Page 2 of 24

exhibits antifeeding properties for surface-feeding insects. TPTH is not currently registered for 

residential uses.

The toxicity and exposure databases are adequate to support human health risk assessment and 

make safety findings under FQPA. An immunotoxicity study is required for registration review 

under the new data requirements for pesticides (40 CFR § 158). Once this study has been 

received and reviewed the toxicological endpoint selection and uncertainty factors may be reevaluated.

The most recent HED human health risk assessment was completed in September of 1999 as part 

of a revised Re-registration Eligibility Decision Document (RED). At that time, the risk 

assessment was reevaluated with respect to the Food Quality Protection Act (FQPA) and 

addressed the susceptibility of infants and children. No dietary risk from food-only was 

identified. However, using drinking water levels of comparison (DWLOCs), dietary risk from 

drinking water were found to exceed the level of concern for chronic (cancer and non-cancer) 

dietary exposures. Several occupational handler scenarios were identified as being of concern. 

HED may consider updating risk assessments during registration review to reflect current dietary 

and occupational exposure policies. In addition, any updated assessment may include potential 

changes resulting from updated toxicology endpoints and uncertainty factors for TPTH.

Introduction

TPTH is a List A reregistration chemical and was the subject of a Registration Standard dated

4/11/84, its associated Guidance Document dated 9/84, and a Reregistration Standard Update

dated 3/18/92. Due to its high toxicity, it was put under Special Review (PD1) in 1985 (50 

FR1107 on 1/9/85). In September 1999, the RED was issued; TPTH remained in Special 

Review status at the time of RED completion and was closed out of Special Review in 2001. As 

part of 1999 RED, an HED human health risk assessment was completed and tolerances were reevaluated in accordance with the FQPA of 1996. A number of data gaps in product and residue

chemistry and toxicology were also identified in 1999 RED and DCI’s were issued. Since then 

toxicological and residue chemistry studies have been submitted. Except for the immunotoxicity

study (Guideline Number: 870.7800) the toxicology data base is complete. The submitted 

residue chemistry studies are under review; the guideline requirements for those studies are still 

considered data gaps. The last risk assessment was conducted as part of the RED in 1999.

TPTH is a fungicide registered for use on pecans, potatoes and sugar beets. In addition, the 

states of MN and ND have eight Section 24C, Special Local Need Registrations for use on sugar 

beets. TPTH is used to control early and late blight on potatoes, leaf spot on sugar beets, scab 

and several other diseases on pecans. In addition to its fungicidical activity, TPTH exhibits 

antifeeding properties for surface-feeding insects. Tolerances are listed in 40 CFR §180.236 for 

the combined residues of the fungicide triphenyltin hydroxide (TPTH) and its monophenyltin 

(MPTH) and diphenyltin (DPTH) hydroxide and oxide metabolites, expressed in terms of parent 

TPTH, in or on pecans (at 0.05 ppm), potatoes (at 0.05 ppm) and sugar beets (tops at 10.0 ppm 

and roots at 0.05 ppm), milk (at 0.06 ppm), fat (at 0.2 ppm), kidney (at 2.0 ppm), liver (at 4.0 
Page 3 of 24

ppm) and meat (at 0.5 ppm) of cattle, goat, horse and sheep, and hog’s fat (at 0.3 ppm), hog’s 

meat (at 0.06 ppm) and hog’s meat byproduct (at 0.3 ppm). 

TPTH is manufactured by members of the TPTH Task Force (AgrEvo, Elf Atochem and Griffin) 

and formulated both as a wettable powder in a water-soluble pack and as a flowable concentrate 

requiring a closed mixing/loading system. These products may be applied as broadcast foliar 

applications using ground or aerial equipment and by chemigation (potatoes only). 

Reregistration of TPTH is being supported only for agricultural uses; it is not supported for 

residential, aquatic or forestry uses. Based on the registered use patterns, there is a potential for 

dietary (via food and water) and occupational exposures to TPTH. The structure, chemical 

names, and other identifiers for TPTH may be found in the chemical identity table attached to 

this document.

Hazard Identification/Toxicology

HED issued a revised RED in 1999, which identified several toxicology data gaps (Levy, 1999). 

In response to Registrant comments, HED placed the developmental Immunotoxicity study in 

reserve. Although there are risks of concern for TPTH related to the immune system in fetal 

and/or neonatal rats, no acceptable guideline or validated protocol existed for a developmental 

immunotoxicity study at the time (Doherty, 2001). Nevertheless, HED recommended that TPTH 

be assessed for potential immunotoxicity using the new immunotoxicity testing guideline

(870.7800) that includes: the antibody plaque-forming cell (PFC) assay or ELISA test and the 

Natural Killer (NK) cell activity assay. 

In response to the Agency’s DCI, the Registrant has submitted a series of studies which includes 

acute and subchronic neurotoxicity studies (MRID 45299901 and 45546001) and a 

Developmental Neurotoxicity (DNT) study (MRID 46055701) accompanied by a milk secretion 

assay in lactating rats (MRID 45890101). These studies have been reviewed and incorporated 

into the updated subchronic, chronic and other toxicity profile table (attached). HED will revisit 

the toxicological points of departure (PODs), uncertainty factors and the FQPA safety factor for 

dietary, and occupational exposure assessments during the registration review process. 

With these evaluated new data, the toxicity database for TPTH is nearly complete. An 

immunotoxicity study is still required in accordance with the 2007 revised toxicology data 

requirement for conventional pesticide registration (40 CFR Part 158).

TPTH is highly toxic, consistently inducing marked to severe toxicity via the oral, dermal or 

inhalation routes (Toxicity Categories II, II and I, respectively). It is also corrosive to the eyes 

and moderately toxic to the skin but not a dermal sensitizer. 

TPTH belongs to a class of chemicals (organotins) known to be immunotoxic. The primary 

treatment-related effects of TPTH via oral exposure are related to immunotoxicity and include: 

decreased leukocytes and immunoglobulins in rats and mice following both subchronic and 

chronic exposures. Decreased spleen weights have also been observed in rats and mice fed diets 

containing TPTH for 28 days. 
Page 4 of 24

In developmental toxicity studies, evidence of possible developmental toxicity was only seen in 

the presence of definitive maternal toxicity in the rat or at levels higher than doses causing 

maternal toxicity in the rabbit. Nevertheless, in a multigenerational reproductive toxicity study, 

offspring toxicity (primarily the F2 offspring), manifested as decreased litter size and decreased 

liver and spleen weights, was observed at a dose ~3 X lower than the dose causing overt toxicity 

(decreased body weight) in the F0, F1 and F2 maternal animals. 

