EPA Registration Division contact: Laura Nollen, (703) 305-7390

Interregional Research Project No. 4 (IR-4)

Pesticide Petition (PP#): 3E8223

EPA has received a pesticide petition (PP# 3E8223) from Interregional Research Project No. 4 

(IR-4), Rutgers, The State University of New Jersey, 500 College Road East, Suite 201W, Princeton, NJ 

08540, proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 

U.S.C. 346a(d), to amend 40 CFR §180.523 by establishing a tolerance for residues of

metaldehyde in or on the follow raw agricultural commodities: Clover, forage at 0.5 parts per million (ppm); 

Clover, hay at 0.5 ppm; Ginseng at 0.05 ppm; Vegetable legume, edible podded, subgroup 6A at 0.8 ppm; 

Pea and bean, succulent shelled, subgroup 6B at 0.2 ppm; Vegetable, foliage of legume, except soybean, 

subgroup 7A at 1.5 ppm; Tomato subgroup 8-10A at 0.24 ppm; Fruit, citrus, group 10-10 at 0.26 ppm. Clover, 

forage and clover, hay are proposed as tolerances with regional registrations.

Upon establishment of the tolerances proposed in “New Tolerances” the petition additionally requests to 

amend 40 CFR §180.523 by removing the established tolerances for residues of

metaldehyde in or on the follow raw agricultural commodities: fruit, citrus, group 10 at 0.26 ppm; and tomato 

at 0.24 ppm.

EPA has determined that the petition contains data or information regarding the elements set forth in section 

408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this 

time or whether the data supports granting of the petition. Additional data may be needed before EPA rules 

on the petition.

A. Residue Chemistry 

1. Plant metabolism. Previously submitted studies sponsored by Lonza Inc., established that 

Metaldehyde can translocate into plants and that the only residue of concern is parent Metaldehyde. The 

translocation studies using 14C-Metaldehyde were conducted in leaf lettuce and sugar beets (MRID 

Nos. 43923301 and 43923302). LSC analysis of the lettuce from the treated lettuce plot showed that the 

lettuce contained an average Total Radioactive Residue (TRR) level (expressed as 14C-Metaldehyde 

equivalents) of 2.44 ppm from the outer leaves and 2.36 ppm from the inner leaves. The corresponding 

values for the beet foliage and roots were 2.87 and 0.61 ppm, respectively. HPLC analysis of treated 

lettuce and beet samples showed that 100% of the radioactivity in the lettuce and beet samples consisted 

of parent 14C-Metaldehyde.

2. Analytical method. A GC/MS analytical method has been developed for analyzing residues of 

Metaldehyde in food crops including all of the crops identified above. The limit of quantitation (LOQ) for the 

method is 0.05 ppm. The method has been validated with respect to specificity and non-analyte interference, 

precision (repeatability), accuracy, sensitivity, linearity of standards, stability of standard solutions and 

precision (replicate injections) by EN-CAS Analytical Laboratories Study No. 99-0055 (MRID# 46010501). 

3. Magnitude of residues. Crop field trials were conducted in all the crops identified in this petition, 

except for the crops covered by the revised crop groupings. A summary of the trials is shown below. All 

of the trials were conducted with the registered end-use product, Deadline M-P, which contains 4% 

Metaldehyde.
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Summary of Residue Studies Conducted with Metaldehyde

Crop Number of Trials Application Rate Results

Ginseng 4 1 lb. a.i./A per 

application

6.0 lb. ai./A per season

There were no 

detectable residues of 

Metaldehyde (LLMV = 

0.05 ppm) found in any

treated or untreated 

dried ginseng root 

samples.

Clover 4 0.798 – 0.838 lb. a.i./A 

(per application)

1.598 – 1.661 lbs. a.i./A 

(per season)

The total residues of 

metaldehyde were in the 

ranges of <0.05 – 0.275 

ppm in forage samples 

and <0.05 - 0.255 ppm 

in hay samples. 

Bean (Succulent 

Shelled)

6 0.997 – 1.000 lbs. a.i./A 

(per application)

2.991 – 3.000 lbs. a.i./A 

(per season)

There were no 

detectable residues of 

Metaldehyde above the 

LLMV of 0.05 ppm in 4 

of the 6 treated field 

trials. Remaining 2 field 

trials, quantifiable 

residues were found in 

the treated samples, 

with the maximum 

residue measured 0.152 

ppm.

