Page 2 of 13 

 Tetramethrin is a pyrethroid insecticide. Pyrethroids are synthetic esters derived from 

naturally occurring pyrethrins. There are no registered food-use applications for tetramethrin 

and no tolerances for specific raw agricultural commodities. Tetramethrin is used to control 

mosquitoes and other insects indoors and outdoors in residential and commercial areas. 

Tetramethrin is also applied directly to pets. 

 The liver is the principal target organ for exposure to tetramethrin. Tetramethrin is 

classified as “Suggestive Evidence of Carcinogenic Potential” based on benign interstitial cell 

adenomas in rats. In the 2008 risk assessments, no risks of concern were identified for dietary, 

occupational, residential, and aggregate exposures, and all risk estimates were below Agency 

levels of concern. 

HED’s Registration Review Scoping Document conclusions are as follows. 1) A dietary 

exposure assessment was not conducted and is not required for Registration Review as there are 

no food uses for tetramethrin and dietary exposure is not expected. 2) Given the limited 

potential exposure and the environmental fate properties of tetramethrin, a quantitative drinking 

water assessment will not be conducted. 3) The residential exposure assessment needs to be 

updated according to current standard operating procedures and may need to be revised if 

incidental oral endpoints change based on newly required toxicity data. 4) The occupational 

exposure assessment needs to be updated to reflect current standard operating procedures. 5) 

The following studies have been requested under a generic data call-in issued in June 2010 based 

the 2010 Amended RED; a rat developmental toxicity study; acute, subchronic, and 

developmental neurotoxicity studies; and an immununotoxicity study. 
Page 3 of 13 

Introduction 

HED has evaluated the existing human health risk assessments for tetramethrin to 

determine whether sufficient data are available and whether a new human health risk assessment 

is needed to support Registration Review. HED has considered the most recent risk assessments 

for tetramethrin, updates to its toxicity, exposure and usage databases, and current Agency 

science policies and risk assessment methods. 

Use Profile 

Tetramethrin is a Type I pyrethroid insecticide. Pyrethroids are synthetic esters derived 

from naturally occurring pyrethrins (which are extracts of chrysanthemum flowers). Type I 

pyrethroids act on axons in the peripheral and central nervous system by interacting with sodium 

channels in mammals and/or insects. Tetramethrin and other pyrethroids are usually combined 

with synergists that enhance insecticidal activity by preventing enzymatic breakdown of the 

pyrethroid. Tetramethrin is not registered for direct application to agricultural crops and there 

are no tolerances for specific raw agricultural commodities. Tetramethrin is registered for use in 

indoor and outdoor residential, institutional, and industrial settings. It is also registered for use 

on pets. Tetramethrin is applied primarily by aerosol cans, handheld sprayers, and foggers. 

Hazard Identification/Toxicology 

 Acceptable subchronic and chronic rodent and dog studies indicate that the liver is the 

primary target organ for effects following repeated oral exposure to tetramethrin. Tetramethrin 

was classified as a “Group C, possible human carcinogen without quantification” by the Cancer 

Peer Review Committee in 1989 based on the presence of benign interstitial cell adenomas in 

both Sprague-Dawley and Long Evans rats. This classification corresponds to a classification of 

as “Suggestive Evidence of Carcinogenic Potential,” under EPA’s 2005 Guidelines for 

Carcinogen Risk Assessment. Tetramethrin exhibits low acute toxicity (Toxicity Category III or 

IV) in rats by oral and dermal routes of exposure. 

 

 For the tetramethrin risk assessments (D292298, 6/18/08), toxicity endpoints or points of 

departure (PODs) were selected for residential and occupational exposure scenarios. A POD for 

incidental oral exposures was selected from a 2-generation rat reproduction study based on 

decreased body weight in parental animals and pups and bile duct effects in parents. The 

incidental oral endpoint was refined based on a benchmark dose analysis (BMD) submitted by 

the registrant and reviewed by HED using the endpoint of body weight on Day 21 in females in 

the F0 and F1 generations. A POD from two subchronic inhalation studies in rats was selected 

for assessment of inhalation exposure pathway for workers and residential handlers/occupants 

based on increased clinical signs that were more indicative of respiratory toxicity/irritation than 

neurotoxicity (e.g. irregular respiration and bradypnea), changes in hematology and urinalysis, 

changes in blood chemistry, and gross pathology findings in the liver and kidney. A POD for 

dermal exposure was not selected based on dermal absorption studies which indicate low dermal 

absorption and a dermal toxicity study in which dermal effects were not observed at the limit 

dose. An uncertainty factor of 1000 was applied in 2008 for all exposure routes (10x for 
Page 4 of 13 

interspecies extrapolation, 10x for intraspecies variation, and 10x for database uncertainty factor 

for the inadequate toxicology database i.e., absence of acceptable neurotoxicity studies). 

