females were adequate to assess the carcinogenic potential of hydramethylnon in rats. This conclusion was based on significant decreases in body weight at higher doses... Under the conditions of this study, the NOAEL was 50 ppm (2.4 mg/kg/day in males, 3.0 mg/kg/day in females), and the LOAEL was 100 ppm (4.9 mg/kg/day in males, 6.2 mg/kg/day in females) based on small, soft testes, decreased testicular weights, and testicular atrophy in males; and decreased body weight gain in females. This study is classified as acceptable and satisfies guideline requirement 83-5 for a chronic feeding/carcinogenicity study in rodents.
-- In a carcinogenicity study, MRID 00101563, groups of 50 male and 50 female Charles River CD-1 mice received diets containing hydramethylnon at dose levels of 0, 25, 50, 100, or 200 ppm (0, 3.57, 6.93, 14.2, or 28.6 mg/kg/day in males, and 0, 4.45, 6.87, 17.3, or 33.1 mg/kg/day in females, based on food consumption) for 18 months. The 200 ppm males and females were sacrificed after 55 weeks because of high mortality. Survival after 18 months at the 50 and 100 ppm doses was 72% and 46% in males, and 66% and 46% in females (compared to control survival of 86% in males and 76% in females). Body weights in the 100 and 200 ppm groups were as much as 13% and 23% less than the controls in males, and as much as 6% and 19% less than the controls in females, respectively. Food consumption was reduced an average of 14% in the 200 ppm males, and 20% in the 200 ppm females. The other groups were comparable...
-- In a prenatal developmental toxicity study, MRID 00061790, groups of 26 pregnant female Sprague-Dawley rats were given oral administration of hydramethylnon at doses of 0, 3, 10, or 30 mg/kg/day on gestation days 6-15. The vehicle controls were dosed with corn oil. The dams were sacrificed and examined on gestation day 20. There were two maternal deaths in the high-dose, presumably due to intubation error. The mid-dose dams weighed as much as 8% less than the controls, and the high-dose dams weighed as much as 16% less than the controls. Body weight gain during the post-dosing interval (gestation days 15-20) was comparable in all groups... Mean high-dose fetal weights were reduced 10% for both sexes, but the other groups were comparable... For maternal toxicity, the NOAEL was 3 mg/kg/day and the LOAEL was 10 mg/kg/day, based on an 8% decrease in body weight and yellowish discoloration of the fat... For developmental toxicity, the NOAEL was 10 mg/kg/day and the LOAEL was 30 mg/kg/day, based on decreased mean fetal weights, increased incidence of rudimentary structures, and increased incidence of incompletely ossified supraoccipital. This study is classified as acceptable and satisfies guideline requirement 83-3(a) for a developmental toxicity study in rats.
-- In a developmental toxicity study, MRID 00101558, groups of 16 impregnated New Zealand rabbits received oral administration of hydramethylnon at doses of 0, 5, 10, or 20 mg/kg/day on gestation days 6-18. The vehicle controls were dosed with corn oil. The does were sacrificed and examined on gestation day 29. Two high-dose does died during the post-treatment period of undetermined causes. Six does aborted, 3 each in the mid and high-dose groups. Dose-related clinical signs seen at the mid and high-dose included soft stool, reduced amount of stool, and ano-genital matting and discharge. The high-dose body weights were as much as 12% less than the controls (gestation day 24). The low and mid-dose body weights were comparable, though slightly less than the controls. The mean number of implantations, corpora lutea, post-implantation loss, early or late resorptions, viable fetuses, and sex distribution were comparable in all groups. The fetal weights in the low, mid, and high-dose groups were 8%, 16%, and 25% lower than the controls; the low-dose was within historical limits. For maternal toxicity, the LOAEL was 5 mg/kg/day based upon body weight established. However, the incidence of soft stool, reduced amount of stool, and body weight loss of less than 6%, at the low-dose, were not considered adverse. At 10 mg/kg/day, ano-genital matting and discharge was also observed, and the same findings, with increased severity, were observed at the 20 mg/kg/day dose level. For developmental toxicity, the NOAEL was 5 mg/kg/day and the LOAEL was 10 mg/kg/day, based upon decreased fetal weight (16%) mg/kg/day. The decreased fetal weight observed at the 5 mg/kg/day was not considered to be treatment-related since the incidences were within historical control ranges . This study is classified as acceptable and satisfies guideline requirement 83-3(b) for a developmental toxicity study in rabbits.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Bone (click on for all fluorinated pesticides)

