[Federal Register Volume 67, Number 247 (Tuesday, December 24, 2002)]
[Notices]
[Pages 78459-78467]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-32400]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2002-0283; FRL-7277-5]


Bronopol; Notice of Filing a Pesticide Petition to Establish a 
Tolerance for a Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket ID number OPP-2002-0283, must be 
received on or before January 23, 2003.

ADDRESSES: Comments may be submitted electronically, by mail, or 
through hand delivery/courier. Follow the detailed instructions as 
provided in Unit I. of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: Bipin Gandhi, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-8380; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, pesticide manufacturer, or 
antimicrobial pesticide manufacturer. Potentially affected entities may 
include, but are not limited to:
    [sbull] Industry (NAICS 111), e.g., Crop production.
    [sbull] Industry (NAICS 112), e.g., Animal production.
    [sbull] Industry (NAICS 311), e.g., Food manufacturing.

[[Page 78460]]

    [sbull] Industry (NAICS 32532), e.g., Pesticide manufacturing.
    [sbull] Industry (NAICS 32561), e.g., Antimicrobial pesticide.
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2002-0283. The 
official public docket consists of the documents specifically 
referenced in this action, any public comments received, and other 
information related to this action. Although a part of the official 
docket, the public docket does not include Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute. The official public docket is the collection of materials 
that is available for public viewing at the Public Information and 
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 
1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The docket telephone number is (703) 305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket facility identified in 
Unit I.B.1. Once in the system, select ``search,'' then key in the 
appropriate docket ID number.
    Certain types of information will not be placed in the EPA Dockets. 
Information claimed as CBI and other information whose disclosure is 
restricted by statute, which is not included in the official public 
docket, will not be available for public viewing in EPA's electronic 
public docket. EPA's policy is that copyrighted material will not be 
placed in EPA's electronic public docket but will be available only in 
printed, paper form in the official public docket. To the extent 
feasible, publicly available docket materials will be made available in 
EPA's electronic public docket. When a document is selected from the 
index list in EPA Dockets, the system will identify whether the 
document is available for viewing in EPA's electronic public docket. 
Although not all docket materials may be available electronically, you 
may still access any of the publicly available docket materials through 
the docket facility identified in Unit I.B. EPA intends to work towards 
providing electronic access to all of the publicly available docket 
materials through EPA's electronic public docket.
    For public commenters, it is important to note that EPA's policy is 
that public comments, whether submitted electronically or in paper, 
will be made available for public viewing in EPA's electronic public 
docket as EPA receives them and without change, unless the comment 
contains copyrighted material, CBI, or other information whose 
disclosure is restricted by statute. When EPA identifies a comment 
containing copyrighted material, EPA will provide a reference to that 
material in the version of the comment that is placed in EPA's 
electronic public docket. The entire printed comment, including the 
copyrighted material, will be available in the public docket.
    Public comments submitted on computer disks that are mailed or 
delivered to the docket will be transferred to EPA's electronic public 
docket. Public comments that are mailed or delivered to the docket will 
be scanned and placed in EPA's electronic public docket. Where 
practical, physical objects will be photographed, and the photograph 
will be placed in EPA's electronic public docket along with a brief 
description written by the docket staff.

C. How and To Whom Do I Submit Comments?

    You may submit comments electronically, by mail, or through hand 
delivery/courier. To ensure proper receipt by EPA, identify the 
appropriate docket ID number in the subject line on the first page of 
your comment. Please ensure that your comments are submitted within the 
specified comment period. Comments received after the close of the 
comment period will be marked ``late.'' EPA is not required to consider 
these late comments. If you wish to submit CBI or information that is 
otherwise protected by statute, please follow the instructions in Unit 
I.D. Do not use EPA Dockets or e-mail to submit CBI or information 
protected by statute.
    1. Electronically. If you submit an electronic comment as 
prescribed in this unit, EPA recommends that you include your name, 
mailing address, and an e-mail address or other contact information in 
the body of your comment. Also include this contact information on the 
outside of any disk or CD ROM you submit, and in any cover letter 
accompanying the disk or CD ROM. This ensures that you can be 
identified as the submitter of the comment and allows EPA to contact 
you in case EPA cannot read your comment due to technical difficulties 
or needs further information on the substance of your comment. EPA's 
policy is that EPA will not edit your comment, and any identifying or 
contact information provided in the body of a comment will be included 
as part of the comment that is placed in the official public docket, 
and made available in EPA's electronic public docket. If EPA cannot 
read your comment due to technical difficulties and cannot contact you 
for clarification, EPA may not be able to consider your comment.
    i. EPA Dockets. Your use of EPA's electronic public docket to 
submit comments to EPA electronically is EPA's preferred method for 
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket, and follow the online instructions for submitting comments. 
Once in the system, select ``search,'' and then key in docket ID number 
OPP-2002-0283. The system is an ``anonymous access'' system, which 
means EPA will not know your identity, e-mail address, or other contact 
information unless you provide it in the body of your comment.
    ii. E-mail. Comments may be sent by e-mail to [email protected], 
Attention: Docket ID Number OPP-2002-0283. In contrast to EPA's 
electronic public docket, EPA's e-mail system is not an ``anonymous 
access'' system. If you send an e-mail comment directly to the docket 
without going through EPA's electronic public docket, EPA's e-mail 
system automatically captures your e-mail address. E-mail addresses 
that are automatically captured by EPA's e-mail system are included as 
part of the comment that is

[[Page 78461]]

placed in the official public docket, and made available in EPA's 
electronic public docket.
    iii. Disk or CD ROM. You may submit comments on a disk or CD ROM 
that you mail to the mailing address identified in Unit I.C.2. These 
electronic submissions will be accepted in WordPerfect or ASCII file 
format. Avoid the use of special characters and any form of encryption.
    2. By mail. Send your comments to: Public Information and Records 
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2002-0283.
    3. By hand delivery or courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Office of Pesticide 
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall 
2, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket 
ID Number OPP-2002-0283. Such deliveries are only accepted during the 
docket's normal hours of operation as identified in Unit I.B.1.

