[Federal Register Volume 67, Number 46 (Friday, March 8, 2002)]
[Notices]
[Pages 10718-10722]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-5445]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-00761; FRL-6825-5]


Reclassification of Certain Inert Ingredients and Rhodamine B

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: EPA intends to reclassify eight inert ingredients from List 2, 
``Potentially Toxic Inerts/High Priority for Testing'' to List 1 
``Inerts of Toxicological Concern.'' These eight inert ingredients have 
been determined to be animal carcinogens, thus meeting one of the 
criteria for reclassification. EPA also intends to reclassify the inert 
ingredient, Rhodamine B, from List 1 to List 4B, ``inerts for which EPA 
has sufficient information to reasonably conclude that the current use 
pattern in pesticide products will not adversely affect public health 
or the environment.'' This reclassification is based on the Agency's 
determination that Rhodamine B when used as a dye in seed treatment is 
not likely to result in residues in food or feed; thus, meeting the 
criteria of List 4B.

DATES: Comments, identified by docket control number OPP-00761, must be 
received on or before May 7, 2002.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I. under SUPPLEMENTARY INFORMATION. To ensure proper 
receipt by EPA, it is imperative that you identify docket control 
number OPP-00761 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: Kathryn Boyle, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: 
(703) 305-6304; fax number: (703) 305-0599; e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    This action is directed to the public in general. This action may, 
however, be of interest to ``those persons who use pesticide products 
and those who formulate pesticide products and therefore are or may be 
required to conduct testing of chemical substances under the Federal 
Food, Drug, and Cosmetic Act (FFDCA), or the Federal Insecticide, 
Fungicide, and Rodenticide

[[Page 10719]]

Act (FIFRA).'' Since other entities may also be interested, the Agency 
has not attempted to describe all the specific entities that may be 
affected by this action. 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 Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/.
    The Agency has established an official record for this action under 
docket control number OPP-00761. The official record consists of the 
documents specifically referenced in this action, any public comments 
received during an applicable comment period, and other information 
related to this action, including any information claimed as 
Confidential Business Information (CBI). This official record includes 
the documents that are physically located in the docket, as well as the 
documents that are referenced in those documents. The public version of 
the official record does not include any information claimed as CBI. 
The public version of the official record, which includes printed, 
paper versions of any electronic comments submitted during an 
applicable comment period, is available for inspection in the Public 
Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 
#2, 1921 Jefferson Davis Hwy., Arlington, VA, from 8:30 a.m. to 4 p.m., 
Monday through Friday, excluding legal holidays. The PIRIB telephone 
number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number OPP-00761 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Hwy., Arlington, VA. The PIRIB is open from 8:30 a.m. 
to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB 
telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in WordPerfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number OPP-00761. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI that I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
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 version of the 
official record. Information not marked confidential will be included 
in the public version of the official record 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. Offer alternative ways to improve the notice or collection 
activity.
    7. Make sure to submit your comments by the deadline in this 
notice.
    8. To ensure proper receipt by EPA, be sure to identify the docket 
control 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. Reclassification of Eight Inert Ingredients from List 2 to List 
1

A. Background

    On April 22, 1987 (52 FR 13305), EPA announced certain policies 
designed to reduce the potential for adverse effects from the use of 
pesticide products containing toxic inert ingredients. In developing 
the policy, the Agency reviewed the available data on chemicals used as 
inert ingredients, and concluded that some inert ingredients had 
potentially significant long-term health and environmental hazards 
associated with their use in pesticide products. The 1987 Notice 
categorized all of the then existing inert ingredients into four lists, 
according to the available information regarding toxicity, i.e., the 
hazard of the chemical. List 1 inert ingredients, described as ``inerts 
of toxicological concern'' were so categorized on the basis of 
toxicological or adverse ecological effects which had been documented 
in studies subject to peer review. The Agency's criteria for placing an 
inert ingredient on List 1 were reviewed by the FIFRA Scientific 
Advisory Panel (SAP).
    One of the criteria for being considered a List 1 inert ingredient 
is to be ``...characterized by the National Toxicology Program (NTP) as 
an animal carcinogen in at least one species and one sex.'' (Inert 
ingredients in Pesticide Products; Policy Statement; Revision and 
Modification of Lists at http://www.epa.gov/opprd001/inerts/fr54.htm). 
NTP Technical Reports describe the results of individual experiments on 
a chemical agent and note the strength of evidence for conclusions 
regarding each study.
    In their technical reports, NTP uses five categories of evidence of 
carcinogenic activity to summarize the strength of the evidence 
observed in

