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

Interregional Research Project No. 4 (IR-4)

Pesticide Petition (PP#): 2E8070

EPA has received a pesticide petition, PP# 2E8070, 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: Grass, forage at 1.5 parts per million 

(ppm); Grass, hay at 1.8 ppm; Leaf petioles subgroup 4B at 0.80 ppm; Peppermint, tops at 3.5 ppm; 

Spearmint, tops at 3.5 ppm; Peppermint, oil at 14 ppm; Spearmint, oil at 14 ppm; Caneberry

subgroup 13-07A at 0.15 ppm; Bushberry subgroup 13-07B at 0.15 ppm; Berry, low growing, 

subgroup 13-07G at 6.25 ppm; Taro, corm at 0.25 ppm; Taro, leaves at 0.60 ppm; Corn, field, grain 

at 0.05 ppm; Corn, field, stover at 0.15 ppm; Corn, field, forage at 0.25 ppm; Corn, sweet, kernel 

plus cob with husks removed at 0.05 ppm; Soybean, seed at 0.05 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.

.
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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.

Summary of Residue Studies Conducted with Metaldehyde

Crop Number of Trials Application Rate Results

Celery 8 1 lb. a.i./A per 

application

4.0 lb. ai./A per season

The treated samples 

from 5/8 trials showed

no Metaldehyde residues 

above the LOQ of 0.05 

ppm. For the other 3 

trials, the total residues 

range from 0.146-0.334 

ppm.

Mint 5 1-.1.02 lb. a.i./A (per 

application)

4.0 - 4.08 lbs. a.i./A (per 

season)

Metaldehyde residues on 

mint tops ranged from

0.626-2.78 ppm.

Soybeans 7 0.400-0.403 lbs. a.i./A 

(per application)

1.200-1.203 lbs. a.i./A 

(per season)

There were no

detectable residues of 

Metaldehyde above the 

LOQ of 0.05 ppm in any

treated soybean samples.

Grass (seed crop) 12 1.59-1.62 lbs. a.i./A (

per application)

6.40-6.43 lbs. a.i./A (per 

season)

Metaldehyde residues 

ranged from 0.0721-

1.42 ppm in forage 

samples and <0.050-

1.29 ppm in hay

samples.
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Crop Number of Trials Application Rate Results

Taro 3 1.0 lb. a.i./A (per 

application)

15 lbs. a.i/A (per 

season)

3/6 of taro leaf samples 

had Metaldehyde 

residues below LOQ of 

0.05 ppm. Of the 

remaining samples, the 

highest residue was 

0.4511 ppm. 4/6 of the 

taro corm samples had 

residues below 0.05 

ppm. Of the two 

remaining samples, the 

highest residue was 

0.1047 ppm.

Corn (field) 20 0.86-1.09 lbs. a.i//A

(per application)

3.99-4.32 lbs a.i./A ( per 

season)

5 additional trials were 

conducted at a 5X rate

(5.00-5.01 lbs a.i./A, per 

application)

Among the 1X-treated 

grain samples, there 

were no detectable 

Metaldehyde residues 

above the LOQ of 0.05 

ppm, except for a single 

sample that was at 0.06 

ppm. At the 5Xtreament level, there 

were no detectable 

residues above the LOQ 

of 0.05 ppm. None of 

the treated samples of 

kernels plus cob with 

husks removed had a 

residues above 0.05 ppm 

though one sample had a 

residue at the LOQ. The 

total residues in the 

forage samples ranged 

from <0.05 to 0.409 

ppm. The total residues 

in the stove samples 

ranged from <0.05 to 

0.111 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. Genotoxicty. 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). 
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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).

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 high-dose 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 
6

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 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
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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 longterm 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.
8

C. Aggregate Exposure

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

Metaldehyde using the Dietary Exposure Evaluation Model (DEEM) and the USDA Continuing 

Survey of Food Intake by Individuals (CSFII, for 1994 to 1996, as contained in DEEM). 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 DEEM acute dietary risk assessment, exposure at the 95th percentile for 

the overall U.S. population was estimated to be 0.00978 mg/kg/day, which results in 

an Margin of Exposure (MOE) of 7668, which is 1.3% of the acute Permissible 

Acceptable Dose (aPAD). The highest exposed population subgroup, children 1-2 

years, had an acute exposure at the 95th percentile that was estimated to be 0.02171

mg/kg bw/day, which results in an MOE of 3454 and 2.9% of aPAD. 

B. Chronic Dietary Exposure. 

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

overall U.S. population was estimated to be 0.0028 mg/kg bw/day, which is 2.8% of 

the cPAD . The highest exposed subgroup, children 1-2 years, had a chronic exposure 

of 0.0058 mg/kg bw/day, which is 5.8% 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). 
9

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 worst-case 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.” 

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 0.00978 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 1.3% of the aRfD at the 95th percentile 

(MOE = 7668). The predicted chronic exposure for the overall U.S. population is 0.0028 mg/kg 

bw/day, or 2.8% of the cRfD (based on the chronic NOAEL of 10 mg/kg bw/day).

Because the predicted exposures, expressed as percentages of the aRfD and cRfD 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. 
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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 0.02171 mg/kg bw/day, 

or 2.9% of the aRfD (MOE =3454). The estimated chronic exposure is 0.0058 mg/kg bw/day

equivalent to 5.8% of the cRfD. Because the predicted exposures, expressed as percentages of the 

aRfD and cRfD 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.