Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. 0418384 

UNITED STATES ENVIRONMENTAL PROTECTlON AGENCY 

WASI llNGTO . D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

DATE: December l , 2015 

SUBJECT: Boric Acid/Sodium Salts of Boric Acid. Human Health Draft Risk Assessment for 

Registration Review. 

PC Codes: 0 11 001, 0 11102, 011103, 011104, 01 1107, DP Ba rcode: 0418384 

01 1110, 011111 , 011112, 011002 

Decision No.: 488334 Registration No.: Multiple Registrations 

Regulatory Action: Registration Review 

Case No.: 0024 

Petition No.: NIA 

Risk Assessment Type: Single Chemical Aggregate 

TXR No.: NIA CAS Nos.: 10043-35-3, 1303-96-4, 11 30-12-4, 12 179-

04-3, 1330-43-4, 12008-4 1-2, 15293-77-3, 1303-86-2 

MRID No.: NIA 40 CFR: 180.1 121, 180.920, 180.940 

FROM: 

L

Matt

D

inn

enn

ea 

h

i

ew 

s 

J

M

. 

Crow

cNe

Hansen

ill

ley, 

y, 

, 

C

B

Bio

h

io

e

lo

mi

log

g

st 

ist 

ist/Ris

~ 

:p..----

k Asse~sorA 

\Ml\..._ \---) M~ 

...___ 

~ O 

(_.,.. 

~ y 

/'/~ 

THROUGH: 

Risk Assessment Branch 11 - V 

Health Effects Division (7509P) 

Timothy C. Dole, CIH, Industrial Hygienist ~~ \ · 

Risk Assessment and Science Support Branch (RASSB) 

Antimicrobials Division (75 1 OP) 

Office of Pesticide Programs 

Christina Swartz, Branch Chief lf.w~ Risk Assessment Branch II 

Christopher Schlosser, Toxicologist/Designated Reviewer 

Kelly 

Risk Assessment 

Lowe, Environme

Review 

nt

Committee 

al Scientist/

(RARC) 

Designated ev ewe 7~~ 

- ....... - / 

~ 

Health Effects Division (7509P) 

Steve Weiss, Branch Chi ef ?ft. u/~ Risk Assessment and Science Support Branch 

Antimicrobials Division (751 OP) 

Office of Pesticide Programs 
Boric Acid/Salts of Boric Acid Draft Risk Assessment 

TO: Moana Appleyard, Chemical Review Manager 

Risk Management and Implementation Branch V 

Pesticide Re-evaluation Division 

Sandra O'Neill, Chemical Review Manager 

Regulatory Management Branch I I 

Antimicrobials Division (751 OP) 

Office of Pesticide Programs 

DP No. 0418384 

As part of Registration Review, the Pesticide Re-evaluation Division (PRO) and the 

Antimicrobials Di vision (AD) of the Office of Pesticide Programs (OPP) has requested 

evaluation of the hazard and exposure data and conduct occupational and residential exposure 

assessments, as needed, to estimate the risk to human health that will result from the currently 

registered uses of pesticides. This memorandum serves as the draft risk assessment (ORA) of the 

dietary, occupational and residential exposure, and aggregate risk from the currently registered 

conventional and antimicrobial uses of boric acid and its sodium salts (sodium tetraborate 

decahydrate, sodium tetraborate pentahydrate, sodium tetraborate anhydrous, disodium 

octaborate tetrahydrate, disodium octaborate anhydrous and sodium metaborate). 

Since the last risk assessment, completed for the Tolerance Reregistration Eligibility Decision 

(TR.ED) process (L. Hansen, 26 July 2006, 0320894), the Health Effects Division (HED) and 

AD have conducted a re-evaluation of the toxicological database including submission of 

additional toxicity studies and a re-assessment of non-dietary risks, including updated residential 

and occupational risk assessments and a risk assessment for exposures via spray drift. The risk 

assessment was provided by Matthew Crowley (RABII), the residue chemistry review was 

provided by Dennis McNeilly (RABIV), the occupational/residential exposure assessment was 

provided by Matthew Crowley (RABII) and Timothy Dole (RASSB/AO), and the hazard 

characterization was provided by Linnea Hansen (RABil). 

Page 2of99 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 3 of 99

Table of Contents

1.0 Executive Summary............................................................................................................... 5

2.0 HED and AD Recommendations........................................................................................... 7

2.1 Data Deficiencies/Conditions of Registration................................................................ 8

2.2 Tolerance Considerations............................................................................................... 8

2.2.1 Enforcement Analytical Method............................................................................... 8

2.2.2 International Harmonization ..................................................................................... 8

2.2.3 Tolerance Recommendations.................................................................................... 8

2.3 Label Recommendations................................................................................................ 9

3.0 Introduction.......................................................................................................................... 10

3.1 Chemical Identity ......................................................................................................... 11

3.2 Physical/Chemical Characteristics............................................................................... 12

3.3 Pesticide Use Pattern .................................................................................................... 12

3.4 Anticipated Exposure Pathways................................................................................... 14

3.5 Consideration of Environmental Justice....................................................................... 14

4.0 Hazard Characterization and Dose-Response Assessment.................................................. 14

4.1 Toxicology Studies Available for Analysis.................................................................. 15

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)................................. 16

4.2.1 Dermal Absorption.................................................................................................. 17

4.3 Toxicological Effects ................................................................................................... 18

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)..................................... 20

4.4.1 Completeness of the Toxicology Database................................................................ 20

4.4.2 Evidence of Neurotoxicity ......................................................................................... 21

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ............ 21

4.4.4 Residual Uncertainty in the Exposure Database........................................................ 21

4.5 Toxicity Endpoint and Point of Departure Selections.................................................. 21

4.5.1 Dose-Response Assessment.................................................................................... 21

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment........ 24

4.5.3 Cancer Classification and Risk Assessment Recommendation.............................. 24

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment............................................................................................................................ 24

4.6 Endocrine Disruptor Screening Program............................................................................. 26

5.0 Dietary Exposure and Risk Assessment .............................................................................. 27

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ...................................... 29

6.1 Residential Handler Exposure ...................................................................................... 30

6.2 Residential Post-application Exposure......................................................................... 34

7.0 Non-Occupational Bystander Post-Application Inhalation Exposure and Risk Estimates.. 37

8.0 Non-Occupational Spray Drift Exposure and Risk Estimates............................................. 37

9.0 Aggregate Exposure/Risk Characterization......................................................................... 38

10.0 Cumulative Exposure/Risk Characterization..................................................................... 39

11.0 Occupational Exposure/Risk Characterization .................................................................. 39

11.1 Occupational Handler Exposure/Risk Estimates.......................................................... 39
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 4 of 99

11.2 Occupational Post-application Exposure/Risk Estimates............................................. 49

11.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates...................... 49

11.2.2 Occupational Post-application Dermal Exposure/Risk Estimates.......................... 49

12.0 Public Health and Pesticide Epidemiology Data ............................................................... 50

13.0 References.......................................................................................................................... 50

13.1 OPP Memoranda .......................................................................................................... 50

13.2 MRID Submissions ...................................................................................................... 51

13.3 Published Literature and Other Documents ................................................................. 56

Appendix A: Toxicity Profile and Executive Summaries............................................................ 59

A.1 Toxicology Data Requirements.................................................................................... 59

A.2 Toxicity Profiles........................................................................................................... 60

A.3 Hazard Identification and Endpoint Selection.............................................................. 66

A.3.1 Acute Reference Dose (aRfD) – All Populations Including Females Age 13-49 and 

Children66

A.3.2 Chronic Reference Dose (cRfD) – All Populations Including Females Age 13-49 and 

Children................................................................................................................................. 66

A.3.3 Incidental Oral Exposure (Short-Term, 1-30 days and Intermediate-Term, 1-6 month)

............................................................................................................................................... 67

A.3.4 Dermal Absorption.................................................................................................. 67

A.3.5 Residential and Occupational Dermal Exposure (Short- and Intermediate-Term; 1-

30 days and 1-6 months)....................................................................................................... 67

A.3.6 Residential and Occupational Inhalation Exposure ................................................ 67

A.4 Executive Summaries................................................................................................... 69

A.4.1 Subchronic Toxicity................................................................................................ 69

A.4.2 Prenatal Developmental Toxicity ........................................................................... 73

A.4.3 Reproductive Toxicity ............................................................................................ 77

A.4.4 Chronic Toxicity ..................................................................................................... 80

A.4.5 Carcinogenicity....................................................................................................... 85

A.4.6 Mutagenicity ........................................................................................................... 86

A.4.7 Neurotoxicity .......................................................................................................... 87

A.4.8 Metabolism ............................................................................................................. 88

A.4.9 Immunotoxicity....................................................................................................... 90

Appendix B: Chemical Identity and Physical/Chemical Properties ............................................ 93

Appendix C: Use Pattern Summary............................................................................................. 95
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 5 of 99

1.0 Executive Summary

Use Profile

Boric acid and its sodium salts are inorganic compounds with registrations for use as active 

ingredients in insecticides, acaricides, herbicides, algaecides, fungicides and wood and material 

preservatives. Products are both liquid and solid formulations ranging from < 1% to 100% active

ingredient and used in agricultural, residential and commercial settings. Boric acid and its 

sodium salts are also present as inert ingredients in pesticide products as well as ingredients in 

non-pesticide consumer products.

Hazard/Toxicology Assessment

The toxicity database for boric acid/sodium salts has been updated since previous assessments 

and is considered complete for the purposes of human health risk assessment. The toxicology 

studies submitted to EPA in support of registration of boric acid/borate salts were conducted on 

boric acid or sodium tetraborate decahydrate (borax). For purposes of toxicological evaluation, 

studies on boric acid and borate salt compounds may be compared, and dosing considered 

equivalent, when they are normalized for exposure to boron (boron equivalents).

Boric acid/borate salts generally show low acute lethality by all routes (Toxicity Categories III or 

IV). Acute dermal and eye irritation potential vary among the different compounds. For 

example, sodium tetraborate decahydrate is Category I for eye irritation and IV for skin irritation, 

while boric acid is Category III for both.

Animal toxicity tests indicate that the testis is a target organ, causing atrophy and decreased 

spermiation, leading to decreased fertility. Other effects were hematological changes and 

decreased body weight. At high doses, clinical signs of toxicity were observed. Absorption is 

very low across intact skin. Increased pre-natal susceptibility was observed in the rat, mouse and 

rabbit: developmental toxicity, including skeletal and visceral variations and malformations and 

decreased fetal body weights, were observed in the presence of less severe, or absence of, 

maternal toxicity. For all exposure scenarios, uncertainty factors (UFs) are 10x for interspecies 

(UFA) variation, 10x for intraspecies (UFH) variation, and 1x for the Food Quality Protection Act 

(FQPA) safety factor. The FQPA factor of 1x is based on an adequate toxicology database, wellcharacterized and clear no observed adverse effect levels (NOAELs) and lowest observed 

adverse effect levels (LOAELs), dose selection being protective of potential developmental 

toxicity, and use of conservative inputs and models for exposure assessment. Thus a total UF of 

100x applies, with estimation of risk in the form of Margins of Exposure (MOEs) based on a 

level of concern (LOC) of 100. 

Boric acid/borate salts are classified as “not likely to be carcinogenic to humans” under the 

Agency’s revised 2005 Cancer Guidelines. Genotoxicity studies did not indicate mutagenic or 

clastogenic potential. Epidemiological data do not indicate any boron exposure-related cancers 

in humans.

Dietary (Food and Water) Exposure and Risk
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 6 of 99

Based on data demonstrating that residues of boron in/on treated commodities are 

indistinguishable from those in/on control samples, and on the expectation that the low 

application rates associated with agricultural uses are not expected to add significantly to 

background levels in drinking water, a quantitative dietary risk assessment was not conducted.

Boric acid/sodium salts are exempt from the requirement of tolerances.

Residential Exposure and Risk

Residential exposure is possible via consumer pesticide use of products containing boric 

acid/sodium salts applied as both liquid sprays/solutions and as solids (dusts, powders, or 

granules) in indoor and outdoor residential settings. Dermal and inhalation exposures are 

possible during application, and dermal, inhalation, and incidental oral exposures (e.g., 

children’s hand-to-mouth exposures) are possible after applications. Post-application incidental 

oral risk estimates for children were found to be of concern for broadcast spray treatments to 

carpets (MOEs < 100), primarily due to the relatively high application rates. All other handler 

and post-application risk estimates were not of concern.

In the 2006 Tolerance Reregistration Eligibility Decision (TRED), boric acid/sodium salt 

exposures via non-pesticide consumer use products (i.e., laundry detergent and general purpose 

cleaners) as well as its presence as an inert ingredient in pesticide products, were also considered 

in the residential exposure pathway for purposes of characterizing the aggregate assessments. 

Those assessments, which did not identify any risks of concern, are included for registration 

review.

Non-Occupational Spray Drift Exposure and Risk 

As no risks of concern were identified from the direct spray lawn use, and the direct spray use on 

home lawns would result in higher dermal and incidental oral exposures than would occur from 

spray drift onto residential areas resulting from agricultural uses, there are no risks of concern for 

exposures resulting from spray drift.

Volatilization/Residential Bystander

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency has developed a Volatilization Screening 

Tool and a subsequent Volatilization Screening Analysis, and during Registration Review, the 

Agency will use this analysis to determine if data (i.e., flux studies) or further analyses are 

required for boric acid/sodium salts.

Aggregate Exposure and Risk

Because the contribution of background dietary intake of boron is implicitly accounted for in the 

background dietary intake by the laboratory animals in the toxicology studies, aggregate risk is 

represented by the non-dietary risk assessment. Non-dietary incidental oral risk estimates for 

children following broadcast spray treatments to carpets were found to be of concern (MOEs < 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 7 of 99

100), primarily due to the relatively high application rates. All other non-dietary (i.e., residential 

handler and post-application) risk estimates for both pesticide and non-pesticide uses were not of 

concern.

Occupational Exposure and Risk

Occupational exposure is possible via professional use of products containing boric acid/sodium 

salts applied as both liquid sprays/solutions and as solids (dusts, powders, or granules) in 

agricultural, commercial and residential settings. Dermal and inhalation exposures are possible 

during and after applications. Inhalation exposures for some occupational handler scenarios 

were the only occupational exposures to have risk estimates of concern (MOEs < 100), requiring 

respirators to mitigate risks. Some labels currently require respirators (and some only under 

certain conditions like in confined spaces), though most do not. For dust applications to 

structural building components (e.g., attics, crawl spaces, soffits, etc.) and agricultural buildings

(e.g., poultry houses) standard respirators (i.e., filtering face-pieces) do not mitigate inhalation 

risk estimates of concern. All other handler and post-application risks were not of concern.

Environmental Justice Considerations

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

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.”

Review of Human Research

This risk assessment relies 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); the Agricultural Handler 

Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force 

(ORETF) database; the Residential SOPs (Lawns/Turf, Indoor Environments); and other 

registrant-submitted handler exposure monitoring studies (MRIDs 44339801, 45250702, 

45333401, 44439901, 45519601, 45167201, 43600102) and a human dermal absorption study 

(MRID 48507005) are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that 

review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics 

review may have included review by the Human Studies Review Board (HSRB). Descriptions 

of data sources, as well as guidance on their use, can be found at the following Agency websites: 

http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/occupational-pesticidehandler-exposure-data, http://www2.epa.gov/pesticide-science-and-assessing-pesticiderisks/occupational-pesticide-post-application-exposure, and http://www2.epa.gov/pesticidescience-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide.

2.0 HED and AD Recommendations

HED and AD have examined all applicable databases for boric acid/sodium salts, and concludes 

that there are no residue chemistry, occupational/residential, or toxicology data deficiencies that 

would preclude the continuation of all registered uses and tolerance exemptions. 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 8 of 99

In terms of human health risk concerns, there are no dietary risks of concern resulting from 

pesticide uses of boric acid and its sodium salts. However, in the context of aggregate exposure 

and continuation of the tolerance exemptions, HED recommends consideration of the risk 

estimates of concern identified for post-application incidental oral exposures resulting from 

broadcast spray treatments to carpets. Additionally, HED and AD recommend reconciling 

default requirements for personal protective equipment (PPE) and restricted entry intervals 

(REIs) during any product label updates/revisions, based on consideration of risks of concern 

identified for some occupational inhalation handler exposures. Finally, modifications to the 

tolerance exemption expressions to more accurately match the chemical names in this regulatory 

case is recommended.

2.1 Data Deficiencies/Conditions of Registration

There are no data deficiencies for boric acid/sodium salts.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Boric acid/sodium salts are exempt from the requirement of tolerances without application rate 

limitations, therefore an enforcement analytical method is not applicable.

2.2.2 International Harmonization

While boric acid/sodium salts are exempt from the requirement of a tolerance in the U.S. and 

there is no Codex maximum residue level (MRL), various countries have boric acid/sodium salts 

tolerances/MRLs by way of default values specified for those respective countries. For example, 

Canada has a default MRL of 0.1 ppm while the European Union (EU) has a default MRL of 

0.01 ppm. Default MRLs are not considered for the purposes of international harmonization.

2.2.3 Tolerance Recommendations

In 1971, exemptions from the requirement of a tolerance were granted for boric acid and sodium 

metaborate “as inert (or occasionally active) ingredients in pesticide formulations applied to 

growing crops only” (40 CFR 180.1001(d); 36 FR 24216). Sodium tetraborate was later added 

to 40 CFR 1001(d) in 1975 (40 FR 48681). In 2004 this citation was changed to 40 CFR 

180.920. 

A petition for an exemption from the requirement of a tolerance as an active ingredient on all 

raw agricultural commodities was submitted in June 1992. In February 1993 HED’s Metabolism 

Committee considered and approved this petition and HED included this decision in its section

for the 1993 Reregistration Eligibility Decision (RED). The tolerance exemption was formalized 

on August 20, 1993 in the Federal Register (58 FR 44282) and discussed in the 1993 RED. 

Additionally, in 2004 EPA issued a final rule that incorporated existing tolerances exemptions 

(21 CFR 178.1010) by the Food and Drug Administration (FDA) thereby establishing under 40 

CFR 180.940 an exemption from the requirement for a tolerance for residues of “boric acid, 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 9 of 99

sodium salt” as an active and inert ingredient in antimicrobial formulations (food-contact surface 

sanitizing solutions). In its chapter for the 2008 TRED HED recommended that all of these 

tolerance exemptions be maintained.

HED continues to recommend the tolerance exemptions in 40 CFR 180.1121, 40 CFR 180.920, 

and 40 CFR 180.940. However, the CFR should, rather than using synonyms or other names, be 

modified to more accurately match the standard chemical names, PC codes, and CAS #’s in this 

regulatory case. The exemptions and comments/recommendations are summarized in Table 

2.2.3.a below.

Table 2.2.3.a. Tolerance Summary for Boric acid and its Sodium Salts

Citation Established Exemption Comments/Recommendations

40 CFR §180.1121

An exemption from the requirement of a tolerance is 

established for residues of the pesticidal chemical boric 

acid and its salts, borax (sodium borate decahydrate), 

disodium octaborate tetrahydrate, boric oxide (boric 

anhydride), sodium borate and sodium metaborate, in 

or on raw agricultural commodities when used as an 

active ingredient in insecticides, herbicides, or 

fungicides preharvest or postharvest in accordance with 

good agricultural practices.

It is unclear which active ingredient is meant 

by “sodium borate”. It is often used as 

another name for borax (sodium borate 

decahydrate). If that is the case, “sodium 

borate” should be deleted from the tolerance 

exemption so it is not listed twice.

40 CFR §180.920

“The following materials are exempted from the 

requirement of a tolerance when used in accordance 

with good agricultural practice as inert (or occasionally 

active) ingredients in pesticide formulations applied to 

growing crops only:

Boric acid (sequestrant)

Sodium metaborate (sequestrant)

Sodium tetraborate (buffering agent; corrosion 

inhibitor)”

The exemption should be more specific in its 

use of “sodium tetraborate”. It is unclear 

whether it includes “sodium tetraborate 

pentahydrate”, “sodium tetraborate 

decahydrate” and “sodium tetraborate

anhydrous”, or just a single one of those 

chemicals. 

40 CFR §180.940(c)

“Residues of the following chemical substances are 

exempted from the requirement of a tolerance when 

used in accordance with good manufacturing practice 

as ingredients in an antimicrobial pesticide formulation, 

provided that the substance is applied on a semipermanent or permanent food-contact surface (other 

than being applied on food packaging) with adequate 

draining before contact with food, (c) The following 

chemical substances when used as ingredients in an 

antimicrobial pesticide formulation may be applied to: 

Food-processing equipment and utensils:

Boric acid, sodium salt”

It is unclear what active ingredient(s) is/are 

intended via use of “Boric acid, sodium salt” 

in the exemption.

However, the CAS# listed in 180.940(c) 

corresponds to sodium metaborate only. 

Thus, if it was intended to only represent 

sodium metaborate, “boric acid, sodium salt” 

should be replaced with “sodium 

metaborate”.

2.3 Label Recommendations

Boric acid/sodium salts product labels vary considerably with respect to requirements for work 

attire and PPE. For example, some labels do not specify any requirements for work attire and/or 

PPE, while others require respirators and coveralls over long-sleeve shirt and long pants. 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 10 of 99

Similarly, restricted entry intervals (REIs) also vary considerably across labels (e.g., 4 hours 

versus 48 hours).

Thus, label corrections/revisions during registration review should be consistently made to 

default to end-use product and/or technical grade active ingredient acute (ocular, dermal, oral, 

and inhalation) toxicity requirements. These requirements may vary since each borate sodium 

salt might have a different acute toxicity profile, in addition to the potential presence of other 

active ingredients in a product. In particular, 4 hour REIs should be evaluated in the context of 

Pesticide Registration (PR) Notice 95-3. The 4 hour REI would not be appropriate for this active 

ingredient class as sodium tetraborate decahydrate is classified as an acute toxicity category I eye 

irritant – a category that typically triggers a 48 hour REI.

Additional PPE label requirements beyond end-use product acute toxicity requirements, such as 

respiratory protection, should be considered as described in the context of any handler risks of 

concern identified in this assessment.

3.0 Introduction

Boron is ubiquitous in the environment as a result of natural (e.g., weathering of rocks, 

geothermal activity, etc.) and anthropogenic (e.g., industrial emissions and wastes) sources (US 

EPA, 2008). It is normally found combined with oxygen as borates, including boric acid and its 

sodium salts, which in water and under normal physiological aqueous conditions exist as 

undissociated boric acid. It is an essential nutrient for plants, and there is some evidence 

suggesting that it may be a required micronutrient in mammals based on studies suggesting it is 

involved in the regulation of metabolism of minerals such as calcium; however, this has not been 

definitively established (Naghii and Samman, 1993).

As pesticidal active ingredients, boric acid and its sodium salts are registered as insecticides, 

acaricides, herbicides, algaecides, fungicides and wood and material preservatives. Products are 

both liquid and solid formulations ranging from < 1% to 100% active ingredient and used in 

agricultural, residential and commercial settings. Products used in residential settings (e.g., dusts 

in homes, crack and crevice sprays, recreational parks, swimming pools), commercial/industrial 

areas (e.g., food handling establishments, airport runways, sewers, transport vehicles) and 

agricultural facilities (e.g., poultry houses, greenhouses) are applied via hand dispersal, handheld 

equipment, or by vehicles. Products used on agricultural food/feed crops are applied via 

handheld sprays or by vehicles; chemigation and aerial applications are prohibited. 

Antimicrobial material preservative products are added during the manufacturing of paints, 

inks/dyes, and coatings, and wood preservation is conducted via brush, trowel, injection, 

pressure treatment, dip diffusion treatment, or mechanized spraying. Boric acid and its sodium 

salts are also present as inert ingredients in pesticide products as well as ingredients in nonpesticide consumer products.

The timeline below provides a brief description of its U.S. pesticide regulatory history.

1948 Boric acid first registered as a pesticide.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 11 of 99

1960 Tolerances established for boric acid and its sodium salts (40 CFR 180.271) on 

cottonseed (30 ppm) and citrus fruits (8 ppm, postharvest). [Year is 

approximate.]

1971 Exemptions from the requirement of a tolerance are granted for boric acid and 

sodium metaborate “as inert (or occasionally active) ingredients in pesticide 

formulations applied to growing crops only.” (40 CFR 180.1001(d); 36 FR 

24216). Sodium tetraborate was later added in 1975 (40 FR 48681).

1986 Boric acid and its sodium salts are assessed for an EPA General Registration 

Standard, requiring producers to submit labels and provide Confidential 

Statements of Formula (CSF).

1993 EPA removed the previously established tolerances (40 CFR 180.271) and 

established an exemption from the requirement for a tolerance for residues of 

boric acid and its sodium salts when used as active ingredients in products applied 

to all raw agricultural commodities (40 CFR 180.1121). Additionally, in the RED 

Document, EPA concluded that all uses were eligible for reregistration provided 

they comply with prevailing labeling requirements.

2004 EPA incorporated existing tolerances exemptions (21 CFR 178.1010) by the Food 

and Drug Administration (FDA) thereby establishing under 40 CFR 180.940 an 

exemption from the requirement for a tolerance for residues of boric acid, sodium 

salt as an active and inert ingredient in antimicrobial formulations (food-contact

surface sanitizing solutions) and changed 40 CFR 180.1001(d) to 40 CFR 

180.920.

2006 Following passage of FQPA in 1996 requiring EPA to reassess all pesticide 

tolerances in the context of aggregate exposure, the boric acid/sodium salts TRED 

was issued. The tolerance exemptions were maintained as EPA determined there 

was reasonable certainty of no harm from aggregate exposure.

2009 EPA issued scoping document in support of Registration Review, outlining 

toxicity and residue chemistry data requirements. Boric acid/sodium salts 

registration review initiated with release of the Registration Review Initial and 

Final Work Plans.

3.1 Chemical Identity

This registration review assessment for boric acid/sodium salts includes the seven (7) compounds

listed below. Boric oxide (PC code 011002) is also included in this regulatory case but does not 

have any active pesticide registrations.

1. Boric acid (PC code 011001)

2. Sodium tetraborate decahydrate (PC code 011102)

3. Sodium tetraborate pentahydrate (PC codes 011110 and 011111)

4. Sodium tetraborate anhydrous (PC code 011112)

5. Disodium octaborate tetrahydrate (PC code 011107)

6. Disodium octaborate anhydrous (PC code 011103)

7. Sodium metaborate (PC code 011104)

Additional nomenclatures and chemical identity information are in Appendix B.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 12 of 99

3.2 Physical/Chemical Characteristics

The physical state of boric acid/sodium salts is generally as a white crystalline powder with low 

vapor pressures (generally < 10-6 mmHg) and low log octanol-water partition coefficients (log 

Kow ≈ -1). Under normal physiological aqueous conditions, boric acid and its sodium salts exist 

as undissociated boric acid. There are no known impurities of concern in any of these boron 

compounds. With the exception of sodium metaborate, which will absorb carbon dioxide to 

form sodium carbonate and borax, these compounds are stable under storage at room 

temperature. A more complete description of the physical and chemical properties of boric 

acid/sodium borate salts is provided in Appendix B.

For purposes of toxicological evaluation and comparison with expected human exposures, 

studies on boric acid and borate salt compounds may be compared, and dosing considered 

equivalent, when they are normalized for exposure to boron (boron equivalents). Molecular 

weight-based percentages of boron for several boron compounds, used to convert to boron 

equivalents, are shown below:

Boron Equivalents as Percentage Boron

Chemical Percent boron

Boric acid 17.5%

Sodium tetraborate decahydrate 11.34%

Sodium tetraborate pentahydrate 14.85%

Sodium tetraborate anhydrous 21.49%

Disodium octaborate tetrahydrate 20.96%

Disodium octaborate anhydrous 25.38%

Sodium metaborate 16.5%

e.g., Boric acid (H3BO3) has a molecular weight of 61.83 g/mol. Boron has an atomic weight of 10.8 g/mol. 

Therefore, as it contains one boron atom, boric acid is 17.5% boron.

3.3 Pesticide Use Pattern

There are many pesticide products containing boric acid or one of its sodium salts as the active 

ingredient. These products include insecticides, acaricides, herbicides, algaecides, fungicides 

and wood and materials preservatives. A summary of the use profile is provided below.

 Registered formulations include dusts, granules/pellets/baits, wettable or water-soluble 

powders/dusts, liquid concentrates, and gels/pastes.

 Use sites include:
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 13 of 99

o Agricultural food/feed crops

 Alfalfa, cane berries, bush berries, coffee, cacao, pome fruit, stone fruit, 

citrus, herbs, tree nuts, peanuts, strawberry, tobacco, leafy vegetables, bulb 

vegetables, corn, cucurbit, fruiting vegetables, legumes, root and tuber 

vegetables, soybean, cotton, herbs, avocado, kava, banana, guava, papaya, 

pineapple, watermelon and grasses

o Residential areas (homes, schools, nursing homes, hospitals, etc.):

 Indoor (pet quarters, floors/carpets, attics; cracks/crevices, around 

appliances, bedding/mattresses);

 Outdoor (lawns, parks, golf courses, building perimeters, patios, 

driveways, trash areas, wood piles, gardens);

o Pre-construction wood material/lumber;

o Wooden structures (utility poles, railroad ties, etc.);

o Structural Building/House Components (wall/cabinet voids, soffits, attic space, 

crawl spaces)

o Swimming pools;

o Food handling/storage/processing sites;

o Agricultural buildings/facilities (e.g., poultry houses);

o Industrial areas;

o Sewers/sewage systems;

o Tree stumps;

o Vehicles (ships, buses, etc.);

o Ant mounds;

o Materials (paints, inks, dyes and gypboard coatings).

 Depending on the use pattern, the percentage of active ingredient ranges from less than 

1% (e.g., liquid concentrate for use on crops) to 100% (e.g., indoor insecticide dusts).

 Application types can be broadcast as well as spot or crack-and-crevice type treatments.

 Applications are made via hand dispersal, handheld equipment (e.g., rotary spreaders, 

handwand sprayers), or vehicles (e.g., tractor-drawn spreaders, airblast sprayers). 

Chemigation and aerial applications are prohibited. The remedial wood treatment 

methods include brush, trowel, spray, injection or wrap applications of liquid or paste 

formulations. The manufacturing facility wood treatment methods include pressure 

treatment and mechanized spraying and dipping.

 Application rates vary depending on the use site/target and formulation. For example, in 

terms of boron equivalents, spray application to crops has a relatively low rate of 0.0018 

lb boron/acre, while applications of dusts to poultry houses has a relatively high rate of 

448 lb boron/acre.

 The minimum retreatment interval for crop uses is 7 days; non-crop uses are applied on 

an as-needed basis.

 Work attire and/or personal protective equipment (PPE) is not specified on many labels 

while on others, such as the crop use product (EPA Reg. No. 72662-3) the label requires 

protective eyewear/goggles, long-sleeve shirt, pants, waterproof gloves, shoes and socks. 

Some labels require use of respiratory protection.

 For many products, such as those not subject to the EPA’s Worker Protection Standard, a 

restricted entry interval (REI) does not apply. Where applicable, the REI varies from 4 

hours on some labels to 48 hours on others.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 14 of 99

Appendix C provides a more detailed listing of representative registered products on which the 

exposure and risk assessment is based. Application rates are presented in terms of boron 

equivalents for purposes of comparison with toxicological studies – conversions from boric acid 

or a sodium salt are performed using the molecular weight composition of boron in the active 

ingredient.

3.4 Anticipated Exposure Pathways

Based on the registered conventional and antimicrobial uses, occupational exposures are 

expected for workers who mix, load, and apply the products, workers who might contact residues 

in previously treated areas and adults and children via non-dietary exposure pathways resulting 

from residential uses and via spray drift resulting from agricultural uses. For both residential and 

occupational scenarios, short- and intermediate-term duration exposures during and after 

application are possible; long-term exposures are not anticipated. Additionally, boric 

acid/sodium salts are also registered for use in/on numerous food/feed crops that may result in 

dietary exposure through food or drinking water.

3.5 Consideration of Environmental Justice

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

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.archives.gov/federal-register/executive-orders/pdf/12898.pdf). As a part of every 

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to 

well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture under the National Health and Nutrition Examination Survey, “What We Eat in 

America,” (NHANES/WWEIA). These food consumption patterns are used in pesticide risk 

assessments for all registered food uses of a pesticide. These data are analyzed and categorized 

by subgroups based on age, season of the year, ethnic group, and region of the country. 

Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups, and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for children, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development, as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

The toxicology studies submitted in support of registration of boric acid/borate salts were 

conducted on boric acid or sodium tetraborate decahydrate (borax). Under normal physiological, 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 15 of 99

aqueous conditions, boric acid and the borate salts exist as undissociated boric acid. The doses 

for studies considered in this review have been converted to boron equivalents using the 

molecular weight-based percentages shown in Section 3.2 to permit comparison of the studies. 

Boron dietary intakes of the laboratory animals from untreated chow and drinking water are 

considered to be an approximation of human dietary intake (i.e., assumed to mimic human 

background dietary exposure), thus no adjustment of the doses to account for background boron 

exposure is needed.

4.1 Toxicology Studies Available for Analysis

The toxicology database for boric acid/sodium borate salts is considered sufficient for hazard 

characterization. Although many of the submitted studies are older and not conducted according 

to current guidelines or Good Laboratory Practice (GLP) standards, when taken as a whole the 

database is considered adequate for assessing risk to humans, and no additional studies are 

required. These studies have been used to characterize boron hazard by several other reviewing 

groups and agencies, including US EPA Integrated Risk Information System (IRIS), the 

European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), the European 

Commission Directorate-General for Health and Consumers (Scientific Committee on Consumer 

Safety), Canadian Pesticide Management Regulatory Agency (PMRA), World Health 

Organization (WHO) and the Agency for Toxic Substances and Disease Registry (ATSDR). 

Numerous published studies on boron compounds have also been considered in this assessment. 

These studies provided information regarding human background dietary exposure, general 

metabolism in the rat, dermal absorption, inhalation toxicity, dose-response and mechanism of 

testicular toxicity, and case reports of human poisonings. 

The studies available for consideration that were submitted to the Agency are:

 rat, mouse and dog subchronic oral toxicity

 dog chronic, rat chronic/oncogenicity, mouse oncogenicity

 rat, mouse and rabbit developmental toxicity

 rat and mouse multi-generation reproductive toxicity

 genotoxicity battery

 rat acute neurotoxicity

 mouse immunotoxicity

 in vivo and in vitro human dermal absorption (reviewed and accepted by the Agency for 

ethical study conduct, memorandum from K. Sherman to C. Swartz dated 1/27/14). 

The HED Hazard and Science Policy Council (HASPOC) concluded the following toxicology 

studies are not required for boric acid/borate salts (TXR No. 0056768, memo dated 2/5/2014 and 

TXR No. 0057245, dated 12/2015):

1. Subchronic Inhalation Study [Guideline # 870.3465], based on lack of adverse effects in 

the dog and rat in a published report, and data supporting physical constraints (visible 

dust in the test chamber at higher test concentrations) that would limit the generation of 

significantly higher test atmosphere concentrations for a repeated-exposure study 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 16 of 99

(Wilding et al., 1959, MRID 48507002; acute inhalation studies MRIDs 43500104, 

43500601, 43500701, 43500801).

2. Subchronic Neurotoxicity Study [Guideline # 870.6200b] based on lack of neurotoxicity 

in the acute neurotoxicity screening study and data indicating that neurotoxicity is not 

likely to be the most sensitive effect.

3. Subchronic (21/28 or 90-day) Dermal Toxicity Study [Guideline # 870.3200 or 

870.3250], based on low absorption (<1%) observed in dermal absorption studies. No 

toxicity would be expected at the limit dose in this study, based on the very low dermal 

absorption and results of oral toxicity studies.

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

A guideline general metabolism study on boric acid or sodium borate salts was not submitted, 

but published studies provide information on ADME in rats (Ku et al., 1991; Vanderpool et al., 

1994; Chapin et al., 1997). Boric acid/borate salts are rapidly and well absorbed following oral 

ingestion. This is supported by the time to maximum plasma concentration (Tmax), which was 

within 3 hours of dosing, absorption of most of the dose by 24 hours, and recovery of >90% of 

the dose in the urine by 72 hours (most was recovered by 24 hours). Only a small percentage is 

excreted in feces. Based on the available pharmacokinetic information, plasma half-life in the rat 

has been estimated at 14-16 hours. The rate of elimination is largely dependent on renal 

clearance. 

Once absorbed, borate salts at physiological pH in aqueous solution are present as boric acid and 

there is no further metabolism. Boric acid is rapidly and evenly distributed by passive diffusion 

to tissues throughout the body. Boric acid does not accumulate in soft tissues (including the 

testes), although it may form (reversible) complexes with biomolecules. Boron levels in bone 

are somewhat higher than in soft tissues, and may clear more slowly, possibly due to binding to 

calcium hydroxyapatite. In male rats given boric acid in the diet, boron levels in bone were 2-3-

fold higher than plasma levels at 1 week, by which time plasma and soft tissue levels had 

reached steady-state. When treatment was stopped, levels of boron in bone declined at a slower 

rate than in other tissues. Although excretion of boric acid is rapid and essentially complete 

within days following dosing, bone boron was reduced by 90% from peak post-dosing levels 

only after an 8-week recovery. 

The ADME of boric acid in humans is considered to be similar to that in the rat (summarized in 

IRIS, 2004). In a review of almost 800 case reports of patients who were admitted for boric acid 

poisoning, the elimination half-life was calculated to be between 4-28 hours (Litovitz et al., 

1988). As with the rat, excretion is considered to depend largely on the rate of renal clearance.

The inhalation study by Wilding (1959) indicated that boron oxide was absorbed following 

inhalation exposure, since it was detected in the urine of rats at several measurement times 

during a 22-week exposure period. At 0.077 mg/L boron oxide, an average of 11.9 mg/kg 

bw/day boron was reportedly excreted, compared to 0.24 mg/kg bw/day in control rats. 

However, the data do not exclude the possibility that some of the measured boron was due to oral 

ingestion of airborne boron oxide particles. Boron levels measured one week after treatment 

ended were comparable to those in controls (earlier time points were not available). In this 

study, no accumulation of boron was seen in tissue samples, including bone, at about 60 hours 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 17 of 99

after exposure. Absorption of boron by production workers following inhalation exposure to 

borate dust showed increased urinary excretion of boron post-shift relative to pre-shift, but as 

with the rat study, it is unclear how much may have been ingested as particles (Culver, 1994).

4.2.1 Dermal Absorption

Guideline dermal toxicity or dermal absorption studies in rodents were not submitted for boric 

acid/borate salts, but acceptable/non-guideline human in vivo and in vitro studies were submitted. 

A dermal toxicity study would be of limited value for assessing dermal toxicity in light of the 

increased quantitative and qualitative susceptibility observed in developmental toxicity studies;

HED HASPOC determined that it was not needed (TXR No. 0057245). A dermal developmental 

toxicity study was not required to assess effects from dermal absorption because as discussed 

below, the available data on dermal absorption of boric acid and borate salts indicate that these 

compounds show negligible absorption across intact skin.

Human in vivo and in vitro dermal absorption studies evaluated boric acid, borax and disodium 

octaborate tetrahydrate (DOT) following a 24-hr exposure. In the in vivo study (MRID 

48507005; reviewed and found to be conducted in an ethically acceptable manner; K. Sherman, 

memorandum dated January 27, 2014), adult male and female volunteers were exposed to 10Benriched 5% boric acid, 5% borax or 10% DOT. The total absorbed dose excreted in the urine 

(expressed as a percentage of the applied dose) was very low for all three compounds, at 

0.226%±0.125 (boric acid), 0.210%±0.194 (borax) and 0.122%±0.108 (DOT). Urinary excretion 

was essentially the same when the same treatments were repeated on skin pretreated with 2% 

aqueous sodium dodecyl sulfate, a mild irritant. 

The low dermal absorption in humans in vivo is consistent with the findings of an in vitro dermal 

absorption study (MRID 48549901) conducted by the same laboratory, although percent dose 

absorbed was higher (0.19% to 1.75% of the applied dose). As with the in vivo study, 

information on absorbable dose remaining in treated skin (following removal of the stratum 

corneum) was not available. However, the findings of the in vivo absorption study are 

considered to be more reliable than the in vitro studies, particularly since there was no indication 

of assessment of skin integrity in the latter.

A published dermal absorption study in the rabbit showed that powdered boric acid, or boric acid 

in talc or aqueous solution, was not absorbed across intact skin (Draize and Kelly, 1959). Boron 

levels in urine of the treated animals were comparable to those in controls. Similarly, no dermal 

absorption was seen in rats treated with boric acid as an ointment or aqueous jelly, but up to 1% 

of the dose was found in urine in rats exposed to the oleaginous ointment preparation (Nielsen, 

1970). Epidemiological studies of workers with high occupational exposure to borate 

compounds (e.g., borax mining) provide only limited information (reviewed in U.S. EPA IRIS, 

2004), but the lack of clearly evident exposure-related effects other than respiratory symptoms 

from inhalation of dust is consistent with the finding of low dermal absorption seen in 

experimental studies.

Based on consideration of the available information on dermal absorption in animals and 

humans, absorption through intact skin is expected to be very limited (less than 1%). This is also 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 18 of 99

consistent with the low Kow for these compounds (0.175). It is noted that other reviewing 

Agencies or organizations, including US EPA IRIS, the European Commission (EC) DirectorateGeneral for Consumer Safety, ATSDR and WHO (IPCS INCHEM), have concluded that boron 

compounds are not absorbed, or very poorly absorbed, through the intact skin. The EC 

considered dermal absorption of 0.5% to be a conservative value based on the available data. 

Thus, for the purposes of risk assessment, dermal absorption is negligible, with estimates of even 

less than 1% considered conservative.

4.3 Toxicological Effects

The testes are the main target organ among all species tested. Seminiferous tubule degeneration, 

reduction in sperm count, atrophy and reduced testicular weights were observed following 

subchronic or chronic oral exposure in the mouse, rat and dog. In the dog, testicular effects were 

observed at comparable dose levels in subchronic and chronic studies. Rats may have shown a 

slight progression of effects with longer exposure duration based on comparative (NOAELs and 

LOAELs in subchronic, chronic and reproduction studies, but this is difficult to determine due to 

the spacing of doses. Testicular atrophy resulted in infertility, as demonstrated in the rat and 

mouse multigeneration reproductive toxicity studies. Ovaries were also a target organ. In the rat 

reproduction studies, reduction in the number of corpora lutea and diminished fertility in mating 

of treated females with untreated males were observed, but the effect on fertility of females 

appears to be considerably less severe than in males at the same dose levels. However, effects 

on the female reproductive tract were not examined in all studies. A few epidemiological studies 

have examined the effects of industrial exposure to boron compounds on human fertility 

(summarized in US EPA IRIS, 2004), but due to limitations in study conduct, the data are 

inconclusive. However, no overt association of exposure with reproductive toxicity was 

identified in the available epidemiological studies.

The mode of action (MOA) for testicular and ovarian toxicity is not known, but several 

published reports have examined aspects of toxicity to the testes in rats (Chapin and Ku, 1994; 

Ku et al., 1991 and 1993; Ku and Chapin, 1994; Fail et al., 1998). As noted above, boron does 

not accumulate in the testes, although tissue concentrations increase with dose. Boron has been 

shown to cause a slight reduction in plasma testosterone in rats, but not enough to inhibit 

spermiation. Co-cultures of Sertoli cells/germ cells in these studies indicate in vitro effects on 

DNA synthesis of mitotic and meiotic germ cells as well as Sertoli cell energy metabolism. Rat 

studies testing increasing dietary concentrations of boron showed that inhibition of spermiation 

may precede, and occur at a lower dose than, atrophy. Inhibition of sperm release was observed 

as early as 5 days after dietary administration at high levels of boric acid, followed by 

disorganized epithelium and release of immature germ cells by Day 21, and atrophic tubules by 

Day 28. Inhibition of spermiation was observed at lower dose groups (mild inhibition and severe 

inhibition, at 26 and 38 mg/kg bw/day boron, respectively), as well as at higher dose levels (52 

and 68 mg/kg bw/day boron) at which atrophy was observed, with a 17 mg/kg bw/day dose

identified as a NOAEL for inhibition of spermiation. Males at the higher dosing levels were 

examined at 8-weeks post-dosing and did not show recovery from atrophy. However, in the rat 

reproductive toxicity studies submitted to the Agency, the same dose was not associated with 

decreased fertility.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 19 of 99

The red blood cell also was affected by boric acid, based on mild depression of hematocrit (Hct) 

and hemoglobin (Hgb) levels in subchronic and chronic studies in the rat and the dog. 

Hemosiderin accumulation in spleen, liver and kidney was reported in the dog following 

subchronic exposure. Clinical signs of toxicity, which included hunched posture, rapid 

respiration, thinness, swollen paws, inflamed eyes, and coarse fur/desquamation, were reported 

in males and females within the first few weeks of treatment in rat oral studies at doses causing 

testicular atrophy. Other effects that have been reported include slightly decreased body weight 

in the rat, dog and mouse, and in mice, splenic depletion (probably secondary to stress). 

Immunotoxicity (decreased sheep red blood cell, or SRBC, anti-antibody-forming plaque cells, 

or anti-AFC, response) was observed in a 28-day mouse immunotoxicity study.

Dermal toxicity data were not submitted, but the available information on dermal absorption, 

previously described, indicates that absorption across intact skin is very low. Toxicity from 

dermal exposure is therefore not expected to occur. 

Data on toxicity from inhalation exposure are very limited. A published report on inhalation 

exposure to boron oxide in the rat and dog for 10-24 weeks did not identify adverse effects 

(Wilding, 1959) up to concentrations resulting in significant chamber dust. Mild respiratory 

irritation (nasal exudate, reddened nares) was observed in the rat at the highest test concentration,

but there were no reported histopathological effects on the lungs or trachea, nor on other tissues, 

including the testes. Dogs were tested at lower exposures and did not show effects on body 

weight, hematological or clinical chemistry parameters, but histopathological evaluations were 

not performed. Epidemiological data on industrial exposure of humans to boron compounds 

(summarized in IRIS, 2004) indicate that workers exposed to high levels of borax dust showed 

some evidence of respiratory, sensory and eye irritation. One study found no indication of 

effects on pulmonary function at exposures up to 14.6 mg/m3for at least 5 years; a second found 

evidence suggestive of respiratory illness from long-term exposure. 

There was no evidence of neurotoxicity in a rat acute neurobehavioral screening study up to the 

limit dose, but there is evidence of potential clinical neurotoxicity in the rat and in humans. 

Dietary studies submitted to the Agency (subchronic, chronic and reproductive toxicity) in the rat 

reported clinical signs of neurotoxicity at high dose levels that were consistent with neurological 

effects (hunched posture, abnormal gait, rapid respiration), but which could also be secondary to 

general malaise or other systemic effects. These findings were seen in the rat at or above doses 

that also caused severe testicular toxicity. Malformations of the central nervous system were 

seen in the rat developmental toxicity study at doses that caused an overall increase in fetal 

malformations. Case reports of accidental human poisonings indicate that neurological effects 

(convulsions, tremors, headaches, restlessness) may occur with exposure to high levels of boric 

acid (summarized in IRIS, 2004). Other species (dog, mouse, rabbit) did not show clinical signs 

at the doses tested. 

There is evidence of increased qualitative and/or quantitative offspring susceptibility in the rat, 

mouse and rabbit. In the rat, decreased fetal weight and increased skeletal abnormalities were 

observed at the LOAEL, with dose-related decreased survival and significant external, visceral 

and skeletal malformations at higher doses, in the absence of maternal toxicity. Similar 

developmental effects were seen in mice in the presence of less severe maternal toxicity (renal 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 20 of 99

tubular dilatation/regeneration). Resorptions, post-implantation loss, decreased fetal weight and 

cardiovascular malformations were observed in rabbits; however maternal toxicity was limited to 

vaginal bleeding, probably secondary to fetal loss. 

In reproductive toxicity studies conducted in the rat and the mouse, decreased fertility, resulting 

in decreased litter sizes, decreased pup weight, and decreased offspring survival, were observed 

at doses causing testicular atrophy and mild decreases in body weight in parental animals. In the 

rat, the number of corpora lutea were also decreased at the same dose. Although fertility of 

females was affected by exposure, the effects in males were more severe. The fertility effects in 

males and females are probably due to the testicular and ovarian effects discussed at the 

beginning of this section.

Boric acid/borate salts did not show evidence of carcinogenicity in the rat or mouse. 

Genotoxicity studies were negative.

Boric acid/borate salts generally show low acute toxicity by oral and dermal routes (Toxicity 

Categories III or IV). Boric acid is Category III for acute inhalation, due to limitations in 

generating test atmosphere concentrations and not mortality (none observed). Dermal and eye 

acute irritation potential vary. Sodium tetraborate decahydrate (borax) is Category I for eye 

irritation and IV for skin irritation, while boric acid is Category III for both.

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

HED recommends that the FQPA SF be reduced to 1x. This recommendation is based on the 

following considerations: (1) an adequate toxicology database that includes developmental and 

reproductive toxicity, neurotoxicity and immunotoxicity studies; (2) although evidence of 

increased quantitative and/or qualitative susceptibility was observed, effects were wellcharacterized and clear NOAELs and LOAELs were established; (3) the doses selected for risk 

assessment are protective of potential developmental toxicity, including potential neurotoxic 

effects (malformations of the central nervous system (CNS)) and of immunotoxic effects, and (4) 

exposure assessments use conservative inputs and models that do not underestimate exposure to 

boric acid/sodium salts.

4.4.1 Completeness of the Toxicology Database

The toxicology database is considered complete for purposes of an FQPA assessment. 

Acceptable developmental toxicity studies in rats, mice and rabbits, multi-generation 

reproduction studies in rats and mice, rat neurotoxicity (acute) and immunotoxicity studies are 

available for FQPA assessment. The studies were well-conducted and a clear NOAEL and 

LOAEL for these malformations was observed. Therefore, a database uncertainty factor (UFDB) 

is not needed.

Although developmental malformations of the nervous system were observed in the rat (see 

Section 4.4.2), a developmental neurotoxicity (DNT) study was not required because these 

findings were reported at dose levels that were significantly higher than the selected point of 

departure (POD), and were also associated with an increase in overall malformations. 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 21 of 99

4.4.2 Evidence of Neurotoxicity

Clinical signs of toxicity that could indicate neurotoxicity (hunched posture, abnormal gait, rapid 

respiration) were observed in rat dietary studies, generally beginning after 1-2 weeks to about 

one month of exposure. However, these symptoms occurred alongside numerous other nonspecific signs and may have reflected general poor health rather than direct effects on the 

nervous system. Neurotoxicity was not observed in the rat acute neurotoxicity study (the 

subchronic neurotoxicity study was waived). In the rat developmental toxicity study, enlarged 

lateral ventricles of the brain, microphthalmia or anophthalmia were observed at doses that also 

caused a general increase in malformations of all tissues and decreased fetal survival. Published 

case reports of human poisonings with boric acid or borate salt compounds have also identified 

clinical signs consistent with CNS toxicity including convulsions, headaches, tremors and 

restlessness. 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

Quantitative and/or qualitative evidence of increased offspring susceptibility, as compared to 

adults, following in utero or postnatal exposure to boric acid/borate salts was observed in 

developmental toxicity studies and multi-generation reproduction studies in all species tested. In 

the rat, decreased fetal weight and increased skeletal abnormalities were observed at the LOAEL, 

with dose-related decreased survival and significant external, visceral and skeletal malformations 

at higher doses, in the absence of maternal toxicity. In the mouse, increased resorptions, 

decreased fetal weight and increased short rib XII were observed in the presence of mild 

maternal renal histopathology. In the rabbit, increased fetal resorptions, mortality and visceral 

abnormalities were observed in the presence of maternal vaginal bleeding. In two- and threegeneration reproductive toxicity studies in the rat and mouse, decreased fertility and decreased 

pup weight and survival were seen at doses causing testicular and ovarian toxicity in parental 

animals. However, in all the studies, effects were well-characterized and clear NOAELs and 

LOAELs were established and the endpoints selected for risk assessment are protective of these 

effects.

 

4.4.4 Residual Uncertainty in the Exposure Database

There is no residual uncertainty in the exposure database that would necessitate retention of the 

FQPA safety factor. Data sources are reasonably representative of the scenarios for which they 

are used to estimate exposure and have been vetted through public peer review processes (e.g., 

FIFRA Scientific Advisory Panels (SAP), HSRB). Additionally, for children’s non-dietary 

incidental oral exposure, chemical-specific residue data were submitted and utilized, which is 

considered more accurate and reliable than default estimates. 

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Dietary Exposure: Based on data demonstrating that residues of boron in/on treated 

commodities are indistinguishable from those in/on control samples, and on the expectation that 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 22 of 99

the low application rates associated with agricultural uses are not expected to add significantly to 

background levels in drinking water, a quantitative dietary risk assessment was not conducted. 

Therefore, acute and chronic dietary reference doses (aRfD and cRfD, respectively) have not 

been selected.

Incidental Oral Exposure (Short-, Intermediate-, and Long-term): For applicable exposure

durations an endpoint was selected based on the 90-day and 2-year dog oral studies (considered 

together to provide the NOAEL and LOAEL) on borax (MRID 40692308 and 40692310). The 

studies are of the appropriate route and duration. The NOAEL of 8.8 mg/kg bw/day (2-year dog 

study, HDT) was selected as the POD, based on hematological effects and testicular atrophy 

observed at the LOAEL of 32 mg/kg bw/day (90-day dog study). The NOAEL from the 2-year 

study was selected because it was higher than the NOAEL from the 90-day study (4.1 mg/kg 

bw/day) as a result of dose-spacing. Testicular atrophy was also observed at 40 mg/kg bw/day in 

a dog 38-week study (only one dose tested). The hematological effects are relevant to all 

exposed populations, which may include young children and females age 13 to 49. The dose is 

protective of toxicity observed in several oral rat studies (clinical findings, testicular atrophy) 

including the subchronic oral rat studies on borax (NOAEL 41 mg/kg bw/day, highest dose 

tested (HDT)) and boric acid (NOAEL/LOAEL 38/125 mg/kg bw/day), as well as the rat chronic 

toxicity study on boric acid and borax (NOAEL/LOAEL 17/58 mg/kg/day), and rat reproductive 

toxicity studies (parental/reproduction/offspring NOAELs/LOAELs 28/82 mg/kg bw/day) and 

developmental toxicity (most sensitive study NOAEL/LOAEL 9.6/13.3 mg/kg bw/day). The 

selected dose and endpoint are also protective of mild renal histopathology seen in pregnant mice 

(≥43 mg/kg bw/day) in the developmental toxicity study. In rabbits, the NOAEL for maternal 

toxicity was 22 mg/kg bw/day; no maternal toxicity was observed in the rat up to 94 mg/kg 

bw/day.

Episodic/non-dietary ingestion of granule formulations: A POD was selected to assess the 

potential ingestion of recently applied granular formulation products (e.g., in turf) by young 

children (e.g., 1 < 2 years old). For this scenario, a dose of 350 mg/kg was selected, based on 

clinical signs (depression, labored/rapid breathing, diarrhea, red crusts on eyes) and mortality 

observed in oral LD50 studies for boric acid and borax at doses ≥439 mg/kg. The LD50 studies 

were selected since no single-dose effects relevant to this subpopulation were observed in other 

guideline toxicology studies. Clinical signs of toxicity in repeated-dosing studies were not 

observed by the first or second day of treatment. In several oral LD50 studies (MRIDs 00056544, 

00064207, 40692303), no effects were observed at doses of 350 mg/kg bw boron equivalents. 

This endpoint is further supported by the lack of toxicity observed in the rat acute neurotoxicity 

screening study at the highest dose level of 350 mg/kg boron equivalents.

Dermal Exposure (Residential and Occupational): A dermal toxicity study is not available. An 

endpoint for assessment of risk from dermal exposure was not selected, based on in vivo dermal 

absorption data in humans and published studies in animals indicating that absorption across 

intact skin is negligible (<1%). Estimation of a dermal NOAEL using the NOAELs from the 

most sensitive oral studies (NOAEL = 8.8 mg/kg/day, dog and 9.6 mg/kg/day, developmental 

rat) using a (conservative) DAF of 1% would yield a dose approaching the limit dose of 1000 

mg/kg bw/day.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 23 of 99

Inhalation Exposure (Residential and Occupational): For all applicable exposure durations an 

oral study (NOAEL of 8.8 mg/kg/day, dog chronic study) was selected, taking into consideration 

a published report on inhalation toxicity in the rat. The requirement for a rat subchronic 

inhalation toxicity study was waived (HED HASPOC, TXR No. 0056768), based on data 

indicating physical limitations in generating test atmosphere concentrations high enough to elicit 

toxicity (Wilding et al., 1959). The published inhalation study did not identify adverse systemic 

or portal of entry effects in the rat at test concentrations up to 0.47 mg/L boron oxide, which is 

equivalent to an estimated oral exposure of about 29 mg/kg bw/day boron in the rat. 

[Calculation: chamber concentration x species specific adjustment factor (respiratory volume 

and body weight) x exposure duration x 0.311 (factor to convert to boron equivalents for boron 

oxide). Thus, for the rat, 0.47 mg/L x 47 (Fisher rat) x 6 hr exposure duration x [5 days/7 days 

per week exposure] x 0.311).]

The dog 90-day and 2-year dietary studies were considered together to derive the POD and 

endpoint. The NOAEL of 8.8 mg/kg bw/day, the HDT in the dog two year dietary toxicity study 

on borax, was selected for both short- and intermediate-term inhalation exposure. The dose was 

selected based on hematological findings (decreased Hct/Hgb and increased hemosiderin 

deposition in the spleen, liver and kidneys) and testicular atrophy observed at the LOAEL of 32 

mg/kg bw/day in the 90-day study. Testicular atrophy was also observed at 40 mg/kg bw/day in 

a dog 38-week study (only one dose tested). A lower NOAEL (4.1 mg/kg bw/day) was 

identified in the dog 90-day dietary study, but was not selected since a higher NOAEL was 

identified for the longer exposure duration that is protective of effects in that study. The findings 

of the 90-day, 38-week and 2-year dietary studies on boric acid were essentially the same as the 

findings from studies on borax. The selected dose is protective of developmental toxicity 

observed in the rat at 13.3 mg/kg bw/day and the rabbit at 43 mg/kg bw/day with developmental 

NOAELs of 9.6 and 22 mg/kg bw/day, respectively. The inhalation absorption of boric 

acid/borate salts is assumed to be 100%. 

In the absence of observed toxicity in the rat inhalation study, the highest exposure concentration 

tested (0.47 mg/L) was assumed to be a NOAEL for portal of entry (POE) and systemic toxicity. 

Human equivalent doses (HEDs) were calculated for comparison to the oral dose of 8.8 

mg/kg/day selected for risk assessment. These doses were not used for risk assessment because 

LOAELs were not identified in the available inhalation study. POE HEDs of 3.65 and 1.49 

mg/kg bw/day (males) were obtained for occupational and non-occupational HEDs, respectively 

(systemic HEDs were higher). Although lower than the oral dose, they are comparable due to 

the differences in UFs used for inhalation HEDs (30) and oral doses (100). The selected oral 

dose is therefore considered protective of potential POE effects from inhalation exposure, as well 

as developmental effects.

Uncertainty Factors: For all exposure scenarios, uncertainty factors (UFs) of 10x for interspecies 

(UFA) and 10x for intraspecies (UFH) variation (total UF of 100x) were used. The 10x 

interspecies and 10x intraspecies factors are considered to be conservative because boric 

acid/borate salts are expected to show similar absorption and tissue distribution among different 

species, and boric acid is not metabolized, thereby reducing potential variability for these 

parameters. The 10x UFA accounts for variability in renal clearance between species that may 

affect elimination of boric acid/borate salts and provides additional protection for the close dose-
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 24 of 99

spacing of the rat developmental NOAEL and LOAEL (9.6 and 13.3 mg/kg bw/day, 

respectively), which are only slightly greater than the selected POD of 8.8 mg/kg bw/day.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Incidental oral and inhalation exposures are being regulated based on the same effects 

(hematological changes, testicular toxicity) observed following oral exposure in the dog; 

therefore, when applicable, their combination is recommended.

4.5.3 Cancer Classification and Risk Assessment Recommendation

There was no evidence of carcinogenicity in cancer studies with mice and rats. Boric acid/borate 

salts are classified as “not likely to be carcinogenic to humans” under the Agency revised (2005) 

Cancer Guidelines. The available studies were not conducted according to current guideline 

standards for carcinogenicity studies, but were considered adequate for assessing carcinogenic 

risk from boron. A two year mouse carcinogenicity study conducted by the National Toxicology 

Program (NTP) tested at only two doses instead of three, but achieved a maximum tolerated dose

(MTD) and was adequate to evaluate carcinogenicity. Rat two year dietary studies on boric acid 

and borax tested smaller groups of animals than recommended, but when considered together, 

animal numbers were sufficient. Dosing was adequate. Some tissues were not examined, but

major organs and gross findings were evaluated, and no treatment-related tumors were seen in 

mice. Other factors support lack of carcinogenicity. Genotoxicity studies did not indicate 

mutagenic or clastogenic potential. Epidemiological data do not indicate any boron exposurerelated cancers in humans. Boron is a ubiquitous, naturally occurring element in food and 

drinking water to which humans are continuously exposed throughout their lifetime, further 

reducing concern for carcinogenicity.

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Summary of Toxicological Doses and Endpoints for Boric Acid/Borate Salts for Use in Dietary and NonOccupational Human Health Risk Assessments. All Doses expressed as boron equivalents.

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

Chronic Acute or chronic dietary risk assessments are not conducted, see Section 5.0.

Dietary

Acute 

Incidental 

Oral 

(ingestion of

granule

formulations)

NOAEL = 350 

mg/kg

UFA= 10x

UFH=10x

 FQPA SF=1x

Residential 

LOC for MOE

= 100

Acute LD50 (boric acid and borax, 3 

studies) – rat

LOAELs ≥439 mg/kg, based on clinical 

signs of toxicity and mortality
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 25 of 99

Summary of Toxicological Doses and Endpoints for Boric Acid/Borate Salts for Use in Dietary and NonOccupational Human Health Risk Assessments. All Doses expressed as boron equivalents.

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Incidental 

Oral (Short-, 

Intermediate-, 

Long-term)

NOAEL= 8.8

mg/kg bw/day

(2-year feeding 

study – dog, 

HDT)

UFA= 10x

UFH=10x

FQPA SF=1x

Residential 

LOC for MOE 

= 100

Subchronic (90-day) and chronic (2-year) 

feeding study (borax) -- dog 

LOAEL (90-day study) = 32 mg/kg 

bw/day, based on hematological effects 

and testicular atrophy

Dermal (all 

durations)

A dermal risk assessment was not performed. Dermal absorption data in humans indicates 

negligible absorption (less than 1%) and is consistent with published reports in laboratory 

animals showing low or no absorption. Estimation of a dermal NOAEL, using available oral 

NOAELs and a DAF of 1%, would give doses approaching the limit dose (1000 mg/kg bw/day).

Inhalation (all 

durations)

NOAEL= 8.8

mg/kg bw/day

(2-year feeding 

study – dog, 

HDT)

100% 

inhalation 

absorption 

assumed.

UFA= 10x

UFH=10x

FQPA SF=1x

Residential 

LOC for MOE 

= 100

Subchronic (90-day) and chronic (2-year) 

feeding study (borax) -- dog 

LOAEL (90-day study) = 32 mg/kg 

bw/day, based on hematological effects 

and testicular atrophy

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the lack of an increase in 

treatment-related increased tumors in rat and mouse carcinogenicity studies.

Point of Departure = 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). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose. RfD = reference dose. HDT – highest dose tested.

Summary of Toxicological Doses and Endpoints for Boric Acid/Borate Salts for Use in Occupational 

Human Health Risk Assessments. All doses expressed as boron equivalents.

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD,

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal ShortTerm (all 

durations)

A dermal risk assessment was not performed. Dermal absorption data in humans indicates 

negligible absorption (less than 1%) and is consistent with published reports in laboratory 

animals showing low or no absorption. Estimation of a dermal NOAEL, using oral NOAELs 

and a DAF of 1%, would give doses approaching the limit dose (1000 mg/kg bw/day). Dermal 

risks are therefore not of concern. 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 26 of 99

Summary of Toxicological Doses and Endpoints for Boric Acid/Borate Salts for Use in Occupational 

Human Health Risk Assessments. All doses expressed as boron equivalents.