Decreased fetal weight was observed in the offspring of rats administered 30 mg/kg/day (LOEL). The NOEL was 10 mg/kg/day. Increased post implantation loss and decreased fetal viability were observed in the offspring of rabbits administered 15 mg/kg/day (LOEL). The NOEL was 5 mg/kg/day. Vertebral anomalies were seen in the offspring of rabbits administered 10 mg/kg/day (LOEL). The NOEL was 5 mg/kg/day.
Ref: USEPA/OPP. Support Document for the Addition of Chemicals from Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule
.

In a prenatal developmental toxicity study, MRID 00061790, groups of 26 pregnant female Sprague-Dawley rats were given oral administration of hydramethylnon at doses of 0, 3, 10, or 30 mg/kg/day on gestation days 6-15. The vehicle controls were dosed with corn oil. The dams were sacrificed and examined on gestation day 20... Skeletal variations were generally comparable in all groups, although the high-dose fetuses had an increase in the incidence of rudimentary structures and \incompletely ossified supraoccipitals... At 30 mg/kg/day, a 16% decrease in maternal body weight, increased incidence of clinical signs (nasal mucus, alopecia, soft stool, staining of the ano-genital fur), yellowish discoloration of the fat, and small thymus were observed. For developmental toxicity, the NOAEL was 10 mg/kg/day and the LOAEL was 30 mg/kg/day, based on decreased mean fetal weights, increased incidence of rudimentary structures, and increased incidence of incompletely ossified supraoccipital. This study is classified as acceptable and satisfies guideline requirement 83-3(a) for a developmental toxicity study in rats.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Cancer: Possible Human Carcinogen - LUNG (click on for all fluorinated pesticides)

Group C -- Possible Human Carcinogen. Lung adenomas & combined adenomas/carcinomas; CD-1 mice (F).
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

Group C--Possible Human Carcinogen. Reviewed 3/ 28/ 91.
Ref: List of Chemicals Evaluated for Carcinogenic Potential. Science Information Management Branch, Health Effects Division, Office of Pesticide Programs, U. S. Environmental Protection Agency. March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm


The Cancer Peer Review Committee determined that hydramethylnon should be classified as a Group C carcinogen, a possible human carcinogen, and recommended that, for the purpose of risk characterization, the Reference Dose approach should be used for quantification of human risk. This classification was based upon statistically significant increases in lung adenomas at 50 and 100 ppm (27% and 27%, respectively) and combined lung adenomas/carcinomas at 25, 50, and 100 ppm (32%, 40%, and 35%, respectively) in female mice. The MTD is between 50 ppm and 100 ppm in both sexes of mice.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Endocrine: Adrenal (click on for all fluorinated pesticides)

- On May 28, 1998, the Agency’s Cancer Peer Review Committee concluded that the dose levels of 100 ppm in males, and 50 ppm in females were adequate to assess the carcinogenic potential of hydramethylnon in rats.... The statistically significant increases in tumors observed in the uterus (adenomatous polyps) and adrenals (medullary adenomas) were not considered to be biologically significant since they were seen at excessive doses (i.e., at 200 ppm). Under the conditions of this study, the NOAEL was 50 ppm (2.4 mg/kg/day in males, 3.0 mg/kg/day in females), and the LOAEL was 100 ppm (4.9 mg/kg/day in males, 6.2 mg/kg/day in females) based on small, soft testes, decreased testicular weights, and testicular atrophy in males; and decreased body weight gain in females. This study is classified as acceptable and satisfies guideline requirement 83-5 for a chronic feeding/carcinogenicity study in rodents.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Endocrine: Suspected Disruptor (click on for all fluorinated pesticides)

"Endocrine Disruptor Effects. EPA is required to develop a screening program to determine whether certain substances (including all pesticides and inerts) ``may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or such other endocrine effect...'' The Agency is currently working with interested stakeholders, including other government agencies, public interest groups, industry and research scientists in developing a screening and testing program and a priority setting scheme to implement this program. Congress has allowed 3 years from the passage of FQPA (August 3, 1999) to implement this program. At that time, EPA may require further testing of this active ingredient and end use products for endocrine disruptor effects."
Ref: Federal Register. March 4, 1998. Pesticide tolerances for emergency exemptions. Final Rule.