 The Office of Pesticide Programs has re-evaluated the need of a 10X FQPA Safety Factor 

for human health risk assessments for pyrethroid pesticides. Based on a review of the available 

guideline and literature studies, the Agency is reducing the FQPA Safety Factor to 1X for adults, 

including women of child-bearing age, and children greater than 6 years of age. However, the 

Agency is retaining a 3X FQPA Safety Factor for children from birth to 6 years of age. The 3X 

is based on age-dependent-pharmacokinetics and is further supported by physiologically-based 

pharmacokinetic (PK) model predictions of a 3-fold increase of pyrethroid concentration in 

juvenile target tissue compared to adults. In addition, there is sufficient evidence that the 

pharmacodynamic (PD) responses are similar in adults and juveniles and therefore a full 10X 

safety factor is not warranted (D381210, 6/27/11). The Agency is expecting additional in vitro

and in vivo data. Pesticide registrants and product formulators (Council for the Advancement of 

Pyrethroid Human Risk Assessment (CAPHRA) are i) conducting in vitro studies demonstrating 

the interaction of pyrethroids exogenously expressed rat and human VGSCs in Xenopus oocytes; 

ii) conducting in vitro studies demonstrating interaction of pyrethroids in rat neurolemma cells; 

iii) developing rat and human PBPK models, including additional pharmacokinetic data; and iv) 

conducting in vivo behavioral testing using auditory startle testing in rats. As more data for 

individual pyrethroids become available, the Agency will determine whether re-evaluation of the 

age-related sensitivity of pyrethroids is appropriate. 

Data Requirements

 A generic data call-in (GDCI-069003-28621) was issued in June 2010 for the following 

studies based on the 2010 Amended RED; 870.3700, a rat developmental toxicity study; 

870.6200, acute, subchronic, and 870.6300, developmental neurotoxicity studies; and 870.7800, 

an immununotoxicity study. The registrant indicated their intent to conduct or cite the required 

studies within the time frames provided in the DCI. The immunotoxicity study was recently 

received by the Agency (8/11) and is undergoing review by HED. Acute toxicity studies, 

identified as data deficiencies in the 2008 HED risk assessment, including inhalation, eye and 

skin irritation, and skin sensitization data for technical tetramethrin were required by the product 

specific data call-in (PDCI-069003-28170) also issued in June 2010. 

Conclusions

Based on HED’s re-evaluation of the toxicity analysis conducted for the 2008 

tetramethrin risk assessment, rat developmental toxicity; acute, subchronic, and developmental 

neurotoxicity; and immunotoxicity studies were required. These studies were previously calledin through the RED GDCI. PODs for oral (dietary, drinking water and incidental oral) exposure 

are adequate but may need to be reevaluated to incorporate required toxicity data and to reflect 

OPP’s reevaluation of the safety factor for pyrethroid pesticides. PODs for inhalation and 

dermal exposures are adequate. 
Page 5 of 13 

Dietary and Drinking Water Exposure 

Tetramethrin currently has no registered food uses and there are no tolerances for specific 

raw agricultural commodities. Tetramethrin is not registered for direct application to agricultural 

crops, livestock animals, or livestock premises, where livestock are used for food. Although 

there are no registered food uses for tetramethrin, there are uses in the home where food may be 

exposed e.g., kitchens. However, labels for these uses have restrictions to prevent/limit food 

exposure e.g., “In the home, all food-processing surfaces and utensils should be covered during 

treatment, or thoroughly washed before use. Cover exposed food.” HED did not conduct a 

quantitative assessment of dietary risk for home uses because, based on label prescriptions most 

(if not all) food will be stored prior to application, any food not stored will likely be covered, and 

residuals from surfaces/utensils are expected to be low due to washing and/or insignificant 

transfer to food. Consequently, food residues are likely to be negligible, and risks are not likely 

to be of concern. 