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD,

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Inhalation 

Short- Term 

(1-30 days)

IntermediateTerm (1-6 

months)

NOAEL= 8.8

mg/kg bw/day

(2-year feeding 

study – dog, 

HDT)

100% 

inhalation 

absorption 

assumed.

UFA= 10x

UFH=10x

Occupational 

LOC for MOE 

= 100

Subchronic (90-day) and chronic (2-year) 

feeding study (borax) -- dog 

LOAEL (90-day study) = 32 mg/kg 

bw/day, based on hematological effects 

and testicular atrophy

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the lack of an increase in 

treatment-related tumors in rat and mouse carcinogenicity studies.

Point of Departure = 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. 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). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. 

HDT = highest dose tested.

4.6 Endocrine Disruptor Screening Program

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal 

Food, Drug, and Cosmetic Act (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 for boric acid and its sodium 

borate salts, 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), boric acid and it sodium borate salts are 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 

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 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 27 of 99

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 (a.i.’s) and 9 inert ingredients. A 

second list of chemicals identified for EDSP screening was published on June 14, 20131and 

includes some pesticides scheduled for Registration Review and chemicals found in water. 

Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of 

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

website.2

5.0 Dietary Exposure and Risk Assessment 

Boron is a ubiquitous, naturally occurring component of food and drinking water to which 

humans are continually exposed. It is an essential nutrient for plants, and there is some evidence 

suggesting that it may be a required micronutrient in mammals based on studies suggesting it is 

involved in the regulation of metabolism of minerals such as calcium; however, this has not been 

definitively established (Naghii and Samman, 1993). Dietary exposure to humans is variable, 

depending upon the foods consumed and the source of drinking water. 

A robust analysis of boron intake, using the 1994-1996 Continuing Survey of Food Intakes by 

Individuals (CSFII), presented “usual” (i.e., long-term) boron intake distributions for various 

population sub-groups as well as characterization of food group sources of boron (Rainey, et al, 

2002). The analysis considered food only – boron intake via drinking water was not estimated. 

Mean usual intake via food for adult males and females, respectively, was 1.28 mg/day and 1.00 

mg/day, and 0.86 mg/day for children 1-3 years old. Fruits, beverages (excluding water), 

vegetables, and grains, in that order, contributed most to boron intake. These results are 

consistent with other published literature estimates of human daily dietary boron intake ranging 

from 0.26 to 7.1 mg/day, with a mean of 1.9 mg/day (equivalent to about 0.03 mg/kg bw/day for 

adults) (Moore, 1997; Rainey, 1999). Based on a review of the EPA’s Office of Water

Regulatory Determinations Support Document for boron, average background drinking water 

concentration is approximately 0.1 mg/L (EPA, 2008). Using the standard HED water 

consumption estimate for adults – approximately 1.4 L/day – boron intake via water would be 

approximately 0.14 mg/day, a much lower amount than intake via food. 

Boric acid/sodium salts is the active ingredient in one product (PREV-AM, EPA Reg. No. 

72662-3, 0.99% sodium tetraborate decahydrate), with uses on a wide variety of agricultural 

 

1

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals

2 http://www2.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-edsp-overview
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 28 of 99

food/feed crops at a low application rate (100 fl. oz./100 gal solution, or approximately 0.0018 lb 

boron equivalents per acre). HED previously recommended that the registrant submit side-byside residue trials on representative crops for PREV-AM to provide confirmatory data to 

demonstrate that its use does not significantly increase boron levels beyond background 

(D346904, R. Loranger/D. McNeilly, 5MAY2008). These studies were submitted in early 2015 

(MRIDs 49735901-15).

The field trial data evaluated PREV-AM applied at a rate of approximately 100 oz product/100 

gallons in Western South Africa. Four to six applications were made at 7 day intervals. The 

samples were harvested one day after the last application. The data included results for only one 

control sample per commodity, hence variability of the control sample is unknown. The boron 

levels in the untreated control were at or near the average in all five treated commodities 

involved in the study. Table 5.0 presents a summary of the results.

Table 5.0 Residue Data for Boron Field Trials

Crop Treatment 

Rate

Untreated Control Results

(ppm)

Treated Samples (ppm)

Individual Results Average

Zucchini 100 oz./100 gal 16.66 21.0, 20.74, 18.17 20.0

Tomatoes 107 oz./100 gal 10.21 9.55, 10.17, 11.79 10.5

Spinach 100 oz./100 gal 30.19 36.97, 30.18, 28.95 30.0

Lettuce 107 oz./100 gal 25.08 25.77, 31.36, 31.73 29.6

Potatoes 100 oz./100 gal 0.7 0.7, 0.7, 0.8 0.73

Information on the magnitude and variability of background levels of boron compounds in plants 

also needs to be considered in the context of differentiation of residues resulting from pesticide 

treatments. Based on a number of articles in the open literature (Andersen, et al, 1994; Hunt, 

1994; Nielsen, 1991), including one detailing a 1994 Food and Drug Administration (FDA) Total 

Diet Study, the highest boron concentrations are typically in nuts, followed by fruits, and then 

vegetables. Examples of levels (ppm boron) in crops are as follows: peanuts 14-19, raisins 7-25, 

peaches 1.9-5.2, apples 1.2-4.3, cherries 1.5-7.0, tomatoes 0.75-2.1, potatoes 0.44-3.3, carrots 

1.8-4.2, green snap beans 0.46-2.5, broccoli 0.9-3.1, celery 2.2-5.0, lettuce 0.3-0.9, spinach 1.2-

10, avocado 5.4-21, prunes 19-27, and whole wheat bread 0.48-0.67.

Although boric acid/sodium salts are registered for use on numerous food/feed crops that may 

result in dietary exposure, no food or drinking water risk assessments were performed. Boron is 

a naturally occurring component of both food and water and is believed to be an essential dietary 

trace nutrient. Due to the expectation that residues in food and water resulting from pesticide use 

of boron would not significantly add to naturally-occurring boron levels, an exemption from the 

requirement of a tolerance for use on raw agricultural commodities was established in 1993 and 

previous regulatory decisions (e.g., the 1993 RED and 2006 TRED) did not include dietary risk 

assessments.

The field trial data described above confirm this expectation, demonstrating that residues in/on 

commodities from treatment with boric acid/sodium salts are indistinguishable from untreated 

commodities. Similarly, although these products are expected to be mobile in the soil and 

readily dissolve in water (present as undissociated acid), the low application rate of agricultural 

products is not expected to add significantly to the background levels naturally occurring in 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 29 of 99

drinking water. Therefore, as in previous regulatory risk assessments, dietary exposure 

assessments have not been conducted for the registration review of boric acid and its sodium 

salts.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are numerous conventional pesticide residential uses of boric acid or its sodium salts as 

active ingredients, from insecticide and fungicide dusts and sprays to granular herbicides. 

Additionally, there are antimicrobial uses in swimming pools and as material and wood 

preservatives. Given these uses, both residential handler and post-application exposures are 

anticipated. 

As described in Section 4.2.1, dermal absorption is very low. Estimates from the human in vivo 

study were approximately 0.2% over 24 hours following administration of dermal loadings 

ranging from 10 to 39 ug/cm2. Dermal exposures are possible for boric acid/sodium salts – some 

likely very high due to use of dust formulations at high application rates. However, because 

absorption (as a fraction of the total amount applied), over a given amount of time, decreases as 

dermal load (mass per skin surface area) increases (Kissel, 2011), use of the dermal absorption 

estimates from the human in vivo study would, even at 0.2%, be an overestimate of dermal 

absorption given the high dermal loadings that would correspond to high dermal exposures (e.g., 

20,800 ug/cm2dermal load estimated for a dust application scenario). Thus, across all scenarios, 

due to negligible dermal absorption, toxicity from dermal exposure is not expected and dermal 

risks are not of concern.

Additionally, in the HED chapter for the 2006 boric acid/sodium salt TRED (L. Hansen, 26-JUL2006, D320894), exposures via non-pesticide consumer use products (i.e., laundry detergent and 

general purpose cleaners) as well as its presence as an inert ingredient in pesticide products were 

also considered to characterize the residential exposure pathway for purposes of an aggregate 

assessment. The TRED determinations included:

 Because boric acid/sodium salts were estimated to be on the order of 1% or less as an 

inert ingredient, risk assessment of its use as an active ingredient in products at amounts 

as high as 100% would be protective of exposures via use of products containing them as 

inerts. 

 A quantitative assessment of non-pesticide consumer use products was conducted and 

found no risks of concern and contribution to aggregate exposure deemed negligible as 

exposures were estimated to be extremely low (MOEs were all greater than 10,000).

HED considers the approach and methods used in the TRED for the inert and non-pesticidal 

consumer use products to still be appropriate; therefore, as the toxicological endpoints and PODs 

used in the TRED assessment have not changed, no updates to this part of the TRED assessment 

have been conducted.

To reflect updates in data and methodologies for other exposure scenarios since previous 

assessments, addressed in the following sections are inhalation exposures for consumers 

mixing/loading and applying boric acid/sodium salt products as well as post-application 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 30 of 99

inhalation and incidental oral exposures resulting from areas previously treated with boric acid 

products. Post-application incidental oral risk estimates for children were found to be of concern 

for broadcast spray treatments to carpets (MOEs < 100), primarily due to the relatively high 

application rates. All other handler and post-application risk estimates resulting from pesticide 

uses were not of concern.

6.1 Residential Handler Exposure

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct tasks related to applications and that 

exposures can vary depending on the specifics of each task. Residential handlers are assumed to 

complete all elements of an application without use of any protective equipment.

The exposure/risk assessment for residential handlers is based on the following scenarios:

 Indoor area treatments (carpets, floors, crack-and-crevice treatments, attics, wall voids, 

crawl spaces, etc.)

o Loading/applying dust/powder formulations with:

 Hand pressure dusters (e.g., bulb dusters, plunger dusters, hand crank 

dusters)

 Power dusters/blowers

 Shaker cans

o Applying granules/baits via hand dispersal

o Mixing/loading/applying wettable dusts/powder formulations with a manually 

pressurized handwand sprayer

o Mixing/loading/applying liquid concentrate formulations with a manually 

pressurized handwand sprayer

o Applying bait gels/pastes

 Outdoor area treatments (lawns, gardens, shrubs/bushes, and fruit/nut trees)

o Loading/applying granule formulations with push-type rotary spreaders

o Applying granule formulations via hand dispersal or with spoons or cups

o Mixing/loading/applying liquid concentrate formulations with:

 Manually pressurized handwand sprayers

 Hose-end sprayers

 Backpack sprayers

 Sprinkler cans

 Swimming pool treatments

o Hand dispersal of powder or granule formulations

 Painting (with paints containing boric acid or a sodium salt as a material preservative) 

using:

o Brush/roller

o Airless sprayer

A series of assumptions and exposure factors served as the basis for completing the residential 

handler risk assessments. Each are detailed in the occupational and residential risk assessments 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 31 of 99

(M. Crowley, 9-NOV-2015, D428582; T. Dole, 13-NOV-2015, D419073), but are also 

summarized below.

 Application Rate: various application rates are outlined in Appendix C.

 Unit Exposures and Area Treated or Amount Handled: scenario/equipment/formulationspecific exposure factors known as “unit exposures” as well as their corresponding

estimates for area treated or amount of solution handled are from HED’s 2012 

Residential SOPs3or standard assumptions for antimicrobial treatments.

 Body weight: for boric acid and its sodium salts, as for other active ingredients with nonsex-specific effects, a body weight of 80 kg is used in risk assessment to represent an 

assessment of the general (adult male and female) population. Though developmental 

and fetal effects were observed, the selected endpoint for the POD is protective of these 

effects and is based on non-sex specific findings.

Residential handler exposure is generally expected to be short-term in duration, though given 

many boric acid/sodium salt labels do not specify treatment frequency and the use of boric acid 

and its sodium salts is likely on an as-needed basis (particularly its residential insecticide use), 

there is potential for intermediate-term handler exposure as well. However, the toxicological 

endpoint selected for the short-term assessment is protective of both short- and intermediate-term 

durations.

Inhalation exposures and risks were calculated for residential handlers assuming no respiratory 

protection; no estimates of inhalation risk were of concern. 

Table 6.1.1 presents detailed exposure and risk calculations.

 

3 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residentialpesticide
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Table 6.1.1. Summary of Residential Handler Risk Estimates for Boric Acid and its Sodium Salts

Use Site 

Category Exposure Scenario App Rate1

Amount 

Handled/Area 

Treated2

Unit Exposure 

(mg/lb ai)3 Dose (mg/kg/day)4

Inhalation MOE5

Inhalation (LOC = 100)

(no respirator)

Inhalation

(no respirator)

Indoor 

treatments

Mixing /

loading / 

applying with a 

manually 

pressurized 

handwand

Liquids 0.15 lb ai/gallon dilute 

solution 0.5 gallons 

dilute 

solution

1.1 0.001 8500

Wettable 

dusts/powders

0.31 lb ai/gallon dilute 

solution 1.1 0.0021 4100

Applying granules/baits via hand 

dispersal 0.000017 lb ai/ft2 1000 ft2 0.38 0.000081 110000

Loading / 

applying 

dusts/powders

Shaker can 0.22 lb ai/20 oz 

container

One 20 oz 

container 18 0.05 180

Power 

duster/blower 0.21 lb ai/lb dust 1 lb dust 18 0.024 370

Bulb Duster 0.21 lb ai/lb dust 0.25 lb dust 1.7 0.0011 7900

Plunger Duster 0.21 lb ai/lb dust 0.5 lb dust 1.7 0.0022 3900

Applying bait gels/pastes No exposure/risks expected from gel/paste formulations.

Outdoor 

treatments

(lawns, 

gardens, 

and trees)

Loading / 

applying 

granules 

Rotary spreader 1.52 lb ai/acre 0.5 acres 0.0026 0.000025 360000

Belly grinder 0.034 lb ai/1000 ft2 1200 ft2 0.039 0.00002 430000

Spoon 0.034 lb ai/1000 ft2 1200 ft2 0.013 0.00054 1300000
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 33 of 99

Table 6.1.1. Summary of Residential Handler Risk Estimates for Boric Acid and its Sodium Salts

Use Site 

Category Exposure Scenario App Rate1

Amount 

Handled/Area 

Treated2

Unit Exposure 

(mg/lb ai)3 Dose (mg/kg/day)4

Inhalation MOE5

Inhalation (LOC = 100)

(no respirator)

Inhalation

(no respirator)

Cup 0.034 lb ai/1000 ft2 1200 ft2 0.087 0.000046 190000

Applying granules via hand 

dispersal 0.034 lb ai/1000 ft2 1200 ft2 0.38 0.0002 44000

Mixing /

loading / 

applying liquids

Manually 

pressurized 

handwand

0.000073 lb ai/gallon 

dilute solution

5 gallons 

dilute 

solution

0.018 8.2E-08 110000000

Hose-end 

sprayer

0.003 lb ai/acre 0.5 acres 0.022 4.1E-07 21000000

Backpack 

sprayer

0.000073 lb ai/gallon 

dilute solution

5 gallons 

dilute 

solution

0.14 6.4E-07 14000000

Sprinkler can 0.000073 lb ai/1000 ft2 1000 ft2 0.022 2.0E-08 440000000

Painting

Brush/roller

1.4% ai

20 lbs paint

(2 gal x 10 

lbs/gal)

0.20 0.0007 13000

Airless sprayer

150 lbs paint 

(15 gal x 10 

lbs/gal)

0.56 0.015 590

Swimming 

Pools Hand dispersal

Powders

0.30 lbs ai/gallon 

water

20,000 

gallons water

0.043 0.003 2,900

Granules 0.0017 0.00013 68,000

1 Based on registered labels outlined in Appendix C. All rates expressed in terms of boron.

2 Based on HED’s 2012 Residential SOPs (http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide) or standard 

assumptions for antimicrobial uses.

3 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) ÷ BW (kg). Expressed 

in terms of boron.

4 Inhalation MOE = Inhalation POD (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

6.2 Residential Post-application Exposure

There is the potential for post-application exposure for individuals exposed as a result of being in 

an environment that has been previously treated with boric acid or a borate sodium salt. The

exposure/risk assessment for residential post-application exposures is based on the following 

scenarios:

 Inhalation exposure for adults and children (1 < 2 years old) following indoor treatments 

(carpets, floors, crack-and-crevice, bedding/mattresses)

 Incidental oral children’s (1< 2 years old) exposure via:

o Contact with treated:

 Turf/lawns

 Carpets and floors

 Wood/lumber (used in decks and playground equipment)

o Ingestion of applied granule formulations

 Incidental water ingestion for adults and children (6 < 11 and 11 < 16 years old) while 

swimming in treated pools

The lifestages selected for each post-application scenario are based on an analysis provided as an 

Appendix in the 2012 Residential SOPs4or, for exposures while swimming in treated pools, as 

outlined in the antimicrobial occupational and residential exposure assessment (T. Dole, 13-

NOV-2015, D419073). While not the only lifestage potentially exposed for these postapplication scenarios, the lifestage that is included in the quantitative assessment is health 

protective for the exposures and risk estimates for any other potentially exposed lifestage.

A series of assumptions and exposure factors served as the basis for completing the residential 

post-application risk assessment. These are outlined in more detail in (M. Crowley, 9-NOV2015, D428582; T. Dole, 13-NOV-2015, D419073), but are summarized briefly below.

 Application Rate: various application rates are outlined in Appendix C.

 Transfer Coefficients, Exposure Time, and other Exposure Factors: 

scenario/formulation-specific exposure factors known as “transfer coefficients” as well as 

exposure time and other post-application exposure factors (e.g., hand-to-mouth contact

factors, water ingestion while swimming) are from HED’s 2012 Residential SOPs5or 

standard assumptions for antimicrobial treatments as outlined in the antimicrobial 

occupational and residential exposure assessment.

 Body weight: for boric acid and its sodium salts, as for other active ingredients with nonsex-specific effects, a body weight of 80 kg is used in risk assessment to represent an 

assessment of the general (adult male and female) population. Though developmental 

and fetal effects were observed, the selected endpoint for the POD is protective of these 

 

4 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residentialpesticide

5 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residentialpesticide 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 35 of 99

effects and is based on non-sex specific findings. For children, the following body 

weights were used where applicable:

o 1 < 2 years old: 11 kg

o 6 < 11 years old: 32 kg

o 11 < 16 years old: 57 kg

 Physiochemical Properties: chemical-specific molecular weights and vapor pressures 

were utilized as necessary (see Appendix B).

 Residue Transferability:

o For post-application exposure via contact with treated turf/lawns, default 

estimates of 1% for liquids and 0.5% for solid formulations were used.

o For post-application exposure via contact with treated indoor carpets and hard 

floors, registrant-submitted studies were used. The studies estimated 

transferability using the “California roller method”6, a method consistent with 

default estimates described in the 2012 Residential SOPs. Across all the studies, 

which included varying types and conditions of carpets, transferability (as a 

percentage of the application rate) of boric acid/sodium salts ranged from 0.03% 

to 0.95%. To represent typical conditions for short-/intermediate-term postapplication risk assessments, transferability of 0.1% is used for dust treatments to 

carpets (selected from MRID 47579901) and 0.4% for dust treatments to hard 

floors and liquid treatments to carpets or hard surfaces (selected from MRID 

47579902, the only result available for these conditions).

o The default transferable surface residue for treated wood is 1 μg/cm2, the highest 

estimate of residue transfer from data that was generated by the Consumer 

Product Safety Commission (CPSC) evaluation of children’s exposure to 

chromate copper arsenate (CCA) treated wood.

Post-application exposures are generally considered short-term in nature, though exposures for 

competitive swimmers via use in swimming pools may present long-term exposures. However, 

the toxicity study from which the inhalation and incidental oral toxicological endpoints were

selected to assess post-application exposures are of sufficient duration to be protective of both 

short- intermediate- and long-term exposure durations.

Where appropriate, post-application inhalation and incidental oral risk estimates are combined 

within the same exposure scenario since they are based on the same toxicological effect. Risk 

estimates of concern were identified for hand-to-mouth exposures for children following indoor 

bedbug treatments (MOE = 8) and indoor carpet spray treatments (MOE = 51). These routes are 

also combined with inhalation exposure, but as inhalation exposure is much lower in comparison 

to the hand-to-mouth exposure, the risk estimates are unchanged. Table 5.2.1 below outlines in 

more detail the exposure scenarios and exposure and risk calculations. 

The application rates for boric acid/sodium salts are relatively high compared with other 

pesticides used for similar purposes. In particular, the bed bug treatment broadcast application 

rate (based on EPA Reg. No. 64405-6) is approximately 6 pounds of boron per 1000 square foot 

 

6 Ross, J.H., Fong, H.R., Thongsinthusak, T., Margetich, S. and Krieger, R. 1991. Measuring Potential Dermal 

Transfer of Surface Pesticide Residue Generated from Indoor Fogger Use: Using the CDFA Roller Method. 

Interim Report II. Chemosphere, Vol. 22. Nos.9-10:975-984
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 36 of 99

of carpet. Crack-and-crevice treatments – which result in substantially less surface residue than 

broadcast treatments – did not result in risk estimates of concern for incidental oral exposure 

scenarios.

Table 6.2.1 Residential Post-application Exposure and Risk Estimates for Boric Acid/Sodium Salts

Lifestage

Post-application Exposure Scenario

Application Rate1 Dose 

(mg/kg/day)2

MOE3

(LOC=100)

Use Site Route of Exposure Routespecific Combined5

Adult

Bed Bug 

treatments Carpets Liquids Inhalation

0.71 lb DOT/gallon dilute 

solution

(0.0058 lb boron/ft2)

0.00051 17000 --

Swimming pools Ingestion of water 35 mg boron/liter 0.034 260 --

Child

(11 < 16

years old)

Swimming pools Ingestion of water 35 mg boron/liter 0.031 280 --

Child

(6 < 11 

years old)

Swimming pools Ingestion of water 35 mg boron/liter 0.055 160 --

Child

(1 < 2 

years old)

Bed Bug 

treatments

Carpets Liquids Inhalation

0.71 lb DOT/gallon dilute 

solution

(0.0058 lb boron/ft2)

0.0022 4000 --

Carpets4 Liquids Hand-to-Mouth 0.0058 lb boron/ft2 1.12 8 8

Object-to-Mouth 0.0058 lb boron/ft2 0.037 240 220

General 

Indoor 

treatments

Carpets4

Liquids Hand-to-Mouth 0.0009 lb boron/ft2 0.17 51 51

Dusts Hand-to-Mouth 0.00068 lb boron/ft2 0.033 270 --

Liquids Object-to-Mouth 0.0009 lb boron/ft2 0.023 380 350

Dusts Object-to-Mouth 0.00068 lb boron/ft2 0.004 2000 --

Hard floors4

Liquids Hand-to-Mouth 0.0009 lb boron/ft2 0.043 200 190

Dusts Hand-to-Mouth 0.00068 lb boron/ft2 0.033 270 --

Liquids Object-to-Mouth 0.0009 lb boron/ft2 0.012 760 620

Dusts Object-to-Mouth 0.00068 lb boron/ft2 0.009 1000 --

Crack-andcrevice

Carpets4

Liquids Hand-to-Mouth 0.0009 lb boron/ft2 0.017 510 460

Dusts Hand-to-Mouth 0.00068 lb boron/ft2 0.0033 2700 --

Liquids Object-to-Mouth 0.0009 lb boron/ft2 0.0023 3800 2000

Dusts Object-to-Mouth 0.00068 lb boron/ft2 0.0004 20000 --

Hard floors4

Liquids Hand-to-Mouth 0.0009 lb boron/ft2 0.0043 2000 1400

Dusts Hand-to-Mouth 0.00068 lb boron/ft2 0.0033 2700 --

Liquids Object-to-Mouth 0.0009 lb boron/ft2 0.0012 7600 2600

Dusts Object-to-Mouth 0.00068 lb boron/ft2 0.0009 10000 --

Outdoor

(lawn, garden, tree 

sprays)

Granules

Hand-to-Mouth

1.52 lb ai/acre

0.0023 3800 --

Object-to-Mouth 0.00014 63000 --

Soil Ingestion 5.1E-05 170000 --

Solid Formulation 

Ingestion

8% boron

(49% sodium metaborate) 2.36 160 --

0.9% boron

(5% boric acid) 0.24 1500 --

Liquids

Hand-to-Mouth

0.003 lb ai/acre

0.00005 19000 --

Object-to-Mouth 0.000001 6300000 --

Soil Ingestion 1E-07 8.7E07 --

Treated wood used in decks and 

play sets Hand-to-mouth 5.25% ai solution 0.018 490 --

1 Based on registered labels outlined in Appendix C. All rates expressed in terms of boron, except for post-application inhalation via 

volatilization, where application rate expressed is expressed in terms of disodium octaborate tetrahydrate in order to calculate volatilization of 

sprays using molecular weight and vapor pressure parameters.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 37 of 99

2 Dose (mg/kg/day) algorithms provided in the 2012 Residential SOPs (http://www2.epa.gov/pesticide-science-and-assessing-pesticiderisks/standard-operating-procedures-residential-pesticide). Expressed in terms of boron.

3 MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day). LOC=100.

4 As previously described, transferability from carpet and hard floors following dust treatments estimated at 0.1% and 0.4% respectively and 

transferability following liquid treatments on carpets and hard floors estimated at 0.4%.

5 Combined MOE = POD (mg/kg/day) ÷ [Inhalation Dose + Oral Dose (mg/kg/day)]. Combined exposures are only applicable for children 1<2. 

When a combined MOE is shown the inhalation component is via the scenario for liquid applications to carpet or hard floors (dose = 0.0022 

mg/kg/day, MOE=4000).

7.0 Non-Occupational Bystander Post-Application Inhalation Exposure and Risk 

Estimates

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-

0037). The agency has evaluated the SAP report and has developed a Volatilization Screening 

Tool and a subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). 

During Registration Review, the Agency will utilize this analysis to determine if data (i.e., flux 

studies) or further analysis are required for boric acid and its sodium salts. However, for some 

additional characterization of bystander exposure and risk via volatilization, post-application 

inhalation exposure following indoor sprays were assessed and no risks of concern were 

identified.

8.0 Non-Occupational Spray Drift Exposure and Risk Estimates

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling onto 50-feet-wide lawns 

coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications that, by definition, should not result in direct exposures to 

individuals because of existing label language and other regulatory requirements intended to 

prevent them.7 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (1 < 2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift thus resulting in an indirect 

 

7 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 38 of 99

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

In order to evaluate the drift potential and associated risks, an approach based on drift modeling 

coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, 

a residential turf assessment based on exposure to deposited residues has been completed to 

address drift from the agricultural applications of boric acid/sodium salts. In the spray drift 

scenario, the deposited residue value was determined based on the amount of spray drift that may 

occur at varying distances from the edge of the treated field using the AgDrift® (v2.1.1) model 

and the Residential Exposure Assessment Standard Operating Procedures Addenda 1: 

Consideration of Spray Drift Policy. Once the deposited residue values were determined, the 

remainder of the spray drift assessment was based on the algorithms and input values specified in 

the recently revised (2012) Standard Operating Procedures For Residential Risk Assessment 

(SOPs).

Boric acid and its sodium salts have existing direct uses on turf, thus it was considered whether 

the risk assessment for that use may be health protective of exposures resulting from spray drift. 

If the maximum application rate on crops adjusted by the amount of drift expected is less than or 

equal to existing turf application rates, the existing turf assessment is considered protective of 

spray drift exposure. The existing maximum single application rate of boric acid/sodium salts 

for various agricultural food/feed crops is 0.0018 lb ai/acre. The highest degree of spray drift 

noted for any application method immediately adjacent to a treated field (Tier 1 output from the 

aerial application using fine to medium spray quality) results in a deposition fraction of 0.26 of 

the application rate. 

A quantitative spray drift assessment for boric acid/sodium salts is not required because the 

maximum application rate to a crop/target site multiplied by the adjustment factor for drift of 

0.26 is less than the maximum direct spray residential turf application rate of 0.003 lb ai/acre 

(i.e., 0.0018 lb ai/A x 0.26 ≤ 0.003 lb ai/A). The turf post-application MOEs based on the 

revised SOPs for Residential Exposure Assessment were assessed and no risks of concern were 

identified.

9.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (i.e., add together) pesticide 

exposures and risks from three major sources: food, drinking water, and residential exposures. 

In an aggregate assessment, exposures from relevant sources are either added together and 

compared to quantitative estimates of hazard (e.g., a NOAEL or PAD) or, in situations when 

routes are compared to different hazard estimates or have different levels of concerns, the risk

estimates (e.g., MOEs) are aggregated. When aggregating exposures and risks from various 

sources, HED considers both the route and duration of exposure.

Because residues of boron in/on food from pesticide use of boric acid/sodium salts is 

indistinguishable from naturally-occurring sources, there is no dietary pesticide exposure 

estimate for the purposes of aggregating exposure. Residential/non-dietary risks of concern for 

children 1 < 2 years old were identified only for post-application incidental oral exposures 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 39 of 99

resulting from broadcast spray treatments to carpets. Because the contribution of background 

dietary intake of boron is implicitly accounted for in the background dietary intake by the 

laboratory animals in the toxicology studies, the residential/non-dietary risk assessment

represents the aggregate risk assessment.

10.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to boric acid and its sodium salts and any other substances, and boric acid and its sodium salts do 

not appear to produce a toxic metabolite produced by other substances. For the purposes of this 

risk assessment, therefore, EPA has not assumed that boric acid and its sodium salts have a 

common mechanism of toxicity with other substances. For information regarding EPA’s efforts 

to determine which chemicals have a common mechanism of toxicity and to evaluate the 

cumulative effects of such chemicals, see the policy statements released by EPA’s Office of 

Pesticide Programs concerning common mechanism determinations and procedures for 

cumulating effects from substances found to have a common mechanism on EPA’s website at 

http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessmentrisk-pesticides.

11.0 Occupational Exposure/Risk Characterization

There are numerous conventional uses of boric acid or its sodium salts as active ingredients, 

from insecticide and fungicide dusts and sprays to granular herbicides. Additionally, there are 

antimicrobial uses in swimming pools and as material and wood preservatives.

Given these uses, both occupational handler and post-application exposures are anticipated. As 

described above, though dermal exposures are possible, due to negligible dermal absorption, 

toxicity from dermal exposure is not expected and dermal risks are not of concern. Therefore, 

addressed below are inhalation exposures for workers mixing/loading and applying boric acid 

products as well as post-application inhalation resulting from areas previously treated with boric 

acid products.

Inhalation exposures for some occupational handler scenarios have risk estimates of concern 

(MOEs < 100), requiring respirators to mitigate risks. For dust applications to structural building 

components (e.g., attics, crawl spaces, soffits, etc.) and agricultural buildings (e.g., poultry 

houses), standard respirators (i.e., filtering face-pieces) do not mitigate inhalation risk estimates 

of concern. No post-application risks are of concern.

11.1 Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 40 of 99

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios:

 Loading granules to support tractor-drawn spreader applications

 Mixing/loading liquids to support applications via:

o Airblast sprayers

o Groundboom sprayers

 Loading/applying granules with:

o Backpacks

o Belly grinders

o Spoons or cups

o Rotary spreaders

 Mixing/loading/applying liquid solutions with:

o Airless sprayer

o Brush/roller

o Backpack sprayers

o Manually-pressurized handwand sprayers

o Mechanically-pressurized handgun sprayers

 Mixing/loading dusts/powders with water and applying with manually pressurized 

handwands and mechanically pressurized handguns

 Applying bait gels/pastes

 Applying dusts with:

o Shaker cans

o Bulb dusters

o Plunger dusters

o Power dusters/blowers

 Applying granules via:

o Hand dispersal

o Tractor-drawn spreaders

 Applying sprays with:

o Airblast sprayers

o Groundboom sprayers

 Pouring solid/powders

 Preservative incorporation into wood via brush, trowel, injection, pressure treatment, dip 

diffusion treatment, and mechanized sprays

A series of assumptions and exposure factors served as the basis for completing the residential 

handler risk assessments. These are outlined in more detail in (M. Crowley, 9-NOV-2015, 

D428582; T. Dole, 13-NOV-2015, D419073), but are summarized briefly below.

 Application Rate: various application rates are outlined in Appendix C.

 Unit Exposures and Area Treated or Amount Handled: scenario/equipment/formulation-
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 41 of 99

specific exposure factors known as “unit exposures” as well as their corresponding

estimates for area treated or amount of solution handled are from HED’s ExpoSAC 

Policy #9.1 or standard assumptions for antimicrobial treatments.