Rat toxicity via the dermal or inhalation routes in subchronic studies consisted of local skin 

irritation at all tested doses (< 5.0 mg/kg/day) for 21 days or death and lung and respiratory 

irritation and edema up to 2 mg/kg/day (0.002 mg/mL). In 1990, TPTH was classified as a group 

B2 – Probable Human Carcinogen, by the HED Carcinogenicity Peer Review Committee, based 

on pituitary and testicular tumors in rats and liver tumors in mice (Sjoblad, 1990). This 

conclusion was reviewed by the Scientific Advisory Panel, and the original classification was 

retained. The Q1* of 1.83 (mg/kg/day)-1remains in place and was used in the carcinogenicity 

risk assessment. There is, however, little support for a mutagenic concern associated with these 

tumors. All toxicity endpoints (cancer and non cancer) will be revisited during registration 

review to ensure they are consistent with current HED policies.

In the acute rat neurotoxicity study, clinical signs, associated with adverse effects on 

neurobehavior were: palpebral closure, piloerection, excessive grooming, and increased activity 

on handling; the peak response occurred within 4-6 hours of dosing. Decreased total and 

ambulatory motor activity was also seen in both sexes following subchronic exposure. In the 

DNT, the maternal animals exhibited neurotoxicity at doses that were not neurotoxic in the pups.

TPTH is related to test substances (particularly trimethyl and triethyl tin) that are known to be 

neurotoxic and are often used as positive controls in neurotoxicity studies. 

In several metabolism studies, the biliary route was identified as the most important in excretion 

of 113SN from TPTH. Most of the label (80-100%) was recovered in the feces; little remained in 

the tissue (≤0.5%). After 24 hours, the kidneys, liver, epididymis and the brain had the most 

label. After 7 days, very little labeled test substance remained in the tissue [highest content was 

in the liver: (0.1356 μg equivalents/gm in males and 0.1612 μg equivalents/gm in females)]. The 

major metabolites of TPTH, which are the same in plants and animals, are diphenyl and 

monophenyl tin. Both of these metabolites are of toxicological concern. In the milk secretion 

study in rats, which accompanied the DNT study, only as much as 0.10 μg/mL of total TPTH or 

its metabolites were found in samples from lactating rats 30 minutes after a single oral dosing or 

6 hours after multiple dosing for 10 days. It is of note that the Agency for Toxic Substances and 

Disease Registry list inorganic or metallic tin as not very toxic due to its poor 

gastrointestinal absorption (ATSDR, 2005).

A dermal absorption factor (DAF) of 10%, which was derived from a comparison of the rabbit 

oral and dermal developmental toxicity test LOAELs, was used for the cancer risk assessment. 
Page 5 of 24

Conclusions: The toxicity database for TPTH is complete except for an immunotoxicity study, 

which is required under the 2007 revised 40CFR Part 158 Toxicology Data Requirements. 

Considerable amounts of new data have been received and reviewed since the 1999 DCI. The 

Point of Departures, endpoints, the uncertainty factors and FQPA Safety Factors for TPTH (see 

Table 7A and 7B) will be reevaluated during registration review based on the review of this 

outstanding data as well as all of the currently available data.

Residue Chemistry and Dietary Exposure

As part of the 1999 RED, a human health risk assessment was completed, tolerances were reevaluated in accordance with the FQPA of 1996, and a number of data deficiencies in residue

chemistry were identified. The guideline requirements for those studies are still data gaps, but

studies have been submitted and are under review. The submitted studies will be evaluated on 

their adequacy to fulfill data requirements for guideline 860.1340, residue analytical method for 

plants (MRID 45531201) and animal commodities (MRID 45350302 & 4531202); guideline

860.1380, storage stability (MRID 45350303 & 45603101); and guideline 860.1360,

multiresidue methods (Morales, J., 2007). HED will complete the review of the submitted studies 

and make decisions during the registration review process. 

The qualitative nature of the residue(s) of TPTH in plants and animals has been adequately 

identified/characterized and is understood. The residues of concern for registered food uses do 

not need revision. HED ROCKS, after studying the BEAD report on new available studies, also 

confirmed that the residue of concern (parent only) in water does not need revision (Scallon, E., 

email, 8/9/2012). The current tolerance expression as listed in the 40 CFR §180.236 has not 

been updated to reflect current HED policies. The tolerance expression will need to be revised 

during the registration review process.

Dietary risk estimates for exposures to TPTH in food and drinking water were calculated in 

1999 and do not reflect current policies and practices. The previous dietary exposure analysis 

was conducted on food only, and the risk from water was evaluated separately using the 

DWLOC method. A dietary exposure assessment aggregating food and water in a quantitative 

analysis, using potentially new toxicological endpoints may need to be conducted.

HED conducted a revised refined acute and chronic (non-cancer and cancer) dietary risk analyses 

for TPTH using the Dietary Exposure Evaluation Model (DEEMTM) in 1999. The refined dietary 

risk assessment utilized anticipated residues (ARs), processing factors and percent crop treated 

(%CT) information for meat and milk (Levy, S., 8/20/99). 

The dietary risk estimates from exposures to food only were below the Agency’s levels of 

concern for the U.S. general population and all population subgroups for acute and chronic 

exposures. At the 99.9th percentile exposure, acute dietary exposure from food only was less 

than 34% of the acute Population Adjusted Dose (aPAD) with the most highly exposed 

population subgroup being females 20+ years old, not pregnant, not nursing. Chronic (noncancer) dietary exposure from food-only was less than 4% of the chronic Population Adjusted 

Dose (cPAD) with the most highly exposed population subgroup being children, 1-6 years old. 
Page 6 of 24

Chronic (cancer) dietary exposure from food-only was 1.1 x 10-6for the general US population. 

Two other scenarios were investigated for chronic (cancer) dietary exposure. In one scenario 

which included only meat and milk, the carcinogenic risk estimate was 9.4 x 10-7for the general 

US population. In the third scenario which excluded sugar beet commodities and meat and milk, 

the carcinogenic risk estimate was reduced to 8.7 x 10-8for the general US population. HED 

previously used drinking water levels of comparison (DWLOCs) to assess the exposure to TPTH 

in drinking water and concluded that the risk from exposure to residues in drinking water was 

above the level of concern for chronic (cancer and non-cancer) dietary exposures. 

Conclusions: A dietary exposure assessment aggregating food and water together in one

quantitative analysis, using newer version of DEEM which utilizes newer consumption data and 

revised population subgroups may need to be conducted. In addition, any updated assessment 

may include potential changes resulting from updated toxicology endpoints.

Residential Exposure

There are no current or pending residential uses associated with TPTH; therefore, a residential 

exposure assessment was not performed nor required during reregistration review. Since there 

are no currently registered residential uses for TPTH, it is not anticipated that a residential 

assessment will need to be conducted during registration review. 