The Environmental Fate and Effects Division (EFED) has not previously conducted a 

quantitative drinking water assessment for tetramethrin. Tetramethrin is used by individual 

homeowners and industrial/commercial property owners, and the use pattern is in individual, 

isolated areas, and in small amounts. These amounts are equivalent to a spray can that may be 

purchased in a supermarket or hardware store. Tetramethrin is not used on a wide scale, such as 

in agriculture or in mosquito abatement by public authorities. The diffuse nature of the use 

pattern makes it unlikely that any harmful amount of tetramethrin will be released in any one 

place and time. Tetramethrin photolyzes rapidly in the air with a half-life of 30 minutes, 

hydrolyzes in water rapidly with half-lives ranging from 0.89-1.06 days at pH 7, and it strongly 

adsorbs to soil and sediment (less tetramethrin available in water column) with Koc values 

ranging from 1289- 2933. Given the limited extent of potential exposure and the fate properties 

of tetramethrin, a quantitative drinking water assessment is not anticipated during registration 

review. 

 

Data Requirements

The data base for the dietary and drinking water assessment is complete. 

Conclusions

A dietary and drinking water assessment is not required for existing uses of tetramethrin. 

Residential Exposure 

 The residential exposure assessment conducted in July, 2008 includes handler and postapplication residential exposure scenarios. Residential handler exposure and risk estimates were 

conducted using HED standard deterministic modeling methodology and default assumptions for 

most exposure scenarios. Residential post-application exposure and risk to tetramethrin was 

assessed using probabilistic modeling approaches. Residential scenarios were assessed for 

exposure via inhalation and incidental ingestion pathways. Dermal exposure was not assessed 

because PODs for dermal exposure were not selected based on absence of adverse effects in 
Page 6 of 13 

dermal toxicity studies. Short and intermediate-term exposures were assessed for residential 

handler and post-application exposure scenarios based on registered uses and expected exposure 

patterns. Residential handler exposure scenarios, assessed using HED OPP’ standard 

deterministic risk assessment methodology showed that estimated risks were not of concern. 

Based on the deterministic post-application assessment, estimated risks of concern were 

identified for inhalation exposure following outdoor total release fogger applications, indoor 

aerosol can space spray treatments, and hand-to-mouth exposures following indoor aerosol can 

treatments, and indoor ready-to-use liquid spray treatments. Exposures from incidental oral and 

inhalation pathways were not combined for tetramethrin because the toxicity endpoints for these 

exposure routes are not based on common toxicity effects. 

 Based on comments submitted to the Agency, HED conducted a refined probabilistic 

assessment of risks using the Cumulative and Aggregate Risk Evaluation System (CARES®

Version 3.0; http://cares.ilsi.org/) for those residential post-application exposure scenarios that 

presented risks of concern based on the deterministic assessment. Probabilistic exposure 

assessment is recognized as a refinement over deterministic assessment because it incorporates 

the full range of exposures and their associated probabilities. All MOEs derived based on the 

probabilistic assessment were above 1000 except for the 100th and 99.9th percentile MOEs for 

indoor non-dietary ingestion exposures. Given the use of conservative assumptions, OPP 

concluded that these results do not indicate risks of concern. 

Addenda were added to the July 2008 tetramethrin risk assessment in April 2009 and 

February 2010. The 2009 assessment was conducted to estimate residential exposures risks from 

a 0.35% tetramethrin indoor space spray product not included in the 2008 assessment. A 

standard deterministic assessment indicated that estimated inhalation risk to residential handlers 

was not a concern for the 0.35% spray product. However, HED’s CARES assessment for this 

use found potential risks of concern for post-application incidental oral exposure to children 

(MOEs < 1000 above the 98.8th percentile). Based on additional comments submitted to EPA, a 

benchmark dose (BMD) analysis of the toxicity endpoint for incidental oral exposure was 

conducted, and HED revised the CARES assessment in February 2010 using the endpoint 

derived based on the BMD analysis. Based on that assessment, estimated risks were not of 

concern for incidental oral exposure to children from the 0.35% spray (i.e., MOEs are > 1000 

(using the BMDL5) at the 99.9th percentile). The tetramethrin RED was amended in April 2010 

to reflect these updated exposure assessments. 

