[Federal Register Volume 60, Number 143 (Wednesday, July 26, 1995)]
[Notices]
[Pages 38329-38331]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-18368]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[OPP-30000/10I; FRL-4944-4]
Lindane: Decision Not To Initiate a Special Review on Kidney
Effects
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: EPA (the Agency) announces its decision not to initiate a
Special Review for pesticide products containing lindane based on
worker health concerns arising from studies showing irreversible renal
effects in the rat. EPA has determined that these effects occur only in
the kidneys of the male rat and are not relevant for human risk
assessment. The Agency is currently developing a strategy to examine
the role organochlorine chemicals, such as lindane, may play as
endocrine disrupters. Should the Agency determine that this or other
effects cause unacceptable risk, it will take appropriate regulatory
action.
FOR FURTHER INFORMATION CONTACT: By mail, David H. Chen, Special Review
and Reregistration Division (7508W), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location, telephone number and e-mail address: Special Review
Branch, Rm. WF32C6, Crystal Station #1, 2800 Crystal Drive, Arlington,
VA., telephone Number: 703-308-8017, internet e-mail address:
chen.david@epamail.epa.gov
SUPPLEMENTARY INFORMATION: On March 18, 1994, EPA announced its
proposed decision (and solicitation for public comment) not to initiate
a Special Review of lindane for male rat kidney effects described in
the September 18, 1985 preliminary notification to lindane registrants
and applicants. The Agency has reviewed the available data in light of
the Agency's 1991 alpha2u-globulin (2u-g) regulatory
policy and the public comments received in response to the March, 1994
announcement. This notice provides the Agency's final decision, its
response to comments, and the rationale for its final decision.
I. Introduction
Background information on pesticide registration and the Special
Review process can be found in the Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA) as amended (7 U.S.C. 136 et seq.), and
appropriate sections under 40 CFR part 154, published on November 27,
1985 (50 FR 49015). For a more comprehensive summary of the legal and
regulatory background pertaining to lindane, refer to the Agency's
proposed decision not to initiate a Special Review on rat kidney
effects, published on March 18, 1994 (59 FR 12916). Below is a summary
of the text of that document.
A. Background
Lindane (gamma-hexachlorocyclohexane) is a broad spectrum
organochlorine insecticide/acaricide registered for control of insects
and other invertebrates on a wide variety of sites. This pesticide is
currently registered for use on field and vegetable crops (including
seed treatments) and non-food crops (ornamental and tobacco),
greenhouse food crops (vegetables), forestry (including Christmas
trees), domestic outdoor and indoor (pets and household uses),
commercial indoor (food/feed storage areas and containers), animal
premises, wood or wooden structures, and human skin/clothing (military
use only).
B. Regulatory History
Between 1977 and 1983, EPA conducted a Special Review that was
based on the carcinogenicity, fetotoxicity/teratogenicity, and
reproductive effects of lindane, and its potential to cause blood
dyscrasia, as well as acute toxicity to aquatic wildlife. In the
Agency's final determination (PD-4) published in 1983, the Agency
canceled the indoor uses of smoke fumigation devices (by May, 1986) and
the use of dips on dogs to control pests other than mites.
Subsequently, the dog dip use was permitted for commercial use (kennel,
farm, and sport dog uses only), provided that additional label
[[Page 38330]]
precautions were added to reduce applicator exposure. All other uses
were allowed to continue with various restrictions. Those restrictions
varied according to the degree of hazard associated with the use, but
typical requirements included protective clothing, label statements
describing necessary precautions, and restrictions of some products to
certified pesticide applicators.
Following the conclusion of the Special Review in 1983, the Agency
received a new 90-day subchronic rat feeding study which showed
histopathological kidney and liver changes. Based on the effects
observed in this study, on September 18, 1985, EPA notified registrants
and applicants for registrations for lindane that the Agency was
considering initiating a new Special Review base on concerns for
workers exposed to lindane as a result of its forestry and uninhabited
building uses.
