Public Information and
Records Integrity Branch
Information Resources and
Services Division (7502C)
Office of Pesticide Programs
1200 Pennsylvania Ave., NW
Washington, D.C. 20460
Attn: Docket control
Dear Sir or Madam:
Attorney General of the State of New York submits these comments on the human
health risk assessment and other related documents for lindane, pursuant to the
Federal Register notice of August 29, 2001 (66 Fed Reg 45677- 45679). For the
reasons set out below, the Revised Human Health Risk Assessment dated July 31,
2001 (“Revised Risk Assessment”), is inadequate to fulfill EPA’s obligations
under the Federal Insecticide, Fungicide and Rodenticide Act and the Food
Quality Protection Act (FQPA) to assure that lindane levels in food and other
sources are protective of public health and are safe for infants and children. In particular, the failure to consider potential exposures to lindane
from non-food sources such as shampoos and lotions used to control head lice
and scabies results in a very substantial underestimation of lindane exposure
in infants and children. This omission,
as well as other inadequacies in the assessment process discussed below,
undermine the validity of the risk assessment and its conclusions.
Failure to justify reduction of the tenfold safety factor. The FQPA
imposes a legal mandate to apply a tenfold safety factor when determining
tolerances because of the susceptibility of infants and children. This tenfold
safety factor may be reduced “only if, on the basis of reliable data, such
[smaller] margin will be safe for infants and children.” FQPA, 21 U.S.C. §
346a(b)(2)(C). In the case of lindane,
the EPA failed adequately to justify the reduction of the tenfold safety factor
to a threefold safety factor. The
scientific rationale provides inadequate legal basis to support this decision
(see page 4 of the Revised Risk Assessment). The tenfold FQPA safety factor
should retained for lindane, as required by FQPA, because of reported increased
susceptibility of infants and children, and other inadequacies in the risk
assessment which are elaborated below.
Evidence of increased susceptibility of the young. EPA states
that it has conducted “a review of reported poisoning incidents associated with
human exposure to lindane (see page 20 of the Revised Risk Assessment). However, as noted by EPA, the review “only included lindane containing products
currently registered for use as seed treatment” (see page 20 of the Revised
Risk Assessment). The omission of other
poisoning incidents that may have occurred from exposure to lindane in other
uses, such as lindane-containing shampoos and lotions, is a serious
limitation. Indeed, given that as a
matter of practical reality, lindane is most likely to expose the young through
shampoos and lotions kept around the house, rather than seed treatments, this
omission renders EPA’s review virtually meaningless. EPA should consult with
the Food and Drug Administration (FDA), whose records include case reports of
adverse effects after use of lindane-containing shampoos and lotions, and may
indicate increased susceptibility of children.
Our office has requested these data from the FDA via the Freedom of Information
risk assessment also appears to ignore data before the EPA on increased
susceptibility of the young. The
statement that “the available data provide no indication of quantitative or
qualitative increased susceptibility in rats from in utero exposure to
lindane in the prenatal developmental study” (see page 15 of the Revised Risk
Assessment) is inconsistent with the statement that “there is [also]
quantitative increased susceptibility demonstrated in the rat developmental
neurotoxicity study” where maternal toxicity was observed at 13.7 milligrams
per kilograms per day (mg/kg/day) and offspring toxicity was observed at 5.6
mg/kg/day (see page 14 of the Revised Risk Assessment). Because offspring were affected at lower
doses than those that induced maternal toxicity, the study provides clear
indication of increased susceptibility of the young. Furthermore, the EPA states that, “The open literature does
contain citations which suggest an increase in susceptibility of fetuses and
young animals exposed to lindane” (see page 3 of the August 2, 2000, memo
containing the Report of the FQPA Safety Factor Committee).
data on increased susceptibility of the young were apparently not taken into
account as well. According to the
Physicians Desk Reference (PDR, 2001), “animal studies indicate that potential
toxic effects of topically applied lindane are greater in the young. Seizures, and, in rare instances, deaths
have been reported after excess dosage, over-exposure, frequent re-applications,
and accidental and intentional ingestion of lindane.” Under the listing ‘contraindications,’ the PDR states, “Lindane
shampoo is contraindicated for premature neonates because their skin may be
more permeable than full term infants and their liver enzymes may not be
sufficiently developed.” Lindane lotion
is also contraindicated. The National
Pediculosis Association in one year received 167 adverse events associated with
the use of lindane (Drug Topics, 1998). In the ATSDR Toxicological Profile on hexachlorocyclohexanes
(including lindane) (ATSDR,1994), increased susceptibility of young animals is
noted as follows: “Studies in animals have substantiated the neurological
symptoms from lindane application. Young
rabbits appeared to be more susceptible than older rabbits (Hanig et al,
1976),” and “Infants, young children, and people with excoriated (peeling) skin
are more susceptible to the toxic effects of lindane than are healthy adult men
and women (Ginsburg et al, 1977).” Finally, recent studies have reported effects on lindane on the young
(see attached reference list). It is
critical that EPA examine (or re-examine) these studies and reports before it
makes a determination to remove or reduce the tenfold safety factor.