http://www.fluoridealert.org/pesticides/Hydramethylnon.FR.Mar4.1998.htm

Endocrine: Testicular (click on for all fluorinated pesticides)

- Mutagenicity There are five acceptable mutagenicity (84-2) studies of hydramethylnon. The findings of adverse effects on spermatocyte and/or spermatogonia in the dominant lethal assay are consistent with the results of the 2-generation reproduction study in rats showing that hydramethylnon is a reproductive toxicant which appears to specifically target the germinal cells and/or tissues in the testes.
- On May 28, 1998, the Agency's Cancer Peer Review Committee concluded that the dose levels of 100 ppm in males, and 50 ppm in females were adequate to assess the carcinogenic potential of hydramethylnon in rats.... The statistically significant increases in tumors observed in the uterus (adenomatous polyps) and adrenals (medullary adenomas) were not considered to be biologically significant since they were seen at excessive doses (i.e., at 200 ppm). Under the conditions of this study, the NOAEL was 50 ppm (2.4 mg/kg/day in males, 3.0 mg/kg/day in females), and the LOAEL was 100 ppm (4.9 mg/kg/day in males, 6.2 mg/kg/day in females) based on small, soft testes, decreased testicular weights, and testicular atrophy in males; and decreased body weight gain in females. This study is classified as acceptable and satisfies guideline requirement 83-5 for a chronic feeding/carcinogenicity study in rodents.
- In a carcinogenicity study, MRID 00101563, groups of 50 male and 50 female Charles River CD-1 mice received diets containing hydramethylnon at dose levels of 0, 25, 50, 100, or 200 ppm (0, 3.57, 6.93, 14.2, or 28.6 mg/kg/day in males, and 0, 4.45, 6.87, 17.3, or 33.1 mg/kg/day in females, based on food consumption) for 18 months. The 200 ppm males and females were sacrificed after 55 weeks because of high mortality. Survival after 18 months at the 50 and 100 ppm doses was 72% and 46% in males, and 66% and 46% in females (compared to control survival of 86% in males and 76% in females)... Histopathologic findings of testicular degeneration in the 50, 100, and 200 ppm males displayed a dose-related pattern of incidence and severity, and included hypospermia, interstitial cell hyperplasia of Leydig cells, and germinal cell degeneration...
- Mutagenicity There are five acceptable mutagenicity (84-2) studies of hydramethylnon. The findings of adverse effects on spermatocyte and/or spermatogonia in the dominant lethal assay are consistent with the results of the 2-generation reproduction study in rats showing that hydramethylnon is a reproductive toxicant which appears to specifically target the germinal cells and/or tissues in the testes.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Hydramethylnon is a male reproductive toxicant which appears to specifically target the germinal cells and/or tissues in the testes... The reproductive NOEL was 25 ppm (1.66 mg/kg/day for males) and the lowest observed effect level (LOEL) was 50 ppm (3.32 mg/kg/day for males), based upon histopathological findings in the testes and the epididymides. Also, at 75 ppm (5.05 mg/kg/day in males), reproductive performance of the males was decreased with longer precoital intervals, lower pregnancy rates, reduced gestation weight gain for females and smaller litters... The evidence of male infertility and testicular atrophy at 90 mg/kg/day in the dominant lethal assay is consistent with similar findings observed in the chronic rat study, the 18-month mouse feeding study, the 2-generation reproduction study, and the 91-day oral gavage study in dogs.
Ref: Federal Register. August 14, 1998. [PF-824; FRL-6023-2]

http://www.fluoridealert.org/pesticides/Hydramethylnon.FR.Aug.14.98.htm

In a 90-day dog feeding study, testicular atrophy was observed at 6 mg/ kg/day (LOEL). The NOEL was 3 mg/kg/day. In a 90-day rat study, dietary administration of 5 mg/kg/day (LOEL) produced testicular atrophy. The NOEL was 2.5 mg/kg/day. Dietary administration of 6.5 mg/kg/day for 18 months produced testicular lesions in mice. The NOEL was 2.75 mg/kg/ day. In a 2-year rat study, dietary administration of 5 mg/kg/day produced decreased testicular weight and testicular atrophy. The NOEL was 2.5 mg/kg/day. In a 3-generation rat reproduction study, oral administration of 5 mg/kg/day produced male infertility. The NOEL was 2.5 mg/kg/day... EPA believes that there is sufficient evidence for listing hydramethylnon on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available reproductive, developmental, and hepatic toxicity data for this chemical.
Ref: USEPA/OPP. Support Document for the Addition of Chemicals from Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule.