 Body weight: for boric acid and its sodium salts, as for other active ingredients with nonsex-specific effects, a body weight of 80 kg is used in risk assessment to represent an 

assessment of the general (adult male and female) population. Though developmental 

and fetal effects were observed, the selected endpoint for the POD is protective of these 

effects and is based on non-sex specific findings.

HED typically classifies exposures from 1 to 30 days as short-term and exposures 30 days to six 

months as intermediate-term. Exposure duration is determined by many things, including the 

exposed population, the use site, the pest pressure triggering the use of the pesticide, and the 

cultural practices surrounding that use site. For most agricultural/commercial uses, it is 

reasonable to believe that occupational handlers will not apply the same chemical every day for 

more than a one-month time frame; however, there may be a large agribusiness and/or 

commercial applicators who may apply a product over a period of weeks (e.g., completing 

multiple applications for multiple clients within a region), or, in the case of antimicrobial 

material and wood preservatives, months. Additionally, given that labels for boric acid and its 

sodium salts products generally do not specify retreatment intervals and its nature as a multi-use 

pesticide (as an insecticide, herbicide, and fungicide), it is not unreasonable to consider 

applicators handling this active ingredient relatively frequently. Thus, both short- and 

intermediate-term exposures are anticipated, as well as long-term exposures specifically for the 

antimicrobial material and wood preservatives. The toxicological endpoint selected is protective 

of all durations.

Product labels vary with respect to work attire and levels of personal protective equipment, with 

some labels not providing any specifications to others requiring use of chemical/water-resistant 

gloves or respirators. Inhalation exposure is assessed assuming no respiratory protection and 

then, when risks of concern might indicate a need for them, assessed assuming different types of 

respirators.

The occupational handler exposure and risk estimates indicate the following scenarios have 

inhalation risk estimates of concern (MOEs < 100) without respiratory protection:

 Loading granules to support tractor-drawn spreader applications in industrial/commercial 

areas

 Applying granules to industrial/commercial areas via:

o Hand dispersal

o Tractor-drawn spreaders

o Spoons or cups

 Applying dusts with:

o Bulb dusters to food handling establishments, warehouses, residential living 

spaces, and structural building components

o Plunger dusters to structural building components

o Power dusters/blowers poultry houses

o Shaker cans to tree stumps
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 42 of 99

 Mixing/loading/applying liquid solutions with mechanically-pressurized handgun 

sprayers and airless sprayers to structural building components

 Mixing/loading dusts/powders with water and applying with:

o Mechanically pressurized handguns to poultry houses

o Manually pressurized handwands to residential living spaces and structural 

building components

 Pouring in powder formulations to treat swimming pools

Hand dispersal of granules in industrial/commercial areas and shaker can applications of dusts to 

tree stumps do not result in risk estimates of concern (MOE ≥ 100) with a respirator that offers 

90% reduction in inhalation exposure (e.g., a half-face cartridge/canister style mask). All other 

scenarios of concern without a respirator do not result in risk estimates of concern with a 

respirator that offers 80% reduction in inhalation exposure (e.g. a quarter-face dust/mist filtering 

face mask).

For the following two scenarios, inhalation exposures are of a magnitude that no standard 

respiratory protection8reduces exposures to a level where inhalation risks are not of concern 

(MOEs ≥ 100):

 Applying dusts with:

o Plunger dusters to structural building components and poultry houses

o Power dusters/blowers to poultry houses

Overall, application rates for boric acid/sodium salts products are relatively high compared to 

other pesticides with similar use patterns – for the scenarios above, some on the order of 100 

pounds of active ingredient or more per acre or almost 1⁄2 pound of active ingredient per gallon of 

dilute solution. These high application rates, as well as, for applicable scenarios, the fact that 

exposure data indicate dust formulations present some of the highest inhalation exposures, is 

driving the presence of inhalation risks.

Table 11.1.1 presents detailed exposure and risk calculations.

 

8 While a self-contained breathing apparatus or a powered-air supply respirator will likely sufficiently reduce 

exposures, it is assumed that these are infeasible/impractical options.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 43 of 99

Table 11.1.1. Summary of Occupational Handler Risk Estimates for Boric Acid and its Sodium Salts

Exposure 

Scenario Crop / Target Category App Rate1

Amount 

Handled/Area 

Treated2

Inhalation3

Unit Exposure 

(ug/lb ai)4

Dose 

(mg/kg/day)5

MOE6

(LOC = 100)

Mixing /

loading / 

applying

liquids 

Backpack 

sprayer 

Nursery, Landscaping (turf, 

trees, plants) 0.000073 lb 

ai/gallon dilute 

solution

40 gallons dilute 

solution

69.1 2.5E-06 3,500,000

Greenhouse 140 5.1E-06 1,700,000

Structural Building 

Components

0.32 lb ai/gallon 

dilute solution 30 0.0048 1800

Manuallypressurized 

Handwand

On-site wood treatment 0.525 lb ai/gallon 30 0.0079 1100

Residential Living Spaces 0.15 lb ai/gallon 

dilute solution 1100 0.083 110

Nursery, Landscaping (turf, 

trees, plants), Greenhouse

0.000073 lb 

ai/gallon dilute 

solution

40 gallons dilute 

solution 30 1.1E-06 8,000,000

Mechanicallypressurized 

handgun

Field Crops (typicalacreage), Landscaping 

(trees, plants), Nursery, 

Orchards/vineyards

1000 gallons 

dilute solution

8.68 7.9E-06 1,100,000

Greenhouse 120 1.1E-04 80,000

Structural Building 

Components

0.32 lb ai/gallon 

dilute solution

79 (NR)

15.8 (PF5)

0.316 (NR)

0.063 (PF5)

28 (NR)

140 (PF5)

Landscaping (turf) 0.003 lb ai/acre 5 acres 1.9 3.6E-07 25,000,000

Airless sprayer Structural Building 

Components

0.32 lb ai/gallon 

dilute solution

40 gallons dilute 

solution

560 (NR)

112 (PF5)

0.09 (NR)

0.018 (PF5)

98 (NR)

490 (PF5)
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 44 of 99

Table 11.1.1. Summary of Occupational Handler Risk Estimates for Boric Acid and its Sodium Salts

Exposure 

Scenario Crop / Target Category App Rate1

Amount 

Handled/Area 

Treated2

Inhalation3

Unit Exposure 

(ug/lb ai)4

Dose 

(mg/kg/day)5

MOE6

(LOC = 100)

Brush/roller 280 0.045 200

Brush/roller On-site wood treatment 0.85 lb ai/gallon 

dilute solution

5 gallons dilute 

solution 280 0.015 590

Mixing / 

loading / 

applying 

wettable 

dusts/ 

powders

Mechanicallypressurized 

handgun

Poultry house 0.15 lb ai/gallon 

dilute solution

1000 gallons 

dilute solution

79 (NR)

15.8 (PF5)

0.149 (NR)

0.03 (PF5)

59 (NR)

300 (PF5)

Manuallypressurized 

Handwand

Residential Living Spaces 0.18 lb ai/gallon 

dilute solution 40 gallons dilute 

solution

1100 (NR)

220 (PF5)

0.099 (NR)

0.0198 (PF5)

89 (NR)

440 (PF5)

Structural building 

components

0.31 lb ai/gallon 

dilute solution

1100 (NR)

220 (PF5)

0.17 (NR)

0.0341 (PF5)

52 (NR)

260 (PF5)

Tree stumps 0.0023 lb ai/ft2 1,000 ft2 of tree 

stumps 30 0.00085 10,000

Loading/ 

applying 

dusts

Bulb duster

Crack and crevice 

(residential areas, 

warehouses, food handling 

establishments)

0.00068 lb ai/ft2 10,000 ft2

1690 (NR)

338 (PF5)

0.144 (NR)

0.029 (PF5)

61 (NR)

310 (PF5)

0.22 lb ai/20 oz 

container

One 20 oz 

container 0.0047 1900

Plunger duster

Structural building 

components 0.0065 lb ai/ft2 10,000 ft2

1690 (NR)

338 (PF5)

169 (PF10)

1.38 (NR)

0.275 (PF5)

0.138 (PF10)

6.4 (NR)

32 (PF5)

64 (PF10)

Industrial/commercial areas 0.00068 lb ai/ft2 10,000 ft2 0.144 (NR)

0.029 (PF5)

61 (NR)

310 (PF5)

Poultry house 0.01 lb ai/ft2 10,000 ft2

2.18 (NR)

0.435 (PF5)

0.218 (PF10)

4 (NR)

20 (PF5)

40 (PF10)

Power 

duster/blower Poultry house 0.01 lb ai/ft2 10,000 ft2

17,500 (NR)

3500 (PF5)

17500 (PF10)

22.5 (NR)

4.5 (PF5)

2.25 (PF10)

< 1 (NR)

2 (PF5)

4 (PF10)
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 45 of 99

Table 11.1.1. Summary of Occupational Handler Risk Estimates for Boric Acid and its Sodium Salts

Exposure 

Scenario Crop / Target Category App Rate1

Amount 

Handled/Area 

Treated2

Inhalation3

Unit Exposure 

(ug/lb ai)4

Dose 

(mg/kg/day)5

MOE6

(LOC = 100)

Shaker can

Greenhouse, Nursery, 

Landscaping 

(plants/flowers), 

Warehouse, Poultry house, 

Foundations/Perimeters

0.22 lb ai/20 oz 

container

One 20 oz 

container 17,500 (NR)

3500 (PF5)

17500 (PF10)

0.048 180

Tree stumps 0.0023 lb ai/ft2 1,000 ft2 of tree 

stumps

0.495 (NR)

0.099 (PF5)

0.05 (PF10)

18 (NR)

89 (PF5)

180 (PF10)

Mixing / 

loading 

liquids

Groundboom

Golf course (tees and 

greens)

0.0018 lb ai/acre

5 acres

0.219

2.5E-08 360,000,000

Golf course (fairways, tees, 

and greens), Field-grown 

ornamentals, 

Orchard/vineyards

40 acres 2.0E-07 44,000,000

Nursery, Greenhouse 60 acres 3.0E-07 30,000,000

Field crops (typical acreage) 80 acres 3.9E-07 22,000,000

Field crops (high acreage) 200 acres 9.9E-07 8,900,000

Airblast

Nursery 20 acres 9.9E-08 89,000,000

Orchards/vineyards 40 acres 2.0E-07 44,000,000

Applying 

sprays

Groundboom Golf course (tees and 

greens) 0.0018 lb ai/acre 5 acres 0.34 3.8E-08 230,000,000
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 46 of 99

Table 11.1.1. Summary of Occupational Handler Risk Estimates for Boric Acid and its Sodium Salts

Exposure 

Scenario Crop / Target Category App Rate1

Amount 

Handled/Area 

Treated2

Inhalation3

Unit Exposure 

(ug/lb ai)4

Dose 

(mg/kg/day)5

MOE6

(LOC = 100)

Golf course (fairways, tees, 

and greens), Field-grown 

ornamentals, 

Orchard/vineyards

40 acres 3.1E-07 29,000,000

Nursery, Greenhouse 60 acres 4.6E-07 19,000,000

Field crops (typical acreage) 80 acres 6.1E-07 14,000,000

Field crops (high acreage) 200 acres 1.5E-06 5,800,000

Airblast

Nursery 20 acres

4.71

2.1E-06 4,100,000

Orchards/vineyards 40 acres 4.2E-06 2,100,000

Mixing/ 

loading 

granules 

Tractor drawn 

spreader

Golf course (fairways, tees, 

and greens) 1.5 lb ai/acre 40 acres

1.7 (NR)

0.34 (PF5)

0.0013 6900

Industrial/commercial areas 105 lb ai/acre 60 acres 0.134 (NR)

0.027 (PF5)

66 (NR)

330 (PF5)

Applying 

granules/ 

baits

Hand dispersal

Residential areas, food 

handling establishments 0.017 lb ai/1000 ft2 10,000 ft2

470 (NR)

94 (PF5)

47 (PF10)

0.001 8500

Foundations/perimeters 1.5 lb ai/acre

1 acre

0.009 1000

Industrial/commercial areas 105 lb ai/acre

0.618 (NR)

0.123 (PF5)

0.062 (PF10)

14 NR)

72 (PF5)

140 (PF10)
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 47 of 99

Table 11.1.1. Summary of Occupational Handler Risk Estimates for Boric Acid and its Sodium Salts

Exposure 

Scenario Crop / Target Category App Rate1

Amount 

Handled/Area 

Treated2

Inhalation3

Unit Exposure 

(ug/lb ai)4

Dose 

(mg/kg/day)5

MOE6

(LOC = 100)

Belly grinder

Landscaping (turf), 

Foundations/perimeters 1.5 lb ai/acre 1 acre

62

0.0012 7600

Industrial/commercial areas 105 lb ai/acre 1 acre 6.51 110

Tractor drawn 

spreader

Golf course (fairways, tees, 

and greens) 1.5 lb ai/acre 40 acres

1.2 (NR)

0.24 (PF5)

0.0009 9800

Industrial/commercial areas 105 lb ai/acre 60 acres 0.095 (NR)

0.019 (PF5)

93 (NR)

470 (PF5)

Rotary 

spreader

Golf course (fairways, tees, 

and greens), Landscaping 

(turf)

1.5 lb ai/acre 5 acres

10

0.0009 9400

Industrial/commercial areas 105 lb ai/acre 5 acres 0.066 130

Spoon

Foundations/perimeters 1.5 lb ai/acre 1 acre

121 (NR)

24.2 (PF5)

0.0023 3900

Industrial/commercial areas 105 lb ai/acre 1 acre 0.159 (NR)

0.032 (PF5)

55 (NR)

280 (PF5)

Cup

Foundations/perimeters 1.5 lb ai/acre 1 acre

12.5

0.00024 37000

Industrial/commercial areas 105 lb ai/acre 1 acre 0.0164 5400

Backpack Industrial/commercial areas 105 lb ai/acre 1 acre 23.8 0.031 280

Airless sprayer Interior/exterior surfaces 1.4% ai by weight 50 gallons 560 0.049 180
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 48 of 99

Table 11.1.1. Summary of Occupational Handler Risk Estimates for Boric Acid and its Sodium Salts

Exposure 

Scenario Crop / Target Category App Rate1

Amount 

Handled/Area 

Treated2

Inhalation3

Unit Exposure 

(ug/lb ai)4

Dose 

(mg/kg/day)5

MOE6

(LOC = 100)

Loading/ 

applying 

paints

Brush/roller 5 gallons 280 0.0025 3500

Applying 

gels/pastes

Crack and crevice (residential areas, 

warehouses, food handling establishments) No exposure/risks expected from gel/paste formulations.

Pouring-in

Powders

Swimming pools 0.3 lb ai/1000 

gallons water

660,000 gallons 

water

43 (NR)

8.6 (PF5)

0.11 (NR)

0.021 (PF5)

80 (NR)

420 (PF5)

Granules 1.7 0.0042 2100

Preservative 

incorporation

Paints, 

inks/dyes, 

coatings

Pouring-in powders/solids 1.4% ai by weight 

of finished material

20,000 lbs 

finished material 43 0.015 590

Wood/lumber

Pressure treatment

(Treatment operator – max. 

scenario)

5.25% ai solution 46 ug/m3 0.0058 1500

Dip Diffusion

(cleaning crew – max. 

scenario)

6.3 % ai solution 890 ug/% ai 0.070 130

Sapstain Treatment

(cleaning crew – max. 

scenario)

3.5% ai solution 890 ug/% ai 0.039 230

1 Based on registered label on registered labels outlined in Appendix C. All rates expressed in terms of boron.

2 Based on Exposure Science Advisory Council Policy #9.1 and standard assumptions for antimicrobial pesticides use.

3 NR = no respirator; PF5 = “Protection Factor 5”, indicating a reduction in exposure of 80%; PF10 = “Protection Factor 10” indicating a reduction in exposure of 90%. Unless noted, results reflect no 

respirator (NR).

4 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 2015).

5 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (kg). Expressed in terms of boron.

6 Inhalation MOE = Inhalation POD (mg/kg/day) ÷ Inhalation Dose (mg/kg/day)
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

11.2 Occupational Post-application Exposure/Risk Estimates

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

Given uses of boric acid/sodium salts, occupational post-application exposures are anticipated. 

Addressed below are inhalation exposures/risks only; though dermal exposures are possible, 

because absorption is negligible, toxicity via the dermal route is not expected; therefore dermal 

risks are not quantitatively addressed. Note also, as boric acid and its sodium salts are classified 

as “Not Likely to be Carcinogenic to Humans” only non-cancer risks are quantified.

11.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-0037). The agency 

has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the agency will utilize this analysis to determine if data (i.e., flux studies) or further 

analysis is required for boric acid/sodium salts.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the agency's risk assessments.

For applications within greenhouses, the Worker Protection Standard for Agricultural Pesticides 

contains requirements for protecting workers from inhalation exposures during and after 

greenhouse applications through the use of ventilation requirements [40 CFR 170.110, (3) 

(Restrictions associated with pesticide applications)]. Additionally, commercial applicators do 

not typically return to the treated areas after an indoor commercial pesticide application (sites 

such as warehouses, food handling establishments, and hotels, etc.) and thus an occupational 

post-application inhalation exposure assessment was not performed for commercial applicators.

11.2.2 Occupational Post-application Dermal Exposure/Risk Estimates
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 50 of 99

As dermal risks are not of concern, restricted-entry intervals (REIs) for boric acid/sodium salts 

default to technical grade active ingredient acute toxicity-based requirements. Currently, REIs 

on product labels vary considerably from 4 hours to 48 hours. These differences may reflect the 

different acute toxicity profiles of the various borate sodium salts, or the presence of an 

additional active ingredient in the product.

12.0 Public Health and Pesticide Epidemiology Data

The Agency has reviewed the available incident data for boric acid and its sodium salts (Memo, 

E. Evans and S. Recore, 1-OCT-2015; D429234). Boric acid was previously reviewed in 2005 

(M. Hawkins and H. Allender, 9/22/05, D320914). At the time, 20 incidents were reported for 

boric acid in Main IDS from 1992 to September 2005. A review of SENSOR-Pesticides from 

1998-2003, found 21 cases involving boric acid, 1 case involving sodium tetraborate 

decahydrate, and 4 cases involving disodium octaborate tetraborate. 

The current IDS analysis from January 1, 2010 through June 8, 2015, shows 10 incidents 

reported to Main IDS involving the single active ingredient boric acid. An additional 17 

incidents were reported involving more than one active ingredient. Three hundred and sixty 

(360) incidents of minor severity and 78 incidents with no or unknown effects were reported to 

Aggregate IDS involving boric acid. In addition, a query of SENSOR-Pesticides 2004-2011 

identifies a total of 104 cases involving boric acid.

Although there were a moderate number of boric acid incidents reported to Main and Aggregate 

IDS (n=466) and SENSOR-Pesticides (n=104), most of these incidents were classified as low 

severity. The effects experienced were generally minimally traumatic and resolved rapidly, 

usually irritation of the skin, eye or respiratory system. Based on the low severity of incidents 

reported to both IDS and SENSOR-Pesticides, there does not appear to be a concern at this time. 

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

analysis will be conducted.

13.0 References

13.1 OPP Memoranda

OPP Memoranda Relevant to Registration Review.

Author Barcode Date Title

M. Crowley D428582 9-Nov-2015 Boric Acid/Sodium Salts of Boric Acid. Occupational and 

Residential Exposure and Risk Assessment for Registration 

Review.

T. Dole D419073 13-NOV-2015 Occupational and Residential Exposure Assessment of the 

Antimicrobial Uses of Boric Acid and Salts for the Registration 

Review Draft Risk Assessment

E. Evans and S. Recore D429234 1-Oct-2015 Boric Acid and its Sodium Salts: Tier I Update Review of 

Human Incidents and Epidemiology for Draft Risk Assessment

J. Leshin TXR# 0057245 Dec-2015 Boric Acid and Sodium Borate Salts: Summary of Hazard and 

Science Policy Council (HASPOC) Meeting on September 3, 

2015: Recommendations on the Requirement of a Subchronic 

Dermal Toxicity Study

K. Rury TXR# 0056768 5-FEB-2014 Boric Acid/Borate Salts: Summary of Hazard and Science 

Policy Council (HASPOC) Meetings of August 15, 2013 and 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 51 of 99

OPP Memoranda Relevant to Registration Review.

Author Barcode Date Title

November 21, 2013: Recommendations on the Need for 

Subchronic Inhalation and Subchronic Neurotoxicity Studies

M. Hawkins and H. 

Allender

D320914 22-SEP-2005 Review of Boric Acid Incident Reports

K. Sherman Not applicable 27-JAN-2014 Ethics Review of Boric Acid Dermal Absorption Study

L. Hansen D359933 6-MAY-2009 Boric Acid/Sodium Salts of Boric Acid. Human Health 

Assessment Scoping Document in Support of Registration 

Review

L. Hansen D320894 26-JUL-2006 Boric Acid/Sodium Borate Salts: HED Chapter of the 

Tolerance Reassessment Eligibility Decision Document.

R. Loranger/D. 

McNeilly

D346904 5-MAY-2008 Borax (Sodium Tetraborate Decahydrate). Label Amendment to 

add Additional Agricultural Crops, Additional Ornamental, and 

Golf Course Use to the Label for Prey-AM Ultra (EPA Reg. 

No. 72662-3) and The Related Request for Exemption from the 

Requirement for a Tolerance

13.2 MRID Submissions

00005622 Weir, R.J. (1966) Final Report: Two-Year Dietary Feeding-Dogs. Hazleton 

Laboratories, Falls Church, VA, Project No. 182-106, July 8, 1966; submitted by

United States Borax. Unpublished report.

00005644 Meyding, G.D. (1961) Boric Acid: Acute Oral Administration – Rats. Hazleton 

Nuclear Science Laboratories, Inc., Palo Alto, CA. Project No. January 25, 1961; 

Submitted by United States Borax. Unpublished Report.

00006719 Hazleton Laboratories, Inc. (1962) Toxicity of Borax and Boric Acid. Received 

June 25, 1969 under 1624-96; submitted by United States Borax and Chemical 

Corp., Los Angeles, CA. Unpublished report.

00064204 Paynter, O.E., Kundzin, M and Kundzin, T. (1963) Boric Acid 90-Day Dietary 

Feeding-Dogs. Hazleton Laboratories, Falls Church, VA, January 17, 1963; 

submitted by U.S. Borax Research Corp., Unpublished report.

00064205 Weir, R.J. (1967) Final Report: 38-Week Dietary Feeding-Dogs. Hazleton 

Laboratories, Falls Church, VA, February, 1967; submitted by United States 

Borax. Unpublished report. 

00064207 Keller, J.G. (1962) Boric Acid: Acute Oral Administration – Rats. Hazleton 

Laboratories, Inc., Falls Church, VA. March 19, 1962; submitted by United 

States Borax. Unpublished report. 

00064208 Keller, J.G. (1962) Acute Oral Administration--Dogs: Boric Acid. Received 

March 5, 1981 under 1624-117; prepared by Hazleton Laboratories, Inc., 

submitted by United States Borax & Chemical Corp., Los Angeles, CA. 

Unpublished report.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 52 of 99

00064209 Estep, C.L. and Teske, R.H. (1968) Acute Application of Sample 713 123A to the

Eyes of Rabbits: S-152A. Received Mar 5, 1981 under 1624-117; prepared by 

Hill Top Research, Inc., submitted by United States Borax & Chemical Corp., Los 

Angeles, Calif. Unpublished report.

00068025 Paynter, O.E., Kundzin, M. and Kundzin, T. (1962) Boric Acid 90-Day Dietary 

Feeding-Rats. Hazleton Laboratories, Falls Church, VA, December 12, 1962; 

submitted by United States Borax. Unpublished report.

00068882 Weir, R.J. and Crews, L.M. (1966) Final Report: Three-Generation Reproduction 

Study-Rats. Hazleton Laboratories, Falls Church, VA, Project No. 182-105, July 

8, 1966; submitted by United States Borax. Unpublished report.

00068883 Weir, R.J. and Wright, D. (1966) Final Report: Two-Year Dietary 

AdministrationAlbino Rats. Hazleton Laboratories, Falls Church, VA, Project 

No. 182-104, July 8, 1966; submitted by United States Borax. Unpublished 

report.

00106011 Conine, D., Weiner, A., Kreuzmann, J. et al. (1982) Acute Dermal Toxicity 

Screen in Rabbits: Primary Skin Irritation Study in Rabbits of Boric Acid (OA 

107-3) for U.S. Borax Research Corporation: Hill Top Research Project No. 82-

0280-21. Received Jul 12, 1982 under 1624-116; prepared by Hill Top Research, 

Inc., submitted by United States Borax & Chemical Corp., Los Angeles, CA. 

Unpublished report.

40692301 Meyding, G.D. (1961) Acute Oral Administration - Rats with Sodium Tetraborate 

Decahydrate. Hazleton-Nuclear Science Corp., Palo Alto, CA. No study number 

provided. January 25, 1961. Unpublished report.

40692302 Meyding, G.D. (1961) Acute Oral Administration - Rats with Sodium Tetraborate

Decahydrate. Hazleton Laboratories, Inc., Vienna, VA. No study number 

provided. August 2, 1961. Unpublished report.

40692303 Keller, J.G. (1962) Acute Oral Administration – Rats with Borax (Sodium 

Tetraborate Decahdyrate). Hazleton Laboratories, Inc., Vienna, VA. No study

number provided. March 16, 1962. Unpublished report.

40692304 Keller, J.G. (1962) Acute Oral Administration – Dogs with Borax (Sodium 

Tetraborate Decahydrate). Hazleton Laboratories, Inc., Vienna, VA. No study 

number provided. March 16, 1962. Unpublished report.

40692505 Paynter, O.E. (1962) 90-Day Dietary Administration – Rats with 20 Mule Team 

Borax (Sodium Tetraborate Decahydrate). Hazleton Laboratories Inc., Falls 

Church, VA. No study No. provided, December 13, 1962. Unpublished report.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 53 of 99

40692306 Weir, R.J. (1963) 90-Day Dietary Administration – Rats with 20 Mule Team 

Borax (Sodium Tetraborate Decahydrate). Hazleton Laboratories, Inc., Vienna, 

VA. No study number provided. February 15, 1963. Unpublished report.

40692307 Paynter, O.E. (1963) 90-Day Dietary Feeding – Dogs with 20 Mule Team Borax 

(Sodium Tetraborate Decahydrate). Hazleton Laboratories, Inc., Vienna, VA. No 

study number provided. February 15, 1963. Unpublished report.

40692308 Weir, R.J. (1967) 38-Week Dietary Feeding – Dogs with 20 Mule Team Borax 

(Sodium Tetraborate Decahydrate). Hazleton Laboratories, Inc., Falls Church, 

VA. No study number provided. February 28, 1967. Unpublished report.

40692309 Weir, R.J. and Crews, L.M. (1967) Two Year Dietary Administration – Albino 

Rats. Borax (Sodium Tetraborate Decahydrate) and Addendum. Hazleton 

Laboratories, Inc., Falls Church, VA. Laboratory Project ID 182-104, April 10, 

1967 (original study on July 8, 1966). Unpublished report.

40692310 Weir, R.J. and Crews, L.M. (1967) Two Year Dietary Feeding – Dogs. Borax 

(Sodium Tetraborate Decahydrate) and Addendum. Hazleton Laboratories, Inc., 

Falls Church, VA. Laboratory Project ID 182-104, April 10, 1967 (original study 

on July 8, 1966). Unpublished report.

40692311 Weir, R.J. and Crews, L.M. (1966) Three-Generation Reproductive Study – Rats 

with Borax (Sodium Tetraborate Decahydrate) and Addendum. Hazleton 

Laboratories, Inc., Vienna, VA. Project No. 182-105. July 8, 1966. Unpublished 

report.

41589101 Fail, George, Grizzle et al. (1990) Reproductive Toxicity of Boric Acid in CD-1 

Swiss Mice. NTP, NIEHS, Research Triangle Park, N.C. Study Number 90-105, 

April 13, 1990. Unpublished report.

41725401 Field, E.A., Price, C.J., Marr, M.C. et al. (1990) Final Report on the 

Developmental Toxicity of Boric Acid (CAS No. 10043-35-3) in Sprague-Dawley 

Rats. EPA Rg. No. 1624-117. Research Triangle Institute and National 

Toxicology Program. Study Number Rt88-BORT, May 1, 1990. Published 

report.

41725402 Field, E.A., Price, C.J., Marr, M.C. et al. (1990) Final Report on the 

Developmental Toxicity of Boric Acid (CAS No. 10043-35-3) in CD-1 Swiss 

Mice. EPA Reg. No. 1624-117. Research Triangle Institute and National 

Toxicology Program. Study Number M188-BORT, December 14, 1990. 

Published report.

41861301 Dieter, M., Bishop, J., Eustis, S. Haseman, J. et al. (1991) Toxicology and 

Carcinogenesis of Boric Acid in B6C3F1 Mice, NTP Technical Report Series 

324. E.G. and G. Mason Research Institute, Study No. TR324, April, 1991. 

Published report.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 54 of 99

42038901 Steward, K.R. (1991) Salmonella/Microsome Plate Incorporation Assay of Boric 

Acid. SRI International, Inc., Menlo Park, CA. Study No. 2389-A200-91, 

August 12, 1991. Unpublished report.

42038902 Rudd, C.J. (1991) Mouse Lymphoma Cell Mutagenesis Assay (tk+/-/tk-/-) of Boric 

Acid. SRI International, Menlo Park, CA. Study Number 2389-G300-91, August 

23, 1991. Unpublished report.

42038903 Bakke, J.P. (1991) Evaluation of the Potential of Boric Acid to Induce 

Unscheduled DNA Synthesis in In Vitro Hepatocyte DNA Repair Assay Using 

the Male F-344 Rat. SRI International, Menlo Park, CA. Study Number 2389-

V50091, August 21, 1991. Unpublished report.

42038904 O’Loughlin, K.G. (1991) Bone Marrow Erythrocyte Micronucleus Assay of Boric 

Acid in Swiss-Webster Mice. SRI International, Menlo Park, CA. Study Number 

2389-C400-91, August 19, 1991. Unpublished report.

42164201 Price, C., Marr, M. and Myers, C. et al. (1991) Developmental Toxicity of Boric 

Acid in New Zealand White Rabbits. NTP and Chemistry and Life Sciences, 

Research Triangle Park, NC. Study No. Rb90-BPORA, October 30, 1991. 

Published report. 

 

42164202 Price, C.; Marr, M. and Myers, C.; et al. (1991) Laboratory Supplement for Final 

Report on the Development Toxicity of Boric Acid in New Zealand White 

Rabbits. National Institute of Environmental Health Science and Research 

Triangle Institute, Lab Project Number: RB90-BORA. Unpublished report. 

43340101 Price, C.J., Marr, M.C. and Myers, C.B. (1994) Determination of NOAEL for 

Developmental Toxicity in Sprague Dawley Rats Exposed to Boric Acid in Feed 

on Gestation Days 0-20 and Evaluation of Post Natal Recovery Through Post

Natal Day 21. Reproduction and Developmental Toxicology Labs, RTI, RTP, 

North Carolina. Study Number 65C5657-200, August 8, 1994. Unpublished 

report.

43500701 Wnorowski, G. (1994) Acute Inhalation Toxicity Limit Test on Boric Acid (in 

Rats). Product Safety Labs, East Brunswick, NJ. Study No. 3311, November 28, 

1994. Unpublished report.

43553201 Reagan, E. and Becci, P. (1985) Acute Dermal Toxicity Study of 20 Mule Team, 

Lot USB-11-84 Sodium Tetraborate Decahydrate in New Zealand White Rabbits. 

Food and Drug Research Laboratories, Inc., Waverly, NY. Study Report No. 

FDRL 8403A, February 20, 1985. Unpublished report.

43553202 Reagan, E. and Becci, P. (1985) Primary Eye Irritation Study of 20 Mule Team, 

Lot USB-11-84 Sodium Tetraborate Decahydrate in New Zealand White Rabbits. 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 55 of 99

Food and Drug Research Laboratories, Inc., Waverly, NY. Study Report No. 

FDRL 8403A, February 8, 1985. Unpublished report.