Conclusions

During registration review, the residential exposure assessment needs to be updated to 

reflect current standard operating procedures. It should be noted that HED does not, as a matter 

of policy, conduct probabilistic residential exposure analyses using CARES. However, the 

registrant may again choose to submit a CARES analysis if desired, based on the results of the 

assessment conducted for registration review. As previously, HED will review any submissions 

for possible inclusion in the registration review assessment. The combined non-food pathway 

exposure assessment for residential uses will need to be reevaluated if PODs change based on 

newly required toxicity data. 
Page 7 of 13 

Occupational Exposure 

Risk assessments were conducted for occupational handler exposure scenarios based on 

registered uses. Occupational post-application scenarios were not assessed because there is no 

dermal endpoint and post-application inhalation exposures are not expected for non-volatile 

compounds such as tetramethrin. Occupational and handler exposure and risks were estimated 

for handheld spray and fogging equipment based on registered labels. Occupational exposure 

and risk estimates indicated occupational exposure scenarios do not present risks of concern (i.e., 

MOEs > 1000). 

Conclusions

The occupational exposure assessment is adequate but needs to be updated to reflect 

current standard operating procedures. Recommended unit exposures for occupational handler 

assessments have generally been derived only from PHED. However, recently both the ORETF 

and AHETF have produced pesticide handler exposure monitoring data that the Agency is using 

in place of PHED (http://www.epa.gov/pesticides/science/handler-exposure-data.html). As more 

reliable data become available (such as that from the AHETF and ORETF), the Agency will 

continue to replace existing data. Reviewers should incorporate new exposure monitoring data, 

as necessary, during Registration Review. 

Incident Report 

An updated incident report was conducted for tetramethrin for Registration Review (K. 

Oo, D392272, 8/11/11). In general, a relatively large number of incidents have been reported 

involving tetramethrin. However, because tetramethrin products are almost always coformulated with other pesticide active ingredients, there are no cases reported for products 

containing tetramethrin present as a single chemical only. Human incident data may warrant 

further analysis for the risk assessment and/or risk management of tetramethrin. 

Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

different taxonomic groups. As part of its reregistration decision, EPA reviewed these data and 

selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), tetramethrin is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 
Page 8 of 13 

EPA has developed the EDSP to determine whether certain substances (including 

pesticide active and other ingredients) may have an effect in humans or wildlife similar to an 

effect produced by a “naturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate.” The EDSP employs a two-tiered approach to making the 

statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify 

the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or 

T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the 

potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP 

where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available 

data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the 

substance, and establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Tetramethrin 

is not among the group of 58 pesticide active ingredients on the initial list to be screened under 

the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data 

call-ins, requiring the submission of EDSP screening assays for tetramethrin. For further 

information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, 

future lists, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/. 

Cumulative 

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative 

risks of chemicals sharing a common mechanism of toxicity. Tetramethrin is a member of the 

pyrethroid/pyrethrin common mechanism group (http://www.regulations.gov; EPA-HQ-OPP2008-0489-0006). The members of this group share the ability to interact with voltage-gated 

sodium channels ultimately leading to neurotoxicity. The cumulative risk assessment for the 

pyrethroids/pyrethrins was published on Nov. 9, 2011 and is available at 

http://www.regulations.gov; EPA-HQ-OPP-2011-0746. No cumulative risks of concern were 

identified allowing the Agency to consider new uses for pyrethroid actives. For information 

regarding EPA’s efforts to evaluate the risk of exposure to pyrethroids, refer to 

http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html. 

Human Studies 

The residential exposure assessment for tetramethrin relied in part on data in the 

residential exposure SOPs from studies in which adult human subjects were intentionally 

exposed to a pesticide or other chemical. Many such studies, involving exposure to many 

different pesticides, comprise generic pesticide exposure databases such as the Outdoor 

Residential Exposure Task Force (ORETF) Database. EPA has reviewed all the studies 

supporting these multi-pesticide generic exposure databases, and has found no clear and 

convincing evidence that the conduct of any of them was either fundamentally unethical or 

significantly deficient relative to the ethical standards prevailing at the time the research was 

conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of 
Page 9 of 13 

Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued 

reliance on these studies. 

The occupational exposure assessment for tetramethrin relied in part on data from studies 

in which adult human subjects were intentionally exposed to a pesticide to determine their 

dermal and inhalation exposure. Many such studies, involving exposure to many different 

pesticides, comprise generic pesticide exposure databases such as the Pesticide Handlers 

Exposure Database (PHED) and the Agricultural Reentry Task Force (ARTF) Database. 

However, recently both the ORETF and AHETF have produced pesticide handler exposure 

monitoring data that the Agency is using in place of PHED 

(http://www.epa.gov/pesticides/science/handler-exposure-data.html). As more reliable data 

become available, the Agency will continue to replace existing data and new exposure 

monitoring data will be incorporated into HED’s Registration Review assessments as necessary. 