Endocrine: Thymus (click on for all fluorinated pesticides)

-In a prenatal developmental toxicity study, MRID 00061790, groups of 26 pregnant female Sprague-Dawley rats were given oral administration of hydramethylnon at doses of 0, 3, 10, or 30 mg/kg/day on gestation days 6-15. The vehicle controls were dosed with corn oil. The dams were sacrificed and examined on gestation day 20... At 30 mg/kg/day, a 16% decrease in maternal body weight, increased incidence of clinical signs (nasal mucus, alopecia, soft stool, staining of the ano-genital fur), yellowish discoloration of the fat, and small thymus were observed. For developmental toxicity, the NOAEL was 10 mg/kg/day and the LOAEL was 30 mg/kg/day, based on decreased mean fetal weights, increased incidence of rudimentary structures, and increased incidence of incompletely ossified supraoccipital. This study is classified as acceptable and satisfies guideline requirement 83-3(a) for a developmental toxicity study in rats.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Endocrine: Uterus (click on for all fluorinated pesticides)

- On May 28, 1998, the Agency's Cancer Peer Review Committee concluded that the dose levels of 100 ppm in males, and 50 ppm in females were adequate to assess the carcinogenic potential of hydramethylnon in rats.... The statistically significant increases in tumors observed in the uterus (adenomatous polyps) and adrenals (medullary adenomas) were not considered to be biologically significant since they were seen at excessive doses (i.e., at 200 ppm). Under the conditions of this study, the NOAEL was 50 ppm (2.4 mg/kg/day in males, 3.0 mg/kg/day in females), and the LOAEL was 100 ppm (4.9 mg/kg/day in males, 6.2 mg/kg/day in females) based on small, soft testes, decreased testicular weights, and testicular atrophy in males; and decreased body weight gain in females. This study is classified as acceptable and satisfies guideline requirement 83-5 for a chronic feeding/carcinogenicity study in rodents.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Kidney (click on for all fluorinated pesticides)

Subchronic Toxicity - In a 90 day feeding study in rats, MRID 00032641, groups of 20 male and 20 female Sprague-Dawley rats were dosed with hydramethylnon in their feed at 0, 50, 100, 200, or 400 ppm (equivalent to 0, 2.5, 5.0, 10.0 or 20.0 mg/kg/day). Due to significant decreases in body weight gain and food consumption during the first two weeks of the study at the highest dose (400 ppm, 20 mg/kg/day), this dose level was reduced to 25 ppm (1.25 mg/kg/day) on study day 15. Thus, the dose levels tested were 0, 25, 50, 100, or 200 ppm (0, 1.25, 2.5, 5.0, or 10.0 mg/kg/day)... On study day 68, a 50 ppm male was sacrificed moribund, and a 200 ppm (10.0 mg/kg/day) female died. The 200 ppm female had a blood urea nitrogen (BUN) value 4-fold higher than that of the controls on day 45. Histopathologic evaluation of this female revealed nephrocalcinosis and hydronephrosis...
-- In a carcinogenicity study, MRID 00101563, groups of 50 male and 50 female Charles River CD-1 mice received diets containing hydramethylnon at dose levels of 0, 25, 50, 100, or 200 ppm (0, 3.57, 6.93, 14.2, or 28.6 mg/kg/day in males, and 0, 4.45, 6.87, 17.3, or 33.1 mg/kg/day in females, based on food consumption) for 18 months. The 200 ppm males and females were sacrificed after 55 weeks because of high mortality. Survival after 18 months at the 50 and 100 ppm doses was 72% and 46% in males, and 66% and 46% in females (compared to control survival of 86% in males and 76% in females)... Dose-related amyloidosis was seen in the kidneys of the 50 and 100 ppm females.
--
In a chronic toxicity/carcinogenicity study, MRID 00101565, groups of 50 male and 50 female Charles River CD rats were fed diets containing hydramethylnon at dose levels of 0, 25, 50, 100, or 200 ppm (0, 1.2, 2.4, 4.9, or 10.0 mg/kg/day in males, and 0, 1.5, 3.0, 6.2, or 12.1 mg/kg/day in females, respectively based on food consumption) for two years... Body weights in the males were as much as 17% less than the controls at 200 ppm, and 5% at 100 ppm. Body weights in the females were as much as 42% less than the controls at 200 ppm, and 22% at 100 ppm. Body weights were comparable in the other groups. Food consumption was reduced an average of 7% in the 200 ppm males, and 16% in the 200 ppm females. The other groups were comparable... Glomerulonephrosis was greater in the treated males and females than in the controls, but there was no dose-response relationship.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