Aggregate Risk Assessment

An aggregate risk assessment may be conducted at the time of registration review to incorporate 

current policies regarding aggregation of exposures from different dietary routes (drinking water 

and food) using the newer version of DEEM which utilizes newer consumption data and revised 

population subgroups. In addition, any updated assessment may include potential changes 

resulting from updated toxicology endpoints.

Occupational Exposure

TPTH, is a restricted use contact fungicide registered for sugar beets, potatoes, and pecans. 

Some of the pests controlled by TPTH include cercospora leaf spot on sugar beets, early and late 

blight, and suppression of the Colorado potato beetle on potatoes, and scab, brown leaf spot, 

downy spot, powdery mildew, liver spot, sooty mold and leaf blotch on pecans. 

TPTH is formulated as a technical product (96 % active ingredient or a.i.), a wettable powder in 

water-soluble bags (80 % a.i.), and a flowable (liquid) concentrate (40 % a.i.). The registered 

products may be applied by ground sprayers and by aerial application. Chemigation is 

prohibited except for application on potatoes. 
Page 7 of 24

Occupational Handlers

In the last risk assessment completed in September 1999 (S. Levy and J. Doherty, D258270), the 

occupational exposure and risk estimates were conducted for short- and intermediate-term 

dermal and inhalation exposure for both private and commercial applicators. Long-term worker 

exposure is not expected. HED determined 10 major exposure scenarios for occupational 

handler exposure. Several occupational handler scenarios exceeded HED level of concern 

(MOEs < 100) at baseline personal protective equipment. These scenarios were then assessed 

with engineering controls that are currently on the labels as well as typical rates. The resulting 

MOEs for two scenarios (mixing and loading liquids and wettable powder for aerial and/or 

chemigation application) still exceeded HED’s level of concern (MOEs < 100) for dermal 

exposure. Mixing and loading liquids for sugar beet aerial application scenario was mitigated to 

a MOE of 170 with applied typical application. However, even with applied typical application 

rates for mixing and loading wettable powder for aerial and/or chemigation application to the 

three crops the risks of concern were not able to be mitigated.

Cancer risk estimates for seven scenarios yielded risks ranging from 8.8 E-5 to 1.4 E-4 for 

commercial applicators. Cancer risk estimates ranged from 3.6 E-6 to 9.1 E-5 for private 

growers. MOEs were mitigated with engineering controls currently on the labels. Cancer 

estimates at baseline for commercial application of spray with ground-boom and air-blast sprayer 

ranged from 1.4 E-04 to 8.3 E-5 while private application MOE ranged from 4.4 E-5 to 4.3 E-6.

No new uses have been registered since the last risk assessment was completed for TPTH;

however, other parameters have changed. Recommended unit exposures for occupational 

handler assessments have generally been derived only from Pesticide Handlers Exposure 

Database (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. New exposure monitoring data will be incorporated, as necessary, during 

registration review.

Post-Application Exposure Results

There are multiple potential sources of dermal exposure to individuals performing postapplication activities in previously-treated TPTH fields. Two studies (MRID 43557401 and 

MRID 4257801) were submitted and previously reviewed during the last risk assessment. MRID 

43557401 is a reentry study of pecan workers while MRID 4257801 is a dislodgeable foliar 

residue study on potatoes and peanuts. The studies resulted in exposure values that were then 

used as surrogate data for several post application exposure scenarios instead of generic transfer 

coefficient values. The post-application assessment indicates that for pecan harvesting, MOEs 

exceed 100 on day zero of application. Cancer risk estimates were greater than 1.0 E-4 until day 

7 to 30 after application depending on field site. MOEs for potato maintenance were greater than 

100 on day zero while sugar beets was greater than 100 on day two of application. Cancer risks 

were less than 1.0 E -04 two days after application for both potatoes and sugar beets. The studies 

may have to be reevaluated due to their age and changes/updates in exposure frequencies and 

durations. In addition, the Agency is in the process of evaluating the SAP report as well as 

available post-application inhalation exposure data generated by the Agricultural Reentry Task 
Page 8 of 24

Force. If new policies or procedures are put into place, the Agency may revisit the need for a 

quantitative occupational post-application inhalation exposure assessment for TPTH.

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. New exposure monitoring data will be incorporated, as necessary, during 

Registration Review.

The restricted entry interval (REI) is based on the acute toxicity of triphenyltin hydroxide

technical material. TPTH has been noted to be a potential eye irritant. TPTH is classified as 

toxicity category II for oral and dermal, and I for inhalation routes. The current reentry interval 

(REI) is 48 hours for all crops; this REI appears to be adequate.

Residential bystander inhalation exposures resulting from off-site transport (e.g., spray drift or 

volatilization) may occur as a result of applications of TPTH. The Agency is in the process of 

evaluating these types of exposures and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. The need for a bystander inhalation risk 

assessment for TPTH should be examined during registration review.

Conclusions: Due to recent occupational exposure science policy updates, existing occupational 

handler and post-application scenarios may have to be reassessed to support registration review. 

These updates include changes to data sources and default assessment inputs for both 

occupational handler and post-application assessments. The assessment may also need to be 

updated to reflect any potential changes to PoDs or new uncertainty factors for TPTH. In 

addition, new typical application rates and daily acreage supplied by BEAD (T. Chandgoyal, 

06/25/12) could also result in changes to the risk estimates. 

Public Health and Pesticide Epidemiology Data

A memo written in 2012 (S. Recore, 07/19/2012, D466848) outlined any incidents reported with 

the chemical TPTH. Based on the low frequency and severity of incident cases reported for 

TPTH, there does not appear to be a concern at this time that would warrant further investigation. 

The Agency will continue to monitor the incident information and if a concern is triggered, 

additional analysis will be included in the risk assessment.

Tolerances and International Harmonization

US permanent tolerances for TPTH are listed in 40 CFR 180.236 and are summarized in the 

attached table. The tolerance expression for TPTH in 40 CFR §180.236 should be changed 
Page 9 of 24

according to HED’s Interim Guidance on Tolerance Expressions (S. Knizner, 5/27/09) as 

follows: 

Tolerances are established for residues of the herbicide triphenyltin hydroxide, 

including its metabolites and degradates, in or on the commodities in the table 

below. Compliance with the tolerance levels specified below is to be 

determined by measuring only the sum of triphenyltin hydroxide (TPTH) and 

its monophenyltin (MPTH) and diphenyltin (DPTH) hydroxide and oxide 

metabolites, calculated as the stoichiometric equivalent of TPTH, in or on the 

commodity.

The Codex Alimentarius Commission and Canada have not established MRLs for residues of 

TPTH.

Environmental Justice

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

document, in accordance with U.S. Executive Order 12898, "Federal Actions to Address 

Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office of 

Pesticide Programs (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 may 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.