43354202 Reagan, E. and Becci, P. (1985) Primary Dermal Irritation Study of 20 Mule 

Team, Lot USB-11-84 Sodium Tetraborate Decahydrate in New Zealand White 

Rabbits. Food and Drug Research Laboratories, Inc., Waverly, NY. Study 

Report No. FDRL 8403A, January 23, 1985. Unpublished report.

44383601 Wnorowski, G. (1994) Acute Inhalation Toxicity Limit Test on Boric Acid (in 

Rats). Product Safety Labs, East Brunswick, NJ. Study No. 5257, July 11, 1997. 

Unpublished report.

46852201 Draize, J.H. and Kelley, E.A. (1959) The Urinary Excretion of Boric Acid 

Preparations following Oral Administration and Topical Applications to Intact 

and Damaged Skin of Rabbits. Toxicol and Applied Pharmacol 1:267-276.

48507005 Hui, X., Wester, R., and Maibach, H. (1995). In vivo percutaneous absorption 

of boric acid, borax, and disodium octaborate tetrahydrate (DOT) in human 

skin. Dept. of Dermatology, Surge Laboratory, University of California, San 

Francisco, CA 93143. Study Number H832-11830-01. December 17, 1995. 

MRID 48507005. Unpublished report.

48549901 Hartway, T.; Wester, R., Maibach, H. (1996) In vitro percutaneous absorption 

of boric acid, Borax, and disodium octaborate tetrahydrate (DOT) in human 

skin. Department of Dermatology Surge Laboratory, University of California; 

Study Number 95SU02, November 11, 1996. Unpublished report.

48773701 Johnson, W. (2012) Single-dose oral (gavage) neurotoxicity limit test of boric 

acid in Sprague-Dawley rats. IIT Research Institute (IITRI), Chicago, IL. 

IITRI Project No. 2328-001, March 7, 2012. Unpublished report.

48786601 Curry P. (2012) Evaluation of the Potential Immunogenic Activity of Boric Acid 

Using the Sheep Red Cell Plaque Forming Assay in Mice. Project number: 

2328/002. IIT Research Institute, Chicago, IL. Unpublished report.

48798001 Curry P. (2012) Evaluation of the Potential Immunogenic Activity of Boric Acid 

Using the Sheep Red Cell Plaque Forming Assay in Mice. Project number: 

2337/001. IIT Research Institute, Chicago, IL. Unpublished report.

49735901 Residue Determination of Prev-AM When Applied on Baby Marrows in the 

Western Cape. Trial Code: 2010-101R. Field trial summary report submitted by 

Screeners Development CC. June 25, 2010.

49735902 Residue Determination of Prev-AM When Applied on Spinach in the Western 

Cape. Trial Code: 2010-103R. Field trial summary report submitted by 

Screeners Development CC. June 25, 2010
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 56 of 99

49735903 Residue Determination of Prev-AM When Applied on Potatoes in the Western 

Cape. Trial Code: 2010-105R. Field trial summary report submitted by 

Screeners Development CC. June 25, 2010.

49735904 Analyses Report for Lettuce Field Trial Code 2010-104R (MRID 49735909). 

BemLab Report No. NR6125/2010. June 10, 2010.

49735907 Analyses Report for Potato Field Trial Code 2010-105R (MRID 49735903). 

BemLab Report No. VR116/2011. January 1, 2011..

49735908 Residue Determination of Prev-AM When Applied on Tomatoes in the Western 

Cape. Trial Code: 2010-102R. Field trial summary report submitted by 

Screeners Development CC. June 25, 2010.

49735909 Residue Determination of Prev-AM When Applied on Lettuce in the Western 

Cape. Trial Code: 2010-104R. Field trial summary report submitted by 

Screeners Development CC. June 25, 2010.

49735911 Analyses Report for Spinach Field Trial Code 2010-103R (MRID 49735902). 

BemLab Report No. NR4659/2010. May 19, 2010.

49735914 Analyses Report for Baby Marrow Field Trial Code 2010-101R (MRID 

49735901). BemLab Report No. NR4355/2010. May 10, 2010.

49735915 Analyses Report for Tomato Field Trial Code 2010-102R (MRID 49735908). 

BemLab Report No. NR4663/2010. May 17, 2010

13.3 Published Literature and Other Documents

Agency for Toxic Substances and Disease Registry (ATSDR) (1992) Toxicological Profile for 

Boron and Compounds. U.S. Public Health Service.

Anderson, D.L., Cunningham, W.C. and Lindstrom, T.R. (1994) Concentrations and Intakes of

H, B, S, K, Na, Cl and NaCl in Foods. J. of Food Comp. and Anal. 7:59-82.

Chapin, R.E. and Ku, W.W. (1994) The Reproductive Toxicity of Boric Acid. Environ. Health 

Perspect. 102(Suppl. 7):87-91.

Chapin, R.E. et al. (1997) The effects of dietary boron on bone strength in rats. Fund. Appl. 

Toxicol. 35:205-215.

Culver, B.D. et al. (1994) The relationship of blood- and urine-boron to boron exposure in 

borax-workers and the usefulness of urine-boron as an exposure marker. Environ. Health 

Perspect. 102 (Suppl. 7):133-137.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 57 of 99

Draize, J.H. and Kelley, E.A. (1959) The Urinary Excretion of Boric Acid Preparations 

following Oral Administration and Topical Applications to Intact and Damaged Skin of Rabbits. 

Toxicol. Appl. Pharmacol. 1: 267-276.

European Commission, Directorate-General for Health and Consumers, Scientific Committee on 

Consumer Safety (2010) Opinion on Boron Compounds. SCCS/1249/09, Revision of 28 

September 2010.

ECETOX European Centre for Ecotoxicology and Toxicology of Chemicals. (1995) Technical 

Report No. 63.

Fail, P.A., Chapin, R.E., Price, C.J. et al. (1998) General, Reproductive, Developmental and 

Endocrine Toxicity of Boronated Compounds. Reprod. Toxicol 12:1-18.

Hunt, C.H., (1994) The Biochemical Effects of Physiologic Amounts of Dietary Boron in 

Animal Nutrition Models. Environmental Health Perspectives 102, Supplement 7, Nov 1994.

Kissel, JC. (2011) The mismeasure of dermal absorption. J Expo Sci Environ Epid. 21(3): 302-

309.

Ku, W.W. et al. (1991) Tissue Disposition of Boron in Male Fischer Rats. Toxicol. Appl. 

Pharmacol 111:145-151.

Ku, W.W. et al. (1993) Testicular Toxicity of Boric Acid (BA): Relationship of Dose to Lesion 

Development and Recovery in the F344 Rat. Reprod. Toxicol. 7:305-319.

Ku, W.W. and Chapin. R.E. (1994) Mechanism of the Testicular Toxicity of Boric Acid in Rats. 

In Vivo and In Vitro Studies. Environ. Health Perspect. 102(Suppl. 7):99-105.

Litovitz, T.L. et al. (1988) Clinical manifestations of toxicity in a series of 784 boric acid 

ingestions. Am. J. Emerg. Med. 6:209-213.

Moore, J.A. (1997) An Assessment of Boric Acid and Borax Using the IEHR Evaluative Process 

for Assessing Human Developmental and Reproductive Toxicity of Agents. Expert Scientific 

Committee. Reprod. Toxicol. 11(1):123-160.

Naghii, M.R. and Samman, S. (1996) The boron content of Selected Foods and the Estimation of 

its Daily Intake Among Free-Living Subjects. J. Am. College Nutr. 15(6):614-619.

National Academy of Sciences Dietary (2001) Reference Intakes-Vitamin A, Vitamin K, 

Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, 

Vanadium and Zinc. 2001. Food and Nutrition Board, Institute of Medicine, p. 773.

National Institute for Occupational Safety and Health (NIOSH). (2001) International Chemical

Safety Cards (ICSC): Boric Acid -- 0991; Sodium tetraborate decahydrate -- 0567; Sodium

tetraborate -- 1229. http://www.cdc.gov/niosh/npg/npg.html
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 58 of 99

Nielsen, F.H. (1991) Nutritional Requirements for Boron, Silicon, Vanadium, Nickel and 

Arsenic: Current Knowledge and Speculation. FASEB J. 5:2661-2667.

Nielsen, G.H. (1970) Percutaneous Absorption of Boric Acid from Boron-Containing 

Preparations in Rats. Acta Pharmacol. et Toxicol. 28:413-424.

Rainey, C.J., Nyquist, L.A., and Strong, R.E. et al. (1999) Daily Boron Intake from the 

American Diet. J. Am. Diet Assoc. 99(3):335-340.

Rainey, et al, (2002) Dietary Boron Intake in the United States: CSFII 1994-1996. J. Food 

Comp and Anal. 15, 237-250.

U.S. EPA (1993) Reregistration Eligibility Decision Decision (RED): Boric Acid and its 

Sodium Salts. Office of Prevention, Pesticides, and Toxic Substances (7508W). EPA 738-R-93-

017.

U.S. EPA (2008). Regulatory Determinations Support Document for Selected Contaminants 

from the Second Drinking Water Contaminant Candidate List (CCL 2). Office of Water. EPA 

815-R-08-012. June 2008.

Vanderpool, R.A., Hof, D. and Johnson, P.E. (1994) Use of inductively coupled plasma-mass 

spectrometry in boron-10 stable isotope experiments with plants, rats, and humans. Environ

Health Perspect. 102 (suppl. 7):13-20.

Wilding, J.L. et al. (1959) The Toxicity of Boron Oxide. American Industrial Hygiene 

Association J. 20(4):284-289.

World Health Organization (WHO). (1998) Environmental Health Criteria 204: Boron. 

International Programme on Chemical Safety (IPCS). Geneva, Switzerland. ISBN 92 4 157204

World Health Organization (WHO) (2003) WHO Guidelines for drinking-water quality. 

WHO/SDE/WSH/03.04/54.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 59 of 99

Appendix A: Toxicity Profile and Executive Summaries

A.1 Toxicology Data Requirements

Requirements (40 CFR 158.340) for food use for boric acid/borate salts are in Table A.1. Use of 

the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table A.1 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

no

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 28 or 90-Day Inhalation..................................................

yes

yes

no1

no

no2

yes

yes

--

--

--

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

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

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

yes

yes

yes

yes

yes

yes

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

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

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

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

870.4300 Chronic/Oncogenicity.....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

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

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

870.5375 Mutagenicity—Structural Chromosomal Aberrations....

870.5395 Mutagenicity—Mammalian Erythrocyte Micronucleus.

870.5550 Mutagenicity—Unscheduled DNA Synthesis................

870.5915 Mutagenicity—In Vivo Sister Chromatid Exchange

yes

yes

yes

yes

yes

no

yes

yes

yes

yes

yes

--

870.6100a Acute Delayed Neurotoxicity. (hen)...............................

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

870.6200a Acute Neurotoxicity Screening Battery (rat) ..................

870.6200b 90 Day Neurotoxicity Screening Battery (rat)................

870.6300 Develop. Neurotoxicity...................................................

no

no

yes

no3

no

--

--

yes

--

--

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

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

no5

yes

--

yes

870.7800 

Immunotoxicity................................................
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 60 of 99

Table A.1 Test Technical

Required Satisfied

yes yes

1 Dermal absorption data and published reports were used to assess dermal toxicity potential.

2 Subchronic inhalation data requirement waived by HED HASPOC (K. Rury, February 15, 2015, TXR No. 

0056768)

3 90-day neurotoxicity screening battery requirement waived by the HED HASPOC (see above citation).

 Requirement fulfilled by published reports

A.2 Toxicity Profiles

Table A.2.a Acute Toxicity Profile - Boric Acid 

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral rat 00006719 LD50 males = 3450 mg/kg 

females = 4080 mg/kg 

III

870.1100 Acute oral beagle dog 00064208 LD50 > 631 mg/kg III

870.1200 Acute dermal rabbit 00106011 LD50 >2 g/kg III

870.1300 Acute inhalation rat 43500701 LC50>2.03 mg/L (no 

deaths)1

III

870.2400 Acute eye irritation rabbit 00064209 Conjunctival irritation 

clearing by Day 4

III

870.2500 Acute dermal irritation rabbit 00106011 Primary irritation score = 

0.1; 1/6 erythema at 72 

hrs

III

1 exposure levels were limited by inability to produce higher test atmosphere concentrations

Table A.2.b Acute Toxicity Profile - Sodium tetraborate decahydrate (Borax) 

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral rat 40692303 LD50 males = 4550 mg/kg 

females = 4980 mg/kg 

III

870.1100 Acute oral dog 40692304 LD50 > 974 mg/kg III

870.1200 Acute dermal rabbit 43553201 LD50 > 2000 mg/kg III

870.1300 Acute inhalation rat 43500801 LC50>2.03 mg/L (no 

deaths) III

870.2400 Acute eye irritation rabbit 43553203 Corrosive I

870.2500 Acute dermal irritation rabbit 43553202 Non-irritating IV
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 61 of 99

Table A.2.c Subchronic, Chronic and Other Toxicity Profiles for Boric Acid and Borate Salts

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Results (Note: all dose levels for NOAELs and 

LOAELS in this table are expressed as mg/kg bw/day 

of boron equivalents)

870.3100

90-Day oral toxicity (rat)

00068025 (1962)

Acceptable/nonguideline together 

with 00068883

0, 0.03, 0.1, 0.3, 1.0 or 3.0% 

boric acid in diet for 90 days. 

Equivalent to 0, 3.9, 13, 38, 124 

or 500 mg/kg bw/day boron

NOAEL = 38 mg/kg bw/day

LOAEL = 124 mg/kg bw/day, based on clinical signs of 

toxicity, decreased body weight, testicular 

atrophy/reduced testicular weights, reduced ovarian 

weights.

870.3100

90-Day oral toxicity (rat)

40692305 (1963)

Acceptable/nonguideline together 

with 40692306

0, 0.0463, 0.154, 0.463, 1.54 or 

4.63% sodium tetraborate 

decahydrate in diet for 90 days. 

Equivalent to 0, 4.0, 14, 42, 125 

or 455 mg/kg bw/day boron

NOAEL = 42 mg/kg bw/day

LOAEL = 125 mg/kg bw/day based on clinical signs of 

toxicity, decr. weight gain and food consumption, decr. 

testes and ovarian weights, testicular atrophy.

870.3100

90-Day oral toxicity (rat, 

male rat only)

40692306 (1963)

Acceptable/nonguideline together 

w/40692305-

0, 0.015, 0.0463, 0.154 or 

0.463% sodium tetraborate 

decahydrate in diet for 90 days. 

Equivalent to 0, 1.3, 4.3, 13.1 or 

41 mg/g/day boron

NOAEL = 41mg/kg bw/day (males only tested)

LOAEL >41 mg/kg bw/day (HDT).

870.3150

90-Day oral toxicity (dog)

00064204 (1963)

Acceptable/nonguideline together 

with 40692308 and 00005622

0, 0.01, 0.1 or 1.0% boric acid in 

diet for 90 days. Equivalent to 0, 

0.46, 4.2 or 35 mg/kg bw/day 

boron

NOAEL = 4.2 mg/kg bw/day

LOAEL = 35 mg/kg bw/day, based on testicular atrophy

870.3150

90-Day oral toxicity (dog)

40692307 (1963)

Acceptable/nonguideline

0, 0.0154, 0.154, 1.54% sodium 

tetraborate decahydrate in diet 

for 90 days. Equivalent to 0, 

0.34/0.25, 4.1/2.6 or 32/23 [M/F] 

mg/kg bw/day boron 

NOAEL = 4.1mg/kg bw/day M/2.6 mg/kg bw/day F

LOAEL = 32 mg/kg bw/day M/23 mg/kg bw/day F, based 

on decr. HCT/Hgb, testicular atrophy, decr. testes weight 

and incr. hemosiderin pigment in spleen, liver, kidneys.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 62 of 99

Table A.2.c Subchronic, Chronic and Other Toxicity Profiles for Boric Acid and Borate Salts

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Results (Note: all dose levels for NOAELs and 

LOAELS in this table are expressed as mg/kg bw/day 

of boron equivalents)

870.3700a

Prenatal developmental 

(rat)

41725401 (1990)

Acceptable/guideline when 

considered together with MRID 

43340101

0, 0.1, 0.2, 0.4% GD 0-20 and 

0.8% GD 6-15 boric acid in diet.

equivalent to 0, 14, 29 or 58 

mg/kg bw/day boron and 94 

mg/kg bw/day boron 

Maternal NOAEL = 94 mg/kg bw/day 

Developmental NOAEL <14 mg/kg bw/day

LOAEL = 14 mg/kg bw/day based on slightly decr. fetal 

body weight. At 29 mg/kg bw/day, skeletal abnormalities 

observed and at 58 and 94 mg/kg bw/day, high incidence 

skeletal and visceral abnormalities, and mortality

870.3700a

Prenatal developmental 

(rat)

43340101 (1994)

Acceptable/guideline

0, 0.025%, 0.050%, 0.075%, 

0.10% or 0.20% boric acid. 

Equivalent to 0, 3.3, 6.3, 9.6, 13.3 

or 25 mg/kg bw/day boron

Maternal NOAEL = 25 mg/kg bw/day (HDT)

LOAEL = not determined (slightly decreased gravid 

uterine weight considered secondary to fetal toxicity)

Developmental NOAEL = 9.6 mg/kg bw/day

LOAEL = 13.3 mg/kg bw/day based on slightly decr. fetal 

body weight, rib XIII abnormalities

870.3700a

Prenatal developmental 

(mouse)

41725402 (1990)

Acceptable/guideline

0, 0.1, 0.2, 0.4% 

boric acid in diet equivalent to 0, 

43, 79 or 176 mg/kg bw/day 

boron

Maternal NOAEL not established <43 mg/kg bw/day

LOAEL = 43 mg/kg bw/day based on renal tubular 

dilatation/regeneration.

Developmental NOAEL = 43 mg/kg bw/day

LOAEL = 79 mg/kg bw/day based on decr. fetal wt, incr. 

resorptions, incr. malformations (short rib XIII, fused rib).

870.3700b

Prenatal developmental 

(rabbit)

42164201, 42164202 (1991)

Acceptable/guideline

0, 62.5, 125 or 250 mg/kg bw/day 

boric acid by gavage.

Equivalent to 0, 11, 22 or 44 

mg/kg bw/day boron 

Maternal NOAEL = 22 mg/kg bw/day

LOAEL = 44 mg/kg bw/day based on incr. intrauterine 

bleeding, decreased unadjusted weight gain during 

treatment (due to decr. gravid uterine weight).

Developmental NOAEL = 22 mg/kg bw/day

LOAEL = 44 mg/kg bw/day based on incr. mortality 

(resorptions, postimplantation loss), decr. fetal weight, 

intraventricular septal defect, enlarged aorta.

870.3800

Reproduction and fertility 

effects (rat)

00068882 (1966)

Acceptable/nonguideline

0, 0.067, 0.20 or 0.67% boric 

acid in the diet. Equivalent to 0, 

8.5/9.7, 27/29 or 85/92 mg/kg 

bw/day [M/F] boron

Parental/Systemic NOAEL = 27 mg/kg bw/day

LOAEL = 85 mg/kg bw/day based on clinical signs, decr. 

body weight, testicular atrophy, decr. testes weight, decr. 

corpora lutea.

Reproductive NOAEL = 27 mg/kg bw/day

LOAEL = 85 mg/kg bw/day based on decr. fertility (no 

litters).

Offspring NOAEL = 27 mg/kg bw/day

LOAEL = 85 mg/kg bw/day based on no litters produced.

870.3800 40692311 (1966)

Acceptable/nonguideline

Parental/Systemic NOAEL = 28 mg/kg bw/day
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 63 of 99

Table A.2.c Subchronic, Chronic and Other Toxicity Profiles for Boric Acid and Borate Salts

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Results (Note: all dose levels for NOAELs and 

LOAELS in this table are expressed as mg/kg bw/day 

of boron equivalents)

Reproduction and fertility 

effects (rat)

0, 0.103, 0.308 or 1.03% sodium 

tetraborate decahydrate in the 

diet. Equivalent to 0, 8.1/9.2, 

28/31 or 82/92 [M/F] mg/kg 

bw/day boron

LOAEL = 82 mg/kg bw/day based on clinical signs, decr. 

body weight, testicular atrophy, decr. testes weight, decr. 

corpora lutea.

Reproductive NOAEL = 28 mg/kg bw/day

LOAEL = 82 mg/kg bw/day based on decr. fertility (no 

litters).

Offspring NOAEL = 28 mg/kg bw/day

LOAEL = 82 mg/kg bw/day based on no litters produced.

870.3800

Reproduction and fertility 

effects (mouse)

41589101 (1990)

Acceptable/guideline

0, 1000, 4500 or 9000 ppm boric 

acid in diet (for P1 matings only 

0 and 1000 ppm groups). 

Equivalent to 0, 27, 111 or 221 

mg/kg bw/day boron

Parental/Systemic NOAEL = 27 mg/kg bw/day

LOAEL = 111 mg/kg bw/day based on decr. testicular 

weight, atrophy and degeneration of seminiferous tubules.

Reproductive NOAEL = 27 mg/kg bw/day

LOAEL = 111 mg/kg bw/day based on decr. fertility.

Offspring NOAEL = 27 mg/kg bw/day

LOAEL = 111 mg/kg bw/day based on decr. pup wt., 

decreased survival and fewer pups born

870.4100b

Chronic toxicity (dog)

00064205 (1967)

Acceptable/nonguideline when 

considered together with 

00005622 and 4366910.

0 or 0.67% boric acid 

decahydrate in diet for 38 

weeks. Equivalent to 0 or 40 

mg/kg bw/day boron 

NOAEL not established (≥ 40 mg/kg bw/day)

LOAEL = 40 mg/kg bw/day, based on testicular atrophy, 

870.4100b

Chronic toxicity (dog)

40692308 (1967)

Acceptable/nonguideline when 

considered together with 

40692307, -09.

0 or 1.03% sodium tetraborate 

decahydrate in diet for 38 

weeks. Equivalent to 0 or 40 

mg/kg bw/day boron 

NOAEL not established (<40 mg/kg bw/day)

LOAEL = 40 mg/kg bw/day based on decr. body wt. gain, 

testicular atrophy.

870.4100b

Chronic toxicity (dog)

00005622 (1966)

Acceptable/nonguideline when 

considered together with 

00005624 and 00064203

0, 0.033, 0.067 or 0.20% boric 

acid in diet for two years. 

Equivalent to 0, 1.6, 3.6 or 10.2 

mg/kg bw/day boron, males and 

0, 1.8, 4.0 or 11.6 mg/kg bw/day 

boron, females

NOAEL = 10.2 mg/kg bw/day

LOAEL not established (≥10.2 mg/kg bw/day)
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 64 of 99

Table A.2.c Subchronic, Chronic and Other Toxicity Profiles for Boric Acid and Borate Salts

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Results (Note: all dose levels for NOAELs and 

LOAELS in this table are expressed as mg/kg bw/day 

of boron equivalents)

870.4100b

Chronic toxicity (dog)

40692310 (1967)

Acceptable/nonguideline when 

considered together with 

40692308.

0, 0.051, 0.103 or 0.309% 

sodium tetraborate 

decahydrate in the diet for two 

years . Equivalent to 0, 1.5, 2.9 

or 8.8 mg/kg bw/day boron 

NOAEL = 8.8 mg/kg bw/day

LOAEL not established (>8.8 mg/kg bw/day)

870.4200

Carcinogenicity

(rat)

00068883 (1966)

Acceptable/nonguideline

0, 0.01, 0.1 or 1.0% boric acid in 

the diet for two years. Equivalent 

to 0, 5.2, 16 or 58 mg/kg bw/day 

boron, males; 0, 6.3, 19 or 70 

mg/kg bw/day boron, females

NOAEL = 16 mg/kg bw/day

LOAEL = 58 mg/kg bw/day, based on clinical signs, 

decreased body weight, decreased testicular weight, 

testicular atrophy, increased anovulatory/involuted 

ovaries, decreased RBC parameters.

no evidence of carcinogenicity

870.4200

Carcinogenicity

(rat)

40692309 (1966)

Acceptable/nonguideline

0, 0.130, 0.308, 1.030% sodium 

tetraborate decahydrate in diet 

for two years. Equivalent to 0, 

7.3, 17 or 58 mg/kg bw/day 

boron 

NOAEL = 17 mg/kg bw/day

LOAEL = 58 mg/kg bw/day based on decr. body weight 

(observed by 3-4 weeks), testicular atrophy, slightly 

decreased hematocrit/hemoglobin.

no evidence of carcinogenicity

870.4300

Carcinogenicity

(mouse)

41861301 (1991)

Acceptable/nonguideline

0, 2500 or 5000 ppm boric acid.

Equivalent to 0, 66 or 192 mg/kg 

bw/day boron in males and 0, 85 

or 212 mg/kg bw/day in females.

Note: equivalent average daily 

doses of boron represent actual 

calculations for males and 

females based on food 

consumption values from the 

report. The study report 

suggested that due to feed 

spillage, actual compound 

consumption may be lower, at 

approximately 48/96 mg/kg 

bw/day.

NOAEL = not established <66 mg/kg bw/day in males; 85

mg/kg bw/day in females

LOAEL = 66 mg/kg bw/day in males, based on slightly 

increased mortality and splenic lymphoid depletion ; 212 

mg/kg bw/day in females, based on decr. body weights. In 

males at 192 mg/kg bw/day, decreased body weights, ; 

testicular atrophy, and interstitial cell atrophy were also 

observed..

no evidence of carcinogenicity
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 65 of 99

Table A.2.c Subchronic, Chronic and Other Toxicity Profiles for Boric Acid and Borate Salts

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Results (Note: all dose levels for NOAELs and 

LOAELS in this table are expressed as mg/kg bw/day 

of boron equivalents)

870.5300 Gene Mutation

Mouse in vitro lymphoma 

forward gene mutation 

assay

42038902 (1991)

Acceptable/guideline

1200-5000 μg/mL boric acid +/-

S9

Negative for induction of mutagenic response in two 

independently performed mouse L5178Y cell lymphoma 

forward mutation assays. Marginal cytotoxicity at 3500-

5000 μg/mL

870.5100 Gene Mutation

S. typhimurium reverse 

gene mutation assay

42038901 (1991)

Acceptable/guideline

10-2500 μg/plate boric acid

Negative for induction of mutagenic response in S. 

typhimurium strains TA1535, TA1537, TA1538, TA98 or 

TA100 in the presence or absence of S9 up to 2500 

μg/plate. No cytotoxicity was observed.

870.5385 Cytogenetics 

Mouse in vivo 

micronucleus assay

42038904 (1991)

Acceptable/guideline

900, 1800 or 3500 mg/kg boric 

acid

Negative for induction of clastogenic response to the bone 

marrow of Swiss mice. No systemic toxicity or target 

cytotoxicity observed up to 3500 mg/kg.

870.5550 Other Effects 

Rat liver in vitro

unscheduled DNA 

synthesis

42038903 (1991)

Acceptable/guideline

5-5000 μg/mL boric acid

Negative for increased unscheduled DNA synthesis in 

cultured rat hepatocytes. Slightly increased percent cells 

in repair at ≥2500 μg/mL in repeat assay were secondary 

to increased cytotoxicity at those dose levels.

870.6200a 

Acute oral neurotoxicity 

screening (rat)

48773701 (2012)

Acceptable/guideline

0 or 2000 mg/kg boric acid 

(limit test)

NOAEL = 2000 mg/kg (350 mg/kg bw/day boron 

equivalents)

A LOAEL for neurotoxicity or systemic toxicity was not 

determined.

870.7600

In vivo dermal absorption

(human)

48507005 (1995)

Acceptable/nonguideline

1.8 mL aqueous 5% boric acid, 

5% borax or 10% disodium 

octaborate tetrahydrate (DOT) on 

30 cm x 30 cm dorsal skin area 

for 24 hr exposure, 8 human 

volunteers.

Exposures and collection 

repeated on skin exposed to 2% 

sodium dodecyl sulfate as an 

irritant.

Absorbed dose as measured in urine (7-day collection 

post-exposure) -/+ SDS skin treatment:

Boric acid – 0.226/0.239% AD 

Borax – 0.210/0.185% AD

DOT – 0.122/0.1- 07% AD

Recoveries = 49 to 64% AD

870.7600

In vitro dermal absorption

(human cadaver skin)

48549901 (1996) 

Acceptable/nonguideline

0.05, 0.5 and 5.0% boric acid

5% borax and 5% DOT.

All tested at 1000 μL/cm2and 

% boric acid also at 2 μL/cm2 on 

a total of 6 skin samples

Absorbed dose in receptor fluid only (skin samples not 

tape-stripped):

Boric acid – 1.75, 0.70, 0.28 and 1.20% AD at 5% (2 

μL/cm2), 5% (1000 μL/cm2), 0.5% and 0.05%, 

respectively

Borax, 5% – 0.41% AD

DOT, 5% – 0.19% AD 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 66 of 99

Table A.2.c Subchronic, Chronic and Other Toxicity Profiles for Boric Acid and Borate Salts

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses

Results (Note: all dose levels for NOAELs and 

LOAELS in this table are expressed as mg/kg bw/day 

of boron equivalents)

Recoveries = 72 to 86% AD

870.7800

Immunotoxicity (mouse)

48786601 (2012) 

0 or 1000 mg/kg boric acid, IV 

injection

Acceptable/guideline

48798001 (2012) 

0, 250, 500, 750 or 1000 mg/kg 

bw/day

Systemic toxicity NOAEL = 1000 mg/kg bw/day (175 

mg/kg bw/day boron equivalents)boron equivalents)

Systemic toxicity LOAEL = not determined

Immunotoxicity NOAEL = 250 mg/kg bw/day (43.8 

mg/kg bw/day boron equivalents)

Immunotoxicity LOAEL = 500 mg/kg bw/day (87.6 

mg/kg bw/day boron equivalents) based on decreased 

SRBC anti-AFC response)

A.3 Hazard Identification and Endpoint Selection

A.3.1 Acute Reference Dose (aRfD) – All Populations Including Females Age 13-49 and 

Children

An aRfD was not established for boric acid/borate salts for assessment of dietary risk for all 

populations. A dietary risk assessment was not conducted because boron is a naturally occurring 

element in food and drinking water, and the contribution of residues from food and drinking 

water due to pesticidal uses is expected to be negligible. Boric acid/borate salts have been 

granted a tolerance exemption.

However, an aRfD for young children has been established in order to assess risk from accidental 

ingestion of granular formulations (e.g., for turf applications). 

Studies Selected: Rat acute oral LD50 studies on boric acid and borax

MRID Nos: 00005644, 00064207, 40692303

Dose and Endpoint for Risk Assessment: NOAELs= 350 mg/kg (all studies), based on clinical 

signs of toxicity (depression, shallow/rapid respiration, diarrhea, red crusts on eyes) and 

mortality) at ≥439 mg/kg.

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability)

Comments about Study/Endpoint/Uncertainty Factors: The rat oral LD50 studies were 

selected because no single-dose effects relevant to this subpopulation (young children) were 

identified in other studies of the toxicology database. The NOAELs for these effects in the acute 

oral LD50 studies are consistent with the acute neurotoxicity study, which did not identify 

toxicity up to 350 mg/kg boron equivalents (limit dose of the ai, HDT). A UFA and UFH of 10x 

(total UF 100x) were selected.

A.3.2 Chronic Reference Dose (cRfD) – All Populations Including Females Age 13-49 and 

Children

A cRfD was not established because a dietary risk assessment is not required (see aRfD, above).
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 67 of 99

A.3.3 Incidental Oral Exposure (Short-Term, 1-30 days and Intermediate-Term, 1-6 

month)

Studies Selected: Dog 90-day and 2-year dietary studies on borax

MRID Nos: 40692307 and 40692310

Dose and Endpoint for Risk Assessment: NOAEL= 8.8 mg/kg bw/day (dog 2-year dietary 

study and HDT), based on hematological effects and testicular atrophy in the dog 90-day study at 

32 mg/kg bw/day

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability)

Comments about Study/Endpoint/Uncertainty Factors: An incidental oral endpoint is 

required for assessment of short-term hand-to-mouth incidental exposure to young children, but 

also for assessment of ingestion of swimming pool water by recreational (short-term exposure) 

and competitive (intermediate-term exposure) swimmers. The selected studies are of the 

appropriate route and duration. The NOAEL from the chronic dog study was selected, rather 

than the lower NOAEL of 4.1 mg/kg bw/day from the 90-day study, because a higher NOAEL 

was identified for the longer exposure duration as a result of dose spacing. The dose and 

endpoints are further supported by subchronic and chronic dietary studies conducted on boric 

acid, which identified testicular toxicity at essentially the same NOAEL and LOAEL. Although 

the studies are old and had limitations that complicated interpretation of the data (e.g., small 

numbers of animals at each time point, lack of reporting of experimental details, etc.), the 

selected dose is protective of effects in other studies, including developmental toxicity observed 

in the rat at the LOAEL of 13.3 mg/kg bw/day (NOAEL = 9.6 mg/kg bw/day) and at higher 

doses in the rabbit and mouse, and of testicular toxicity and other effects observed in the rat and 

mouse, observed in various studies at ≥43 mg/kg bw/day. The selected endpoints are protective 

of all exposed populations, including young children and females age 13 to 49. A UFA and UFH

of 10x (total UF 100x) were selected.