D. How Should I Submit CBI To the Agency?

    Do not submit information that you consider to be CBI 
electronically through EPA's electronic public docket or by e-mail. You 
may claim information that you submit to EPA as CBI by marking any part 
or all of that information as CBI (if you submit CBI on disk or CD ROM, 
mark the outside of the disk or CD ROM as CBI and then identify 
electronically within the disk or CD ROM the specific information that 
is CBI). Information so marked will not be disclosed except in 
accordance with procedures set forth in 40 CFR part 2.
    In addition to one complete version of the comment that includes 
any information claimed as CBI, a copy of the comment that does not 
contain the information claimed as CBI must be submitted for inclusion 
in the public docket and EPA's electronic public docket. If you submit 
the copy that does not contain CBI on disk or CD ROM, mark the outside 
of the disk or CD ROM clearly that it does not contain CBI. Information 
not marked as CBI will be included in the public docket and EPA's 
electronic public docket without prior notice. If you have any 
questions about CBI or the procedures for claiming CBI, please consult 
the person listed under FOR FURTHER INFORMATION CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
ID number assigned to this action in the subject line on the first page 
of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in FFDCA section 408(d)(2); however, 
EPA has not fully evaluated the sufficiency of the submitted data at 
this time or whether the data support granting of the petition. 
Additional data may be needed before EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.


    Dated: December 10, 2002.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by FFDCA section 408(d)(3). The summary of the petition was 
prepared by the petitioner and represents the view of the petitioner. 
The petition summary announces the availability of a description of the 
analytical methods available to EPA for the detection and measurement 
of the pesticide chemical residues or an explanation of why no such 
method is needed.

PP 2E6475

    EPA has received a pesticide petition (PP 2E6475) from BASF 
Corporation: 3000 Continental Drive - North, Mount Olive, NJ 07828-
1234; proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 
346a(d), to amend 40 CFR part 180 to establish an exemption from the 
requirement of a tolerance for 2-bromo-2-nitro-1,3-propanediol 
(Bronopol) (CAS Reg. No. 52-51-7) in or on all raw agricultural 
commodities when used as an in-can preservative in pesticide 
formulations applied to growing crops, raw agricultural commodities 
after harvest, and animals. EPA has determined that the petition 
contains data or information regarding the elements set forth in 
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated 
the sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. Residue chemistry data are not generally 
required by EPA regarding tolerance exemption petitions. Consequently 
no plant metabolism data have been generated.
    2. Analytical method. Since this petition is for an exemption from 
the requirement of a tolerance, an enforcement analytical method for 2-
bromo-2-nitro-1, 3-propanediol is not needed.
    3. Magnitude of residues. Based on the proposed amount of 2-bromo-
2-nitro-1,3-propanediol to be used in the final products (0.04% or less 
by weight of the total formulation) and the recommended frequency and 
rates of application to growing crops, raw agricultural commodities 
after harvest, and animals, the residues are expected to be essentially 
undetectable and not toxicologically significant.

B. Toxicological Profile

    1. Acute toxicity. Bronopol was given as single oral doses of 200, 
280, 390, 550, or 770 mg/kg, as a solution in distilled water, to 
groups of ten male and ten female rats. The rats were observed for a 
seven-day period. Overt signs of toxicity were seen immediately after 
dosing with 280 mg/kg or more, and within 1 hour in males given 200 mg/
kg. The signs included sedation, wheezing, gasping, nasal exudate, 
cyanosis, increased salivation and ataxia. Animals given 550 or 770 mg/
kg

[[Page 78462]]