Endocrine Disruption Screening Program

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), TPTH is subject to the endocrine

screening part of the Endocrine Disruptor Screening Program (EDSP). 

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 
Page 10 of 24

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. TPTH 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 callins, requiring the submission of EDSP screening assays for TPTH. 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 Risk Assessments 

At this time, EPA does not have available data to determine whether TPTH has a common 

mechanism of toxicity with other substances. EPA has not made a common mechanism of 

toxicity finding as to TPTH and any other substances, and TPTH does not appear to produce a 

toxic metabolite produced by other substances which have tolerances in the U.S. Therefore, 

EPA has not assumed that TPTH has a common mechanism of toxicity with other substances.

Human Studies

Previous assessments relied in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), are subject to ethics review 

pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics 

requirements. Future assessments will rely on the most current and updated data from a variety 

of sources. All data used are subject to ethics review pursuant to 40 CFR 26. Descriptions of 

data sources as well as guidance on their use can be found at 

http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

Data Requirements / Deficiencies

Guideline Number: 870.7800 - Study Title: Immunotoxicity
Page 11 of 24

References

Author Barcode Date Title

Sarah Levy D258010 9/8/1999 TPTH: Revised Acute and Chronic (Non-Cancer and 

Cancer) Dietary Exposure Analyses for the HED 

Revised Risk Assessment.

Sarah Levy D259257 9/21/1999 TPTH (Triphenyltin Hydroxide): HED Revised Risk 

Assessment for the Reregistration Eligibility Decision 

(RED) Document. 

Sarah 

Levey, and 

John 

Doherty

D258270 08/31/1999 TPTH: Response to EPA Transmittal of the 

Preliminary HED Risk Assessment for TPTH, PC Code 

#083601, DP Barcode: D258270. 

Tara 

Chandgoyal 

07/25/2012 BEAD Chemical Profile for Registration Review: 

Triphenyltin Hydroxide (TPTH) also known as Fentin 

Hydroxide (083601)

Kelly 

O’Rourke

D250108 05/06/1999 Occupational and Residential Exposure Assessment 

and Recommendations for the Reregistration Eligibility 

Decision Document for Triphenyltin Hydroxide 

(TPTH)

Doherty, J. 

and 

Rowland, J. 

TXR 

012972

11/13/1998 Triphenyltin hydroxide: Report of the Hazard 

Identification Assessment Review Committee

Doherty, J. TXR 

014509

3/23/2001 Triphenyltin hydroxide: Report of the Hazard 

Identification Assessment Review Committee: 

Reconsideration on the need for a developmental 

immunotoxicity study and sustaining the requirement 

for the developmental neurotoxicity study

Sjoblad, R. TXR No. 

0052679

5/24/1990 Peer Review of Triphenyltin hydroxide (TPTH)
Page 12 of 24

Table 1 - Chemical Identity 

Common Name triphenyltin hydroxide

IUPAC name triphenylstannanylium hydroxide

CAS name Stannane, hydroxytriphenylPC Code 083601

CAS registry number 76-87-9

Registration Review 

Case No. 

0099

Chemical Structure 

Sn OH

TPTH is a fine white powder with a melting point of 118-120 C, bulk density of 0.2758 g/mL at

25 C, octanol/water partition coefficient (log Kow) of 3.268, and vapor pressure of < 1x10-7torr

at 25 C. TPTH is practically insoluble in water (8 ppm), and is moderately soluble in most

organic solvents (acetone 70 g/L; benzene 41 g/L; 1,2-dichloromethane 74 g/L; ether 28 g/L;

ethanol 10 g/L; and methylene chloride 171 g/L).
Page 13 of 24

Table 2 - Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.236

Combined residues of the fungicide triphenyltin 

hydroxide (TPTH) and its monophenyltin 

(MPTH) and diphenyltin (DPTH) hydroxide 

and oxide metabolites, expressed in terms of 

parent TPTH.

None None

Commodity

Tolerance (ppm) /Maximum Residue Limit 

(mg/kg)

US Canada Mexico1 Codex

Beet, sugar, roots 0.05

Beet, sugar, tops 10.0

Cattle, fat 0.2

Cattle, kidney 2.0

Cattle, liver 4.0

Cattle, meat 0.5

Goat, fat 0.2

Goat, kidney 2.0

Goat, liver 4.0

Goat, meat 0.5

Hog, fat 0.3

Hog, meat 0.06

Hog, meat byproducts 0.3

Horse, fat 0.2

Horse, kidney 2.0

Horse, liver 4.0

Horse, meat 0.5

Milk 0.06

Pecan 0.05

Potato 0.05

Sheep, fat 0.2

Sheep, kidney 2.0

Sheep, liver 4.0

Sheep, meat 0.5

Completed: M. Negussie; 08/17/2012

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Page 14 of 24

Table 3 - Summary of Registered Use Patterns and Formulations for Triphenyltin 

Hydroxide TPTH

Reg No % AI Product Type Application 

Equipment Use Sites

246640 96 % Technical

Ground spray 

and aerial and 

(chemigation 

allowed on 

potatoes only)

Pecan trees, Potatoes, and/or Sugar 

Beets

5514671 96 % Technical

5514672 80 % Wettable Soluble 

packet

5514684 40 % Flowable Liquid 

concentrate

62719443 80 %

Water-dispersible 

granules in water 

soluble packets

70506198 96% Technical

70506212 40 % Flowable Liquid 

concentrate

1812279 96 % Technical

70506214 80 % Wettable Soluble 

packet

352699 80 % Wettable Soluble 

packet

Table 4 - Status of Required Toxicological Studies

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity......................................................

870.1200 Acute Dermal Toxicity.................................................

870.1300 Acute Inhalation Toxicity.............................................

870.2400 Primary Eye Irritation...................................................

870.2500 Primary Dermal Irritation .............................................

870.2600 Dermal Sensitization ....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)..............................................

870.3150 Oral Subchronic (nonrodent)........................................

870.3200 21/28-Day Dermal........................................................

870.3250 90-Day Dermal.............................................................

870.3465 90-Day Inhalation.........................................................

yes

yes

yes

no

no1

yes

yes

yes

---

yes

870.3700 Developmental Toxicity (rodent) .................................

870.3700 Developmental Toxicity (nonrodent) ...........................

870.3800 Reproduction ................................................................

yes

yes

yes

yes

yes

yes

870.4100 Chronic Toxicity (rodent).............................................

870.4100 Chronic Toxicity (nonrodent).......................................

870.4200 Oncogenicity (rat).........................................................

870.4200 Oncogenicity (mouse) ..................................................

870.4300 Chronic/Oncogenicity (mouse) ....................................

870.4500 Chronic/Oncogenicity (rat)...........................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes
Page 15 of 24

Table 4 - Status of Required Toxicological Studies

Test Technical

Required Satisfied

870.5100 Mutagenicity—Gene Mutation - bacterial....................

870.5300 Mutagenicity—Gene Mutation - mammalian...............

870.5375 Mutagenicity—Structural Chromosomal Aberrations..

870.5385 Mutagenicity—Structural Chromosomal Aberrations..

870.5395 Mutagenicity—Micronucleus assay .............................

870.5550 Mutagenicity—Other Genotoxic Effects......................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.6100 Acute Delayed Neurotox. (hen)....................................