A.3.4 Dermal Absorption

As summarized in Section 4.3.2, the available data in humans and animals indicate that boric 

acid/borate salts are very poorly absorbed across intact skin. In vivo dermal absorption data in 

humans indicates that absorption is likely to be <1% across intact skin. Published studies in the 

rat and rabbit also support negligible absorption.

A.3.5 Residential and Occupational Dermal Exposure (Short- and Intermediate-Term; 1-

30 days and 1-6 months)

A dermal exposure assessment was not performed. Although dermal exposure is anticipated for 

many use patterns during application and post-application, studies in humans and laboratory 

animals indicate that the absorption of boric acid and its sodium borate salts across intact skin is 

negligible. Estimation of a dermal NOAEL using the most sensitive available oral NOAELs 

(8.8-9.6 mg/kg bw/day) and using a conservative DAF of 1% would yield doses near the limit 

dose of 1000 mg/kg bw/day.

A.3.6 Residential and Occupational Inhalation Exposure 

Studies Selected: Dog 90-day and 2-year dietary studies on borax
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 68 of 99

MRID Nos: 40692307 and 40692310

Dose and Endpoint for Risk Assessment: NOAEL= 8.8 mg/kg bw/day (dog 2-year dietary 

study and HDT), based on testicular atrophy in the dog 90-day study at 32 mg/kg bw/day

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability)

Comments about Study/Endpoint/Uncertainty Factors: Oral data were selected for this 

exposure scenario. A subchronic inhalation toxicity study was not available because the 

requirement was waived. The NOAEL from the chronic dog study was selected, rather than the 

lower NOAEL of 4.1 mg/kg bw/day from the 90-day study, because a higher NOAEL was 

identified for the longer exposure duration as a result of dose spacing. The dose and endpoint are 

further supported by subchronic and chronic dietary studies conducted on boric acid, which 

identified testicular toxicity at essentially the same NOAEL and LOAEL. Although the studies 

are old and had limitations that complicated interpretation of the data (e.g., small numbers of 

animals at each time point, lack of reporting of experimental details, etc.), the selected dose is 

protective of effects in other studies, including developmental toxicity observed in the rat at the 

LOAEL of 13.3 mg/kg bw/day (NOAEL = 9.6 mg/kg bw/day) and at higher doses in the rabbit 

and mouse, and of testicular toxicity and other effects observed in the rat and mouse, observed in 

various studies at ≥43 mg/kg bw/day. Absorption via the inhalation route is assumed to be 

100%. The UFA and UFH of 10x (total UF 100x) were selected.

Although a subchronic inhalation study was not conducted, a published inhalation study in the 

rat and dog on boron oxide (Wilding et al., 1959), submitted in support of the waiver request, 

provided some information on inhalation exposure up to 22 weeks and was considered in 

determining the inhalation exposure dose and endpoint. No adverse effects, including 

histopathological findings, were identified in the rat up to exposure concentrations of 0.470 mg/L 

(dogs were tested at a lower concentration and showed no effects on body weight or clinical 

chemistry/hematology parameters; histopathology was not examined). Rats showed evidence of 

mild respiratory sensory irritation at this dose, based on nasal discharge, which was not 

considered adverse. In order to compare the selected oral dose to the inhalation study, the 

highest exposure concentration was assumed to be a NOAEL in the absence of a LOAEL. 

Human equivalent doses (HEDs) were estimated from this study (HASPOC memo, TXR No. 

0056768):

Estimated Occupational and Non-occupational Human Equivalent Concentrations (HEC) and Doses (HED), 

expressed in Boron Equivalents, for Rats Exposed to Boron Oxide via Inhalation (Wilding study)

Exposure group, mg/L boron oxide

Males Females

0.077 0.175 0.470 0.077 0.175 0.470

Occupational (adjusted for boron equivalents)

HEC, systemic (mg/L) 0.056 0.129 0.344 0.060 0.134 0.359

HEC, POE (mg/L) 0.003 0.0071 0.0184 0.00145 0.00322 0.010

HED, systemic 

(mg/kg/day) 11.10 25.57 68.19 11.89 26.56 71.17

HED, POE (mg/kg/day) 0.59 1.41 3.65 0.29 0.64 1.98

Non-occupational (adjusted for boron equivalents)

HEC, systemic (mg/L) 0.0134 0.0306 0.0820 0.0142 0.032 0.086

HEC, POE (mg/L) 0.00071 0.0017 0.00438 0.000346 0.000768 0.00245

HED, systemic 

(mg/kg/day) 4.55 10.4 27.87 4.83 10.87 29.22

HED, POE (mg/kg/day) 0.24 0.58 1.49 0.12 0.26 0.83
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 69 of 99

For occupational HED calculations, HED = HEC (mg/L) x 11.8 (conversion factor, L/hr-kg BW) x 1 x 2.1 (assigned activity 

factor, handheld spray application) x 8 hr/day exposure. For non-occupational HED calculations, HED = HEC (mg/L) x 11.8 

(conversion factor, L/hr-kg BW) x 1.2 (assigned activity factor, residential handler) x 24 hr/day exposure. Shaded values 

highlight the HEDs for highest exposure level tested in this study.

Estimated portal of entry (POE) HEDs at the highest dose tested were calculated at 3.65 and 1.49 

mg/kg/day for occupational and non-occupational exposure (males), respectively. Although the 

doses are lower than the oral NOAEL, the total UF is also lower (30 vs. 100 for oral exposure) 

and therefore after inclusion of the UFs for assessing risk, the inhalation and oral doses are 

comparable. The oral studies were therefore used to select an endpoint because a LOAEL was 

identified and the NOAEL is protective of potential POE effects. 

A.4 Executive Summaries

A.4.1 Subchronic Toxicity

870.310090-Day Oral Toxicity – Rat

(1) Borax

In a subchronic oral toxicity study (MRID 40692305), sodium tetraborate decahydrate (borax 

technical, about 105% of theoretical purity) was administered to 10 Charles River Sprague 

Dawley rats/sex/dose in the diet at dose levels of 0, 0.0463%, 0.154%, 0.463%, 1.54% or 4.63% 

(equivalent to an average daily intake of 0, 34, 113, 339, 1057 or 4610 mg/kg bw/day test 

material; 0, 4.0, 14, 42, 125 or 544 mg/kg bw/day boron equivalents) for 13 weeks. 

At 0.0463%, complete testicular atrophy in 4/10 males was reported, with these animals also 

showing reduced testicular weights. However, since a dose-response was not observed at 

0.154% (0/10) or 0.463% (1/10), this was not considered a treatment-related finding (further 

supported by lack of testicular effects at similar dose levels in another rat subchronic study, 

MRID 40692306, and a chronic rat study, MRID 40692309). The incidence of testicular atrophy 

at the low dose, together with a reduction in body weight gain in the early weeks of the study, 

but not after week 4 of the study, could be due to an error in dosage or animal group mixup at the 

study start, but the reason is unknown. At 0.463%, one male showed spermatogenic arrest. At 

1.54%, clinical signs of toxicity, beginning during the first week of treatment and continuing 

throughout treatment (including rapid respiration, hunched posture, thinness, swollen paws, 

inflamed eyes, coarse fur/desquamation; during the later weeks, protruding penis and shrunken 

scrotum in males and an unsteady gait in 3 females were observed; incidence for most signs not 

given in report), decreased body weight/weight gain (beginning in the first weeks of the study) in 

males (-53%/-67% at termination below controls) and females (-19%/-32% below controls at 

termination), decreased weekly food consumption (on a g/animal/day basis reduced about 40-

50% below controls) and complete testicular atrophy in 10/10 males were observed. Testicular 

and ovary weights were significantly reduced (-77% and -42%, respectively); relative weights 

were also reduced (by -54% and -32%, respectively). At 4.63%, all animals on study died 

between weeks 1-5 and were in poor condition within the first week, including rapid respiration, 

swollen paws, coarse fur, hunched position and unsure gait, bloody nasal discharge, inflamed 

eyes and emaciation. Histopathological examination was not performed on the high dose 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 70 of 99

animals due to autolysis. The LOAEL is 1.54% (1057 mg/kg/day test material; 125 

mg/kg/day boron equivalents), based on decreased body weight, clinical signs and testicular 

atrophy. The NOAEL is 0.463% (339 mg/kg/day test material; 42 mg/kg/day boron 

equivalents).

This 90-day oral toxicity study in the rat is classified as acceptable/non-guideline. Although the 

study was not conducted according to standard Agency guidelines (lacking clinical chemistry 

and hematology data, and microscopic evaluation of some tissues), when taken together with a 

second 90-day study in the rat (MRID 40692306) and a two-year rat study (MRID 40692309), 

are considered adequate for regulatory purposes and satisfy the guideline requirement for a 90-

day oral toxicity study (OPPTS 870.3100; OECD 408) in the rat. A new study is not required at 

this time.

(2) Borax

In a subchronic oral toxicity study (MRID 40692306), sodium tetraborate decahydrate (borax 

technical, analyzed at about 105% of theoretical) was administered to 10 male Charles River 

Sprague Dawley rats/dose in the diet at dose levels of 0, 0.0154%, 0.0463%, 0.154% or 0.463% 

(equivalent to 0, 11.7, 35.5, 115 or 362 mg/kg/day test material; 0, 1.3, 4.3, 13.1 or 41 

mg/kg/day boron equivalents) for 13 weeks. Clinical chemistries (blood, urine), hematology and 

ophthalmologic evaluations were not performed.

There were no treatment-related effects observed on clinical signs, mortality, body 

weight/weight gain, food consumption, organ weights or gross/microscopic pathology at any 

dose tested. The NOAEL for systemic toxicity in male rats is 0.463% (41 mg/kg/day 

elemental boron). A LOAEL was not determined in this study.

This 90-day oral toxicity study in the rat is classified as acceptable/nonguideline. The study 

was conducted using only males and numerous parameters were not examined. It does not on its 

own satisfy the guideline requirement for a 90-day oral toxicity study (OPPTS 870.3100; OECD 

408) in the rat. However, it provides useful information to supplement a second 90-day rat 

subchronic study on borax (MRID 40692306) and support selection of a subchronic NOAEL in 

the rat (42 mg/kg/day boron equivalents) and may be used for regulatory purposes.

(1) Boric acid

In a subchronic oral toxicity study (MRID 00068025), boric acid (technical grade, 98.97% a.i.) 

was administered to 10 Charles River Sprague-Dawley rats/sex/dose at dietary concentrations of 

0, 0.03, 0.1, 0.3, 1.0 or 3.0% (equivalent to average daily intakes of 0, 3.9, 12.8, 38.0, 123.6 or 

500 mg/kg/day boron equivalents). 

At 0.3%, one male showed complete atrophy of about 1/3 of the tubules (not used to determine 

LOAEL based on single finding). At 1.0%, clinical signs of toxicity indicating poor condition, 

beginning at week 3 and continuing through treatment (hunched posture, labored breathing, 

piloerection, desquamation, inflamed eyes, swollen paws), significantly reduced mean body 

weight (at termination, -42% less than controls for males and 15% below controls for females), 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 71 of 99

reduced testicular size in all males, markedly reduced mean abs/rel testicular weights (-76%/-

56% less than controls), complete atrophy of the testes with increased epithelial cells (all males), 

reduced mean abs/rel ovarian weights (-27%/-20%) with no microscopic correlates. Males 

showed a slight increase in lipid content and cell size of the adrenal zona reticularis but this 

finding was not considered adverse. At 3.0%, excessive toxicity was observed in all animals 

(hunched position, desquamation of skin on tail and paws, rapid/labored breathing, shrunken 

testes, unsure gait, weight loss) and all animals died (males by 3 weeks, females by 6 weeks). At 

necropsy, blood in the lungs, congestion of kidneys, livers and adrenals were seen. The LOAEL 

is 1.0% (123.6 mg/kg/day boron equivalents), based on clinical signs of toxicity and 

decreased body weight in both sexes, and testicular atrophy and decreased testicular 

weight. The NOAEL is 0.3% (38 mg/kg/day boron equivalents).

This 90-day oral toxicity study in the rat is classified as acceptable (nonguideline). Although 

the study was not conducted according to standard Agency guidelines (lacking clinical chemistry 

and hematology data), the data, when taken together with a two-year rat study (MRID 

00068883), are considered adequate for regulatory purposes and satisfy the guideline 

requirement for a 90-day oral toxicity study (OPPTS 870.3100; OECD 408) in the rat. A new 

study is not required at this time.

870.3150 90-Day Oral Toxicity - Dog

1. Borax

In a subchronic oral toxicity study (MRID 40692307), sodium tetraborate decahydrate (technical 

borax, analyzed at 105% of theoretical value) was administered for 13 weeks to 5 beagle 

dogs/sex/dose in the diet at dose levels of 0, 0.0154, 0.154 or 1.54% (in males, equivalent to 

average daily intakes of 0, 2.9, 35 or 268 mg/kg/day test material and 0, 0.34, 4.1 or 32 

mg/kg/day boron equivalents; in females, to 0, 2.1, 22 or 192 mg/kg/day test material; 0, 0.25, 

2.6 or 23 mg/kg/day boron equivalents). Clinical chemistry evaluations were limited to blood 

urea nitrogen and non-fasting glucose, and urinalysis.

At 1.54% in males, testicular atrophy (complete in 4 males and partial in one) and significantly 

reduced testes weight (abs/rel., -44%/-45% below controls), slightly but statistically significantly 

decreased hematocrit/hemoglobin at 13 weeks in both sexes (-15%/-11% males and -6%/-11% 

females; not reduced at earlier times) and increased hemosiderin pigment in spleen, liver and 

kidneys was observed. Relative thyroid weights in males were significantly lower at the high 

dose (-23%) but no effects were seen in females. An increase in the width of the adrenal cortex 

in females and a slight increase in epithelial nests of the thyroid in males were reported; slightly 

widened adrenal cortex in females and slightly increased proportion of epithelial nests in males 

were also reported at 0.154% but were of uncertain toxicological significance and were not used 

to establish a LOAEL for this study. The report also noted that at 0.154%, 5/5 males showed 

artifactual distortion of tubules in the outer third of the testes. Based on this description, this 

observation was not considered an adverse effect of treatment. It was also not observed in the 

dog 2-year study at similar or higher dose levels. There were no treatment-related changes in 

mortality, clinical signs of toxicity, body weight, food consumption or clinical chemistries (body 

weight gains were slightly lower at high dose but overall weights showed no differences). The 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 72 of 99

LOAEL is 1.54% (in males, 268 mg/kg/day test material and 32 mg/kg/day boron 

equivalents; in females, 192 mg/kg/day test material and 23 mg/kg/day boron equivalents), 

based on testicular histopathology and slightly decreased hematocrit/hemoglobin. The 

NOAEL is 0.154% (in males, 35 mg/kg/day test material and 4.1 mg/kg/day boron 

equivalents; in females, 22 mg/kg/day test material and 2.6 mg/kg/day boron equivalents).

This 90-day oral toxicity study in the dog is classified as acceptable/nonguideline and satisfies 

the guideline requirement for a 90-day oral toxicity study (OPPTS 870.3150; OECD 409) in the 

dog when considered together with 38-week and 2-year dietary dog studies on borax, and 

the 90-day, 39-week and 2-year dog studies on boric acid. This study was not conducted 

according to standard guideline procedures-several clinical chemistry parameters were not 

examined and histopathological examination was missing some tissues. However, the study is 

considered to be acceptable for regulatory purposes.

2. Boric acid

In a subchronic oral toxicity study (MRID 00064204), boric acid (purity not specified in this 

report; batch received same date, Oct. 12, 1961, as batch used in chronic dog studies from same 

laboratory having purity of 99.94%) was administered in the diet to 5 beagle dogs/sex/dose for 

90 days at dietary concentrations of 0, 0.01, 0.1 or 1.0% (equivalent to average daily intakes of 

0, 0.46, 4.2 or 35 mg/kg/day boron equivalent).

At 0.1%, males showed artifactual distortion of the outer third of the testes and lower testes 

weights (abs /rel. 14.3 g/0.15% vs. 17.2 g/0.20%, controls). Because this was apparently an 

artifact of fixation, did not appear to have affected spermatogenesis and was not seen in the 2 

year dog study at comparable doses, it was not used to establish the LOAEL. Similarly, 

appearance of squamous metaplasia in the thyroids of 2 males was not seen in other studies at 

similar boron concentrations and was not considered treatment-related. Slight changes in the 

adrenal glands of females (better developed reticularis) were not considered to be adverse. At 

1.0%, males showed a significant reduction in mean abs/rel testes weight (10.4 g/0.12% vs. 17.2 

g/0.20%, controls) and severe testicular atrophy in all males, with complete degeneration of the 

spermatogenic epithelium in 4/5 males. Abs/rel liver weights in females were significantly 

increased (345 g/4.1% vs 235 g/2.5%) but no correlating microscopic findings were reported and 

increased width of the adrenal zona reticularis and glomerulosa was reported. There were no 

apparent treatment-related effects on survival, clinical symptoms, nor clear effects on body 

weights (one mid and one high dose female showed body weight fluctuations, which appeared to 

be secondary to poor acceptance of the test diet), hematology, clinical chemistry parameters or 

gross pathology. The LOAEL is 1.0% boric acid (35 mg/day boron equivalents), based on 

testicular atrophy. The NOAEL is 0.1% boric acid (4.2 mg/kg/day boron equivalents).

This study is classified as acceptable (nonguideline) and satisfies the guideline requirement for 

a 90-day oral toxicity study in the dog (OPPTS 870.3150; OECD 409) when considered 

together with 38-week and 2-year dietary dog studies on boric acid. It was not conducted 

according to current standard study guideline procedures-several clinical chemistry parameters 

were not examined and histopathological examination was missing some tissues. Furthermore, 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 73 of 99

artifactual effects in mid dose male testes complicated interpretation of the data. However, it is 

considered to be acceptable for regulatory purposes in consideration with the chronic studies. 

870.3200 21/28-Day Dermal Toxicity – Rat

Study not available

870.3465 90-Day Inhalation – Rat

Study not available

A.4.2 Prenatal Developmental Toxicity

870.3700a Prenatal Developmental Toxicity Study - Rat

(1) Boric acid

In an oral developmental toxicity study (MRID 43340101), boric acid (technical, 99% a.i., lot no. 

872703) was administered to 28-32 pregnant Sprague-Dawley rats/dose/phase group in the diet

at dose levels of 0, 0.025%, 0.05%, 0.075%, 0.10% or 0.20% (equivalent to average daily intakes 

of 0, 19, 36, 55, 76 or 143 mg/kg bw/day boric acid and 0, 3.3, 6.3, 9.6, 13.3 or 25 mg/kg bw/day 

from days 0 through 20 of gestation. The study was conducted in two phases: in Phase I, 

developmental toxicity was examined in fetuses from dams sacrificed on GD 20. In Phase II, 

dams were treated at the same dose levels, then allowed to deliver their litters. Dams and pups 

were sacrificed on postnatal day 21 for evaluation of persistence of developmental effects. In 

addition, liver and kidney weights of dams were recorded.

Maternal toxicity: In both the pre- and postnatal phases, no maternal toxicity was observed for 

survival, clinical signs of toxicity, body weight, food consumption, cesarean parameters or gross 

pathology. At 0.2% boric acid, slightly reduced gravid uterine weight was observed (-10% 

below controls, not statistically significant). The decrease was considered secondary to 

decreases in fetal weights and therefore not indicative of direct maternal toxicity. Right kidney 

weights were increased about 10% in Phase I dams, but the change was not seen during Phase II 

and was considered adverse. The maternal NOAEL is 143 mg/kg bw/day boric acid (25 

mg/kg bw/day boron equivalents, HDT). A maternal LOAEL was not determined (>25

mg/kg bw/day boron equivalents).

Developmental toxicity: Study Phase I: At 13.3 mg/kg bw/day boron equivalents, mean fetal 

body weight was decreased in males and females (-6.1% and -7.1% below controls, both 

p<0.05). An increased incidence of short rib XIII (fetal 17% vs. 9%, controls, p<0.05; litter 

incidence not increased) and wavy rib XIII (fetal 10%/litter 6% vs. 0%, controls, p<0.05) was 

observed. Historical control data provided for short rib (0.14%) and wavy rib (0.2%) showed a 

very low incidence. These findings were also increased in MRID 41725401 at 14 mg/kg/day. In 

Phase II, the incidence of short rib XIII was also increased at 25 mg/kg/day (affecting 16 fetuses 

in 6 litters, vs. 0 in controls). Pup weights were comparable in all dose levels at PND Day 21. 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 74 of 99

The developmental LOAEL is 76 mg/kg bw/day boric acid (13.3 mg/kg bw/day boron 

equivalents), based on decreased fetal weight and rib abnormalities. The developmental 

NOAEL is 33 mg/kg bw/day (9.6 mg/kg bw/day boron equivalents).

The developmental toxicity study in the rat is classified acceptable/guideline and satisfies the 

guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in the 

rat. 

(2) Boric acid

In a developmental toxicity study (MRIDs 41725401, main report and 42377101, supplement), 

29 pregnant Crl CD(BR)VAF/Plus outbred Sprague-Dawley rats/dose group were administered 

boric acid (technical, 98-99% a.i.) in the diet at concentrations of 0, 0.1, 0.2 or 0.4% (equivalent 

to an average daily dose of 0, 78, 163 or 330 mg/kg/day boric acid and 0, 14, 29 or 58 mg/kg/day 

of boron equivalents) from gestation days 0 through 20 (dosing schedule designed to allow 

plasma boron levels to reach steady state prior to implantation to mimic low-dose exposure from 

food). Additional control and high dose groups of 14 pregnant rats each were administered the 

test diet at 0% or 0.8% from gestation days 6 through 15 (equivalent to an average daily dose of 

539 mg/kg/day boric acid and 94 mg/kg/day boron equivalents). In addition, dams’ kidney and 

liver weights were measured and kidneys were examined microscopically.

Maternal toxicity: (Treatment GD 6-20) - At 0.2%, statistically significantly increased relative 

kidney weight (right and left) was observed (about +10% above controls), with a similar but 

non-significant increase in absolute right and left kidney weight; relative liver weight was also 

increased (+5%, p<0.05); however, these marginal changes, seen at comparable increases at 

higher dose levels, were not considered to be adverse. At 0.4%, a statistically significant 

reduction in body weight gain (-10% below controls) and gravid uterine weight (-30% below 

controls) were observed, but body weight was not decreased when adjusted for the gravid uterine 

weight. Water intake was increased between GD 18-20 (23%). Statistically significantly 

increased left kidney weight (+8%; right similar increase but not significant) was also seen. One 

or two animals per dose had evidence of mild renal nephropathy but a dose-response was not 

observed and the findings were not considered adverse. At 0.8%, (treatment only GD 6-15), 

mean body weight gain and gravid uterine weight during treatment were about -58 to -59% 

lower than controls, but did not show a change when corrected for uterine weight. Food 

consumption was slightly lower (-13%) than controls and water intake was decreased between 

GD 6-9 (-17%). No treatment-related effects on survival or clinical signs were reported. Mild 

nephropathy in 0, 2, 1, 2, 1 and 0 females (control to high dose of 0.8%, respectively) was also 

considered incidental due to lack of dose response. The maternal toxicity NOAEL is 0.8% 

(539 mg/kg/day boric acid; 94 mg/kg/day boron equivalents). A LOAEL was not 

determined in this study.

Developmental toxicity: At 0.1%, mean fetal body weight was statistically significantly reduced 

(-6% less than controls). The incidences of wavy rib XIII and short rib XIII were increased (% 

litter incidence/% fetuses per litter 14.29/1.0% and 17.86%/2.43%, respectively, compared to 

3.57%/0.36% in controls). The increases were not statistically significant but historical control 

fetal incidence was very low for both abnormalities, suggesting a treatment-related effect at this 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 75 of 99

dose. At 0.2%, decreased mean fetal weight (-13% below controls), and statistically 

significantly increased incidences of the litter incidence of short rib XIII, wavy rib XIII and cleft 

sternum were reported. At 0.4%, increased fetal resorptions, rib XIII agenesis (24 fetuses vs. 0 

in controls), enlarged lateral ventricles in the brain (21 vs. 0 fetuses in controls; fetal incidence 

0.5%) were observed (fetal weight -37% below controls). At the high dose of 0.8% (GD 6-15 

exposure only), prenatal mortality (live fetuses per litter mean 9.71 vs. 15.39-15.69 in other 

groups) was observed. Numerous gross malformations (short and curly tail, anophthalmia, 

microphthalmia), visceral malformations (cardiovascular defects, convoluted retina, enlarged 

lateral ventricles of the brain) were observed along with rib XIII agenesis, short rib XIII and cleft 

sternum. At 0.4% and 0.8%, 100% of the litters were affected with skeletal malformations and 

variations; visceral malformations were reported in 36% and 86% of litters, respectively. The 

developmental toxicity LOAEL is 0.1% (78 mg/kg/day boric acid; 14 mg/kg/day boron 

equivalents), based on decreased fetal weight and marginally increased incidence of Rib 

XIII variations. A developmental toxicity NOAEL was not determined in this study. 

However, a subsequent developmental toxicity study was conducted by the same lab 

(MRID 43340101) and identified a NOAEL/LOAEL of 9.6/13.6 mg/kg/day, based on 

comparable findings.

This developmental toxicity study in the rat is classified acceptable/nonguideline and satisfies 

the guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in 

the rat, when it is considered together with another rat developmental toxicity study, MRID 

43340101, which identified a NOAEL/LOAEL of 9.6/13.3 mg/kg/day for developmental 

toxicity based on the same effects. The test material was administered via the diet instead of 

gavage to mimic human dietary exposure.

870.3700a Prenatal Developmental Toxicity Study – Mouse

In a developmental toxicity study (MRID 41725402), boric acid (lot no. 872703, 98-99% a.i.)

was administered to 29 female CD-1 Swiss mice/dose in the diet at dose levels of 0%, 0.1%, 

0.2% or 0.4% (equivalent to 0, 248, 452 or 1003 mg/kg/day boric acid and 0, mg/kg/day boron 

equivalents) from days 0 through 17 of gestation, inclusive. In addition to the standard 

evaluations performed in developmental toxicity studies, randomly selected kidneys from 10 

dams/dose group were prepared for microscopic examination.

Maternal toxicity: At 0.1%, an increased incidence of renal tubular dilatation was reported (from 

control to high dose, 0/10, 2/10, 8/10 and 10/10, respectively). The lesions were classified as 

mild dilatation, with minimal regeneration in some of the animals also present at an incidence 

increasing with dose. At 0.4%, maternal body weight gain was significantly reduced (-21% 

below controls), although corrected weight gains were unaffected; therefore this change was not 

considered adverse. Relative kidney weights (left and right individually) were significantly 

increased by about 30% (left kidney absolute weights also increased by 15%), with pale kidneys 

observed grossly. A transient increase in food and water consumption (both +15%) was reported 

on Days 15-17. There were no treatment-related effects on clinical signs or mortality. The 

maternal LOAEL is 0.1% (248 mg/kg bw/day boric acid; 43 mg/kg/day boron equivalents), 

based on renal pathology. A maternal NOAEL was not established in this study. 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 76 of 99

Developmental toxicity: At 0.2%, mean fetal weight was significantly reduced (11% below 

controls, p<0.05) and the percent with short rib XIII per litter was increased (7.5%, increasing to 

20% at 0.4%, compared to 0% in controls). The total number of fetuses affected at 0.2% and 

0.4% were 2/309 and 10/250, respectively. At 0.4%, the percent of litters with resorptions and % 

resorptions per litter were increased (+65% and +216%, respectively). The developmental 

LOAEL is 0.2% (452 mg/kg bw/day boric acid; 79 mg/kg/day boron equivalents), based on 

decreased fetal weight and increased incidence of short rib XIII. The developmental 

NOAEL is 0.1% (248 mg/kg/day boric acid; 43 mg/kg bw/day boron equivalents).

This developmental toxicity study in the mouse is classified acceptable/guideline and satisfies 

the guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in 

the rodent. The test material was administered in the diet instead of by gavage to mimic human 

dietary exposure, and from GD 0-17 instead of 6-17. These variations do not adversely affect the 

conduct of the study. The study is considered acceptable for regulatory purposes.

870.3700b Prenatal Developmental Toxicity Study - Rabbit

In a developmental toxicity study (MRID 42164201, -02), boric acid (technical, 99% a.i., lot no. 

872703) was administered to 30 pregnant, artificially inseminated New Zealand White 

rabbits/dose by gavage in distilled water (5 mL/kg bw dose volume) at dose levels of 62.5, 125 

or 250 mg/kg/day administered daily from gestation days 6 through 19, inclusive (equivalent to 

0, 11, 22 or 44 mg/kg/day of boron equivalents). Several animals were removed from all dose 

groups (due to abortions, experimental error, injury); pregnancy was observed (control to high 

dose, respectively) in 18/24, 23/26, 20/23 and 22/23 does.

Maternal toxicity: At 250 mg/kg bw/day, vaginal bleeding was observed, between GD 19-30, in 

a total of 14 does, none of which had live fetuses on GD 30. Does showed weight loss during 

treatment (-137 g vs. gain of 93 g, controls), but the decrease was due primarily to decreased 

gravid uterine weight related to fetal loss, based on corrected weight gains. Food consumption 

during treatment was reduced by 37% compared to controls. There were no treatment-related 

increases in maternal mortality. The maternal LOAEL is 250 mg/kg bw/day (44 mg/kg 

bw/day boron equivalents), based on increased vaginal bleeding associated with fetal loss 

and decreased food consumption. The maternal NOAEL is 125 mg/kg bw/day (22 mg/kg 

bw/day boron equivalents).

Developmental toxicity: At 250 mg/kg bw/day, the total number of live litters was greatly 

reduced, with only 6 litters (14 fetuses) available for evaluation. Fetal resorptions/dam were 

increased (7.8, p<0.05, vs. 0.72, controls) due to increases in early resorptions. A total of 140 

early resorptions, vs. 4 in controls, were observed. Post-implantation loss was high (92.6 vs 7.0, 

controls). Mean fetal weight showed a decrease (41.1 g vs. 44.8 g, controls, not significant). In 

the surviving fetuses, an increase in visceral malformations, primarily intraventricular septal 

defects or abnormalities of the great vessels, was observed. There were no treatment-related 

increases in external or skeletal malformations or variations. The developmental LOAEL is 

250 mg/kg/day (44 mg/kg bw/day boron equivalents), based on increased fetal loss, 

decreased fetal weight and increased malformations. The developmental NOAEL is 125

mg/kg bw/day (22 mg/kg bw/day boron equivalents).
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 77 of 99

The developmental toxicity study in the rabbit is classified as acceptable/guideline and satisfies 

the guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in 

the rabbit.

A.4.3 Reproductive Toxicity

870.3800 Reproduction and Fertility Effects – Rat

(1) Borax

In an oral three-generation reproduction study (MRID 40692311), sodium tetraborate 

decahydrate (borax tech., analyzed at 103-105% of theoretical boron content) was administered 

to 8 male and 16 female Charles River CD rats/dose in the diet at continuous dose levels of 0, 

0.103%, 0.308% or 1.03% (in males, equivalent to 0, 0, 72, 218 or 729 mg/kg/day test material 

and 0, 8.1, 28 or 82 mg/kg/day boron equivalents; in females, equivalent to 0, 81, 241 or 814 

mg/kg/day test material and 0, 9.2, 31 or 92 mg/kg/day boron equivalents). After a 14-week 

premating period, one male and two females were mated for up to 21 days. Two matings per 

generation were performed to produce two litters. An exception to the protocol was taken for the 

1.03% P1 repeat matings due to no conceptions in the first mating: untreated males were used 

with the treated females for the subsequent P1 matings. The high dosing group was not 

continued for P2 and P3 generations due to insufficient successful matings from either attempted 

P1 mating.