also had slow or labored respiration, and two females became prostrate. 
Most deaths occurred within 19 hours after dosing, but some occurred up 
to 72 hours. There were no gross abnormalities at autopsy of the 
decedents or in animals killed at the end of the study. The 
LD50 in male rats was 307 mg/kg and in female rats was 342 
mg/kg.
    In a further oral study groups of ten male rats were given single 
doses of Bronopol at 36, 54, 80, 120, 270, 400, or 600 mg/kg, as a 
suspension in 0.4% aqueous Cellosize solution. The rats were observed 
for up to ten days after treatment. Overt signs of toxicity were seen 
within 30 minutes after dosing with 80 mg/kg or more, and included 
wheezing, gasping or labored respiration and nasal exudate. Animals in 
the higher dose groups were inactive and adopted a low or hunched body 
position. Deaths occurred in these groups up to five days after 
treatment; macroscopic findings in the decedents included evidence of 
gastrointestinal irritation at 120 mg/kg or more, enlarged and dark red 
adrenals in some animals given 400 or 600 mg/kg, small spleens in a few 
rats given 80 or 120 mg/kg, and pale areas on the livers at 600 mg/kg. 
At terminal autopsy, one animal given 400 mg/kg also had a small 
spleen. Statistical analysis of the mortality data indicated that the 
LD50 was 254 mg/kg.
    In an acute inhalation study a group of six rats and two groups of 
eight rats were exposed for 6-hour periods to Bronopol dust at nominal 
concentrations of 5, 0.5, or 0.05 mg per liter air respectively. The 
animals were then kept under observation for up to 14 days. Exposure of 
rats to 5 mg dust per liter air caused severe eye irritation, dyspnea 
and loss of bodyweight. Exposure to 0.5 mg dust per liter air caused 
only slight eye irritation and mild dyspnea, while no definite signs of 
irritation were observed in animals exposed to 0.05 mg dust per air.
    In a second inhalation study four groups of 10 rats (5 males and 5 
females) were exposed to Bronopol at 0 (filtered air negative control), 
0.038, 0.089 or 0.588 mg/ by inhalation (nose-only) over a period of 4 
hours. Exposure was followed by an observation period of 14 days. In 
the high dose group one animal died overnight after exposure, and 2 
more animals were killed during the following day because of severe eye 
inflammation. Signs of marked irritancy were recorded in high dose 
animals but disappeared by the third observation day. Minor treatment-
related signs (piloerection and hunched posture) were observed on the 
day of treatment in some intermediate dose rats. There was no effect in 
the low dose group. There were no treatment-related effects on body 
weight or treatment-related pathological findings except for local 
dermatitis and ulceration in 2 high dose animals possibly attributable 
to dermal exposure to the test article.
    Several studies as summarized below determined 2-bromo-2-nitro-1,3-
propanediol to be irritant to the eye. Bronopol in polyethylene glycol 
300-0.1 ml volumes of 0.5 or 2% Bronopol in polyethylene glycol 300 
were instilled into one eye of each of six rabbits, three rabbits per 
concentration. The other eye in each case was treated with solvent 
only. The 2% solution was instilled only once, whereas the 0.5% 
solution was instilled on four successive days. The 2% solution of 
Bronopol in polyethylene glycol 300, instilled once, caused moderate 
inflammation and slight conjunctival edema which subsided after 5 
hours. The 0.5% solution, instilled on four successive days, had 
effects similar to those produced by the solvent alone.
    Bronopol in saline - Two drops of a solution containing 0.5% w/v 
Bronopol in normal saline were applied to one eye of three New Zealand 
White rabbits once daily on four successive days. The other eye 
(control) of each rabbit was treated with normal saline. The eyes were 
examined for irritation at 15 and 30 minutes, and at 1, 2, 3, 4, and 24 
hours after treatment each day. One rabbit developed moderate 
inflammation and very slight edema of the conjunctiva between two and 
four hours after the first application, but this subsided within 24 
hours. No other reactions were observed.
    Bronopol in polyethylene glycol 400 - One drop of Bronopol at 0 
(vehicle control), 0.5, 2, or 5% in polyethylene glycol 400 was added 
to one eye of 12 rabbits, 3 animals per test concentration. The other 
eye of each rabbit was left untreated. After 24 hours the eyes were 
irrigated with 300 ml of lukewarm water. Ocular reactions were assessed 
according to the FDA method at 1, 24, 48, and 72 hours, and then 7, 14, 
and 21 days after treatment.Immediately after treatment, with all the 
solutions, most rabbits exhibited head shaking and blinking and/or 
rubbing the treated eye. After 1 hour all the animals developed 
conjunctival reactions which had largely subsided by 24 hours, except 
in the most severely affected cases. One rabbit treated with 5% 
Bronopol had conjunctival reactions that persisted for 72 hours. The 
lower concentrations produced less severe and less persistent 
conjunctival reactions, and none of the concentrations elicited 
reactions in the cornea or iris. It was concluded that Bronopol in 
polyethylene glycol 400 was irritant at 5% but not at 2 or 0.5%, when 
instilled once only into the eye of the New Zealand White rabbit.
    Bronopol is also irritant to the skin. In a cumulative irritancy 
study dilutions of Bronopol at 0 (vehicle control), 0.1, 0.5, 1, 2.5, 
and 5% in petrolatum was applied daily for 21 days to the same site on 
the back of 8 men. The treatment sites were occluded. Readings were 
made daily on a scale of 0 to 4. The skin irritancy threshold 
concentration of Bronopol was approximately 0.5 to 1.0%. To determine 
if the subjects had been sensitized, they were further elicited after a 
10-day rest period. Two subjects reacted at 0.5 and 1% Bronopol. One 
reacted at 0.1%. These men received a product use test consisting of 
applications (without patching) to the cubital fossa twice daily for 7 
days. These were negative.
    In a single, 4 hour, semi-occluded dermal application of undiluted 
Bronopol to the skin of six rabbits produced severe dermal reactions, 
including eschar formation, necrosis and severe edema. Other adverse 
dermal reactions noted were slight hemorrhage of the dermal 
capillaries, blanching or brown discoloration of the skin, desquamation 
and scar tissue. The absence of fur growth was also occasionally noted 
on day fourteen with further effects indicative of corrosion. A primary 
irritation index of 6.2 was produced and evidence of corrosive effects 
were noted fourteen days after treatment. Undiluted Bronopol was found 
to be a severe irritant/corrosive to rabbit skin.
    An acute rabbit dermal toxicity study gave a dermal LD50 
of > 2,000 mg/kg body weight. The study was based on the EEC, OECD and 
EPA/OPPTS guidelines. A single oral dose of 2,000 mg/kg body weight of 
the test material preparation in 0.5% Tylose was applied in a group of 
ten rats (five males and five females) to the clipped epidermis (dorsal 
and dorsolateral parts of the trunk) and covered by a semi occlusive 
dressing for 24 hours. No mortality occurred. Signs of toxicity noted 
in the 2,000 mg/kg groups comprised poor general state, dyspnea and 
apathy. Findings were observed until including study day 1. The 
following skin effects were observed at the application site: white 
discoloration, erythema, edema, eczematoid skin change, scaling, and 
crust formation. Findings were observed until termination of the study. 
The animals did not gain weight during the first post exposure 
observation week but restarted to gain weight thereafter. No 
abnormalities were noted in the animals necropsied at the end of the 
study,

[[Page 78463]]