EPA has reviewed all the studies supporting these multi-pesticide generic exposure databases, 

and has found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards prevailing at 

the time the research was conducted. All applicable requirements of EPA’s Rule for the 

Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no 

regulatory barrier to continued reliance on these studies. 

Environmental Justice 

Potential areas of environmental justice concerns, to the extent possible, were considered 

in the human-health risk assessment, in accordance with U.S. Executive Order 12898, “Federal 

Actions to Address Environmental Justice in Minority Populations and Low-Income 

Populations,” (http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The 

OPP typically considers the highest potential exposures from the legal use of a pesticide when 

conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who might be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information. 

Conclusions/Future Actions Needed 

The actions needed in the future Registration Review for tetramethrin are listed below. 

Hazard Identification and Endpoint Selection

The following studies were required based on the 2008 tetramethrin risk assessment and have 

been called-in through the RED GDCI; 870.3700, a rat developmental toxicity study; 870.6200, 

acute, subchronic, and 870.6300, developmental neurotoxicity studies; and 870.7800, an 

immununotoxicity study. The registrant indicated their intent to conduct or cite the required 

studies within the time frames provided in the RED DCI. A recently submitted immunotoxicity 

study is currently under review. 
Page 10 of 13 

Dietary and Drinking Water Exposure and Risk

A dietary exposure assessment is not required. A drinking water exposure assessment is not 

required. 

Residential Exposure and Risk

The residential risk assessment needs to be updated to reflect current policies and SOPs. 

Aggregate Exposure and Risk

The aggregate exposure assessment is adequate but may need to be reevaluated if PODs change 

based on submission and review of newly required toxicity data. 

Occupational Exposure and Risk

The occupational exposure assessment needs updated to reflect current policies and SOPs. 

Incident Report

In general, a relatively large number of incidents have been reported involving tetramethrin. 

Although there is no case reported for products containing tetramethrin present as a single 

chemical only, human incident data may warrant further analysis for the risk assessment and/or 

risk management of tetramethrin. 

References 

Tetramethrin: Risk Assessment for Reregistration Eligibility Decision, B. Daiss, D292298, 

6/18/08 

Tetramethrin: Phase IV Revised Occupational and Residential Exposure Assessment and 

Recommendations for the Reregistration Eligibility Decision M. Crowley, D292299, 6/13/08 

Revised Drinking Water Assessment for tetramethrin use as a rapid knockdown agent against 

flying and crawling insects, I. Abdel-Saheb, D292294, 2/5/08 

HED Review of “Evaluation of Potential Human Health Risks Associated with Residential Uses 

of Tetramethrin: Supplemental Assessment for Indoor Space Spray” M Crowley 

4/27/09 

HED Review of “Evaluation of Potential Human Health Risks Associated with Residential Uses 

of Tetramethrin: Revised Supplemental – Short-Term Oral Benchmark Dose Analysis” M. 

Crowley, D372749, 2/25/10 

Tetramethrin: Benchmark Dose Analysis of Toxicity Endpoint for Incidental Oral Exposure, B. 

Daiss, 1/6/09 

Pyrethroids: Evaluation of Data from Developmental Neurotoxicity Studies and Consideration of 

Comparative Sensitivity, E. Scollon, D37 1723, 1/20/10 

Tetramethrin: Review of Human Incidents. K. Oo, D392272, 8/11/11 
Page 11 of 13 

Re-Evaluation of the FQPA Safety Factor for Pyrethroid Pesticides, E. Scollon, A. Lowit, 

D381210, 6/27/11 

Re-Evaluation of the FQPA Safety Factor for Pyrethroid Pesticides, E. Scollon, A. Lowit, 

D381210, 6/27/11 

 
Page 12 of 13 

Attachments 

Chemical Identity 

Table 1. Tetramethrin Nomenclature

Chemical structure 

N

O

O O

O

Common name Tetramethrin 

IUPAC name cyclohex-1-ene-1,2 dicarboximidomethyl (lRS, 3RS; lRS, 3SR)-2,2-dimethyl-3- 

(2- methylprop-1-enyl) cyclopropane carboxylate

CAS name 

CAS registry number 7696-12-0 

Summary of Toxicological Points of Departure 

Summary of Toxicological Doses and Endpoints for d-Tetramethrin for Use in Dietary and Non-Occupational 

Human Health Risk Assessments 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty/FQPA 

Safety Factors 

RfD, PAD, 

LOC for Risk 

Assessment 

Study and Toxicological Effects 

Acute Dietary 

(General 

Population, 

including Infants 

and Children) 

An acute RfD for the general population or any population subgroups was not selected because no 

effect attributable to a single (or few) day(s) oral exposure was observed in animal studies. 