Bean and Pea (Edible 

Podded)

7 (bean)

3 (pea)

0.988 – 1.004 lbs. a.i./A 

( per application)

2.988 – 3.012 lbs. a.i./A 

(per season)

Metaldehyde residues 

were in the range <0.05-

0.432 ppm in edible 

podded beans and 

<0.050-0.258 ppm for 

edible podded peas, 

0.0600-0.668 ppm for 

bean foliage, and <0.05 

– 0.352 ppm for pea 

foliage.

Pea (Succulent Shelled) 7 0.999 – 1.083 lb. a.i./A 

(per application)

2.997 – 3.246 lbs. a.i/A 

(per season)

Metaldehyde residues 

were in the range <0.05 

– 0.140 ppm
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4. Magnitude of the Residue in Animals. Metaldehyde is a cyclic tetramer of acetaldehyde. Therefore, 

metabolism in animal systems will result in the release of acetaldehyde, a normal body constituent. The 

metabolism of acetaldehyde, a normal body constituent and major degradate of ethanol, is well 

documented and understood. On the basis of this rationale the Agency granted waivers from conducting 

both nature and magnitude of the residue studies in animals with Metaldehyde.]

B. Toxicological Profile

1. Acute toxicity. The acute oral LD50s in rats and mice were determined to be 283 and 425 mg/kg, 

respectively. The acute dermal LD50 and acute inhalation LC50 in rats were determined to be > 5 g/kg and 

> 15 mg/l, respectively (MRID#s 131434 and 131429). When instilled into the eye of the rabbit, slight transient 

iridial and conjunctival irritation were observed during the first 48 hours after instillation (MRID# 42068801). 

No irritation was observed when Metaldehyde was applied to the skin of the rabbit (MRID# 131971). In a 

dermal sensitization study conducted in guinea pigs, Metaldehyde was shown to be nonsensitizing (MRID# 

153405).

2. Genotoxicity. A battery of tests has been conducted including assays for gene mutation in bacterial cells 

(MRID#s 131433 and 41553205), chromosomal aberrations in mammalian cells (MRID# 163832), an in vitro

gene mutation assay in mouse lymphoma L5178Y cells (MRID#s 41553206 and 42044007) an in vivo

micronucleus test in the mouse (MRID# 42044006). Metaldehyde was not active in any of these assays

3. Reproductive and developmental toxicity. A developmental toxicity study in rats was conducted at 

Metaldehyde dose levels of 0, 25, 75 and 150 mg/kg/day (MRID# 41656001). The doses were 

administered via oral gavage on gestational days 6 – 15. The maternal no-observed effect level (NOEL) 

was 75 mg/kg/day and the developmental NOEL was greater than the highest dose level tested of 

150 mg/kg/day. 

A developmental toxicity study in New Zealand White rabbits was conducted at Metaldehyde dose levels 

of 0, 10, 40 and 80 mg/kg/day (MRID# 41590501). There was no impact on gestational parameters, or 

external, visceral or skeletal variations or malformations at any of the dose levels tested. The maternal 

and developmental toxicity NOEL was greater than the highest dose tested (80 mg/kg/day). 

A two-generation reproduction study was conducted in rats fed diets containing 0, 50, 1000 and 2000 ppm of 

Metaldehyde (MRID# 42823101). No effects on the reproductive parameters, litter viability or pup survival 

were observed during either generation. The NOEL for adult toxicity was 50 ppm; the NOEL for offspring was 

1000 ppm and the NOEL for reproductive effects was greater than 2000 ppm. 

4. Subchronic toxicity. A 90-day repeated dose dietary neurotoxicity study in Sprague-Dawley CD

®

rats 

was conducted at Metaldehyde dietary concentrations of 0, 100, 500 and 2500 ppm (equivalent to 0, 8, 39 

and 185 mg/kg/day, respectively) (MRID# 46223401). With the exception of one female in the 2500 ppm 

treatment group that showed loss of hind limb function, increased respiration, wet fur, and red/brown 

staining around the anogenital region, no clinical signs of toxicity were observed in any of the dose groups. 