except in the skin of the application site, where incrustation and full 
thickness necrosis (9/10 animals) was observed. Under the conditions of 
this study, the acute dermal median lethal dose (LD50) of 
the test substance was found to be greater than 2000 mg/kg body weight 
for male and female animals.
    2-bromo-2-nitro-1,3-propanediol is classed as a weak skin 
sensitizer as indicated in four Magnusson and Kligman guinea pig skin 
sensitization studies as summarized below.
    Study 1 - The test method was the Magnusson and Kligman guinea pig 
maximization test, but using 10 test animals, 4 treated controls and 4 
untreated controls. Induction in the test animals was by intradermal 
injections of 0.03% w/v Bronopol in saline and Complete Freunds 
Adjuvant in the shoulder region. The induction process was supplemented 
7 days later by 1.5% w/v Bronopol in distilled water applied under 
occlusion to the injection sites. Fourteen days later the animals were 
challenged on the shaved flank by occluded patch with 0.4% w/v Bronopol 
in distilled water. Twenty-four hours after the challenge the patch was 
removed and the reaction site examined 24 and 48 hours after removal. A 
further 3 challenges were made at either 1 or 2 week intervals. The 
treated controls were 4 guinea pigs treated the same as the test 
animals except that the test substance was omitted from the intradermal 
injection and the covered patch induction procedures. At each challenge 
4 previously untreated animals were challenged as per the test animals. 
This group formed the untreated control. In the Magnusson and Kligman 
Maximization test, sensitization is normally assessed after one 
challenge. At this stage in this test there was no sensitization. One 
animal was sensitized after 2 challenges and a further animal after 3 
challenges. In this test 2/10 animals sensitized after one challenge is 
classified as a mild sensitizer (Grade II), but since 3 challenges were 
necessary before 2/10 animals were sensitized, the sensitization 
potential must be regarded as less than mild, hence Bronopol was found 
to be a weak sensitizer by this method.
    Study 2 - Induction was carried out as in Study 1 except that 9 
guinea pigs were used; induction was 0.02% Bronopol in saline and 
induction supplementation was 6-7 days later with 5% Bronopol in 
saline. Fourteen days later the animals were challenged (24 hour 
occluded patch) with 1% Bronopol in saline. One week later the animals 
were subjected to a cross-reaction challenge with 2% formalin. Further 
challenges were made with Bronopol and formalin after 2 and 3 weeks. 
Any challenge reactions were recorded after 24 and 48 hours. 2/9 
animals showed sensitization reactions to Bronopol at challenge 1. 
Animals were not challenged with Bronopol at challenge 2. No 
sensitization reactions were seen at challenge 3 and 1/9 animals showed 
an equivocal reaction at challenge 4. 1/9 animals showed an equivocal 
reaction to formalin at challenge 2, but there was no evidence of 
cross-reaction at challenges 3 and 4. It was concluded that Bronopol 
was a weak sensitizer under the conditions of this test. There was no 
significant evidence of cross-reaction to challenge with formalin.
    Study 3 - Induction was carried out as in Study 1 except that 9 
guinea pigs were used; induction was 0.02% Bronopol in saline and 
induction supplementation was 6-7 days later with 2.5% Bronopol in 
saline. Fourteen days later the animals were challenged (24 hour 
occluded patch) with 0.25% Bronopol in saline; a second challenge was 
made after a further 7 days. Any challenge reactions were recorded 
after 24 and 48 hours. There was no evidence of sensitization in the 9 
animals tested at either challenge, and it was concluded that Bronopol 
was not a sensitizer under the conditions of this test.
    Study 4 - Induction was carried out as in Study 1 except that 
induction was 0.02% Myacide BT (a minimum of 98% Bronopol) in saline 
and induction supplementation was 6-7 days later with 2.5% Myacide BT 
in saline. Fourteen days later the animals were challenged (24 hour 
occluded patch) with 0.25% Myacide BT in saline; a second challenge was 
made after a further 7 days. Any challenge reactions were recorded 
after 24 and 48 hours. There was no evidence of sensitization in the 10 
animals tested at either challenge, and it was concluded that Myacide 
BT was not a sensitizer under the conditions of this test. The overall 
conclusion was that Bronopol has a very low, and variable, 
sensitization potential in the stringent Magnusson and Kligman guinea 
pig maximization test and is at most a weak sensitizer in this species. 
There was no evidence that the animals had become sensitized to 
formalin.
    2. Genotoxicty. Mutagenicity studies including in vitro/in vivo in 
mouse erythrocytes (micronucleus assay), chromosomal aberration test in 
human lymphocytes, Salmonella typhimurium plate (Ames) tests with and 
without activation were negative. Bronopol did not induce mutations in 
the in vitro bacterial mutagenicity assay (TX 86004) or the V79 cell 
mutation assay (TX 86043), neither was there evidence of activity in 
assays for host-mediated bacterial mutagenicity or dominant lethality 
conducted in mice TX 74034). Furthermore, there was no increase in the 
incidence of micronuclei in polychromatic erythrocytes of bone marrow 
from male and female mice, 24, 48, or 72 hours after administration of 
single oral doses up to a maximum tolerated level of 160 mg/kg (TX 
86001). However, weak in vitro clastogenic activity was detected in 
cultured human lymphocytes exposed for 24 hours, in the absence of S-9, 
to Bronopol at 30 [mu]g/ml (TX 86049). Bronopol is normally self-
stabilizing at about pH 4 in aqueous media, but decomposes at elevated 
temperature and more alkaline pH to release formaldehyde as a breakdown 
product. Under the conditions of the human lymphocyte chromosome assay, 
only about 10% of an initial 30 [mu]g/ml concentration of Bronopol in 
the culture medium (pH 6.9) could be detected by analysis after 2 hours 
incubation at 370 C (DT 86029), and a formaldehyde concentration of 4.2 
[mu]g/ml was found at this time (DT 86030); the calculated value for 
formaldehyde released from complete breakdown of the 30 [mu]g/ml 
concentration of Bronopol is 4.5 [mu]g/ml. Formaldehyde shows 
clastogenic properties in vitro that include the induction of 
chromosome aberrations in human lymphocytes. Furthermore, in a 
lymphocyte assay conducted in-house (TX 86050), formaldehyde, in the 
absence of S-9 activation, elicited chromosome damage that was 
qualitatively and quantitatively similar to that seen in the assay of 
Bronopol. These findings, supported by the analytical data, indicate 
that the in vitro clastogenicity seen with Bronopol is due to its 
breakdown to formaldehyde. Although formaldehyde is a clastogen in 
vitro, its reactivity precludes distribution in vivo, so it is inactive 
in bone marrow and germ cells. The relative instability of Bronopol, 
like that of other non-carcinogenic formaldehyde-releasing agents, does 
not allow it to transport formaldehyde to these sites. In contrast, the 
carcinogen, hexamethylphosphoramide (HMPA), is more stable and requires 
metabolic activation to release formaldehyde; as a result, HMPA is 
clastogenic in bone marrow and has adverse effects in germ cells. In 
conclusion, the testing of Bronopol over a wide range of genetic 
endpoints has revealed only a single adverse finding, namely weak in 
vitro clastogenicity, and this result is clearly