Parental toxicity: At 1.03%, clinical signs (coarse fur, scaly tails, hunched posture) and 

decreased body weight were observed in P1 males during much of premating (up to -14% to -

16% below controls)(but not in later parental generations). Testicular atrophy with severely 

decreased testes abs/rel weights was observed in all P1 males. In females, the number of 

functioning ovaries was lower than normal (4/15), although the controls were not examined for 

comparison. No subsequent generations were tested at this dose level. The parental toxicity 

LOAEL is 1.03% (males/females 729/814 mg/kg/day test material; 82/92 mg/kg/day boron 

equivalents), based on clinical signs, decreased body weight and testicular atrophy/reduced 

ovarian function. The NOAEL is 0.308% (males/females 218/241 mg/kg/day test material; 

28/31 mg/kg/day boron equivalents).

Offspring toxicity: At 1.03%, no litters were born. In the second mating with untreated 

males, there were only 2 litters and 1 abortion; no pups survived past Day 3 postpartum 

(died or cannibalized). The offspring toxicity LOAEL is 1.03% (males/females 729/814 

mg/kg/day test material; 82/92 mg/kg/day boron equivalents), based on fetal/pup mortality. The 

NOAEL is 0.308% (males/females 218/241 mg/kg/day test material; 28/31 mg/kg/day boron 

equivalents). 

Reproductive toxicity: At 1.03%, no litters were produced in the first P1 mating. The second P1 

mating with untreated males resulted in 2 litters and 1 abortion out of 16 matings. All pups were 

either cannibalized or died by Day 3 postpartum. Testes of parental P1 males showed complete 

atrophy and P1 females had a lower than normal number of functioning ovaries (4/15 with 

corpora lutea; however controls were not examined); the study authors concluded that the latter 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 78 of 99

finding was insufficient to completely account for the low fertility observed with untreated males 

and that some other effect on ovarian function or implantation was occurring. The reproductive 

toxicity LOAEL is 1.03% (males/females 729/814 mg/kg/day test material; 82/92 mg/kg/day 

boron equivalents), based on reduced fertility. The NOAEL is 0.308% (males/females 

218/241 mg/kg/day test material; 28/31 mg/kg/day boron equivalents).

This study is classified as acceptable/nonguideline and satisfies the guideline requirement for a 

multi-generation reproductive study (OPPTS 870.3800; OECD 416) in the rodent (rat). 

Although the study had several deficiencies (incomplete histopathology evaluation, 2:1 matings, 

less than 20 pregnant females/group, lack of gestation period data and low lactation indices in 

control animals), the data are considered acceptable for regulatory purposes and a new study is 

not required at this time, based on consideration of this data together with other studies on

reproductive/developmental toxicity of boric acid and systemic toxicity in the rat. 

(2) Boric acid

In an oral three-generation reproductive toxicity study (MRID 00068882), boric acid (technical 

grade, 98.7% a.i.) was administered continuously in the diet to 8 male and 16 female Sprague 

Dawley rats/dose at concentrations of 0, 0.067%, 0.20% or 0.67% (equivalent to average daily 

boron intakes of 0, 8.5, 26.6 or 85 mg/kg/day, males and 0, 9.7, 29 or 91.6 mg/kg/day, females). 

Matings (2 females per male) were conducted over three generations, with two matings 

performed per generation. The high dosing group was not continued for P2 and P3 generations 

due to lack of litters.

Parental toxicity: At 0.67%, clinical signs of toxicity were reported, body weights of males and 

females were decreased and at autopsy, testes of males were visibly atrophied (not examined 

microscopically but confirmed by lack of spermiation in other feeding studies). About half of 

the females showed evidence of reduced ovulation. The parental toxicity LOAEL is 0.67%

(85/92 mg/kg/day boron equivalents), based on clinical signs of toxicity, decreased body 

weights, testicular atrophy and reduced ovulation. The NOAEL is 0.20% (27/29 mg/kg/day 

boron equivalents).

Reproductive toxicity: At 0.67%, no litters were produced. As noted for parental toxicity, testes 

were atrophied and ovaries showed signs of reduced ovulation. A cross-mating of the treated 

females with males administered untreated diet was unsuccessful, indicating effects on the 

female reproductive system as well as the male (the authors did not consider the reduced 

ovulation sufficient to explain the complete lack of fertility, indicating a more pronounced effect 

on males). The reproductive toxicity LOAEL is 0.67% (85/92 mg/kg/day boron 

equivalents), based sharply reduced fertility related to testicular atrophy, reduced 

ovulation. The NOAEL is 0.20% (27/29 mg/kg/day boron equivalents).

Offspring toxicity: At 0.67%, no litters were produced. A cross-mating of treated females with 

untreated males resulted in reduced numbers of P1 litters and pup survival. The offspring 

toxicity LOAEL is 0.67% (85/97 mg/kg/day boron equivalents), based on reduced pup 

survival from a treated female/untreated male mating. The NOAEL is 0.20% (27/29 

mg/kg/day boron equivalents).
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 79 of 99

This study is classified acceptable/nonguideline and satisfies the guideline requirement for a 

multi-generation reproductive study (OPPTS 870.3800; OECD 416) in the rodent (rat). Although 

the study had several deficiencies (incomplete histopathology evaluation, 2:1 matings, less than 

20 pregnant females/group, lack of gestation period data and low lactation indices in control 

animals), the data are considered acceptable for regulatory purposes and a new study is not 

required at this time, based on consideration of this data together with other studies on 

reproductive/developmental toxicity and systemic toxicity of boron in the rat.

870.3800 Reproduction and Fertility Effects – Mouse

In a two-generation oral reproduction study (MRID 41589101), boric acid (99% a.i., batch/lot 

#872703) was administered in the diet to 38 CD-1 Swiss mice/sex at 0 mg/kg/day and to

19-20 CD-1 Swiss mice/sex/dose at continuous dose levels of 0, 1000, 4500 or 9000 ppm 

(equivalent to 0, 152, 636 or 1262 mg/kg/day test material and 0, 27, 111 or 221 mg/kg/day 

boron equivalents). For the F1 generation, only 0 and 1000 ppm doses were administered due to 

reduced fertility seen in the F0 generation at the higher doses. The study was performed by NTP 

according to the reproductive assessment by continuous breeding (RACB) protocol. Animals 

were given a one week premating period and a 14-week cohabitation period, followed by a 

holding period. Litters born during cohabitation were removed by 24 hr postpartum; those born 

later remained with the dams for 21 days. In addition, a cross-over mating period between 

20/sex/dose of control and mid dose males and females to determine the affected sex and an 

offspring assessment, in which F1 offspring from the continuous F0 mating litters were selected, 

were performed.

Parental toxicity: At 4500 ppm (F0 parental animals only), decreased body weight in females (at 

week 18, -23%; considered largely secondary to lower fertility rather than direct toxicity) and 

sharply decreased abs/rel testes weight (-40 to-50% of controls) and degeneration of 

seminiferous tubules (17/20 males) were observed; a decrease in cauda epididymides and 

prostate weights were also noted. Sperm showed a significantly lower concentration per mg 

caudal tissue (-72%), motility (–32%) and a higher percentage of abnormal sperm (61% vs. 11%, 

controls). A slight but statistically significant reduction in adrenal/kidney weight was also 

observed in females (-9%). At 9000 ppm, mean body weight gain was significantly decreased in 

males and females. In addition to severe reduction in testicular weights and seminiferous tubule 

atrophy, 12/15 males produced no sperm and those that did had only 50% of sperm being motile. 

Lacrimation, exophthalmos and cloudiness of the eyes were observed. In F1 parental animals at 

1000 ppm in the second generation fertility assessment, slight decreases in sperm concentration 

and percent abnormal (not significant) were reported, but no effects on fertility were observed, 

and the changes were not considered adverse. A parental systemic LOAEL is 4500 ppm (636 

mg/kg/day test material; 111 mg/kg/day boron equivalents), based on decreased testicular 

weight in males and possibly adrenal/kidney weight decrease in females. The parental 

systemic NOAEL is 1000 ppm (152 mg/kg bw/day test material; 27 mg/kg/day boron 

equivalents).

Offspring toxicity: At 4500 ppm (F1 pups only), mean pup weight was decreased (-14% below 

controls at birth) and reductions in the average number of litters per pair (2.3 vs. 4.7, controls), 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 80 of 99

number of live pups per litter (8.67 vs. 13.52, controls) and % alive at birth (-11%) were 

observed. A slight reduction (3-4%) in female and combined male and female pup weight (but 

not male) adjusted for litter size in the second generation (F2) mating at 1000 ppm was 

considered incidental. The offspring LOAEL is 4500 ppm (636 mg/kg/day test material; 111 

mg/kg/day boron equivalents), based on reduced pup weight and decreased live pups at 

birth. The offspring NOAEL is 1000 ppm (152 mg/kg bw/day test material; 27 mg/kg/day 

boron equivalents). 

Reproductive toxicity: At 4500 ppm (F0 mating), fertility was sharply reduced (44% vs. 94%, 

controls). The number of days to litter in the F0 continuous breeding portion increased after the 

second litter, with the number of dams producing litters and live pups per litter also decreasing 

with each litter. In the crossover mating evaluation, mating/fertility indices were sharply 

reduced in matings of treated males with control females (30%/5% vs. 79%/74%, controls) but 

also slightly affected in matings of treated females with control males (70%/64%), thereby 

indicating that although effects were greater on males, some effect on females was also present. 

Testicular effects are described under parental toxicity, above. At 9000 ppm, no litters were 

produced and males showed decreased sperm concentration and motility, as described above 

under parental toxicity. The reproductive LOAEL is 4500 ppm (636 mg/kg/day test material; 

111 mg/kg/day boron equivalents), based on reduced fertility and reduced sperm 

concentration. The reproductive NOAEL is 1000 ppm (152 mg/kg bw/day test material; 27 

mg/kg/day boron equivalents). 

This study is classified as acceptable/nonguideline and satisfies the guideline requirement for a 

multi-generation reproductive study (OPPTS 870.3800; OECD 416) in the rodent (mouse). The 

study was not conducted according to Agency guidelines and some deficiencies are noted 

(including only one dose level in the P1 mating, incomplete histopathology, nonguideline mating 

protocol). However, this study, conducted by the NTP, provides sufficient information to 

characterize the reproductive toxicity of boric acid and is considered acceptable for regulatory 

purposes. Findings are consistent with 3-generation reproduction studies in the rat on boric acid 

and borax (MRIDs and 40692311, respectively).

A.4.4 Chronic Toxicity

870.4100a (870.4300) Chronic Toxicity/Carcinogenicity – Rat

(1) Borax

In an oral carcinogenicity study (MRID 40692309), borax (sodium tetraborate decahydrate tech., 

103.2-105.4% of theoretical value) was administered to 70 control and 35 treated SpragueDawley Charles River cesarean-derived rats/sex/dose in the diet at dose levels of

0 (control), 0.103%, 0.308% or 1.03% (equivalent to 0, 65, 154 or 515 mg/kg/day test material; 

0, 7.3, 17 or 58 mg/kg bw/day for elemental boron) for two years. Interim sacrifices of 5 

animals/sex/dose were performed at weeks 28 and 56. 

At 1.030%, clinical signs attributed to treatment and observed beginning at weeks 4-6 included 

dry scaly tails, rough fur, hunched appearance, wheezing, bloody nasal and ocular discharge, 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 81 of 99

drooping, inflamed eyelids, swollen paw pads, abnormally long claws and shrunken scrotum. 

The report noted that most animals showed effects by 26 weeks and that severity increased with 

time. Detailed incidence data were not provided in the study report. Mean body weight/weight 

gain were reduced in both males (-16%/-19% below controls) and females (-33%/-41% below 

controls), with decreases observed beginning in the first weeks of treatment. Significant 

reductions in absolute and relative testes weight (between -60 to -80% below controls) at 6, 12 

and 24 months’ sacrifice were observed. The latter correlated with grossly visible small testes, 

testicular tubular atrophy (primarily severe, observed in all animals examined at 6, 12 and 24 

months) and a possible increase in testicular calcific arteriosclerosis. Hematocrit and 

hemoglobin were slightly decreased in both sexes at several time points, beginning at month 2 

(Hct -5% to -13% and Hgb -10 to -14%; sporadic statistically significant changes seen). There 

were no treatment-related effects on survival (control to high dose males 58%, 76%, 64% and 

72%; females 67%, 68%, 58% and 80%), clinical chemistry or urinalysis parameters. The 

systemic toxicity LOAEL is 1.03% (515 mg/kg/day test material and 58 mg/kg/day 

elemental boron), based on decreased body weight, clinical signs of toxicity, decreased RBC 

parameters and testicular pathology. The NOAEL is 0.308% (154 mg/kg/day test material 

and 17 mg/kg/day elemental boron).

At the doses tested, there was not a treatment related increase in tumor incidence when compared 

to controls. Dosing was considered adequate based on observations of clinical signs, decreased 

body weight, slight hematological changes and testicular atrophy.

This carcinogenicity study in the rat is classified as acceptable/nonguideline and satisfies the 

guideline requirement for a chronic toxicity/carcinogenicity study [OPPTS 870.4200; OECD 

451] in rats. The study was conducted prior to EPA’s GLP guidelines and therefore certain 

aspects of the study design are lacking. It is noted that some clinical chemistry parameters were 

not evaluated and that ophthalmologic examinations and microscopic examination of the eyes 

were not performed. In addition, the percent survival of mid dose males as presented in the study 

report (76.9%) differed from calculation from the individual animal survival data (64%); 

however, this discrepancy has been clarified by the registrant and 64% is the correct value.

(2) Boric acid 

 In an oral chronic toxicity/carcinogenicity study (MRID 00068883), boric acid (technical,

98.7% a.i.) was administered in the diet to 35 Sprague Dawley rats/sex/dose at 0.067, 0.20 or

0.67% (equivalent to average daily intakes of 0, 5.2, 16 or 58 mg/kg/day, males and 0, 6.3, 19 or 

70 mg/kg/day, respectively, females). In addition, control groups of 70/sex were administered 

untreated diet. Interim sacrifice groups (5/sex/dose) were evaluated at 26 and 52 weeks. Samples 

of blood, urine and feces were collected at 26, 52 and 104 weeks for boron balance analyses; 

select tissue samples were also collected from 5 animals/sex at sacrifice times for boron 

analyses. 

At 0.67%, clinical signs of toxicity beginning at 4-6 weeks (hunched posture, desquamation of 

tail and paws, swollen paws, inflamed eyes, respiratory effects and shrunken scrotum), decreased 

mean body weights, low red blood cell volume and hemoglobin in males and decreased abs/rel 

testes weight and severe testicular atrophy (by 26 weeks, progressing in severity with time). In 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 82 of 99

females, anovulatory ovaries were observed. At 104 weeks control, low and mid dose males also 

showed signs of atrophy. The incidence was not increased but severity showed a slight increase; 

however, given the advanced age of the rats, this was not considered clearly treatment-related. 

Boron balance studies showed that there was no significant accumulation in tissues, although 

levels of treated animals were higher than controls. Boron blood levels increased with dose. 

The LOAEL is 0.67% (58 mg/kg/day boron equivalents), based on clinical signs, decreased 

body weight, hematological changes in males, testicular atrophy and possibly increased 

anovulatory ovaries. The NOAEL is 0.20% (16 mg/kg/day boron equivalents).

There was no evidence of a treatment-related increase in tumors. Dosing was considered 

adequate based on significant toxicity at the highest dose tested.

This carcinogenicity study in the rat is classified as acceptable/nonguideline and satisfies the 

guideline requirement for a chronic toxicity/carcinogenicity study [OPPTS 870.4200; OECD 

451] in rats. It is noted that some clinical chemistry parameters were not evaluated, 

ophthalmologic examinations were not performed and some tissues were not examined 

microscopically. However, it is considered an acceptable study for regulatory purposes.

870.4100b Chronic Toxicity - Dog

(1) Borax

In a chronic toxicity study (MRID 40692310), borax (sodium tetraborate decahydrate, lot 

number and purity not provided but analyzed boron content 103.2-105.4% of theoretical value) 

was administered to four beagle dogs/sex/dose in the diet at dose levels of 0, 0.051%, 0.103% or 

0.309% (equivalent to average daily intakes of 0, 13, 26 or 77 mg/kg bw/day test material and 0, 

1.5, 2.9 or 8.8 mg/kg bw/day boron equivalents) for 104 weeks. Of the 4 animals/sex/dose, one 

male and one female/dose group were sacrificed at week 52 for an interim evaluation; and one 

male and one female from the control and high dose group only were sacrificed at week 117 for a 

recovery assessment, with removal of the test diet at week 104. Only limited clinical chemistry 

parameters were evaluated and ophthalmologic examinations were not performed. Urine and 

blood were examined for boron levels in 1 animal/sex/dose at various time points between one 

and 27 months. Samples of sperm were collected from 2 controls and 2 high dose males prior to 

sacrifice. Samples of brain, liver, kidney, body fat and muscle were collected from all animals at 

sacrifice for the same purpose.

There were no treatment-related effects on mortality, clinical signs of toxicity, body weight, food 

consumption, hematology, clinical chemistry, organ weights or gross/microscopic pathology that 

were considered to be clearly associated with treatment. At 0.302%, one of two males sacrificed 

at 104 weeks showed testicular atrophy and reduced testicular weight along with no sperm. The 

study pathologist determined that based on the characteristics of the histological findings, the 

atrophy was of recent origin and therefore not likely to be treatment-related. A second high dose 

male had low sperm count; however the reliability of the sperm assessment is unclear since the 

method for sperm collection was not described, and sperm were seen in this animal at study 

termination. Slight to moderate findings of atrophy or depression of spermatogenesis were 

reported in low and mid-dose (1-2/3) dogs, but these effects were not considered likely to be 

treatment related since a clear dose-response was not observed, slight atrophy was also observed 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 83 of 99

in the control male at 117 weeks, and the effects were not observed at similar dose levels in the 

dog 90-day studies. Furthermore, no testicular effects were observed in the control or treated 

males sacrificed at 52 weeks. Examination of excreta and tissues for boron showed that (1) 

steady-state levels were achieved within 1-2 weeks; (2) tissue accumulation did not occur to a 

significant level. However, levels in the testes, the main target organ, were not evaluated. One 

0.103% female was pregnant and gave birth during week 64 to two live and two dead pups. The 

NOAEL is 77 mg/kg bw/day borax (8.8 mg/kg/day boron equivalents; HDT). A LOAEL 

was not established (>77 mg/kg/day).

This chronic study is classified as acceptable/nonguideline and, when considered together with 

the 90-day and 38-week dietary toxicity studies on borax in the dog (MRIDs 40692307 and -08),

satisfies the guideline requirement for a chronic oral study [OPPTS 870.4100, OECD 452] in the 

dog (nonrodent). The conclusions are also supported by subchronic and chronic dog studies 

conducted concurrently on boric acid. The study was conducted prior to enactment of the US 

EPA GLP guidelines. The number of dogs per dose group (4 at study initiation) was reduced at 

the 104 week terminal sacrifice due to assignment of 1 animal/sex/group each to a 52-week 

interim sacrifice and to a 117-week recovery sacrifice, but since the testicular lesions are 

observed by 90 days’ exposure (MRID 40692307), for purposes of evaluating this effect (and 

other toxicity), the dogs from the 52 and 104-week sacrifice times may be considered together. 

Test material concentration was not examined in the diet preparations. Evaluation of clinical and 

chemistries and hematology was incomplete. Although this two year dietary study in the dog 

was originally classified as “Supplementary” due to lack of effects, the HED RfD Committee 

determined that taken together with the 38-week study and the 90-day study, there are sufficient 

data to adequately characterize the chronic toxicity of borate to the dog (memoranda dated 

November 24, 1993 and June 12, 1995).

(2) Borax

In a chronic toxicity study (MRID 40692308), sodium tetraborate decahydrate (borax technical, 

lot no. and purity not provided but analyzed at 103.29 to 105.10% of theoretical boron content) 

was administered to 4 beagle dogs/sex/dose in the diet at dose levels of 0 or 1.03% (for 

males/females, equivalent to 0 or 348/400 mg/kg/day test material; 0 or 40/46 mg/kg/day boron 

equivalents) for up to 38 weeks. Two animals/dose/sex were sacrificed at week 26, one treated 

male and female and two controls/sex at week 38 and one treated animal/sex was maintained on 

basal diet for a three week recovery phase and sacrificed at week 41.

At 1.03%, decreased body weight gain was observed in males and females (-10 to -11% below 

controls). In males, testicular atrophy and decreased testicular weight were observed. At 26 

weeks, 2/2 males showed generalized spermatogenic arrest at the spermatocyte stage, 

progressing to complete atrophy of the seminiferous epithelium in some tubules, whereas 1⁄2 

controls showed scattered atrophy. At 38 weeks, 1 control male showed severe degeneration of 

the seminiferous tubules and 1 showed 10-15% of tubules undergoing degenerative changes; 1 

treated male showed 5-10% of the tubules undergoing degenerative changes. At 41 weeks, 1 

treated male showed a moderate tubular degeneration and evidence of complete cessation of 

spermatogenesis. Absolute and relative testicular weights of treated animals were also reduced 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 84 of 99

(35% to -45%). No increases in boron levels were reported in blood, brain, liver, fat, kidney or 

muscle in dogs sacrificed at 26 or 38 weeks, but an increase in urinary boron was observed. 

Excretion was complete before 4 days after cessation of treatment. There were no treatmentrelated effects on survival, clinical signs of toxicity. The LOAEL is 1.03% (40/46 mg/kg/day, 

males/females), based on decreased body weight gain in males and females and testicular 

atrophy in males. A NOAEL was not determined in this study.

This chronic study in the dog is classified acceptable/nonguideline when considered together 

with the findings of a two-year dietary study in the dog (MRID 40692310); by itself it does 

not satisfy the guideline requirement for a chronic oral study [OPPTS 870.4100, OECD 452] in 

the dog. The study was conducted prior to enactment of EPA GLP Guidelines. Only a single 

dose was tested, a small number of animals were available for each time point evaluation and 

only limited clinical chemistry parameters were evaluated. At this time, the data requirement for 

a chronic oral toxicity study in the dog is considered to be satisfied and no additional data are 

required.

(3) Boric acid

In a 38-week oral toxicity study (MRID 00064205), boric acid (technical grade,

$99.4% a.i.) was administered in the diet to 4 beagle dogs/sex/dose at concentrations of 0 or 

0.67% (equivalent to average daily dietary intakes of 0 or 40 mg/kg/day boron equivalent, 

respectively). At week 26, 2 dogs/sex dose were sacrificed. At week 38, the remaining 2 

control animals/sex and one treated animal/sex were sacrificed. The remaining treated animals 

(1/sex) were administered untreated diet for 25 days, then evaluated for recovery. Hematologic 

and clinical chemistry parameters were examined at week 0, 4, 12, 26 and 38. Sperm sample 

collection was attempted for all males on the study at week 26 but only a few samples were 

successfully collected. In addition, boron levels were examined in blood, urine and feces 

collected throughout the study and tissue levels were analyzed at sacrifice times.

At 0.67%, complete atrophy of the seminiferous epithelium was observed in both males 

sacrificed at 26 weeks, compared to slight atrophy in one control male. At 38 weeks, both the 

control and treated male showed testicular atrophy and arrest of spermiation, although effects 

were more severe in the treated male. The male retained on the untreated diet for an additional 

25 days did not show testicular effects, suggesting reversibility may occur. There were no 

apparent treatment-related effects on survival, clinical signs of toxicity, body weight. Sperm 

collection at week 26 resulted either in no sample obtained or no sperm seen (variable sperm 

counts were seen in 3 control males, with no sample obtained from one). Boron balance studies 

indicated that there was not significant accumulation in tissues. Urinary levels were increased 

but boron was excreted out within a few days of stopping the test diet. The systemic toxicity 

LOAEL is 0.67% (40 mg/kg/day boron equivalents), based on testicular atrophy and arrest 

of spermiation. The NOAEL was not determined since only a single dose was tested.

This chronic study in the dog is classified acceptable/nonguideline when considered together 

with the findings of a 90-day and a two-year dietary study in the dog (MRIDs 00064203 

and 00005622); by itself it does not satisfy the guideline requirement for a chronic oral study 

[OPPTS 870.4100, OECD 452] in the dog. Only a single dose was tested, a small number of 

animals were available for each time point evaluation, only limited clinical chemistry parameters 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 85 of 99

were evaluated and histopathology was not complete. At this time, the data requirement for a 

chronic oral toxicity study in the dog is considered to be satisfied and no additional data are 

required.

(4) Boric acid

In a chronic oral toxicity study (MRID 00005622), boric acid (technical grade,

$98.7% a.i.) was administered in the diet to 4 beagle dogs/sex/dose at concentrations of 0.033, 

0.067 or 0.20% for up to two years (equivalent to average daily intakes of 0, 1.6, 3.6 or 10.2 

mg/kg/day boron equivalents, males and 0, 1.8, 4.0 or 11.6 mg/kg/day boron equivalents, 

females). One animal/sex/dose group was sacrificed at 12 months for interim evaluation. At 24 

months, two control and high dose animals/sex were sacrificed and three low and mid dose 

animals/sex were sacrificed. The remaining control and high dose animals were continued on 

untreated diet for 3 months and were sacrificed at 27 months to evaluate recovery. Boron 

balance studies were also performed by determining boron in blood, urine and feces at several 

study intervals from control and high dose dogs. Tissue samples were also analyzed for boron at 

the sacrifice intervals.

Clear treatment-related effects were not observed. At 12 months slight focal atrophy of the testes 

was seen at 0.20%. At 24 months, one male had complete testicular atrophy but the second male 

was normal. There was slight testicular atrophy in the control and treated male in the recovery 

group. Because of the duration of the study, lack of significant atrophy at 12 months and small 

number of animals, the testicular atrophy at 24 months is noted, but of uncertain relationship to 

treatment. Boron balance studies indicated that it did not accumulate in tissues, with levels 

reaching steady state by 1-2 weeks. Boron was completely eliminated by 9 days after 

eliminating the test diet. The NOAEL is 0.20% (10.2 mg/kg/day boron equivalents). A 

LOAEL was not achieved.

This chronic study in the dog is classified as acceptable/nonguideline and satisfies the guideline 

requirement for a chronic oral study [OPPTS 870.4100, OECD 452] in the dog when considered 

together with MRIDs 00005624, a 38-week dietary dog study and 00064203, a 90-day dog 

study), which together establish an effect level. The study was conducted prior to current 

guideline standards and is deficient in several respects (small numbers of animals at sacrifice 

times, incomplete clinical chemistry parameters and histopathology, etc.). However, it is 

considered acceptable for regulatory purposes in conjunction with the other studies.

A.4.5 Carcinogenicity

870.4200a Carcinogenicity Study - rat

See 870.4100a (870.4300)

870.4200b Carcinogenicity (feeding) - Mouse

In an oral carcinogenicity study (MRID 41863101), boric acid (technical, 99.7% a.i., lot no. 

051479) was administered to 50 B6C3F1 mice/sex/dose in the diet at dose levels of 0, 2500 or 

5000 ppm (equivalent to 0, 400-500 or 1100-1200 mg/kg bw/day boric acid, respectively; boron 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 86 of 99

equivalents 0, 66 or 192 mg/kg bw/day, males and 85 or 212 mg/kg bw/day, females) for two 

years. An interim sacrifice group was not included in the study. It is noted that the study authors 

stated that actual compound consumption may have been lower in this study due to spillage of 

test diets, which they estimated at about 48 and 96 mg/kg bw/day.

At 2500 ppm, reduced survival of males was seen in the last weeks of the study (60% vs. 82%, 

controls); female survival was unaffected (control to high dose 66%, 66% and 74%, 

respectively). Splenic lymphoid depletion in males (controls to high dose 5/48, 11/49 and 25/48, 

respectively) was considered secondary to stress. At 5000 ppm, survival of males was reduced 

compared to controls during the second year of treatment (at termination, 44% at high dose vs. 

82%, controls. Mean body weights showed decreases of about 11-17% in both sexes beginning 

at about week 32. Increases in testicular atrophy (control to high dose 3/49, 6/50 and 27/47) and 

interstitial cell hyperplasia (0/49, 0/50 and 7/47) were also observed. An increase in pulmonary 

hemorrhage in females (4%, 10%, 24%) was considered of uncertain relationship to treatment, 

and was not observed in males. No treatment-related effects on clinical signs of toxicity were 

reported. Clinical pathology, hematology, ophthalmologic and organ weight data were not 

collected in this study. The LOAEL for males is 2500 ppm (66 mg/kg/day boron equivalents, 

based on decreased survival and increased splenic lymphoid depletion. A NOAEL for 

males was not identified. The LOAEL for females is 5000 ppm (212 mg/kg/day boron 

equivalents), based on decreased body weight. The NOAEL is 2500 ppm (85 mg/kg/day 

boron equivalents). 

At the doses tested, there was not a treatment related increase in tumor incidence when compared 

to controls. A marginal increase in the incidence of hepatocellular carcinomas in low dose males

(control to high dose overall rates 5/50, 12/50 and 8/49) and combined hepatocellular adenomas 

and carcinomas (control to high dose overall rates 14/50, 19/50 and 15/49) in treated males were 

not considered treatment-related because they were within historical control range and did not 

show a dose-response. An increased combined incidence of subcutaneous tumors (fibromas, 

sarcomas, fibrosarcomas, neurofibrosarcomas) in mid dose males (2/50, 10/50 and 2/150) was 

not considered treatment-related because of the variability in spontaneous occurrence of these 

tumors in historical controls and lack of a dose-response. Dosing was considered adequate based 

on decreased survival and decreased body weights in both sexes, along with splenic lymphoid 

depletion and testicular lesions in males.

This carcinogenicity study in the mouse is classified as acceptable/guideline and satisfies the 

guideline requirement for a carcinogenicity study [OPPTS 870.4200b; OECD 451] in mice. 

Several study deficiencies are noted for this report, including lack of hematology and organ 

weight data. IT is noted that NTP carcinogenicity studies do not routinely assess clinical 

pathology and organ weights. However, MTDs were achieved for both sexes and the study is 

considered adequate for the purposes of assessing the carcinogenicity of boric acid in the mouse.

A.4.6 Mutagenicity

Gene Mutation
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 87 of 99

Guideline 870.5100, Bacterial reverse 

gene mutation (Ames Assay)

MRID 42038901

Acceptable/guideline

Tested at 10-2500 μg/plate boric acid

Negative for induction of mutagenic response in S. typhimurium strains 

TA1535, TA1537, TA1538, TA98 or TA100 in the presence or absence 

of S9 up to 2500 μg/plate. No cytotoxicity was observed.

Guideline 870.5300, Mammalian 

forward gene mutation, Mouse 

lymphoma L5178Y cell 

MRID 42038902

Acceptable/guideline

Tested at 1200-5000 μg/mL boric acid +/-S9

Negative for induction of mutagenic response in two independently 

performed mouse L5178Y cell lymphoma forward mutation assays. 

Marginal cytotoxicity at 3500-5000 μg/mL.

Cytogenetics

Guideline 870.5385, in vivo

micronucleus assay, Mouse 

MRID 42038904

Acceptable/guideline

Tested at 900, 1800 or 3500 mg/kg bw boric acid

Negative for induction of clastogenic response to the bone marrow of 

Swiss mice. No systemic toxicity or target cytotoxicity observed up to 

3500 mg/kg bw.

Other Genotoxicity

870.5550, Unscheduled DNA 

synthesis, in vivo Rat liver

MRID 42038903

Acceptable/guideline 

Tested at 5 – 5000 μg/mL boric acid

Negative for increased unscheduled DNA synthesis in cultured rat 

hepatocytes. Slightly increased percent cells in repair at ≥2500 μg/mL in 

repeat assay were considered secondary to increased cytotoxicity at those 

dose levels.

A.4.7 Neurotoxicity

870.6100 Delayed Neurotoxicity Study - Hen

Study not available

870.6200 Acute Neurotoxicity Screening Battery

In an acute neurotoxicity (limit dose) study (MRID 48773701), groups of ~7-week-old SpragueDawley [Crl:CD®(SD)] rats (10/sex/dose) were given a single oral (gavage) dose of boric acid 

(supplied as 56.73% a.i. boron oxide, Lot # 8C20) in 1% (w/v) aqueous carboxymethyl cellulose 

at the limit dose of 2000 mg/kg bw (350 mg/kg bw boron equivalents) and observed for 14 days. 