Incomplete toxicological database.
The statement that “the
toxicological database is complete,” is in conflict with the statement
that “although the developmental
toxicity study in rabbits was classified as unacceptable, the committee
concluded that a new study is not required” (see page 15 of the Revised Risk
Assessment). In fact, the EPA lists
five toxicological data requirements (prenatal development in rabbit,
carcinogenicity in mice, gene mutation mammalian cell, dominant lethal assay,
and in vivo sister chromatid exchange) that are missing from the toxicological
database, which are included as “Data Needs” (see page 48 of the Revised Risk
Assessment). Absent a truly complete toxicological database, the tenfold safety
factor may not be removed.
Evidence of developmental effects. The statement that “the offspring effects
seen in the developmental neurotoxicity study were the same as those seen in
the two-generation reproduction study” (see page 15 of the Revised Risk
Assessment), provides further support for retaining, rather than reducing, the
tenfold safety factor.
Incomplete exposure assessment. The EPA exposure assessment underestimates
potential exposures for infants and children to lindane, particularly from
non-food sources such as potential dermal, ingestion and inhalation exposure
due to contact with lindane-containing shampoos and lotions used for treatment
of head lice and scabies. Although
there are no allowed residential (home) applications, lindane continues to be
used at home for personal use for human treatment of head lice and scabies
(Alpharma, 2001; Revised Risk Assessment, page 1; and the Handbook of Pediatric
Environmental Health, 1999, page 194).
A survey of 238 families in Missouri between June 1989 and March 1990
found that 9.2% of the families reported using Kwell shampoo (containing
lindane) for lice control (Davis et al., 1992). The FDA in 1996 investigated claims that lindane-containing
shampoos and lotions caused neurological damage in children. FDA scientists found that “parents may be
inclined to overuse the product in their zeal to treat children as quickly as
possible” and that “its overuse can be harmful” (FDA, 1996). These uses are not considered in the Revised
Risk Assessment despite the fact that this use alone is likely to provide
exposure to children far in excess of estimated dietary exposures. EPA failed to account for these non-dietary
exposures and risks to children when considering children’s exposure to
is also evidence that such home use results in contamination of water supplies
from rinsing off lindane containing shampoos and lotions (see Lindane.org,
2001). According to the Los Angeles
County Sanitation District, an estimated 42 pounds per year of lindane derived
from pediculicides and scabicides enters their water treatment facilities
(Heil, A, 2001). Also, by its own accounting, EPA found drinking water
contaminated by lindane in nearly all regions of the United States, in both
surface and groundwater (see page 5 of the Revised Risk Assessment).
In addition, the statement
that “adequate actual data, surrogate data, and/or modeling outputs are
available to satisfactorily assess food exposure and to provide a screening
level drinking water exposure assessment” neglects to account for other
substantial exposures, for example, from exposure to lindane in breast milk and
by in utero exposure (ATSDR, 1994, pages 111-114), and from the use of lindane
in shampoos and lotions used to treat scabies and head lice.
as the Revised Risk Assessment acknowledges, lindane is “both moderately mobile
and highly persistent (soil half life of 2.6 years)” (see page 9 of the Revised
Risk Assessment). These characteristics
can lead to residues on food crops grown in or near soil that may have been
treated with lindane in the past. These
inadvertent lindane and lindane residue exposures should be considered in the
Inadequate assessment of margins of exposure. The acute and chronic dietary
margins of exposure (comparison of the lowest dose of concern and the average
daily exposure dose) calculated by EPA are shown in the Revised Risk Assessment
on page 31, Table 5. Exposure to
lindane from dermal exposure is not included. Because potential exposure to
lindane via shampoos and lotions used for the treatment of head lice and
scabies were not considered, the margins of exposure are based on faulty
assumptions. Given the unaccounted
exposure to lindane from this source for infants and toddlers, the margins of
exposure would be greatly reduced (i.e., would provide an inadequate margin of
exposure) if, as required by FQPA,
these sources of additional exposure to lindane were taken into
account. Even without this change, the
EPA notes that some of the occupational lindane exposures have a margin of
exposure that indicates that the exposure is above EPA’s level of concern (see
page 47 of the Revised Risk Assessment and Table 13).