[[Page 78464]]

attributable to the release of formaldehyde from Bronopol under the 
conditions of the lymphocyte assay. The consensus of negative findings 
in short-term in vitro tests, together with the negative finding in an 
in vivo test for chromosome damage and the absence of oncogenicity in 
the life span studies in rats and mice (see below), indicates that 
Bronopol does not present a genotoxic hazard.
    In a 2-year rat (drinking water) chronic toxicity and 
tumorgenicity, Bronopol dissolved in tap water was dosed to 28 day old 
rats in 4 groups (45 male and 45 female in the main groups and 15 male 
and 15 female in the satellite groups) via the drinking water for 104 
weeks at 0 (untreated control), 10, 40, and 160 mg/kg/day. The main 
groups were reserved for evaluation of tumorigenic potential and were 
not used for blood and urine samples during the study; the satellite 
groups were used for blood and urine samples during the study and were 
not included in the tumorigenicity assessment. The results at the 
various dose levels may be summarized as follows:
    160 mg/kg/day
    [sbull] Reduced grooming activity during the final year of 
treatment.
    [sbull] Significantly increased mortality.
    [sbull] Reduced weight gain from week 3 onwards among males and 
from week 7 onwards among females.
    [sbull] Lower food intake among males from week 13 onwards.
    [sbull] Marked reduction in water intake throughout the dosing 
period and an associated reduction in urine volume noted at weeks 25, 
52, and 103.
    [sbull] Increase incidence of progressive glomerulonephrosis in 
males and females.
    [sbull] At week 52, urine repeatedly positive for hemoglobin in 4/
10 males and 1/10 females, at week 77 in 4/10 males and 3/10 females, 
and at week 103 in 10/10 males and 1/10 females.
    [sbull] Stomach lesions in 20 males and 15 females and the gastric 
lymph nodes showed dilation of the sinusoids in 4 males and 5 females.
    [sbull] Squamous metaplasia, inflammation or atrophic acini in the 
salivary glands of 12 males and 11 females.
    40 mg/kg/day
    [sbull] Reduced weight gain from weeks 27 to 78 among males.
    [sbull] Lower food intake from weeks 53 to 78 among males.
    [sbull] Moderate reduction in water intake throughout the dosing 
period.
    [sbull] At week 77, urine repeatedly positive for hemoglobin in 6/
10 males and at week 103 in 3/10 males.
    [sbull] Stomach lesion in 1 male.
    [sbull] Squamous metaplasia, inflammation or atrophic acini in the 
salivary glands of 12 males and 2 females.
    10 mg/kg/day
    [sbull] Small but definite reduction in water intake throughout the 
dosing period.
    [sbull] At week 77, urine repeatedly positive for hemoglobin in 2/
10 males and at week 103 in 2/9 males.
    [sbull] Stomach lesions in 1 male and 1 female.
    [sbull] Squamous metaplasia and/or inflammation or atrophic acini 
in the salivary glands of 5 males and 1 female.
    Control
    [sbull] At week 52, urine repeatedly positive for hemoglobin in 1/
10 males and 0/10 females, at week 77 in 2/10 males and 0/10 females, 
and at week 103 in 3/10 males and 1/10 females.
    [sbull] Stomach lesions in 1 male and 2 females.
    [sbull] Squamous metaplasia and/or inflammation or atrophic acini 
in the salivary glands of 3 males and 2 females.
    The evidence of toxic effects related to the administration of 
Bronopol was a reduction in food intake, impaired food utilization 
efficiency associated with reduced bodyweight gain, and increased 
mortality. Changes in the stomach and gastric lymph nodes were 
attributed to the irritant effect of Bronopol. Unpalatability reduced 
the water intake and was associated with a reduced output of urine, an 
increased incidence of hemoglobinuria and an exacerbation of the 
spontaneous incidence of progressive glomerulonephrosis. Treatment with 
Bronopol exacerbated a spontaneous change in the salivary glands. These 
effects were dose related and apart from a small effect on water intake 
that was related to palatability, there was no evidence of toxicity at 
10 mg/kg/day. There was no evidence to suggest that the administration 
of Bronopol affected the tumor incidence. In summary, the study gave a 
systemic no observed adverse effect level (NOAEL) of 10 mg/kg/day, a 
lowest effect level (LEL) of 40 mg/kg/day and found 2-bromo-2-nitro-
1,3-propanediol (Bronopol) to be not carcinogenic.
    3. Reproductive and developmental toxicity. In a two-generation 
reproduction study in rats Bronopol was administered to rats in the 
drinking water at concentrations of 25, 70, or 200 mg/kg/day. Thirteen 
males and 26 females were treated for a minimum of 80 days prior to 
mating. They were mated on two separate occasions to produce the F1a 
and F1b litters. Weanlings from the F1b litters were randomly selected 
(13 males and 26 females) to become parents of the next generation. The 
F1 parents were treated for a minimum of 87 days prior to mating, and 
were mated on two separate occasions to produce the F2a and F2b 
litters. In the F0 generation, one female from each of the control and 
low-dose groups, and one male and five females from the high-dose group 
died or were sacrificed in extremis during the study; in the F1 
generation, one female from each of the low-, mid- and high-dose groups 
died before the end of the study. There were no treatment-related 
aspects, so these deaths were considered to have been incidental to 
Bronopol. Food consumption for the high-dose group was consistently 
lower than controls for the F0 males, for F0 females during the initial 
two weeks of treatment and the lactation periods for both mates, and 
for F1 females during the lactation period of the F2a mate. Water 
consumption was reduced in all treated groups, in a dose-related 
manner, throughout most of the study; this contributed to the lower 
achieved dosages of Bronopol that animals received, namely 22.55, 55.2, 
or 147 mg/kg. The female fertility index for the high-dose group was 
slightly lower than control at the F1 mate only. Mean body weights of 
the offspring of the F0 and F1 high-dose parents (F1a and F1b, and F2a 
and F2b, respectively) were lower than the control throughout the 
lactation periods. Mean body weights of the F1b pups from the low- and 
mid-dose groups were slightly lower than control on day 21 of the 
lactation period. There were no other test article-related macroscopic 
or microscopic changes. There was a dose-related increase in the kidney 
weights of treated F0 females, though the difference between the low 
dose group and controls was minimal. In the high-dose group animals 
there was a decrease in the absolute weights of the livers, and 
possibly also the hearts, of F1 males, and in the absolute liver 
weights of F2b males and females; these females also had lower absolute 
kidney weights. In conclusion, ingestion of Bronopol elicited signs of 
toxicity at all dosages, though the only reproductive or litter 
parameter affected at the 25 and 70 mg/kg/day dosages was body weight 
of F1b pups at weaning, where a minimal decrease was seen.
    An early rat dermal developmental toxicity study gave a maternal 
NOAEL > 40 mg/kg/day (HDT) considering 2-bromo-2-nitro-1,3-propanediol 
as a severe dermal irritant in rats. Further development toxicity 
studies have been carried out for both the rat and the rabbit. In the 
rat study three groups of 24 timed-mated female rats were dosed once 
daily, orally by gavage, with