Acute Dietary 

(Females 13-49 

years of age) 

NOAEL = 

30 

mg/kg/day 

UFA= 10x 

UFH=10x 

FQPA SF= 10x 

UFDB

Acute RfD = 

0.030 

mg/kg/day 

aPAD = 0.030 

mg/kg/day 

Developmental Toxicity Study – rabbit 

Developmental LOAEL = 100 mg/kg/day 

based on spina bifida 

Chronic Dietary 

(All Populations) 

NOAEL= 

7.1 

mg/kg/day 

UFA= 10x 

UFH= 10x 

FQPA SF= 10x 

UFDB

Chronic RfD = 

0.007 

mg/kg/day 

cPAD = 0.007 

mg/kg/day 

Chronic Toxicity study in dogs 

Chronic toxicity LOAEL = 26.8 mg/kg/day 

based on hepatocellular enlargement in the 

liver and focal degeneration in the adrenal 

cortex in both sexes. 
Page 13 of 13 

Summary of Toxicological Doses and Endpoints for d-Tetramethrin for Use in Dietary and Non-Occupational 

Human Health Risk Assessments 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty/FQPA 

Safety Factors 

RfD, PAD, 

LOC for Risk 

Assessment 

Study and Toxicological Effects 

Incidental Oral 

Short-Term (1-30 

days) and 

Intermediate-Term 

(1-6 months) 

BMDL10 = 

100 

mg/kg/day 

UFA= 10 x 

UFH= 10 x 

FQPA SF= 10 x 

UFDB 

Residential 

LOC for MOE 

= 1000 

2-generation rat reproduction study. The 

NOAEL is 1000 ppm (50 mg/kg/day). The 

LOAEL is 3000 ppm (150 mg/kg/day) 

based on decreased body weight (4-6%) 

and increased liver weight in F0 and F1 

parental animals, and an increase in 

absolute and relative spleen weight, and 

decreased absolute uterine weight in F1 

adults and on decreased body weight gain 

during lactation of F2b pups, and 

decreased litter size of F1b litters at day 1, 

decreased absolute heart and kidney weight 

in F2b males, increased relative liver 

weight in male and female F2b pups. 

Dermal All 

Durations 

Dermal toxicity systemic LOAEL = not established 

21/28 Dermal toxicity study in rats dermal toxicity systemic LOAEL not established up to 1000 

mg/kg/day (HDT) 

Inhalation ShortTerm (1-30 days) 

and 

Intermediate-Term 

(1-6 months) 

NOAEL= 

0.104 mg/L 

(26.6 

mg/kg/day) 

UFA= 10 x 

UFH= 10 x 

FQPA SF= 10 x 

UFDB

Residential 

LOC for MOE 

= 1000 

90 Day inhalation toxicity study LOAEL = 

0.291 mg/L (74.4 mg/kg/day) based on 

histopathological changes in the nasal 

turbinates. 

Cancer (oral, 

dermal, inhalation) 

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant 

tumor increases in two adequate rodent carcinogenicity studies. 

 Summary of Toxicological Doses and Endpoints for [Chemical] for Use in Occupational Human Health Risk 

Assessments 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty 

Factors 

Level of Concern 

for Risk 

Assessment 

Study and Toxicological Effects 

Dermal All 

Durations 

Dermal toxicity systemic LOAEL = not established 

21/28 Dermal toxicity study in rats dermal toxicity systemic LOAEL not established up to 1000 

mg/kg/day (HDT) 

Inhalation ShortTerm (1-30 days) 

and 

Intermediate-Term 

(1-6 months) 

NOAEL= 

0.104 mg/L 

(26.6 

mg/kg/day) 

UFA= 10 x 

UFH = 10 x 

UFDB = 10 x 

Occupational LOC 

for MOE = 1000 

90 Day inhalation toxicity study LOAEL = 

0.291 mg/L (74.4 mg/kg/day) based on 

histopathological changes in the nasal 

turbinates. 

Cancer (oral, 

dermal, inhalation) 

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant 

tumor increases in two adequate rodent carcinogenicity studies. 

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to 

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL 

= no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspecies). UFDB = to account for the absence of key date (i.e., lack of a critical study). FQPA SF = FQPA Safety 

Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = 

level of concern. N/A = not applicable.