Females in the 2500 ppm treatment group had decreased body weight gain during the first week of the 

study. No treatment-related effects were observed in the behavioral, functional or sensory assessments 

of neurotoxicity. The NOEL for neurotoxicity was considered to be 500 ppm (39 mg/kg/day).
4

5. Chronic toxicity. A six-month chronic toxicity study was conducted in Beagle dogs (MRID# 131432). 

Metaldehyde dose levels of 0, 20, 60 and 90 mg/kg/day were administered via the diet. No clear evidence 

of systemic toxicity was observed in any of the treatment groups. 

A 52-week chronic toxicity study in dogs was conducted by administering Metaldehyde via the diet at 

concentrations of 0, 10, 30 and 90 mg/kg/day (MRID# 46378401). Clinical signs observed in the highdose group included ataxia, emesis, salivation, tremor and twitching. Reduced body weight gain, changes 

in hematological and biochemical parameters and in increased absolute and relative liver weight also were 

noted for the animals in this group. Histopathology revealed morphological changes in the testes and 

prostate of the animals treated with 90 mg/kg/day in the form of an atrophy and/or degeneration of the 

germinative epithelium with giant cells. One mid- and high-dose female and one mid-dose male died prior 

to the terminal sacrifice. The study director attributed all three deaths to treatment with Metaldehyde and 

defined the no-observed adverse effect level (NOAEL) as 10 mg/kg/day on this basis. Since there were 

no other treatment-related effects observed in the 30 mg/kg/day dose group, it is somewhat questionable 

as to whether or not the two deaths in the mid dose group should be attributed to Metaldehyde treatment.

An oncogenicity study was conducted for a period of 78 weeks in Charles River CD-1

® mice (MRID# 

42737201). Metaldehyde dietary concentrations of 0, 25, 100 and 300 ppm were evaluated (equivalent to 

4, 16 and 49 mg/kg/day for the males and 0, 5, 20 and 60 mg/kg/day for the females, respectively). The 

only treatment-related effect was hepatocellular hypertrophy in the 300 ppm dose group. Pair wise 

comparisons and/or life table analyses did not indicate any treatment-related effects on survival, tumor 

incidence or time to tumor. 

Because the criteria for a maximum tolerated dose was not satisfied in the initial oncogenicity study, a 

second 78-week chronic oncogenicity study was conducted in Charles River CD-1

® mice (MRID# 

44625101). In this study, Metaldehyde dietary concentrations of 0 and 1000 ppm were evaluated 

(equivalent to 0 and 135 mg/kg/day for the males and 0 and 163 mg/kg/day for the females). The 

exposure of mice to 1000 ppm of Metaldehyde in the diet did not result in clinical signs of toxicity or 

changes in survival, body weight, hematology or toxicologically significant changes in food consumption. 

Treatment-related increases in liver weight and histopathological lesions in the liver of male mice, and to a 

lesser extent, of female mice were observed. Significant histopathologic lesions observed in Metaldehyde 

treated mice included hepatocellular hypertrophy in male and female mice and single cell necrosis, focal 

and multifocal necrosis, pigment accumulation, sinusoidal histiocytosis and hepatocellular adenoma in 

male mice. A small increase in the incidence of hepatocellular eosinophilic cell foci or hepatocellular 

adenoma in female mice treated with 1000 ppm Metaldehyde also was observed. The nature of these 

changes was consistent with an adaptive hypertrophic response of the liver to an increase in metabolic 

demand with subsequent development of proliferative changes and hepatocellular toxicity. There were no 

other treatment-related findings.

A cell proliferation assay (MRID# 44810901) was conducted in order to further investigate the mechanism 

by which the increase in benign liver tumors occurred in the mouse oncogenicity study. Archival material 

from a mouse 90-day dose range-finding study was used for this evaluation. A clear dose response for 

cell proliferation in the liver was observed in this assay. These findings support the conclusion that the 

increased incidence of benign liver tumors observed in the mouse oncogenicity study resulted from cell 

proliferative effects secondary to cytotoxicity rather than a direct oncogenic effect of Metaldehyde. 