[[Page 78465]]

solutions of Bronopol at dose levels of 10, 28, or 80 mg/kg/day from 
days 6 to 15 of pregnancy, inclusive. A similar group of females were 
dosed with the vehicle (purified water acidified to pH 4) by the same 
route and over the same period, and served as controls. Maternal 
clinical signs, bodyweights and food consumption were recorded. On day 
20 of pregnancy, the females were killed and a necropsy was performed. 
Numbers of corpora lutea and live and dead implantations were recorded. 
Live fetuses were weighed, sexed and examined for external and visceral 
abnormalities. Two thirds of the fetuses were also examined for 
skeletal abnormalities. There was evidence of maternal toxicity 
following oral gavage administration of Bronopol at 80 mg/kg/day, 
characterized by retarded bodyweight gain over days 6 to 7 of 
pregnancy. There was no evidence of maternal toxicity at either 10 or 
28 mg/kg/day. There was no evidence of developmental toxicity at any of 
the dose levels investigated. There may be an association of treatment 
at 80 mg/kg/day with advanced ossification of sacral arches and at 28 
and 80 mg/kg/day with advanced ossification of the forelimb phalanges. 
However, neither of these findings in these groups was unusually 
advanced when compared to historical background data.
    In a second study using rabbit groups of 18, 19, or 20 timed-mated 
female animals were dosed daily between 7 and 19 days of pregnancy, 
inclusive, by the oral route with aqueous solutions of Bronopol at dose 
levels of 0 (control), 5, 20, 40, and 80 mg/kg/day. Day 0 of pregnancy 
was the day of mating. 80 mg/kg/day was selected as a level which 
should elicit maternal effects. However, in the event that the effects 
may have been too severe, 40 mg/kg/day was selected as the next highest 
level known to be tolerated by the pregnant rabbit. The lower dose 
level of 5 mg/kg/day and the intermediate dose level of 20 mg/kg/day 
were expected to be `no effect' levels. Maternal clinical condition, 
bodyweight, and food consumption were recorded. The females were killed 
on day 28 of pregnancy and a necropsy was performed. They were weighed, 
sexed and examined for external, visceral, and skeletal abnormalities. 
At 80 mg/kg/day, Bronopol elicited severe maternal toxicity at the 
onset of dosing. The animals recovered after dosing ceased, but the 
outcome of pregnancy was affected. There was embryotoxicity 
characterized by growth retardation and a slightly higher than expected 
incidence of fetal abnormalities. This embryotoxicity was considered 
likely to be related to the maternal toxicity. At 40 mg/kg/day, which 
was considered to be the highest level likely to be tolerated by the 
pregnant rabbit without eliciting severe maternal toxicity, there was 
no evidence of adverse effects of treatment on the pregnant rabbit or 
developing embryos. This dose level was therefore considered to be the 
`no effect' level of Bronopol with regard to developmental toxicity.
    4. Subchronic toxicity. A 13-week rat gavage study showed a NOAEL 
of 20 mg/kg/day and a lowest observed adverse effect level (LOAEL) of 
80 mg/kg/day. Bronopol as a solution in distilled water was dosed to CD 
rats (4 groups of 20 males and 20 females) by oral gavage once per day, 
seven days per week for 13 weeks at 0 (untreated control), 20, 80, and 
160 mg/kg/day. Reaction to treatment was as follows:
    160 mg/kg/day - Severe respiratory distress and abdominal 
distension; reduced bodyweight gain and food consumption; death of 22 
males and 14 females (includes 4 male and 3 female rats which replaced 
rats dying after one dose); all surviving rats were killed on day 9; 
autopsy showed gaseous and fluid distension of the gastro-intestinal 
tract in the majority of decedents; ulceration, epithelial hyperplasia 
and hyperkeratosis or congested vessels in the stomachs of 2 males and 
4 females.
    80 mg/kg/day - Severe respiratory distress and abdominal 
distension, the latter sign confined to 6 males and 6 females which 
subsequently died. At week 6, only 4 males and 2 females showed slight 
respiratory difficulty. Seven males and 9 females died with autopsy 
showing gaseous and fluid distension of the gastro-intestinal tract; 
reduced bodyweight gain and food consumption for the first week of 
treatment only; renal changes in 2 males.
    20 mg/kg/day - In one male, respiratory distress, which 
subsequently regressed; renal changes in 2 males.
    A 13-week dog gavage study showed a NOAEL of 8 mg/kg/day and LOAEL 
of 20 mg/kg/day. Bronopol dissolved in water was dosed to Beagle dogs 
(4 groups of 3 males and 3 females) by oral gavage once per day, seven 
days per week for 3 months (13 weeks) at 0 (untreated control), 4, 8, 
and 20 mg/kg/day. One pair of dogs was dosed at levels of 20- 40 mg/kg/
day, over a period of 2 weeks in order to determine the vomiting 
threshold of Bronopol. This was found to be at a dosage of 
approximately 20 mg/kg/day. During the study vomiting occurred within 
30 minutes of dosing and no other clinical signs were observed. 
Macroscopic post mortem examination revealed no abnormalities. In the 
main study there were no deaths. Vomiting, mainly at 20 mg/kg/day, 
within 0.5 hour of dosing was observed with occasional passage of 
liquid feces and red-stained mucus in isolated animals, both dosed and 
control. There were no adverse effects on food or water consumption, or 
on bodyweight. There were no abnormalities of the eye; no macroscopic 
post mortem abnormalities; or morphological changes or variations from 
normal in histological tissue examination which could be related to 
dosage of the test compound. After dosing for 6 weeks, one animal 
receiving 8 mg/kg/day had a serum alkaline phosphatase value 
approximating to the upper limit of normality of 35 King Armstrong 
units; after 12 weeks, however, the value was well within normal 
limits. After dosing for 12 weeks the group mean total white cell 
count, although within normal limits, was significantly lower in dogs 
receiving 8 and 20 mg/kg/day than in the controls. One animal receiving 
4 mg/kg/day had a serum glutamic-pyruvic transaminase value after 12 
weeks which exceeded the upper limit of normality of 50 mU/ml. Apart 
from the liver of one dog receiving 20 mg/kg/day which was heavier than 
would normally be expected, all organ weights were within normal 
limits. However, when expressed as a percentage of bodyweight the mean 
liver and spleen weights for dogs receiving 20 mg/kg/day were 
significantly heavier than the control values.
    5. Chronic toxicity. A 2-year toxicity/carcinogenicity Bronopol 
study (administration via drinking water) in rats showed a NOAEL of >= 
7 mg/kg/day and a LEL of < 32 mg/kg/day. For more detail see the 
carcinogenicity summary in Unit B.2.
    In a study on potential local and tumorigenic effects from repeated 
dermal application to mice Bronopol dissolved in 90% acetone/water was 
applied to the shaved dorsum of 3 groups of mice (52 male and 52 female 
per group) at 0 (vehicle control), 0.2%, and 0.5%. Application was at 
the rate of 0.3 ml per mouse on three days (Monday, Wednesday, and 
Friday) in each week for 80 weeks. The results are summarized as 
follows:
    [sbull] Among some mice treated with 0.5% Bronopol, there was 
minimal hair loss at the periphery of the shaved area during the first 
three weeks of treatment.
    [sbull] A marginally inferior survival rate was recorded among male 
mice, although the prime cause of death