18-Month Feeding (oncogenic) - mouse: Systemic NOEL=25 ppm (2.75 mg/kg/day); Systemic LEL=50 ppm (3.75 mg/kg/day) (increased testicular lesions, decreased body weight gain, increased renal amyloidosis); core grade minimum (American Cyanamid, 1982d).
Ref: US EPA IRIS for Amdro (CASRN
67485-29-4).
http://www.epa.gov/iris/subst/0207.htm

Chronic toxicity... In an 18-month cancer assay, hydramethylnon at about 3.8 mg/kg/day was associated with amyloidosis, a syndrome in which abnormal protein deposition in the kidney fitration unit (glomerulus) results in damage [13].
Ref: E X T O X N E T Extension Toxicology Network Pesticide Information Profiles for Hydramethylnon.
http://ace.ace.orst.edu/info/extoxnet/pips/hydramet.htm

Lung (click on for all fluorinated pesticides)

Group C -- Possible Human Carcinogen. Lung adenomas & combined adenomas/carcinomas; CD-1 mice (F).
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

The Cancer Peer Review Committee determined that hydramethylnon should be classified as a Group C carcinogen, a possible human carcinogen, and recommended that, for the purpose of risk characterization, the Reference Dose approach should be used for quantification of human risk. This classification was based upon statistically significant increases in lung adenomas at 50 and 100 ppm (27% and 27%, respectively) and combined lung adenomas/carcinomas at 25, 50, and 100 ppm (32%, 40%, and 35%, respectively) in female mice. The MTD is between 50 ppm and 100 ppm in both sexes of mice.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.

http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Reproductive / Developmental (click on for all fluorinated pesticides)

- Mutagenicity There are five acceptable mutagenicity (84-2) studies of hydramethylnon. The findings of adverse effects on spermatocyte and/or spermatogonia in the dominant lethal assay are consistent with the results of the 2-generation reproduction study in rats showing that hydramethylnon is a reproductive toxicant which appears to specifically target the germinal cells and/or tissues in the testes.
- On May 28, 1998, the Agency's Cancer Peer Review Committee concluded that the dose levels of 100 ppm in males, and 50 ppm in females were adequate to assess the carcinogenic potential of hydramethylnon in rats.... The statistically significant increases in tumors observed in the uterus (adenomatous polyps) and adrenals (medullary adenomas) were not considered to be biologically significant since they were seen at excessive doses (i.e., at 200 ppm). Under the conditions of this study, the NOAEL was 50 ppm (2.4 mg/kg/day in males, 3.0 mg/kg/day in females), and the LOAEL was 100 ppm (4.9 mg/kg/day in males, 6.2 mg/kg/day in females) based on small, soft testes, decreased testicular weights, and testicular atrophy in males; and decreased body weight gain in females. This study is classified as acceptable and satisfies guideline requirement 83-5 for a chronic feeding/carcinogenicity study in rodents.
- In a carcinogenicity study, MRID 00101563, groups of 50 male and 50 female Charles River CD-1 mice received diets containing hydramethylnon at dose levels of 0, 25, 50, 100, or 200 ppm (0, 3.57, 6.93, 14.2, or 28.6 mg/kg/day in males, and 0, 4.45, 6.87, 17.3, or 33.1 mg/kg/day in females, based on food consumption) for 18 months. The 200 ppm males and females were sacrificed after 55 weeks because of high mortality. Survival after 18 months at the 50 and 100 ppm doses was 72% and 46% in males, and 66% and 46% in females (compared to control survival of 86% in males and 76% in females)... Histopathologic findings of testicular degeneration in the 50, 100, and 200 ppm males displayed a dose-related pattern of incidence and severity, and included hypospermia, interstitial cell hyperplasia of Leydig cells, and germinal cell degeneration...
- Mutagenicity There are five acceptable mutagenicity (84-2) studies of hydramethylnon. The findings of adverse effects on spermatocyte and/or spermatogonia in the dominant lethal assay are consistent with the results of the 2-generation reproduction study in rats showing that hydramethylnon is a reproductive toxicant which appears to specifically target the germinal cells and/or tissues in the testes.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Environmental (click on for all fluorinated pesticides)