870.6100 90-Day Neurotoxicity (hen) .........................................

870.6200 Acute Neurotox. Screening Battery (rat)......................

870.6200 Chronic Neurotox. Screening Battery (rat)...................

870.6300 Develop. Neuro ............................................................

no

no

yes

yes

no1

---

---

yes

yes

yes

870.7485 General Metabolism .....................................................

870.7600 Dermal Penetration.......................................................

870.7800 Immunotoxicity

yes

no1

yes

yes

yes

no

1 These studies were not required, yet they were submitted and subsequently were reviewed by HED and found to 

be scientifically acceptable.

Acute Toxicity

Table 5A - Acute Toxicity Profile - Triphenyltin Hydroxide (96%A.I/1981)1

Guideline

No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute Oral-rat 00124210 LD50 = 165 mg/kg (M)

156 mg/kg (F)

II

870.1200 Acute Dermal-rat

00124214

LD50 = 1600 mg/kg II

870.1300 Acute Inhalation-rat

00124212

LC50 =60.3 μg/L I

870.2400 Primary Eye Irritation

00139034

Corrosive I

870.2500 Primary Skin Irritation

00139034

PIS = 2.8 III

870.2600 Dermal Sensitization Several

Studies (e.g., 

00124216)

Negative in the Buehler

assay.

Not considered a 

sensitizer.

1 All studies classified as ACCEPTABLE or otherwise determined to contain useful data.
Page 16 of 24

Table 5B - Acute Toxicity Profile - Triphenyltin Hydroxide (80%A.I 2003) 1

Guideline

No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute Oral-rat

45883303

LD50 = >50 mg/kg (M&F) II

870.1200 Acute Dermal-rat

45883304

LD50 = >200 mg/kg

(M&F)

II

870.1300 Acute Inhalation-rat

45883305

LC50 =0.06 mg/L

(M&F)

I

870.2400 Primary Eye Irritation

45883306

Corrosive I

870.2500 Primary Skin Irritation

45883307

PDII = 3.0

Moderate irritant

III

1 All studies classified as ACCEPTABLE or otherwise determined to contain useful data.

Table 6 - Subchronic, Chronic and Other Toxicity Profile of Triphenyltin Hydroxide. 

Guideline 

No./Study Type

MRID 

No.(year)/Classification/Doses: 

Results

870.3100 

Subchronic (13-

Week) feeding in 

rats 

00157771 (1986)

Acceptable/Guideline

0, 4, 20, 100 ppm; M/F = 0.30/0.35, 

1.56/1.72, 7.41/7.85 mg/kg/day

NOAEL: < 0.33 mg/kg/day [M & F] (NOTE: 

Decreased IgG antibodies at this dose) 

LOAEL = 7.63 mg/kg/day: decreased body 

weight and gain and food consumption (M & F). 

870.3100

Subchronic (13-

Week) feeding in 

mice 

00157952 (1986)

Classified as “Useable”

1

0, 4, 20, 80 ppm; M/F = 0.62/0.88, 

3.44/4.12, 18.28/20.64 mg/kg/day 

No NOAEL or LOAEL was assigned. Observed 

effects:

Immunotoxicity: decreases in IgA and IgM 

antibodies at 4 ppm (M & F). 

Systemic: Decreased adrenal weight at 4 ppm 

(F) and decreased ovary weight and increased 

liver weight (M & F) at 80 ppm. 

870.3100

Subchronic (13-

Week) feeding -

Guinea pig 

00086467( 1960)

Unacceptable

0, 2.5, 5, 20, 50 ppm

~0, 0.1, 0.2, 0.4, 2 mg/kg/day

NOAEL < 2.5 ppm (estimated to be 0.1 

mg/kg/day) (lowest dose tested): decreased 

leukocyte counts. 

870.31150

Subchronic 

feeding 

-dog

No valid study. Refer to chronic feeding study below.

870.3465

Subchronic (90-

day) inhalationrats

41017701 (1989)

Acceptable/Guideline

0, 0.014, 0.34, 2.0 mg/m3 (M & F)

0, 0. 86, 0.454, 1.950 mg/m3 (F)

NOAEL = 0.00034 mg/L

LOAEL = 0.002 mg/L: deaths and lung and 

respiratory irritation and edema.

870.3200 00142880 (1985) Systemic:
Page 17 of 24

Table 6 - Subchronic, Chronic and Other Toxicity Profile of Triphenyltin Hydroxide. 

Guideline 

No./Study Type

MRID 

No.(year)/Classification/Doses: 

Results

21-day dermal -

rats 

Acceptable/Guideline

0, 5, 10, 20 mg/kg/day

NOAEL > 20 mg/kg/day. No systemic effects 

at highest dose tested. 

Local:

NOAEL < 5 mg/kg/day. Local irritation 

(considered reversible).

870.3700a

Developmental 

toxicity - rat; one 

of several studies

00142878 (1985) 2

0, 0.35, 1.00, 2.80, 8.00 mg/kg/day

Maternal toxicity:

NOAEL = 1 mg/kg/day; LOAEL = 2.8 

mg/kg/day: decreased body weight and food 

consumption. 

Developmental toxicity:

NOAEL = 2.8 mg/kg/day; LOAEL = 8 

mg/kg/day: decreased fetal weight and increased 

sternebrae unossified (Typical response seen at 

this dose level in other studies). At 8 mg/kg/day, 

poor pup survival or smaller litter size and less 

viable fetuses also seen in other studies. 

870.3700b

Developmental 

toxicity -

rabbit/oral

40104801 (1987)

Acceptable/Guideline

0, 0.1, 0.3, 0.9 mg/kg/day

Maternal toxicity:

NOAEL = 0.1 mg/kg/day; LOAEL = 0.3 

mg/kg/day: decreased body weight gain.

Developmental toxicity:

NOAEL = 0.3 mg/kg/day; LOAEL = 0.9 

mg/kg/day: lower fetal body weight and 

increased incidents of unossified hyoid body 

and/or arches. 

870.3700b

Developmental 

toxicity -

rabbit/dermal 

42909101 (1993)

Acceptable/Guideline

0, 1.5, 2.25, 3.0 mg/kg/day

Maternal and developmental toxicity:

NOAEL and LOAEL > 3 mg/kg/day. No 

effects at highest dose tested. 