[[Page 78466]]

among decedents showed no relation to treatment.
    [sbull] Between weeks 26 and 52, an inferior bodyweight gain was 
recorded among male mice treated with 0.5% Bronopol, although 
bodyweight gain over the 80 week treatment period was comparable with 
that of the controls. Bodyweight gain among other treated mice was not 
disturbed by treatment.
    [sbull] Food intake and efficiency of food utilization showed no 
disturbance by treatment.
    [sbull] Macroscopic examination of decedents and mice killed after 
80 weeks of treatment, revealed pathology which was common to some 
animals from control and treated groups.
    [sbull] Microscopic examination of decedents and mice killed at 
termination revealed changes consistent with the age and strain of 
mouse employed.
    [sbull] Treatment with Bronopol did not alter the spontaneous tumor 
profile of the mice.
    6. Animal metabolism. Rat and dogs were used in a metabolic study 
with both oral and cutaneous dosing as follows: Oral Dosing in Rats was 
by stomach tube with aqueous solutions of [14C]-Bronopol (1 mg/kg). 
Oral Dosing Dogs - Beagle dogs were dosed with [14C]-Bronopol (2 mg) 
mixed with unlabelled Bronopol (6-8 mg) as an aqueous solution in 
gelatin capsules. Cutaneous Dosing Rats and Rabbits - Initially 
solutions of [14C]-Bronopol (4 mg/kg) in water, acetone and acetone/
water (9:1, v/v) were applied to the clipped backs of rats to determine 
the influence of the vehicle on percutaneous absorption. Acetone was 
determined to be the preferred application vehicle. In the main tests 
an acetone solution of [14C]-Bronopol (4.8 mg/ml) was applied to 
shaved/depilated areas of the backs of rats and rabbits at the rates of 
0.05 ml per rat and 0.2-0.4 ml per rabbit, the treated areas being 
occluded with secured polythene. After an oral dose of [14C]-Bronopol 
(1 mg/kg) to rats or dogs, the radioactivity was completely absorbed, 
evenly distributed and rapidly excreted. Excretion was almost complete 
in 24 hours. During 5 days, rats excreted 83.3% in the urine, 5.8% in 
the feces (via the bile) and 8.4% in the expired air; 1.6% was still 
retained probably by incorporation into pathways of intermediary 
metabolism of [14C]-glycerol produced by biotransformation of [14C]-
Bronopol. During 5 days, dogs excreted 81.8% in the urine and 3.1% in 
the feces. After an oral dose of [14C]-Bronopol (1 mg/kg), peak blood 
levels of radioactivity were reached in rats and dogs within 2 hours, 
and declined with an initial half-life of 4 +/- 1 hour. After an oral 
dose of [14C]-Bronopol (1 mg/kg) to the rat and the dog, Bronopol and 
its metabolites were evenly distributed. Only in tissues concerned with 
excretion did levels of radioactivity exceed those in the blood. When 
applied to the skin of rats, [14C]-Bronopol was absorbed to a greater 
extent from an acetone solvent vehicle than from water:acetone (1:9, v/
v) or water alone. In rats, at least 7 and 15% of an applied dose was 
percutaneously absorbed during 24 and 96 hours respectively. In 
rabbits, at least 9% of an applied dose was percutaneously absorbed 
during 24 hours. Pretreatment of rabbit skin with a depilatory enhanced 
absorption. Microhistoautoradiographs of rabbit skin showed that [14C]-
Bronopol was mainly localized on the epidermis around the hair 
follicles. The limited percutaneous absorption of Bronopol may occur 
through the hair follicles. Five metabolites, which were more polar 
than Bronopol, were detected in the urine of rats and dogs given an 
oral dose of [14C]-Bronopol. One metabolite, shown by comparison of 
infra-red and mass spectra with synthetic material to be 2-
nitropropane-1,3-diol, accounted for more than 40% of the administered 
dose. Unchanged Bronopol, which is unstable in plasma, was not 
detected. A similar pattern of urinary metabolites of [14C]-Bronopol 
was found after cutaneous application as after oral administration of 
the compound.
    Further metabolic studies were carried out in male and female rats 
following single oral doses of [14C]-Bronopol at 10 and 50 mg/kg and 
repeated dosing at 10 mg/kg/day with Bronopol for 14 days followed by a 
single oral dose, 10 mg/kg of [14C]-Bronopol. The compound was well 
absorbed and rapidly excreted mainly via urine. Radioactivity found in 
the carcass and tissues at 168 hours after dosing accounted for less 
than 3% of dose. There were no major consistent differences between 
male and female rats. Bronopol was highly metabolized and intact 
compound was not detected in the urine. The urinary metabolite 
chromatographic patterns contained numerous polar metabolites and 
similar patterns were found for each group. The major metabolite 
observed was equivalent to desbromo-bronopol (2-nitro-propane-1,3-
diol). Extensive metabolism led to radiolabeled one-carbon units 
excreted as carbon dioxide in expired air.
    7. Metabolite toxicology. As determined in the animal metabolism 
studies in Unit B.6. numerous polar metabolites were identified in 
urine from rat and dog. Unchanged 2-bromo-2-nitro-1,3-propanediol was 
not detected. The major peak in most samples corresponded to 
desbromobronopol (debrominated bronopol), i.e. 2-nitropropane-1, 3-
diol. This metabolite is not considered of toxicological concern.
    8. Endocrine disruption. No specific tests have been conducted with 
2-bromo-2-nitro-1,3-propanediol to determine whether the chemical may 
have an effect in humans that is similar to an effect produced by a 
naturally occurring estrogen or other endocrine effects. However, there 
were no significant findings in other relevant toxicity tests, i.e., 
teratology and multi-generation reproduction studies, which would 
suggest that 2-bromo-2-nitro-1,3-propanediol produces effects 
characteristic of the disruption of endocrine functions.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. The proposed use of 2-bromo-2-nitro-
1, 3-propanediol as a preservative in end-use pesticide formulations 
applied to growing crops, raw agricultural commodities after harvest, 
and animals is not expected to result in any significant additional, 
dietary exposure, due to the low concentration of 2-bromo-2-nitro-1, 3-
propanediol employed in the formulation and the extremely low 
probability of significant contact by the general public following 
treatment.
    2-bromo-2-nitro-1, 3-propanediol has FDA approval for indirect food 
contact use as a preservative in adhesives that are components of food 
packaging or storage materials (21 CFR 175.105); as a slimicide for use 
in pulp and papermaking at a maximum level of 0.6 lb/ton of dry weight 
fiber (21 CFR 176.300); and paper components in contact with aqueous 
and fatty foods at a level not to exceed 0.01% by weight of those 
components (21 CFR 176.170). These uses are not expected to result in 
quantifiable residues of 2-bromo-2-nitro-1, 3-propanediol in the diet. 
Uses as a preservative in concentrates of agricultural pesticide 
products also is not expected to be a source of quantifiable residues 
in food.
    There are no acute or chronic toxicological concerns associated 
with the proposed use of 2-bromo-2-nitro-1,3-propanediol as an inert 
ingredient in concentrates of agricultural pesticide products. An acute 
dietary risk assessment, therefore, is not required. Chronic exposure 
to 2-bromo-2-nitropropane-1, 3-diol through food is essentially 
insignificant.
    ii. Drinking water. Contamination of drinking water would not be 
expected to