[[Page 10720]]

each experiment. These categories (``no evidence,'' ``equivocal 
evidence,'' ``some evidence,'' ``clear evidence,'' and ``inadequate 
study'') have been used by NTP since the 1980s. Two of the categories 
are for positive results, which demonstrate that a chemical is 
carcinogenic for laboratory animals under the conditions of the study 
and indicate that exposure to the chemical has the potential for hazard 
to humans. ``Clear evidence'' of carcinogenic activity is demonstrated 
by studies that are interpreted as showing a dose-related increase of 
malignant neoplasms or of a combination of malignant and benign 
neoplasms, or a marked increase of benign neoplasms if there is an 
indication from this or other studies of the ability of such tumors to 
progress to malignancy. ``Some evidence'' of carcinogenicity is 
demonstrated by studies that are interpreted as showing a chemically-
related increased incidence of neoplasms (malignant, benign, or 
combined) in which the strength of the response is less than that 
required for clear evidence.

B. NTP Technical Reports for the Eight Inert Ingredients

    For the purpose of reclassifying a List 2 inert ingredient to a 
List 1 inert ingredient the two categories (described above) for 
positive results (``clear evidence'' and ``some evidence,'') meet the 
List 1 placement criteria of being characterized by NTP as an animal 
carcinogen in at least one species and one sex. The data in the NTP 
Technical Reports as described in the table and summaries below fully 
support a reclassification to List 1 for the following inert 
ingredients. The complete reports are available at http://ntp-server.niehs.nih.gov/.

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          NTP Report Number                    Category             Inert Ingredient           CAS Reg. No.
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TR-424                                 Some evidence            2-Benzyl-4-chlorophenol  120-32-1
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TR-484                                 Some evidence            2-Butoxyethanol          111-76-2
                                                                 (ethylene glycol
                                                                 monobutyl ether)
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TR-213                                 Some evidence            Butyl benzyl             85-68-7
TR-458                                                          Phthalate
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TR-478                                 Clear evidence           Diethanolamine           11-42-2
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TR-466                                 Clear evidence           Ethylbenzene             100-41-l4
                                       Some evidence
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TR-329                                 Clear evidence           1,2-                     106-88-7
                                                                 Epoxybutane(butylene
                                                                 oxide)
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TR-332                                 Some evidence            2-Mercaptobenzothiazole  149-30-4
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TR-461                                 Clear evidence           Nitromethane             75-52-5
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    1. 2-Benzyl-4-chlorophenol. There were two chronic toxicity/
carcinogenicity gavage studies performed on 2-benzyl-4-chlorophenol, 
which is also known as o-benzyl-p-chlorophenol. Under the conditions of 
the 2-year rat study, there was no evidence of carcinogenic activity in 
male rats and there was equivocal evidence of carcinogenic activity in 
female rats based on the occurrence of two rare renal transitional cell 
carcinomas. Under the conditions of the 2-year study, in mice there was 
some evidence of carcinogenic activity in male mice based on increased 
incidences of renal tubule ademona and renal tubule adenoma or 
carcinoma (combined) and there was no evidence of carcinogenic activity 
in female mice.
    2. Butyl benzyl phthalate. There was a 2-year chronic toxicity/
carcinogenicity study in rats performed using butyl benzyl phthalate. 
As evaluated in 1997, under the conditions of this study, there was 
some evidence of carcinogenic activity in male rats based on increased 
incidences of pancreatic acinar cell adenoma and of acinar cell adenoma 
or carcinoma (combined) and there was equivocal evidence of 
carcinogenic activity in females rats based on the marginally increased 
incidences of pancreatic acinar cell adenoma and of transitional 
epithelial papilloma of the urinary bladder. Results of mutagenicity 
testing, a mouse bone marrow sister chromatic exchange test were 
positive at sample times of 23 and 42 hours. Chromosomal aberrations 
were induced in bone marrow cells of male mice sampled 17 hours after 
intraperitoneal injection of butyl benzyl phthalate.
    3. 2-Butoxyethanol. There were two inhalation chronic toxicity/
carcinogenicity studies performed on 2-butoxyethanol. Under the 
conditions of these studies, there was no evidence of carcinogenic 
activity in male rats. There was equivocal evidence of carcinogenic 
activity in female rats based on the increased combined incidences of 
benign or malignant pheochromocytoma (mainly benign) of the adrenal 
medulla. There was some evidence of carcinogenic activity in male mice 
based on increased incidences of hemangiosarcoma of the liver. There 
was some evidence of carcinogenic activity in female mice based on 
increased incidences of fore stomach squamous cell papilloma or 
carcinoma (mainly papilloma).
    2-Butoxyethanol has also been reviewed by a team of Agency health 
scientists. The results of this recent review on (December 31, 1999) 
can be located on the Agency's website at http://www.epa.gov/ngispgm3/iris/subst/0500.htm. In accordance with the 1996 proposed Guidelines 
for Carcinogen Risk Assessment, 2-butoxyethanol has been classified as 
a chemical whose carcinogenic potential for humans cannot be 
determined, but for which there is suggestive evidence that raises 
concern for carcinogenic effects. This classification was based on the 
reviews of the NTP studies, the fact that 2-butoxyethanol is generally 
negative in genotoxicity tests and the uncertainty of the relevance of 
these tumors to humans. Thus, while 2-butoxyethanol has not been 
classified as a known/likely human carcinogen, it also cannot be 
classified as not likely to be a human carcinogen. Indeed, it was 
clearly stated that there was ``suggestive evidence that raises concern 
for carcinogenic effects.''