870.3800

Reproductive 

toxicity - rat 

00162655 (1986)

Acceptable/Guideline

0, 0.5, 18.5, 50 ppm

~0, 0.25, 0.925, 2.5 mg/kg/day

Parental toxicity:

NOAEL = 0.925 mg/kg/day; LOAEL = 2.5 

mg/kg/day: decreased body weight.

Developmental toxicity:

NOAEL = 0.25 mg/kg/day; LOAEL = 0.925 

mg/kg/day: decreased litter size, liver and 

spleen weights. 

870.4100a

Chronic toxicity –

rat

00080390 (1970)

Acceptable/Nonguideline

0, 0.5, 1, 2, 5, 10 ppm

~0, 0.025, 0.05, 0.1, 0.25, 0.5 

mg/kg/day (M & F)

NOAEL = 0.1 mg/kg/day; LOAEL = 0.25 

mg/kg/day: decreased leukocyte counts (M & 

F)

870.4100b

Chronic toxicity –

dog

40285501 (1987)

0, 2, 6, 18 ppm

Classified as Reserved

0, 0.062, 0.206, 0.562 mg/kg/day (M)

0, 0.071, 0.213, 0.624 mg/kg/day (F)

NOAEL and LOAEL > 0.562 mg/kg/day (M)

0.624 mg/kg/day (F). No effects at the highest 

dose tested. 

870.4200b 41087501 (1989) NOAEL < 0.85 mg/kg/day (lowest dose tested) 
Page 18 of 24

Table 6 - Subchronic, Chronic and Other Toxicity Profile of Triphenyltin Hydroxide. 

Guideline 

No./Study Type

MRID 

No.(year)/Classification/Doses: 

Results

Carcinogenicity –

mouse

Acceptable/Guideline

0, 5, 20, 80 ppm

0.85, 3.50, 15.24 mg/kg/day (M)

0, 1.36, 4.56, 20.16 mg/kg/day (F)

based on decreased in immunoglobulins. 

Particularly IgA and IgM in either males or 

females. 

Positive for hepatocellular adenomas and 

carcinomas. Dose levels considered adequate. 

870.4300

Combined chronic 

toxicity/carcinogenicity - rat

41085702 (1989)

Acceptable/Guideline

0, 5, 20, 80 ppm

0, 0.3, 1.3, 6.2 mg/kg/day (M)

0, 0.4, 1.6, 6.2 mg/kg/day (F)

NOAEL not established.

LOAEL <5 ppm (lowest dose tested; 0.3 

mg/kg/day, M; 0.4 mg/kg/day, F): deaths in 

females and decreases in immunoglobulins 

(IgG, IgG2a, IgG2c, IgA).

Positive for pituitary and testicular tumors. 

Dose levels considered adequate

870.5100 

Bacterial reverse 

gene mutation test

00125264 (1981)

Acceptable/Guideline

0.3125 – 5 μg/plate +/-S9

Salmonella typhimurium strains 

TA11535, TA1537, TA1538, TA98, 

TA100

312.5 – 5000 μg/plate +/-S9

Escherichia coli strain WP2 uvrA

Not mutagenic in S. typhimurium or E. coli ± 

metabolic activation. 

Gene mutation in 

yeast

00152224 (1985)

Acceptable/Nonguideline

0, 0.05, 0.1, 0.5, 1.0 μg/mL –S9 

0, 1, 10, 50, 100 μg/mL +S9

Schizosaccharomyces pombe

Not mutagenic ± metabolic activation up to 

cytotoxic concentrations (0.1 μg/mL –S9; 100 

μg/mL +S9)

870.5300

In vitro

mammalian cell 

gene mutation 

test

00152226 (1985)

Acceptable/Guideline

L5178Y Mouse lymphoma cells

0, 10, 15, 23, 30, 45, 60, 80, 100, 125, 

150 ng/mL –S9

0, 40, 70, 100, 150, 200, 250, 300, 400, 

500, 600 ng/mL +S9

Borderline positive in the presence of S-9 mix 

but negative in absence of S-9. 

870.5375

In vitro

mammalian 

chromosome 

aberration test 

00152223 (1985)

Acceptable/Guideline

Human lymphocytes

0, 0.03125, 0.0625, 0.125, 0.25, 0.5, 1 

μg/mL –S9

0, 0.25, 0.5, 1, 2 μg/mL +S9

Positive for inducing chromosome aberrations ± 

S-9. Study demonstrates clastogenic property of 

TPTH. 

870.5385

Mammalian bone 

marrow 

chromosomal 

aberration test

in vivo

40371102 (1987)

Acceptable/Guideline

Chinese hamsters

0, 20, 50, 80 mg/kg (single gavage 

dose)

Negative up to a dose that caused overt toxicity 

to the test animals and cytotoxicity to the bone 

marrow (80 mg/kg). 

870.5395 00152225 (1985) Negative up to a dose (140 mg/kg) causing overt 
Page 19 of 24

Table 6 - Subchronic, Chronic and Other Toxicity Profile of Triphenyltin Hydroxide. 

Guideline 

No./Study Type

MRID 

No.(year)/Classification/Doses: 

Results

Micronucleus 

assay

in vivo NMRI 

mouse bone 

marrow

Acceptable/Guideline

0, 35, 70, 140 mg/kg (oral gavage)

High dose = 77% of LD50

toxicity. 

870.5450

Dominant lethal 

assay SpragueDawley rats

00125265 (1978)

Acceptable

0, 3, 20, 38, 150 mg/kg; consecutive 5 

daily gavage doses and 10 successive 

matings for 10 weeks

Negative at up to 38 mg/kg/day. At 150 

mg/kg/day, high rate of deaths. 

870.5575

Mitotic gene 

conversion assay 

00155521 (1985)

Acceptable/nonguideline

Saccharomyces cerevisiae D4

0, 0.1, 1, 3, 5 μg/mL –S9

0, 1, 5, 10, 15 μg/mL +S9

Negative in S. cerevisiae ± S-9 metabolic 

activation.

870.5550

Unscheduled DNA 

synthesis in 

mammalian cells 

00155522 (1985)

Acceptable/Guideline

Primary rat hepatocytes

0, 0.1, 0.025, 0.05, 0.1, 0.25, 0.5, 1.0, 

2.0 μg/mL

Negative up to cytotoxic concentrations

(≥ 1.0 μg/mL) 

870.6200a

Acute 

neurotoxicity rat

45350301 (2001)

0, 10, 50, 75, 125 mg/kg, oral gavage

Range finder study 

NOAL & LOAEL not determined. Most 

common clinical signs (all doses): palpebral 

closure, piloerection, rocking, lurching, swaying 

when walking, decreased urination and 

defecation (M& F). Findings occurred in a 

dose-related manner; peak effect observed at 4-6 

hours for all treatment groups. 