[[Page 78467]]

occur under the proposed use conditions of 2-bromo-2-nitro-1, 3-
propanediol as a preservative at very low concentrations in pesticide 
products intended for applications, principally to growing crops, raw 
agricultural commodities after harvest, and animals; as either a direct 
pour-on application or as a spray. Neither method of application is 
expected to contaminate water supplies intended for human consumption. 
Bronopol is not applied to water and is not used for the disinfection 
of human or animal drinking water.
    2. Non-dietary exposure. 2-bromo-2-nitro-1, 3-propanediol is used 
as an industrial biocide for the prevention of biofouling in areas such 
as recirculating water in cooling towers and evaporative condensers, 
air conditioners, air washers and humidifier systems, oil, gas and 
industrial process water, metal working fluids and paper mill pulp and 
process water; and for the preservation of surfactants, adhesives, 
starch, pigment and extender slurries, paints, latex and antifoam 
emulsions, absorbent clays, water based printing inks and print 
solutions, water based pesticides and chemical toilet solutions. The 
margins of exposure (MOEs) calculated for direct applicators 
occupationally exposed by either the dermal or inhalation route, based 
on worst-case estimates, revealed there is no level for concern. 
Estimated exposures to professional painters using paint preserved with 
2-bromo-2-nitro-1, 3-propanediol were used as the worst-case for 
estimating secondary occupational exposure risk. MOEs were not exceeded 
and EPA has concluded that risk associated with secondary exposure are 
not of concern.
    2-bromo-2-nitro-1, 3-propanediol is also used in the preservation 
of consumer, household and institutional products. Based on the worst-
case estimate for professional painters chronically exposed to 2-bromo-
2-nitro-1, 3-propanediol, EPA has concluded that risk associated with 
these uses are not of concern.
    2-bromo-2-nitro-1, 3-propanediol also is used to preserve 
pharmaceuticals, cosmetics, and toiletries, which are regulated by FDA. 
The Cosmetic, Toiletries and Fragrance Association's (CTFA's) Cosmetic 
Ingredient Review (1980) states that 2-bromo-2-nitro-1,3-propanediol is 
safe as a cosmetic ingredient at concentrations up to 0.1% except where 
there is a risk of nitrosamine or nitrosamide formation. Similarly, 2-
bromo-2-nitro-1,3-propanediol is listed in Annex VI of the EC Cosmetics 
directive as an approved preservative for use up to 0.1% except where 
there is a risk of nitrosamine formation.
    Based on toxicity data, an aggregate risk or likelihood of the 
occurrence of an adverse health effect resulting from all routes of 
exposure to 2-bromo-2-nitro-1, 3-propanediol is not expected.

D. Cumulative Effects

    There is no reliable information that would indicate or suggest 
that 2-bromo-2-nitro-1, 3-propanediol has any toxic effects on mammals 
that would be cumulative with those of any other chemical.

E. Safety Determination

    1. U.S. population. The reference dose (RfD) for 2-bromo-2-nitro-1, 
3-propanediol based on the 2-year chronic study (drinking water) in 
rats with a NOAEL of 10 mg/kg/day and using an uncertainty factor of 
100 is calculated to be 0.1 mg/kg of body weight (bwt)/day. The 
estimated worst-case theoretical maximum residue contribution (TMRC) 
resulting from this action will be 0.000024 mg/kg/bwt/day for the 
overall U.S. population and represents 0.024 percent of the RfD. Based 
upon this information and review of its use, EPA has found that, when 
used in accordance with good agricultural practice, this ingredient is 
useful and a tolerance is not necessary to protect the public health.
    2. Infants and children. Nothing in the available literature would 
suggest that infants and children are more sensitive to the effects of 
2-bromo-2-nitro-1, 3-propanediol than adults. Exposure of infants to 2-
bromo-2-nitro-1, 3-propanediol resulting from its proposed use as an 
inert ingredient in certain pesticide formulations is expected to be 
negligible and will not put infants and children at increased risk.

F. International Tolerances

    BASF Corporation is not aware of the existence of any international 
tolerances for 2-bromo-2-nitro-1, 3-propanediol.

[FR Doc. 02-32400 Filed 12-23-02; 8:45 am]
BILLING CODE 6560-50-S