Dosing volume was 10 mL/kg bw. A group of control animals was administered vehicle only. 

Neurobehavioral assessment (functional observational battery (FOB) and motor activity testing) 

were performed in 10 animals/sex/group pre-test, on Day 1 at the estimated time of peak effect 

determined by plasma Tmax (stated to be within 2-3 hours of dosing based on published data), and 

on Days 7 and 14. Cholinesterase activity was not determined. At study termination, 5

animals/sex/group were euthanized and perfused in situ for neuropathological examination. All 

of the perfused animals were subjected to histopathological evaluation of brain and peripheral 

nervous system tissues. 

No definitive, adverse effects of treatment with the limit dose were noted. All rats survived to 

study termination, and no treatment-related clinical signs were noted. Body weight gain of 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 88 of 99

treated males was reduced by 16% over Days 1-14 (p≤0.05), but was not accompanied by 

decreases in absolute body weight and was due in part to lower initial mean body weight. 

Furthermore, feed consumption was not measured, so it is not known if treated male rats 

exhibited a concomitant decrease in feed consumption. Absolute body weight and body weight 

gain of treated female rats were comparable to that of controls. 

Treatment with the limit dose did not result in neurotoxicity in male or female rats as assessed by 

functional observation battery (FOB), motor activity counts, gross necropsy, brain weight, or 

neuropathological examination. Brain weights of male rats were slightly increased (8% above 

controls) in the treated group but this change was not associated with microscopic changes in the 

brain and was therefore not considered a treatment-related effect or an adverse change. Positive 

control studies demonstrated the ability of the testing laboratory to conduct neurotoxicity 

screening assessments.

Based on a lack of effects in this study, the NOAEL for male and female Sprague Dawley 

rats (neurotoxicity and systemic toxicity) was ≥ 2000 mg/kg bw (350 mg/kg bw boron 

equivalents). A LOAEL was not established. 

This neurotoxicity study is classified as acceptable (guideline) and satisfies the guideline 

requirement for an acute neurotoxicity study in rats (870.6200a; OECD 424). Although only a 

single dose was evaluated, the test material was administered at the limit dose.

870.6200 Subchronic Neurotoxicity Screening Battery

Study not available

870.6300 Developmental Neurotoxicity Study

Study not available

A.4.8 Metabolism

870.7485 Metabolism - Rat

Study not available

870.7600 Dermal Absorption - Human

(1) In vivo

In an in vivo dermal penetration study (MRID 48507005) 1.8 mL of enriched 10B (>99% purity)

5% boric acid in water (Lot No. BL-EV-94-36 (BA)), 5% borax in water (Lot No. 1797-16), or

10% disodium octaborate tetrahydrate in water (DOT, Lot No. 0797-17) was applied to the upper 

dorsal skin of 8 healthy male and female human volunteers/dose group between the ages of 22 

and 50 years. The amount of test material applied was determined by weighing the dosing 

microsyringe prior to and after dosing. The test materials were applied to an area 30 x 30 cm and 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 89 of 99

were allowed to remain in contact with the skin for 24 hours before washing. T-shirts were worn 

by the test subjects to protect the treated area and allow collection of residual test material 

following application. Subjects were asked to follow dietary restrictions during the test period, 

thereby avoiding certain foods known to contain higher boron levels. Six days after the initial 

application, the skin was irritated with a 2% sodium lauryl sulfate (SLS) solution and the same 

test materials re-administered the following day. Urine was collected at 24-hour intervals 4 days 

pre-treatment; following treatment with the test materials for 7 days; and for 7 days following 

treatment after skin irritation with 2% sodium lauryl sulfate (SLS) for determination of 10B 

recovery. The urine, skin wash gauze, and T-shirts were assayed by inductively coupled plasmamass spectrometry for 10B content and the determination of the 10B/11B ratio. The study was 

conducted in accordance with human studies’ ethical conduct guidelines.

Following dermal treatment of human volunteers with 10B enriched 5% Boric Acid, 5% Borax, 

or 10% DOT, very limited absorption occurred. Boric acid absorption, as percent of administered dose, was 0.226 ± 0.125%, with flux and permeability constants calculated as 0.0094 

μg/cm2/hour and 1.9 × 10-7cm/hour, respectively. Borax, as percent of administered dose 

absorbed, was 0.210 ± 0.194%, with flux and permeability constants calculated as 0.00875 

μg/cm2/hour and 1.8 × 10-7cm/hour, respectively. DOT percent of administered dose absorbed 

dose was 0.122 ± 0.108%, with flux and permeability constants calculated as 0.010 μg/cm2/hour

and 1.0 × 10-7cm/hour, respectively. Approximately 60% (49-64%) of the administered topical 

dose was recovered after 24 hours in the T-shirt covering the dosed skin and the skin washes. 

Pre-treatment of the skin with the irritant 2% sodium lauryl sulfate had essentially no effect on 

boron skin absorption for all three dosage forms; with 0.239 ± 0.174% recovered after boric acid 

treatment, 0.185 ± 0.219% following borax treatment, and 0.107 ± 0.134% following DOT 

treatment. No skin irritation was noted following treatment with any of the test materials; transepidermal water loss was reportedly measured, but data were not provided. The results show 

that the in vivo dermal absorption of boron was low and unaffected by mild skin irritation. 

The percent of absorbed dose measured for the three test materials used in this study may be 

arbitrarily low since the amount of boron in soft tissues and bone were not determined. These 

cannot be readily determined in an in vivo human-based study. The determination of percent of 

absorbed dose is also hampered by the moderate recovery of the administered 10B dose (49 –

64%) and lack of information regarding absorbable dose remaining in the skin. However these 

limitations are balanced somewhat by (1) the known rapid elimination of boron compounds and 

low retention in tissues following absorption (>90% by 3 days post-dosing), which suggests that 

a significant level of radioactivity would not be retained in tissues; (2) the long (24 hr) exposure 

period, which would provide a higher absorption level compared to the standard 6-8 hr exposure; 

(3) collection of urine for 7 days following dosing, during which time most of the absorbable 

dose would be expected to have been absorbed and excreted. The low level of absorbed dose in 

the urine is also consistent with other published studies conducted in animals. Given the rapid 

excretion and low percent absorbed dose after 7 days, it seems unlikely that significantly more of 

the dose would be excreted at later times. Although recovery of total radioactivity was low, 

adjustment of the absorbed dose for the low recovery (i.e., 50%) would still give a low 

absorption value (<0.5%). Therefore absorption is likely to be very low. The composition of 

treatment groups by sex and age, individual or group transepidermal water loss (TEWL)

measurements, individual or group skin irritation scores, and readily useable individual test 
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 90 of 99

material absorption data were not located in the study report. Therefore, verification of the 

reported results by repeat analysis were not possible. However, the value of repeat analysis is 

questionable given the low percent of dose for each test material recovered. 

This in vivo human study is considered Acceptable/Non-guideline. Although the study has 

several limitations, including relatively low recovery of radioactivity and sampling of urine only,

it provides information regarding dermal absorption in humans and is consistent with published 

data indicating low or no dermal absorption of boric acid/borate salts across undamaged skin.

(2) In vitro

In an in vitro skin permeability study (MRID 48549901), human (cadaver) thigh skin was 

assessed over 24 hours following treatment with 10B–enriched boric acid [0.05%, 0.5%, or 5% 

w/v; Batch No. BL-EV-94-36(BA); 99.6% a.i.], Borax (5% w/v; Batch No. 1797-16; 100% a.i.), 

or disodium octaborate tetrahydrate [DOT; 5% w/v; Batch No. 1797-17; 99.8% a.i.]. Boric acid 

(5%) was tested at 2 μl/cm2 and 1000 μl/cm2. The other two concentrations of boric acid, as 

well as Borax and DOT were tested at 1000 μl/cm2. The test materials were applied to the upper 

side of the skin samples in flow-through test cells. Receptor fluid was collected every 4 hours, 

the skin samples were washed, and the receptor fluid, washings, and skin samples were analyzed 

for the test materials. The skin samples were not tape-stripped following washing to remove the 

outer stratum corneum and were not included in the estimation of absorbed dose. It is noted that 

the study report did not indicate whether an assessment of skin integrity was performed.

The mean percent boric acid dose absorbed (present in the receptor fluid) at the three different 

concentrations did not vary markedly (0.28 – 1.20%). The 95% confidence intervals overlapped 

in every case. The mean rates of flux were 0.25, 0.58, and 14.58 μg/cm2/hr for the 0.05%, 0.5%, 

and 5% boric acid concentrations, respectively. Flux did not vary strictly in proportion with the 

percent concentration of boric acid, but the permeability constants were relatively consistent 

across the concentration range tested. The 5% boric acid test using only a 2 μl/cm2 application 

rate, which mimicked conditions of an in vivo study with boric acid (MRID 48507005), resulted 

in 1.75% dose absorbed and a permeability constant that was two orders of magnitude lower than 

the constants observed in the 1000 μl/cm2 tests (“infinite dose” tests). These results indicate that 

caution should be used when extrapolating in vitro studies conducted at infinite doses to in vivo 

situations of finite doses. Most of the boric acid doses were recovered in the 24-hour skin 

washings with 72.4 ± 9.1%, 86.0 ± 5.9%, and 81.9 ± 2.9% for the 0.05, 0.5, and 5% 

concentrations, respectively, for the 1000 μl/cm2 tests. The permeability data obtained on 5% 

Borax and 10% DOT tested at 1000 μl/cm2 were similar to that obtained on 5% boric acid at 

1000 μl/cm2 (0.41% and 0.19% of dose absorbed for Borax and DOT, respectively). 

This in vitro skin permeability study using human (cadaver) skin is acceptable/nonguideline, 

but does not satisfy the guideline requirement for a dermal penetration study (870.7600). The 

study provides useful supplemental information to the OCSPP 870.7600 requirement.

A.4.9 Immunotoxicity

870.7800 Immunotoxicity – Mouse
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 91 of 99

In an immunotoxicity study (MRID# 48786601), Boric acid (56.37%, Lot No. 8C20) in 

carboxymethyl cellulose (10 mL/kg) was administered to female B6C3F1mice (10/group) by 

gavage at 0 or 1000 mg/kg/day for 28 consecutive days (0 or 175 boron equivalents). On study 

Day 25, all animals in all groups were immunized with a single intravenous injection of the 

antigen, sheep red blood cells 2x108 SRBC/animal. Positive control group consisted of 10 

females received 80 mg/kg of cyclophosphamide (CPH) in saline by intraperitoneal injection, 24 

hours before sacrificed. Animals were sacrificed on Day 29. All animals were evaluated for 

mortality, clinical signs, body weight changes and food consumption, spleen and thymus 

weights. A T-cell dependent antibody response (TDAR) was assessed with an antibody plaqueforming cells (AFC) assay. 

There were no effects of test substance treatment on mortality, body weight, clinical signs, food 

consumption, and spleen and thymus weights. There was a statistically significant decrease 

(p≤0.05) in the specific activity (AFC/10

6

live splenocytes) and total activity (AFC/spleen) in the 

1000 mg/kg group when compared to the vehicle control group. 

In a follow-up study (MRID# 48798001), Boric acid (56.37%, Lot No. 8C20) in carboxymethyl 

cellulose (10 mL/kg) was administered to female B6C3F1mice (10/group) by gavage at dose 

levels of 0, 250, 500, 750 or 1000 mg/kg/day (0, 43.8, 87.5, 131.3 or 175 mg/kg/day boron 

equivalents) for 28 consecutive days. On study Day 25, all animals in all groups were 

immunized with a single intravenous injection of the antigen, sheep red blood cells 3x108

SRBC/animal. Positive control group consisted of 10 females received 80 mg/kg of 

cyclophosphamide (CPH) in saline by intraperitoneal injection, 24 hours before sacrificed. 

Animals were sacrificed on Day 29. All animals were evaluated for mortality, clinical signs, 

body weight changes and food consumption, spleen and thymus weights. TDAR was assessed 

with an anti-SRBC AFC assay. 

There were no effects of test substance treatment on mortality, clinical signs, body weight, food 

consumption, and spleen and thymus weights. 

The systemic toxicity NOAEL is 1000 mg/kg/day (175 mg/kg/day boron equivalents); the 

LOAEL was not established, tested at the Limit Dose.

There were no statistically significant differences of thymus and spleen weights in treated groups 

when compared to the vehicle control group in both studies. The anti-SRBC antibody plaqueforming cell data showed decreases in the specific activity (AFC/106

live splenocytes) and total 

activity (AFC/spleen) with statistical significances observed in the 500, 750, and 1000 mg/kg 

groups. A high inter-individual variability was noted in all the treatment groups as well as in the 

control group. Evaluation of individual animal data of this study showed a dose-dependent 

decrease of anti-SRBC AFC response. It is to be noted that the total viable cells in the spleen of 

treated groups were lower than the vehicle control group and the cell viability was low in the 

treated groups as well as in the vehicle control group. Animals in the positive control group 

showed marked decreases in the anti-SRBC AFC response. The positive control group 

confirmed the validity of the immunotoxicity assay.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 92 of 99

The Natural Killer (NK) cells activity was not evaluated in both studies. Under the HED 

guidance, a NK cells activity assay is not needed if a suppression of TDAR was established.

Under conditions of this study, the immunotoxicity NOAEL is 250 mg/kg/day 

(43.8mg/kg/day boron equivalents); the LOAEL is 500 mg/kg/day (87.5 mg/kg/day boron 

equivalents), based on decreases of anti-SRBC AFC responses.

These immunotoxicity studies are classified acceptable/guideline and satisfies the guideline 

requirement for an immunotoxicity study (OPPTS 870.7800) in mice.
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 93 of 99

Appendix B: Chemical Identity and Physical/Chemical Properties

Table B.1 Nomenclature of Boric Acid and its Sodium Salts

Common 

name

Boric acid

Sodium 

tetraborate 

decahydrate

Sodium 

tetraborate 

pentahydrate

Sodium 

tetraborate 

anhydrous

Disodium 

octaborate 

tetrahydrate

Disodium 

octaborate 

anhydrous

Sodium 

metaborate

Empirical 

Formula H3BO3 Na2B4O710H20 Na2B4O75H20 Na2B4O7 Na2B8O134H20 Na2B8O13 NaBO2

Other 

names

orthoboric 

acid, 

boracid 

acid

borax 

decahydrate, 

borax 10 mol, 

disodium 

tetraborate 

decahydrate, 

sodium borate 

decahydrate, 

sodium 

pyroborate 

10H20, sodium 

biborate 10H20

disodium 

tetraborate 

pentahydrate, 

borax 

pentahydrate, 

sodium borate 

pentahydrate, 

sodium 

biborate 5H20, 

sodium 

pyroborate 

5H20

borax 

(anhydrous), 

sodium 

borate 

(anhydrous), 

sodium 

biborate 

(anhydrous), 

sodium 

pyroborate 

(anhydrous)

sodium 

octaborate 

tetrahydrate

Boron 

sodium 

oxide

Boric acid, 

sodium 

salt

PC Code 011001 011102 011110 and 

011111 011112 011103 011107 011104

CAS 

Registry 

Number

10043-35-

3

1303-96-4

11130-12-4 or 

12179-04-3

1330-43-4

12008-41-2,

12280-03-4

12008-41-

2

15293-77-

3, 7775-

19-1

Table B.2 Physical/Chemical Properties of Boric acid and its Sodium Salts

Chemical

Molecular 

weight

(g/mole)

Physical 

state

Melting 

point

Solubility 

in water pH

Density/ 

Specific 

Gravity

Vapor 

Pressure

Estimated 

Octanol/ 

Water

Partition 

Coefficient

Boric Acid 61.9

Solid 

crystalline 

powder

171oC

5.6 

g/100mL

5.1

(1% solution 

at 20oC)

1.51 at 

20 oC 

oC

< 10-4

torr at 

20oC

0.175

Sodium 

tetraborate 

decahydrate

381.87 crystalline 

powder 75oC

4.70 g/100 

mL at 

20oC

9.2

(1% solution 

at 20oC)

1.73 < 10-6

torr 0.175

Sodium 

tetraborate 

pentahydrate

291.35 milky white 

alkaline salt < 200oC

3.59% at 

20oC

9.2

(1% solution 

at 20oC)

1.82 < 10-6

torr No data

Sodium 

tetraborate 

anhydrous

201.27

Solid 

crystalline 

or 

amorphous

742oC

2.56 g/100 

mL at 

20oC

No data 2.37 < 10-6

torr No data

Disodium 

octaborate 

tetrahydrate

412.31 Powder 815oC

9.5% at 

20oC

8.5

(1% solution 

at 23oC)

25-35 

lbs/ft3

< 10-6

torr No data
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 94 of 99

Table B.2 Physical/Chemical Properties of Boric acid and its Sodium Salts

Chemical

Molecular 

weight

(g/mole)

Physical 

state

Melting 

point

Solubility 

in water pH

Density/ 

Specific 

Gravity

Vapor 

Pressure

Estimated 

Octanol/ 

Water

Partition 

Coefficient

Disodium 

octaborate 

anhydrous

340.31 Solid rods No data No data No data

1.8 

g/mL at 

20oC

< 10-6

torr No data

Sodium 

metaborate 65.82

Solid white 

pieces or 

powder

966oC

Soluble, 

no value 

reported

11.82 (6% 

solution)

51-61 

lb/ft3

< 10-6

torr No data

Sources: U.S. EPA (1993), NIOSH (2001)
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 95 of 99

Appendix C: Use Pattern Summary

Table C.1. Summary of Registered Use Directions for Boric Acid and its Sodium Salts

Application 

Type/Equip/etc.

Formulation 

[Representative EPA 

Reg. No.]

Maximum Application Rate1 PPE/Work Attire, REI, 

Retreatment

Grass/Turf (Homes, Parks, Golf courses), Ant mounds, Building Perimeters

Broadcast application 

via:

 Tractor-drawn 

spreader

 Hand dispersal

 Belly grinder

 Cup/Spoon

 Push-type rotary 

spreader

Granule (insecticide)

EPA Reg. No. 19713-

522 (Drexel Borxel)

5% boric acid

Product rate 4 lb product/1000 ft2

 Retreatment not 

specified

 PPE: eyewear/goggles, 

long sleeve shirt, long 

pants, waterproof gloves, 

shoes/socks

 REI not specified

Active 

ingredient rate

0.2 lb boric acid/1000 ft2

9 lb boric acid/acre

Boron 

equivalent rate

1.5 lb boron/acre

0.035 lb boron/1000 ft2

Golf Course Turf and Agricultural Food/Feed Crops

(alfalfa, cane berries, bush berries, coffee, cacao, pome fruit, stone fruit, citrus, herbs, tree nuts, peanuts, strawberry, 

tobacco, Brassica leafy vegetables, bulb vegetables, corn, cucurbit, fruiting vegetables, leafy vegetables, except 

Brassica, legumes, root and tuber vegetables, soybean, cotton, herbs, avocado, kava, banana, guava, papaya, 

pineapple, watermelon and grasses) and Golf Course Turf

Broadcast application 

via:

 Groundboom 

sprayer

 Airblast sprayer

 Chemigation 

and aerial 

application is 

prohibited

Liquid concentrate 

(insecticide)

EPA Reg. No. 72662-3

(Prev-Am Ultra)

0.99% sodium 

tetraborohydrate 

decahydrate (STD)

Product rate

100 fl oz/100 gal soln

25 gal soln/acre

 Minimum retreatment is 

7 days.

 PPE: eyewear/goggles, 

long sleeve shirt, long 

pants, waterproof gloves, 

shoes/socks

 REI: 12 hours

Active 

ingredient rate

0.00065 lb STD/gal soln

(product rate * 8.34 

lb/gal soln * 0.99% ai)

0.016 lb STD/acre

(0.00065 lb STD/gal soln 

* 25 gal soln/acre)

Boron 

equivalent rate 0.0018 lb boron/acre

Home gardens, lawns, greenhouses, ornamentals, shrubs

Broadcast application 

via hand sprayers 

(e.g., hose-end 

sprayers, handwand 

sprayers)

Liquid concentrate 

(insecticide)

EPA Reg. No. 72662-5

(Prev-Gard)

0.99% sodium 

tetraborohydrate 

decahydrate (STD)

Product rate

1 fl oz. product/gal soln.

1 gal soln/1000 ft2

 Spray every 7-10 days or 

as frequently as every 4 

days

 PPE: eyewear/goggles, 

long sleeve shirt, long 

pants, waterproof gloves, 

shoes/socks

 REI: 12 hours

Active 

ingredient rate

0.00065 lb STD/gal 

soln/1000 ft2

(product rate * 8.34 

lb/gal soln * 0.99% ai)

0.03 lb STD/acre

Boron 

equivalent rate

0.000073 lb boron/gal 

soln/1000 ft2

0.003 lb boron/acre

Tree Stumps
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 96 of 99

Table C.1. Summary of Registered Use Directions for Boric Acid and its Sodium Salts

Application 

Type/Equip/etc.

Formulation 

[Representative EPA 

Reg. No.]

Maximum Application Rate1 PPE/Work Attire, REI, 

Retreatment

Application via 

shaker can or hand 

sprayers

Dust/powder 

(fungicide)

EPA Reg. No. 2935-

501

(Sporax)

100% sodium 

tetraborohydrate 

decahydrate (STD)

Product rate

1 lb/50 ft2stump surface 

(equiv. 250 six inch 

stumps)

1 lb/gal soln/50 ft2stump 

surface (assume 1 gallon 

water dilution)

 Spray every 7-10 days or 

as frequently as every 4 

days

 PPE: eyewear/goggles, 

long sleeve shirt, long 

pants (or coveralls), 

waterproof gloves, 

shoes/socks

 REI: 48 hours

Active 

ingredient rate

1 lb STD/gal soln/50 ft2

(product rate * 100% ai)

Boron 

equivalent rate

0.11 lb boron/gal soln/50 

ft2

0.0023 lb boron/gal 

soln/ft2

Indoor Crack-and-crevice (Residential, Commercial, Recreational) and Sewers

Application via 

shaker can, bulb 

dusters, power 

dusters

Dust (insecticide)

EPA Reg. No. 56-73

(Eaton’s Answer)

99% boric acid

Product rate

20 oz container

12 oz/190 ft2

 No retreatment, PPE, or 

REI specified

Active 

ingredient rate

19.8 oz boric acid/20 oz 

container

11.9 oz boric acid/190 ft2

Boron 

equivalent rate

0.22 lb boron/20 oz 

container

0.00068 lb boron/ft2

30 lb boron/acre

Application via hand 

dispersal

Granule (insecticide)

EPA Reg. No. 64405-2

(Redzone Bait)

5% boric acid

Product rate 2 lb/1000 ft2

 PPE: eyewear/goggles, 

long sleeve shirt, long 

pants, waterproof gloves, 

shoes/socks

 REI: 4 hours

 No retreatment specified

Active 

ingredient rate 0.1 lb boric acid/1000 ft2

Boron 

equivalent rate

0.017 lb boron/1000 ft2

0.76 lb boron/acre

Structural Building/House Components (wall/cabinet voids, soffits, attic space, crawl spaces)

Application via bulb 

and power dusters

Dust/Wettable Powder

(insecticide/fungicide)

EPA Reg. No. 64405-8

(Nibor Borate)

98% disodium 

octaborate tetrahydrate 

(DOT)

Product rate

0.5 oz/ft2

1.5 lb/gal water

 PPE: eyewear/goggles, 

long sleeve shirt, long 

pants, waterproof gloves, 

shoes/socks, respirator in 

confined spaces

 REI: 48 hours

 No retreatment specified

Active 

ingredient rate

0.49 oz DOT/ft2

1.47 lb DOT/gal soln

Boron 

equivalent rate

0.21 lb boron/lb product

0.1 oz boron/ft2

0.0065 lb boron/ft2

0.31 lb boron/gal soln
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 97 of 99

Table C.1. Summary of Registered Use Directions for Boric Acid and its Sodium Salts

Application 

Type/Equip/etc.

Formulation 

[Representative EPA 

Reg. No.]

Maximum Application Rate1 PPE/Work Attire, REI, 

Retreatment

Application via hand 

sprayers (backpack, 

handgun, airless 

sprayers, 

brush/rollers)

Liquid concentrate 

(insecticide/fungicide)

EPA Reg. No. 83465-1

(GB-40)

40% disodium 

octaborate tetrahydrate 

(DOT)

Product rate

1 gallon product per 1 

gallon water = 1 gal

prod/2 gal soln

(1 gallon product = 11.5 

lbs)

 PPE: eyewear/goggles, 

long sleeve shirt, long 

pants, chemical resistant 

gloves, shoes/socks, 

respirator in confined 

spaces

 REI: 48 hours

 No retreatment specified

Active 

ingredient rate

2.3 lb DOT/gal soln

(product rate * 40% ai)

Boron 

equivalent rate 0.32 lb boron/gal soln

Poultry House, Soil/Manure, Garbage/Municipal Dumps

Application via bulb 

and power dusters 

and via hand sprayers

Dust/Wettable Powder 

(insecticide)

EPA Reg. No. 1624-11

(Polybor 3)

98% disodium 

octaborate tetrahydrate 

(DOT)

Product rate

5 lb/100 ft2

2 lb/gal water

3 gal soln/100 ft2

 PPE: eyewear/goggles, 

long sleeve shirt, long 

pants, chemical resistant 

gloves, shoes/socks, 

respirator under certain 

conditions

 REI not specified

 No retreatment specified

Active 

ingredient rate

4.9 lb DOT/100 ft2

0.65 lb DOT/gal soln

Boron 

equivalent rate

1 lb boron/100 ft2

0.14 lb boron/gal soln

448 lb boron/acre

Indoor Residential Carpets, Rugs, Upholstery

Application via hand 

sprayers

RTU Solution 

(insecticide)

EPA Reg. No. 64405-6

(RTU Flea Spray)

8.5% disodium 

octaborate tetrahydrate 

(DOT)

Product rate 1 gal/750 ft2

 No retreatment, PPE, or 

REI specified

Active 

ingredient rate

0.71 lb DOT/gal soln

(1 gal prod * 8.34 lb/gal 

* 8.5% ai)

0.00095 lb DOT/ft2

Boron 

equivalent rate

0.15 lb boron/gal soln

0.0002 lb boron/ft2

Application via hand 

sprayers

Dust/Wettable powder 

(insecticide)

EPA Reg. No. 67419-1

(Ecology Works)

98% disodium 

octaborate tetrahydrate 

(DOT)

Product rate

1 cup/0.5 gal water

1 cup/100 ft2

 Reapply every 8 weeks

 No PPE or REI specified

Active 

ingredient rate

0.86 lb DOT/gal soln

(1 cup * 200 grams/cup * 

1 lb/454 grams * 98% ai)

0.0043 lb DOT/ft2

Boron 

equivalent rate

0.18 lb boron/gal soln

0.0009 lb boron/ft2

Bed Bug Treatments (Mattresses, Bed Frames, Floorboards, Baseboards, Carpets, Walls)
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 98 of 99

Table C.1. Summary of Registered Use Directions for Boric Acid and its Sodium Salts

Application 

Type/Equip/etc.

Formulation 

[Representative EPA 

Reg. No.]

Maximum Application Rate1 PPE/Work Attire, REI, 

Retreatment

Application via hand 

sprayers

RTU Solution 

(insecticide)

EPA Reg. No. 64405-6

(RTU Flea Spray)

8.5% disodium 

octaborate tetrahydrate 

(DOT)

Product rate 5 ounces/ft2

 No retreatment, PPE, or 

REI specified

Active 

ingredient rate

0.71 lb DOT/gal soln

(1 gal prod * 8.34 lb/gal 

* 8.5% ai)

0.028 lb DOT/ft2

Boron 

equivalent rate

0.15 lb boron/gal soln

0.0058 lb boron/ft2

Industrial Areas, Lots, Fence Lines, Runways and Underneath Asphalt, Wood Decks, Bleachers

Broadcast application 

via:

 Tractor-drawn 

spreader

 Hand dispersal

 Belly grinder

 Cup/Spoon

 Push-type rotary 

spreader

 Backpack

Granule (herbicide)

EPA Reg. No. 33560-

46 (Barespot)

49% sodium metaborate

Product rate 3 lb product/100 ft2

 PPE: eyewear/goggles, 

coveralls over long 

sleeve shirt and long 

pants, chemical resistant 

gloves, shoes/socks

 REI not specified

 No retreatment specified

Active 

ingredient rate

1.5 lb sodium 

metaborate/100 ft2

653 lb sodium 

metaborate/acre

Boron 

equivalent rate 105 lb boron/acre

Swimming Pools

Pour-in

Solid/Tablet

(antimicrobial)

EPA Reg. No. 1258-

1276 (Endure)

100% sodium 

tetraborate pentahydrate

Product rate 2 lb/1000 gallons water

 PPE: eyewear/goggles

 REI not applicable

 No retreatment specified

Active 

ingredient rate

2 lb sodium tetraborate 

pentahydrate/1000 

gallons water

Boron 

equivalent rate

0.3 lb boron/1000 

gallons (35 mg/L)

Materials Preservatives (Paints, Gypboard Coatings, Inks and Dyes)

Pour-in

Solid/Powder

(preservative)

EPA Reg. No. 1624-

130 (Optibor Guard)

100% Boric acid

Product rate 8% by weight of finished 

product

 PPE: not specified

 REI not applicable

 No retreatment specified

Active 

ingredient rate

8% boric acid by weight 

of finished product

Boron 

equivalent rate

1.4% boron by weight of 

finished product

Wood Preservative (Pre-construction/Lumber)

Pressure Treatment

Emulsifiable 

concentrate

(preservative)

EPA Reg. No. 3008-

120 (ORD-1302)

25% Disodium 

octaborate tetrahydrate

Product rate 25% DOT in solution

 PPE: not specified

 REI not applicable

 No retreatment specified

Active 

ingredient rate 25% DOT in solution

Boron 

equivalent rate 5.25% in solution
Boric Acid/Salts of Boric Acid Draft Risk Assessment DP No. D418384

Page 99 of 99

Table C.1. Summary of Registered Use Directions for Boric Acid and its Sodium Salts

Application 

Type/Equip/etc.

Formulation 

[Representative EPA 

Reg. No.]

Maximum Application Rate1 PPE/Work Attire, REI, 

Retreatment

Dip Diffusion

Solid/Powder

(preservative)

EPA Reg. No. 74940-1 

(Preservabalance)

99% Disodium 

octaborate tetrahydrate

Product rate 280 lbs/100 gallons 

solution

 PPE: not specified

 REI not applicable

 No retreatment specified

Active 

ingredient rate

280 lbs DOT/100 gallons 

solution

Boron 

equivalent rate

59 lb boron/100 gallons 

solution

Sapstain Treatment

Solution

(preservative)

EPA Reg. No. 60061-

122 (Timbertreat ICA20)

20% Boric acid

Product rate 20% boric acid solution

 PPE: waterproof gloves, 

eye protection, longsleeved shirt, long pants, 

chemical-resistant 

footwear, dust/mist 

respirator, chemical 

resistant apron

 REI not applicable

 No retreatment specified

Active 

ingredient rate 20% boric acid solution

Boron 

equivalent rate 3.5 % boron solution

Remedial Wood Treatment (On-site spray)

Manually pressurized

handwand

Ready-to-use Solution

(antimicrobial)

EPA Reg. No. 19713-

286 (Lum-Bor)

98% Disodium 

octaborate tetrahydrate

(DOT)

Product rate 25% solution  PPE: waterproof gloves, 

eye protection, longsleeved shirt, long pants, 

shoes, dust/mist 

respirator

 REI not applicable

 No retreatment specified

Active 

ingredient rate

25% DOT solution (2.5 

lb DOT/gallon solution)

Boron 

equivalent rate

0.525 lb boron/gallon 

solution

Trowel or brush

Ready-to-use Solution

(antimicrobial)

EPA Reg. No. 83933-2 

(Bioguard TriBor Paste)

45% Sodium tetraborate 

pentahydrate, 10% 

boric acid

Product rate 45% STP, 10% boric 

acid

 PPE: not specified

 REI not applicable

 No retreatment specified

Active 

ingredient rate

45% STP, 10% boric 

acid

Boron 

equivalent rate

0.85 lb boron/gallon 

solution