870.6200a

Acute 

neurotoxicity 

screening battery 

rat

45299901 (2000)

Acceptable/Guideline

0, 5, 25, 75 mg/kg (M&F), oral gavage

NOAEL = Not established. LOAEL = 5 mg/kg:

Clinical signs of toxicity (excessive grooming, 

increased activity on handling, and piloerection 

in both sexes).

870.6200b

Subchronic (13 

weeks) 

neurotoxicity 

screening battery 

rat

45546001 (2001)

Acceptable/Guideline

0, 5, 20, 80 ppm dietary

0, 0.4, 1.4, 5.7 mg/kg/day (M)

0, 0.4,1.6, 6.1 mg/kg/day (F)

NOAEL = 20 ppm (1.4/1.6 mg/kg/day in M/F)

LOAEL = 80 ppm (5.7/6.1 mg/kg/day in M/F): 

decreased body weight, body weight gains, and 

food consumption (M&F). Decreased total and 

ambulatory motor activity in both sexes 

870.6300

Developmental 

neurotoxicity study

rat

46055701 (2003) 

Acceptable/Non-guideline

0, 1, 2.5, 5 mg/kg/day, oral gavage

Maternal

NOAEL = 1 mg/kg/day

LOAEL = 2.5 mg/kg/day: clinical conditions 

(i.e., pallor, piloerection, red discharge from the 

vagina, and low body temperature) requiring 

sacrifice in one animal; these conditions were 

similar to those seen in dams at the next higher 

dose. 

Neurotoxicity, manifested as different grades of: 
Page 20 of 24

Table 6 - Subchronic, Chronic and Other Toxicity Profile of Triphenyltin Hydroxide. 

Guideline 

No./Study Type

MRID 

No.(year)/Classification/Doses: 

Results

ease of handling during functional observational 

battery (FOB), consisting of: reactivity, reduced 

rearing and activity levels at 5 mg/kg/day.

Offspring

NOAEL = 2.5 mg/kg/day

LOAEL = 5 mg/kg/day: decreased body 

weight and body weight gain

No adverse neurological effects on motor 

activity, auditory startle response, learning and 

memory, brain weights, brain morphology or 

neuropathology at any dose. 

Special Study

Milk secretion 

study rat

45890101 (2003)

Acceptable/Non-guideline

0, 4 mg/kg single oral gavage

Milk sampled at 0.5, 1, 3, 6, 24 hours 

post-dosing

0, 4 mg/kg/day for 10 days oral gavage

Milk sampled at 6 or 24 hours postdosing on Days 5 or 10 and on Day15.

Systemic effects: No effects of treatment

observed on clinical signs, mortality or body 

weight.

Transfer to milk: No detectable residues found 

in samples from lactating rats. 

Mean concentration 

Study Day 5

6 hrs - Mean conc. parent TPTH = 0.05 μg/mL

Total TPTH (plus metabolite) = 0.06 μg/mL

24 hrs - parent TPTH below the limit of 

detection (LOD = <0.02 μg/mL) 

Study Day 10

6 hrs - Mean conc. parent TPTH = 0.09 μg/mL

Total TPTH (plus metabolite) = 0.10 μg/mL

24 hrs - parent TPTH below the limit of 

detection; total TPTH = 0.03 μg/mL. 

Study Day 15

No TPTH or its metabolite found in milk.

Data indicate that TPTH is transferred to the 

milk of lactating dams at the maximum low 

level of 0.09 μg/mL after receiving multiple 

daily oral doses of 4 mg/kg/day for 10 days. 

870.7485

General 

metabolism

(several studies 

1986 to 1989)

Six studies 1986 to 1989:

41387201

41309101

41309102

40029405

40029406

40029407

Acceptable 

The contributions from six studies combine to 

meet the general metabolism requirement for 

TPTH. The 14C studies are confounded by the 

fact that the labeled phenyl group splits off and 

the fate of the parent compound is not followed. 

Thus, the labeled phenyl may be excreted in the 

urine but this does not represent excretion of 

intact TPTH. The 113Sn labeled TPTH studies 

follow the fate of the tin although this may be as 

triphenyl, diphenyl or monophenyl or as tin 

itself. The biliary route is the most important in 

excretion of 113Sn from TPTH. Most of the 
Page 21 of 24

Table 6 - Subchronic, Chronic and Other Toxicity Profile of Triphenyltin Hydroxide. 

Guideline 

No./Study Type

MRID 

No.(year)/Classification/Doses: 

Results

label (80-100% in several studies) is recovered 

in the feces. Little remains in tissues (for 

example, ≤ 0.5%). After 24 hours, the kidneys, 

liver epididymis and brain had the most label. 

After 7 days, little remained in the tissues 

[highest content was in the liver: (0.1356 μg 

equivalents/gm in M and 0.1612 μg 

equivalents/gm in F)]. The major metabolites of 

TPTH, which are the same in plants and 

animals, are diphenyl and monophenyl tin. 

Both of these metabolites are of toxicological 

concern.

870.7600

Dermal penetration 

rat

Several studies 1986 and 1987

00156684

40073001

40198301

Acceptable

Studies demonstrate that TPTH adheres to the 

skin and only a small percentage (<1%) is 

absorbed in 10 hours. The TPTH remaining on 

the skin can potentially be absorbed over time. 

Because of complications involved with 

adherence to the skin, a dermal absorption factor 

of 10% was derived by comparing the oral and 

dermal developmental toxicity studies.

870.7800

Special 

Immunotoxicity

Studies (28 days)

Dietary

Several studies 1982 to 1990

41518200 (1990)

Acceptable

Rats

0, 0.07, 0.34 1.71, 3.37, 8.16

mg/kg/day (M)

0, 0.07, 0.37, 1.82, 3.4, 8.32, 

mg/kg/day (F)

Mice

0, 0.19, 1.00, 4.64, 8.80, 20.21 

mg/kg/day (M)

0, 0.23, 1.15, 5.46,10.04, 21.48 

mg/kg/day (F)

-----------------------------------------------

40200301 (1986)

Unclassified

0, 2.5 mg/kg/day 10 consecutive days

(Female Wistar rats); oral gavage

In rats (41518200):

NOAEL = 1.82 mg/kg/day; LOAEL = 3.4 

mg/kg/day: decreases in IgG. At higher doses: 

decreased spleen weight, white blood cells 

(WBCs) and circulating lymphocytes. 

In mice 

NOAEL = 0.23 mg/kg/day, LOAEL = 1.15 

mg/kg/day: decreased spleen weight absolute 

and relative. At higher doses: decreased IgM, 

WBC, neutrophils and circulating lymphocytes. 