if the full tenfold FQPA safety factor were used in this assessment, as legally
mandated, the resultant margins of exposure would indicate that the exposure is
above EPA’s level of concern, and would fail adequately to protect infants and
Lack of cumulative risk assessment. EPA did not conduct a cumulative risk
assessment for pesticides that may have a common mechanism of toxicity as
lindane, as required by FQPA, 21 U.S.C. § 346a (b)(2)(D)(u). EPA justified this failure by asserting a
lack of available data and by assuming, without basis, that lindane does not
have a common mechanism of toxicity with other chemicals. However, there is evidence of common
mechanism of toxicity between lindane and malathion (Dikshith et al., 1978,
reported in ATSDR, 1994), and between lindane and dieldrin (Brannen et al.,
1998). ATSDR also reports on evidence
that the metabolism of lindane can be altered by exposure to other chlorinated
hydrocarbon insecticides. Exposure to
various chlorinated hydrocarbon insecticides, including lindane, is thought to
produce generalized non-specific induction of microsomal enzymes. Induction of mixed-function oxidase activity
by other chlorinated hydrocarbon insecticides stimulate the selective effect on
the oxidiative degradation of lindane (Chadwick and Freal, 1972).
Lack of evaluation of potential endocrine disrupter effects. EPA did not
adequately evaluate the results of its own evaluation of potential endocrine
disrupter effects of lindane. EPA
conducted an abbreviated review of possible endocrine disrupter effects, and
found that, “based on available scientific literature, lindane has
characteristics of an endocrine disrupting compound. The compound exhibits effects on birds, mammals and possibly
fish” (see EFED RED Chapter for Lindane, pages 13-14). Since evidence of endocrine disrupter
effects have been demonstrated and have been noted by EPA (see EFED RED Chapter
for Lindane, pages 2 and 13-14), the reduction of the tenfold safety factor is
Lack of adequate review of current tolerances. The
tolerances for lindane should undergo a full review by the EPA to determine
whether the tolerances are protective of infants and children under FQPA, and
to determine whether the tolerances adequately address the nature of lindane
residues in plants and ruminants.
Tolerances are currently established under 40 CFR § 180.133 for residues
of lindane in/on various raw agricultural commodities; the only food/feed use
of lindane which is being supported for re-registration is seed treatment on
broccoli, Brussels sprouts, cabbage, canola, cauliflower, spinach, lettuce,
radish, and cereal grains (excluding rice and wild rice)(see page 2 of the
Revised Risk Assessment). The tolerance
reassessment summary for lindane is presented in Table 4 (page 21 of the Revised
Risk Assessment). EPA acknowledges
that “The nature of the residue in
plants and ruminants is not adequately understood” (see page 21 of Revised Risk
tolerances for fat of meat from cattle, goats, horses, and sheep (currently 7
parts per million, ppm), and in the fat of meat from hogs (currently 4 ppm) are
listed as “To Be Determined” (see Table 4, page 22 of the Revised Risk
Assessment). No tolerances have been
established for poultry fat or for processed food/feed commodities (see page 2
of the Revised Risk Assessment) even though lindane residues were reported in
the FDA Total Diet Study (FDA, 2000).
The EPA states that “the Agency will re-calculate the maximum
theoretical dietary burden for [fat of cattle, goats, horses, sheep, hogs,
poultry] and re-assess the adequacy of the available animal feeding studies
when the requested residue data for livestock feed items have been received and
evaluated.” The lack of such data
should compel the EPA to withdraw the tolerances until such time as the
requested information is provided and assessed by EPA.
In summary, EPA has not fulfilled its mandate to
protect children under FQPA because it has underestimated exposure and risks
due to lindane, and has violated FQPA’s mandate to apply a tenfold safety
factor for children’s protection.
Should you have any questions about the submitted information, please
contact me at (518) 474-9267, and I will be happy to discuss these issues with
Senior Public Health Scientist
Alpharma, 2001. Personal communication with J. Schreiber.
ATSDR, 1994. Agency for Toxic Substances and Disease
Registry. 2001 Toxicological Profiles
on CD-ROM. Hexachlorocyclohexanes.
Brannen, K., Devaud, L., Liu,
J., Lauder, J., 1998. Prenatal exposure
to neurotoxicants dieldrin or lindane alters tert-butylbicyclophosphorothionate
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Beard, A., Bartlewski, P.,
Chandolia, R., et al., 1999. Reproductive and endocrine function in rams
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Beard, A., Rawlings, N.,
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Chadwick, R. and Freal, J.,
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