A chronic toxicity/oncogenicity study was conducted for a period of 104 weeks in Sprague-Dawley CD

®

rats 

(MRID# 42203601). Metaldehyde dietary concentrations of 0, 50, 1000 or 5000 ppm (equivalent to 0, 2, 44, 

and 224 mg/kg/day for the males and 0, 3, 60 and 314 mg/kg/day for the females) were evaluated. No 

biologically significant differences in mortality, clinical signs of toxicity, palpable masses or food consumption 

were observed in any of the treatment groups. Treatment of both male and female rats with 5000 ppm

Metaldehyde resulted in decreased body weight and weight gain throughout the test period, increases in both 

absolute and relative liver weights, and an a numerical increase in the incidence of females at necropsy with 

liver masses and/or nodules at necropsy. Increased serum globulin and increased serum cholesterol for 
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females only, hepatocellular hypertrophy for males and females, and a questionable increase in the incidence 

of females with hepatocellular adenomas were observed in the high-dose group. These benign neoplasms 

occurred late in the course of the study and were within the range of historical control incidences for the same 

tumor. Therefore, this small numerical increase in hepatocellular adenomas was attributed to an uncommonly

low number of such tumors in the concurrent control animals. Treatment-related effects in animals fed diets 

containing 1000 ppm Metaldehyde were lower body weight and body weight gain in the males and females for 

the first year of the study, increased serum cholesterol for females only, and hepatocellular hypertrophy for 

males and females. The NOEL for systemic toxicity after 104 weeks of dietary administration to rats was 

50 ppm (2.0 mg/kg/day for males and 3.0 mg/kg/day for females).

Based on the toxicology data base assembled for Metaldehyde, the acute NOAEL is considered to be 75 

mg/kg/day and the acute Reference Dose (RfD), using a 100x safety factor is 0.75 mg/kg/day. The chronic 

NOEL is considered to be 10 mg/kg/day and the chronic RfD, using a 100x safety factor, is 0.1 mg/kg/day.

6. Animal metabolism. A study was conducted in Charles River CD®rats to determine the absorption, 

distribution, metabolism and excretion patterns of 14C-Metaldehyde following oral dose administration 

(MRID# 42300901). The results of the study showed that orally administered Metaldehyde is readily absorbed 

from the gastrointestinal tract and quantitatively metabolized to acetaldehyde, which in turn is converted to 

acetyl-C0A as it enters the Krebs cycle. This allowed the 14C label to be eliminated as 14C-C02 and to enter the 

two carbon pool resulting in persistent 14C residues in tissue. The majority of the Metaldehyde was eliminated 

as 14C-CO2. 

7. Metabolite toxicology. The only residue found in plants was parent Metaldehyde. In animal systems, 

Metaldehyde is metabolized to acetaldehyde (a normal body constituent) and CO2. Therefore, only parent 

Metaldehyde is included in the proposed tolerance expressions and in the risk exposure assessment.

8. Endocrine disruption. No special studies investigating the potential estrogenic or other endocrine effects 

of Metaldehyde have been conducted. However, the standard battery of required toxicology studies has been 

completed. These include an evaluation of the potential effects on reproduction and development, and an 

evaluation of the pathology of the endocrine organs following repeated or long-term exposure to doses that far 

exceed likely human exposures. Based on these studies there is no evidence to suggest that Metaldehyde 

has an adverse effect on the endocrine system.

C. Aggregate Exposure

1. Dietary exposure. Acute and chronic dietary risk assessments were conducted for Metaldehyde using 

the Cumulative and Aggravate Risk Evaluation System (CARES) and the USDA Continuing Survey of 

Food Intake by Individuals (CSFII, for 1987 through 1994). Existing crop tolerances and the proposed 

tolerances noted in this document were used. The results of both the chronic and acute dietary and 

clearly demonstrate a reasonable certainty that no harm will result from the proposed uses of 

Metaldehyde.

A. Acute Dietary Exposure. 

Based on the CARES acute dietary risk assessment, exposure at the 95th percentile for the 

overall U.S. population was estimated to be 0.00314 mg/kg/day, which results in a Margin of 

Exposure (MOE) of 23876, which is 0.42% of the acute Permissible Acceptable Dose (aPAD). 
6

The highest exposed population subgroup, children 1-2 years, had an acute exposure at the 

95th percentile that was estimated to be 0.00801 mg/kg/day, which results in an MOE of 9364 

and 1.07% of aPAD. 