[[Page 10721]]

 Under the Agency's 1986 Guideline, 2-butoxyethanol would be judged as 
Group C, possible human carcinogen. Based on the evidence of 
carcinogenicity in mice,2-butoxyethanol meets the criteria for 
inclusion on List 1 of being an animal carcinogen in at least one 
species and one sex.
    4. Diethanolamine. There were two dermal chronic toxicity/
carcinogenicity studies performed on diethanolamine. Under the 
conditions of these 2-year studies, there was no evidence of 
carcinogenic activity of diethanolamine in male or female rats. There 
was clear evidence of carcinogenic activity of diethanolamine in male 
and female mice based on increased incidences of liver neoplasms in 
males and females and increased incidences of renal tubule neoplasms in 
males.
    5. Ethylbenzene. There were two inhalation chronic toxicity/
carcinogenicity studies performed on ethylbenzene. Under the conditions 
of the 2-year rat study, there was clear evidence of carcinogenic 
activity in male rats based on increased incidences of renal tubule 
neoplasms. The incidences of testicular adenomas were also increased. 
There was some evidence of carcinogenic activity in female rats based 
on increased incidences of renal tubule adenomas. There was some 
evidence of carcinogenic activity in male mice based on increased 
incidences of alveolar/bronchiolar neoplasms and in female mice based 
on increased incidences of hepatocellular neoplasms.
    6. 1,2-Epoxybutane. There were two inhalation chronic toxicity/
carcinogenicity studies performed on 1,2-epoxybutane. Under the 
conditions of these studies, there was clear evidence of carcinogenic 
activity in male rats based on an increased incidence of papillary 
adenomas of the nasal cavity, alveolar/bronchiolar carcinomas, and 
alveolar/bronchiolar adenomas and carcinomas (combined). There was 
equivocal evidence of carcinogenic activity for female rats based on 
papillary adenomas of the nasal cavity. There was no evidence of 
carcinogenic activity in male or female mice. 1,2-Epoxybutane was 
mutagenic in Salmonella typhimurium strains, induced forward mutations 
in mouse lymphoma cells, and induced chromosomal aberrations and sister 
chromatid exchanges in chinese hamster ovary (CHO) cells.
    7. 2-Mercaptobenzothiazole. There were two gavage chronic toxicity/
carcinogenicity studies performed on 2-mercaptobenzothiazole. Under the 
conditions of the studies, there was some evidence of carcinogenic 
activity in male rats indicated by increased incidences of mononuclear 
cell leukemia, pancreatic acinar cell adenomas, adrenal gland 
pheochromocytomas, and preputial gland adenomas or carcinomas 
(combined), and in female rats, based on increased incidences of 
adrenal gland pheochromocytomas and pituitary gland adenomas. There was 
no evidence of carcinogenic activity in male mice. There was equivocal 
evidence of carcinogenic activity for female mice based on increased 
incidences of hepatocellular adenomas or carcinomas (combined).
    8. Nitromethane. There were two inhalation chronic toxicity/
carcinogenicity studies performed on nitromethane. Under the conditions 
of these studies, there was no evidence of carcinogenic activity in 
male rats. There was clear evidence of carcinogenic activity in female 
rats based on increased incidences of mammary gland fibroadenomas and 
carcinomas, in male mice based on increased incidences of harderian 
gland adenomas and carcinomas, and in female mice based on increased 
incidences of liver neoplasms (primarily adenomas) and harderian gland 
adenomas and carcinomas. Increased incidences of alveolar/bronchiolar 
adenomas and carcinomas in male and female mice exposed to nitromethane 
were also considered to be related to administration of nitromethane.