The 96-hour LC 50 in the Chanel Catfish was 90 ppb. Bioaccumulation factors in bluegill sunfish are 1300 for the whole fish, 780 for the fillet, and 1900 for viscera. EPA believes that there is sufficient evidence for listing hydramethylon on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data and the potential for bioaccumulation.
Ref: USEPA/OPP. Support Document for the Addition of Chemicals from Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule

Hydramethylon
Table 9: Freshwater Fish Acute Toxicity

Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998. http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Species/ (Flow-through or Static) % ai 96-hour LC50 (ppm)* Toxicity Category MRID Study Classification
Rainbow trout (Oncorhynchus mykiss) 92% 0.15 Highly toxic 00052857 Acceptable
Bluegill sunfish (Lepomis macrochirus) 92% 1.7 Moderately 00061708 Acceptable
Channel catfish (Ictalurus punctatus) 92% 0.09 Very highly toxic 00061707 Acceptable

Ref: Acute Aquatic Ecotoxicity Summaries for Hydramethylnon on All Taxa Groups. PAN Pesticides Database - Chemical Toxicity Studies on Aquatic Organisms.
http://www.pesticideinfo.org/List_AquireAcuteSum.jsp?Rec_Id=PC33088
Common Name Scientific Name Avg Species LC50 (ug/L) LC50 Std Dev Number of Studies Avg Species Rating Outlier Result for Organism Group?

Fish

Channel catfish Ictalurus punctatus 96.7 24.9 3 Very Highly Toxic  
Bluegill Lepomis macrochirus 910.0 790.0 2 Highly Toxic  
Rainbow trout,donaldson trout Oncorhynchus mykiss 128.7 37.5 3 Highly Toxic  
Fathead minnow Pimephales promelas 157.5 82.5 2 Highly Toxic  

 


A February 15, 2005, check at the Code of Federal Regulations for Hydramethylnon: this insecticide is permitted in or on 3 food commodities in the United States. The following list identifies these crops for which EPA has set pesticide tolerances.

[Code of Federal Regulations]
[Title 40, Volume 22]
[Revised as of July 1, 2004]
From the U.S. Government Printing Office via GPO Access
[CITE: 40CFR180.395]
[Page 428-429]

TITLE 40--PROTECTION OF ENVIRONMENT

CHAPTER I--ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)

PART 180_TOLERANCES AND EXEMPTIONS FROM TOLERANCES FOR PESTICIDE CHEMICALS
IN FOOD--Table of Contents

Subpart C_Specific Tolerances

Sec. 180.395 Hydramethylnon; tolerances for residues.
(a) General. Tolerances are established for residues of the
insecticide tetrahydro-5,5-dimethyl-2(1H)-pyrimidinone(3-(4-(tri fluoro
methyl) phenyl)-1-(2-(4-(tri fluoro methyl) phenyl) ethenyl)-2-pro penyl
i dene)hy dra zone in or on the following raw agricultural commodities:
Commodity

As of
October 8,
2003

PPM

As of
February 15,
2005

PPM

CFR
Grass (pasture and rangeland)
0.05 0.05 180.395
Grass hay (pasture and rangeland) 0.05 0.05 180.395
GRASS, RANGE, HAY 0.05 Not listed this way 180.395
Pineapple 0.05 0.05 180.395
(b) Section 18 emergency exemptions. Time-limited tolerances are
established for residues of the insecticide hydramethylnon; tetrahydro-
5,5-dimethyl-2-(1H)-pyrimidinoine(3-(4-trifluoromethyl)phenyl)-1-[2-
[4(trifluoromethly)phenyl]ethenyl)-2-propenylidene) hydrazone in
connection with the use of the pesticides under section 18 emergency
exemptions granted by EPA. The tolerance will expire and is revoked on
the date specified in the following table.
Commodity

As of
October 8,
2003

PPM

As of
February 15,
2005

PPM

Expiration/ Revocation Date
Pineapple 0.05 0.05 6/30/05
(c) Tolerances with regional registrations. [Reserved]
[[Page 429]]
(d) Indirect or inadvertent residues. [Reserved]
 
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