----------------------------------------------------------

Systemic: 

No adverse effects

Immunosuppression: 

No evidence of increased susceptibility to 

Triticella spiralia.

1 Classified on a trial basis by HIARC (see HIARC, 1998).

2

Selected by HIARC as the most representative rat developmental studies with TPTH. Initial concerns for 

hydronephrosis and hydroureter, which were observed in this study, were removed by the data from subsequent 

studies that did not demonstrate this effect (HIARC, 1998).
Page 22 of 24

Table 7A - Triphenyltin Hydroxide: Summary of Toxicological Doses and Endpoints for Use in 

Dietary and Non-Occupational Human Health Risk Assessments.

Exposure

Scenario Point of 

Departure

Uncertainty/ 

FQPA Safety 

Factors 

RfD, PAD, Level 

of Concern for 

Risk 

Assessments 

Study and Toxicological Effects

Acute Dietary –

Females 13+

NOAEL = 

0.3 mg/kg/day

UFA = 10

UFH = 10

FQPA SF = 3X

Acute RfD = 

0.003 mg/kg/day

aPAD = 0.001

mg/kg/day

Developmental Toxicity Study in 

Rabbits (MRID 40104801)

LOAEL = 0.9 mg/kg/day based on 

lower fetal body weight and 

increased incidents of unossified 

hyoid body and/or arches in rabbit 

fetuses

Points of Departure not previously selected for this exposure scenario

Chronic Dietary

(All populations) NOAEL =

0.1 mg/kg/day

UFA = 10

UFH = 10

UFD = 3 a

FQPA SF = 10X 

Chronic RfD = 

0.0003

mg/kg/day 

cPAD = 

0.00003 

mg/kg/day

Chronic feeding –Rats

(MRID 00080390)

LOAEL = 0.25 mg/kg/day based on 

decreased leukocyte counts 

Incidental Oral 

Short-Term 

(1-30 days)

Points of Departure not previously selected for this exposure scenario

Incidental Oral 

Intermediate-Term 

(1- 6 months)

Points of Departure not previously selected for this exposure scenario

Dermal ShortTerm (1 to 30 

days) and 

Intermediate-Term

(1 to 6 months)

NOAEL = 3 

mg/kg/day

UFA = 10

UFH = 10

FQPA SF = 10X 

Residential LOC 

for MOE = 1000

Dermal Developmental toxicity –

Rabbits (MRID 42909101)

Maternal and developmental: 

LOAEL = >3 mg/kg/day. No effects 

at highest dose tested. 

Dermal LongTerm (> 6 months)Use pattern does not indicate that exposure will be for this interval.

Inhalation ShortTerm (1 to 30 

days) and 

Intermediate-Term

(1 to 6 months)

NOAEL = 

0.00034 mg/L

UFA = 10

UFH = 10

FQPA SF = 10X 

Residential LOC 

for MOE = 1000

Subchronic Inhalation toxicity - Rat 

(MRID 41011701) 

LOAEL = 0.02 mg/L based on death 

and respiratory irritation and edema. 

Inhalation Long 

Term (> 6 months) 

Use pattern does not indicate that exposure will be for this interval.

Cancer (oral, 

dermal, inhalation)

Oral Q1* = 1.83 

(mg/kg/day)-1 TPTH is classified as a B2 Carcinogen, Probable Human Carcinogen based on pituitary 

and testicular tumors in rats and liver tumors in mice. A dermal absorption factor of 

10% should be used for this risk assessmentb. An inhalation absorption factor of 100% 

should be used for this risk assessment.
Page 23 of 24

Table 7A - Triphenyltin Hydroxide: Summary of Toxicological Doses and Endpoints for Use in 

Dietary and Non-Occupational Human Health Risk Assessments.

Exposure

Scenario Point of 

Departure

Uncertainty/ 

FQPA Safety 

Factors 

RfD, PAD, Level 

of Concern for 

Risk 

Assessments 

Study and Toxicological Effects

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). MOE = margin of exposure. LOC = level of concern. N/A = not applicable. UF = uncertainty factor. FQPA SF 

= Special FQPA safety factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of 

exposure. 

a UFD = Database Uncertainty Factor; HIARC recommended that in addition to the inter-species extrapolation and the intraspecies variation an extra 3X be applied because of the instability of the test material in the diet in the 1970 study (MRID 

00080390) and because of the potential for increased mortality in the 1989 study (MRID 41085702) near the LOAEL (Doherty 

and Rowland, 1998). 

b Based on a comparison of the LOAELs from the oral developmental toxicity test in rabbits and the dermal developmental 

toxicity test in rabbits.
Page 24 of 24

Table 7B - Triphenyltin Hydroxide: Summary of Toxicological Doses and Endpoints for Use in 

Occupational Human Health Risk Assessments.

Exposure

Scenario Point of 

Departure

Uncertainty/ 

FQPA Safety 

Factors 

RfD, PAD, Level 

of Concern for 

Risk 

Assessments 

Study and Toxicological Effects

Dermal ShortTerm (1 to 30 

days) and 

Intermediate-Term

(1 to 6 months)

NOAEL = 3 

mg/kg/day

UFA = 10

UFH = 10

FQPA SF = 10X 

Occupational 

LOC for MOE = 

100 

Dermal Developmental toxicity –

Rabbits (MRID 42909101)

Maternal and developmental: 

LOAEL = >3 mg/kg/day. No effects 

at highest dose tested. 

Dermal LongTerm (> 6 months)Use pattern does not indicate that exposure will be for this interval.

Inhalation ShortTerm (1 to 30 

days) and 

Intermediate-Term

(1 to 6 months)

NOAEL = 

0.00034 mg/L

UFA = 10

UFH = 10

FQPA SF = 10X 

Occupational 

LOC for MOE = 

100

Subchronic Inhalation toxicity - Rat 

(MRID 41011701) 

LOAEL = 0.02 mg/L based on death 

and respiratory irritation and edema. 

Inhalation Long 

Term (> 6 months) 

Use pattern does not indicate that exposure will be for this interval.

Cancer (oral, 

dermal, inhalation)

Oral Q1* = 1.83 

(mg/kg/day)-1 TPTH is classified as a B2 Carcinogen, Probable Human Carcinogen based on 

pituitary and testicular tumors in rats and liver tumors in mice. A dermal 

absorption factor of 10% should be used for this risk assessmenta. An 

inhalation absorption factor of 100% should be used for this risk assessment.

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). MOE = margin of exposure. LOC = level of concern. N/A = not applicable. UF = uncertainty factor. FQPA SF 

= Special FQPA safety factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of 

exposure. 

a Based on a comparison of the LOAELs from the oral developmental toxicity test in rabbits and the dermal developmental 

toxicity test in rabbits.