C. Future Actions

    EPA solicits comments upon the conclusions set forth in this 
Notice. The Agency will review and evaluate any submitted comments, and 
will then publish a final Notice in the Federal Register to complete 
the reclassification of these chemicals. After the publication of that 
Notice, as an immediate step to inform users and the general public of 
the presence of an inert of toxicological concern, EPA anticipates 
requiring that the presence of the reclassified List 1 inert ingredient 
be disclosed on the label. Registrants of a product that contains one 
or more inert ingredients that are the subject of this notice will 
receive correspondence from the Agency concerning the procedures for 
label disclosure.
    EPA also anticipates that products containing one or more of these 
reclassified List 1 inert ingredients will be subject to a Data-Call-In 
(DCI) Notice. This DCI (expected to be issued in the near future) would 
require the submission of an extensive data set to support the 
continued use of these List 1 inert ingredients in pesticide products. 
The Agency would also provide in the DCI a list of all registrants or 
designated agents whose products contain one or more of these List 1 
inert ingredients, which will allow registrants to form groups for the 
purposes of data generation and submission.

III. Reclassification of Rhodamine B from List 1 to List 4B

A. Background

    The previously described Federal Register notice published on April 
22, 1987 (52 FR 13305), also established List 4 inert ingredients 
``inerts of minimal concern.'' On November 22, 1989 (54 FR 48314), List 
4 was further subdivided into List 4A and 4B. List 4B inert ingredients 
are ``inerts for which EPA has sufficient information to reasonably 
conclude that the current use pattern in pesticide products will not 
adversely affect public health or the environment.''
    Rhodamine B's current classification as a List 1 inert ingredient 
is due to its carcinogenicity. A Rhodamine B DCI Notice was issued in 
February 1993 that required registrants of products containing 
Rhodamine B to generate additional toxicity data (to further define the 
hazard) and exposure data to support the continued registration of 
their products. If submitted, these data would have been used to 
perform a risk assessment to support all uses of Rhodamine B. However, 
as a result of the issuance of the DCI, most of the existing uses of 
Rhodamine B as an inert ingredient were not supported. Registrants of 
non-seed treatment pesticide products either reformulated their 
products to use substitutes for Rhodamine B or voluntarily canceled 
those products containing Rhodamine B rather than generate data to 
support the use of Rhodamine B as a food-use. However, several 
registrants wished to retain the use of Rhodamine B as a dye in seed 
treatment pesticide formulations. They submitted to the Agency a 
radiolabeled magnitude of the residue study in which Rhodamine B was 
used to dye seeds that were then planted and grown to harvest.
    In the Federal Register of August 2, 2001 (66 FR 40170) (FRL-6598-
4), EPA issued a proposal pursuant to section 408 of the FFDCA, 21 
U.S.C. 346a as amended by the Food Quality Protection Act (FQPA) 
(Public Law 104-170) to limit the uses of Rhodamine B as a dye in seed 
treatment only. As explained in the proposed rule, based on its review 
and evaluation of the submitted data, EPA concluded that use of 
Rhodamine B as a dye in seed treatment is a non-food use, because the 
use is not likely to result in residues in food or feed.

[[Page 10722]]

 Therefore, neither a tolerance nor a tolerance exemption is needed for 
the use of Rhodamine B as a dye in seed treatment pesticide products.
    The final rule was published on December 27, 2001 (66 FR 66769) 
(FRL-6813-6). The Rhodamine B use pattern is now limited to use as a 
dye in seed treatment, and for a period of 3 years Rhodamine B can also 
be used as a dye in animal ear tag pesticide products. This 3-year time 
frame is needed to allow those pesticide ear tag products containing 
Rhodamine B to clear the channels of trade.

B. Future Actions

    Rhodamine B's classification as a carcinogen remains unchanged. 
However, the Agency no longer considers List 1 classification for 
Rhodamine B for its use as a dye in seed treatment pesticide products 
to be appropriate. List 1 classifications are made according to hazard 
criteria only. However, the December 27, 2001 Federal Register limited 
the use of Rhodamine B to a specified use pattern. A List 4B inert 
ingredient is considered to be an inert ingredient for which the 
available toxicity (hazard) information when paired with the available 
exposure information indicates no reasonable expectation of adverse 
effects. Rhodamine B now meets the definition of a List 4B, and will be 
reclassified as such.
    Those persons desiring to register products containing Rhodamine B 
as an inert ingredient for any uses other than as a dye in seed 
treatment would need to submit an extensive data set similar to that 
required in the 1993 Rhodamine B DCI. These data would be used by the 
Agency in a risk assessment on the proposed use. If, the risk 
assessment supports the required safety finding, then the use would be 
approved.

List of Subjects

    Environmental protection, pesticides and pests.

    Dated: February 26, 2002.
  Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 02-5445 Filed 3-7-02; 8:45 am]
BILLING CODE 6560-50-S