The subchronic feeding study showed that lindane causes
histopathological lesions, primarily in the kidney of male rats, and
also in the liver of male and female rats. The kidney lesions were not
completely reversed after a 6-week recovery period on a lindane-free
diet. These renal changes included tubular degeneration, hyaline
droplets, tubular casts, tubular distention, interstitial nephritis,
and basophilic tubules. No adverse effects on kidney structure in
female rats were noted. The liver effects (hepatocellular hypertrophy)
were not regarded as a specific response to lindane because they are
related to increased detoxification processes, and are considered a
typical response and defensive mechanism to the presence of foreign
substances.
Subsequent to the initial demonstration of lindane induced rat
kidney lesions, the Agency required and received a number of additional
toxicological studies aimed at elucidating the observed kidney effects.
In summary, only male rats demonstrated the lindane induced kidney
effects; while mice, rabbits and female rats did not. In the rat
chronic feeding/carcinogenicity study, male Wistar rats demonstrated
the characteristic 2u-g kidney histopathological sequence
of kidney lesions associated with increased ``accumulation of hyaline
droplets containing 2u-g'', ``necrosis of tubule
epithelium'' leading to tubular degeneration, and subsequent formation
of granular casts, without any evidence of lindane induced kidney
tumors. (Refer to ``Alpha2u-Globulin: Association with Chemically
Induced Renal Toxicity and Neoplasia in the Male Rat'', Risk Assessment
Forum Monograph (EPA/625/391/019F, September 1991, page 2). The
Monograph is available through the U.S. Government Printing Office:
1992-648-003/41809. A chemical analysis of the kidney for evidence of
increased levels of 2u-g revealed clear and pronounced
compound dose-related increases in this protein. Furthermore, the
exacerbation of hyaline droplets was due to the apparent binding of the
2u-g to lindane as an adduct, which accumulates in the
kidney proximal tubules and cannot be excreted (refer to Monograph,
page 92). Lindane is one of a group of 2u-g chemical
inducers tested that has been shown to produce ``the sequence of
lesions characteristic of the 2u-g syndrome'' in the
absence of renal tubule tumors in the male Wistar rat (refer to
Monograph, page 89).
In the above Monograph, the Agency outlined its regulatory policy
for human risk assessment for chemical agents that affect the male rat
kidney through the 2u-g mechanism (refer to Monograph,
page 89). This policy states ``if a compound induces alpha 2u-globulin
accumulation in hyaline droplets, the associated nephropathy in male
rats is not an appropriate endpoint to determine noncancer (systemic)
effects potentially occurring in humans. Likewise, quantitative
estimates of noncancer risk (e.g., reference doses and margin of
exposure determinations) are based on other endpoints.'' In the case of
lindane, the Agency has reviewed the weight-of-evidence in light of the
1991 2u-g policy, and has concluded that the observed
renal effects were the result of the 2u-g mechanism. The
potential for lindane to induce kidney lesions in male rats is not
currently regarded as being relevant to human health risk assessment.
Therefore, the renal effects observed do not provide a basis for a
Special Review of lindane.
II. Comments Received on the Proposed Notice Not to Initiate a
Special Review on Kidney Effects
In its March, 1994 proposal not to initiate a Special Review, the
Agency provided a 60-day comment period, which ended on May 17, 1994.
EPA received five sets of comments, most of which were responses from
public interest groups.
Comment. All of the commenters urged the Agency not to abandon the
Special Review of lindane because there are additional health concerns
beyond kidney effects that are currently not under consideration in the
review by EPA.