B. Chronic Dietary Exposure. 

i. Food: Based on the CARES chronic dietary risk assessment, the exposure for the overall 

U.S. population was estimated to be 0.0010 mg/kg bw/day, which is 1.03% of the cPAD. The 

highest exposed subgroup, children 1-2 years, had a chronic exposure of 0.0027 mg/kg 

bw/day, which is 2.67% of the cPAD. 

2. Non-dietary exposure. A deterministic non-dietary (non-occupational) risk assessment using the 

Residential Exposure Assessment (Rex) model was performed for Metaldehyde applied to the ground in 

and around ornamental plants, small fruit and berry plants, fruit trees, vegetable garden areas (MRID# 

46524302). The maximum application rate of 3.5 lbs of active ingredient (a.i.) per acre was used. 

A separate assessment for use of Metaldehyde in lawn care applications was also performed (MRID# 

46524304). 

The results for the non-dietary (non-occupational) risk assessment indicate that acceptable MOEs exist 

for the vegetable garden (and by inference small fruits and berries), ornamental, and tree care hand 

dispersion scenarios. Using worst-case conditions (e.g., no gloves during application, maximum 

application rates, 1,000 square feet being treated for each setting, i.e., gardens, ornamentals and trees), 

the overall aggregate MOE for the adult applicator (dermal and inhalation routes) was approximately 400 

assuming the same person applied granules to all three settings (vegetable gardens, ornamentals, and 

trees) on the same day. 

The results of the screening-level, non-dietary (residential) consumer applicator (dermal and inhalation) 

and post-application (adult dermal, and child dermal and incidental ingestion) risk analysis for 

Metaldehyde use for lawn care, demonstrate that acceptable Margins of Exposure (MOEs) exist for 

various lawn care methods evaluated, i.e., spot treatment of lawns via hand dispersion of granules or low 

pressure hand-wand spraying, or granular broadcast treatment of lawns via push-spreaders. Using worstcase conditions (e.g., no gloves during application, maximum application rates, high contact reentry

activities on the day of broadcast treatment), the overall total intake ranged from approximately 0.232 

mg/kg/day for the adult applicator (dermal and inhalation routes; MOE= 3950) for granular lawn broadcast 

treatment (push spreader) to 0.0328 mg/kg/day (MOE = 30,370) for spot treatment using a low pressure 

hand-wand sprayer. 

Based on this assessment, it can be concluded that the potential residential/consumer application exposures 

associated with the use of Metaldehyde-based products for slug and snail control are associated with a 

“reasonable certainty of no harm.” 
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D. Cumulative Effects

There is no evidence to indicate or suggest that Metaldehyde has any toxic effects on mammals that would be 

cumulative with those of any other chemicals.

E. Safety Determination

1. U.S. population. As indicated above, the predicted acute exposure is 0.00314 mg/kg day. Based on 

the acute NOAEL and reference dose (75 and 0.75 mg/kg bw/day, respectively), this exposure estimate 

results in intake of approximately 0.42% of the aPAD at the 95th percentile (MOE = 23876). The predicted 

chronic exposure for the overall U.S. population is 0.0010 mg/kg bw/day, or 1.03% of the cPAD (based on 

the chronic NOAEL of 10 mg/kg bw/day).

Because the predicted exposures, expressed as percentages of the aPAD and cPAD are well below 100%, 

there is reasonable certainty that no acute or chronic effects in the U.S. population would result from dietary

exposure to Metaldehyde. 

2. Infants and children. The population subgroup with the highest level of acute exposure at the 95th

percentile is children 1-2 years of age. The estimated acute exposure is 0.00801 mg/kg bw/day, or 1.07% of 

the aPAD (MOE =9364). The estimated chronic exposure is 0.0027 mg/kg bw/day equivalent to 2.67% of the 

cPAD. Because the predicted exposures, expressed as percentages of the aPAD and cPAD are well below 

100%, there is reasonable certainty that no acute or chronic effects would result in the population subgroup 

with the highest level of exposure (children 1-2 years) from dietary exposure to Metaldehyde. 

F. International Tolerances

No incompatibilities with international tolerances are expected.