Agency Response. In 1983, EPA concluded a major Special Review
effort of lindane based on carcinogenicity, fetotoxicity/
teratogenicity, reproductive effects, and acute effects on aquatic
organisms. This effort resulted in the cancellation of indoor uses of
smoke fumigation devices and greatly limited the use of pet dips on
dogs. In addition, there were uses that were allowed to continue only
if certain imposed restrictions were implemented. The restrictions were
based on the degree of associated hazards, and included changes in
warning labels, the wearing of protective clothing, and restrictions to
limit uses to certified pest control operators. Today's action only
deals with the concerns originally raised in the 1985 preliminary
notification to registrants and applicants of lindane, that is, kidney
effects to workers exposed to lindane in forestry and uninhabited
building uses. The Agency has concluded that the unique kidney effects
induced via the 2u-g mechanism in the rat have no direct
biological relevance for human risk assessment. Consequently, there is
no basis for initiating a Special Review of lindane due to the kidney
effects at this time. However, the Agency recognizes that
organochlorine pesticides, such as lindane, can cause endocrine
disruption that may be associated with risk concerns. The Agency is
currently developing a strategy to look at organochlorine pesticides as
a group to examine their role as endocrine disrupters. Although the
Agency is not initiating a Special Review on lindane for kidney
effects, the findings from a comprehensive examination of the group of
chemicals could lead to further regulatory action on lindane.
Comment. Several commenters pointed to concerns for breast cancer,
neurotoxic, endocrine-disruption and other health effects from the
continued use of lindane products. The commenters urged that EPA take
more aggressive actions to further reduce risk.
Agency Response. The issues raised by the commenters were not
Special Review triggers in the 1985 preliminary notification letter to
registrants of lindane. Also, the identification of a possible toxic
response or health concern to a given chemical does not always indicate
that Special Review criteria have been exceeded. The recently completed
rat carcinogenicity study did not demonstrate an association between
lindane exposure and carcinogenicity. Presently, the Agency does not
have a mouse carcinogenicity study that meets current acceptance
criteria and a new study has been requested. However, the literature
reports suggesting an apparent relationship between lindane and breast
cancer in humans require further
[[Page 38331]]
evaluation. Investigation is underway at the National Cancer Institute
to determine whether the association found in these studies can be
confirmed. The possible endocrine effects reported in the literature to
date have not been evident in those studies conducted in rats reviewed
by the Agency, nor has immunotoxicity been indicated to be a critical
endpoint for lindane toxicity. The Agency is considering additional
data requirements for reregistration, including a neurotoxicity study,
and the need for requiring special studies to assess both
immunotoxicity and endocrine effects. The Agency is currently
developing a strategy for examining the role of organochlorine
chemicals as endocrine disrupters. Such an effort could result in the
Agency pursuing further regulatory action against lindane. Today's
action only deals with the kidney effects and does not preclude the
Agency from taking future regulatory action against this chemical based
on the risk concerns raised above.
Comment. Several commenters suggested EPA ban further use of
lindane because the severity of the pesticide's environmental and
health concerns have already caused regulators in more than a dozen
countries to ban or severely restrict the use of this chemical.
Agency Response. EPA updates and reviews its scientific database on
a routine basis for new evidence on chemicals which may identify risk
concerns. Any regulatory action must meet the scrutiny of sound science
and be consistent with the statutes and regulations governing pesticide
registration and use. The Agency will exercise its authority to ban or
restrict the use of pesticides when such action is necessary to protect
against unreasonable adverse effects.
III. Reregistration Activities
EPA is considering what additional toxicological data are necessary
to support continued registration, which include carcinogenicity and
developmental neurotoxicity studies. Upon receipt and review of any of
these studies, the Agency could initiate a Special Review or take other
appropriate regulatory action if risk concerns are raised.
IV. Conclusion
Today's notice announces the Agency's final decision that the
lindane induced kidney effects observed in male rats are not relevant
for human risk assessment, nor do these effects meet the risk criteria
for initiation of a Special Review. Because EPA no longer believes
there is a renal-related hazard posed to humans, the Agency will not
initiate a Special Review for this effect. The Agency is developing a
strategy to look at the role of organochlorine pesticides, such as
lindane, may play as endocrine disrupters to better understand the
risks from this group of chemicals. This action does not preclude the
Agency from taking action on this chemical in the future as new
information on this or any other risk concern becomes known.
Dated: July 19, 1995.
Lynn R. Goldman,
Assistant Administrator for Prevention, Pesticides and Toxic
Substances.
[FR Doc. 95-18368 Filed 7-25-95; 8:45 am]
BILLING CODE 6560-50-F
