Public Information and Records Integrity Branch (PIRIB)
Information Resources and Services Division (7502C)
Office of Pesticide Programs (OPP)
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC  20640

 Docket Control Number OPP-34239B – Lindane Revised Risk Assessment

Comments Submitted on Behalf of the Natural Resources Defense Council

 By Gina M. Solomon, M.D., M.P.H.

Senior Scientist

April 1, 2002

The Natural Resources Defense Council (NRDC) is submitting the following comments on the revised risk assessment for lindane on behalf of our over 500,000 members nationwide. Many of our members are pregnant or have children who may be disproportionately exposed and susceptible to the health effects of a neurotoxic and endocrine disrupting chemical such as lindane. We receive calls from our members, and members of the general public, with questions related to exposure to lindane used for treatment of head lice or scabies. Our work has focused for decades on risks to infants and children from exposure to toxic chemicals, pesticides, and endocrine disruptors. We are therefore directly affected by EPA’s risk assessment for lindane. NRDC has no financial interest in the manufacture or use of lindane or lindane-containing products.

We are deeply disturbed to observe that EPA has essentially ignored over a thousand comments from health groups, environmental groups, public agencies, and members of the public on the Lindane Preliminary Risk Assessment. Most importantly, EPA failed to adequately address three major concerns with the lindane risk assessment: (1) the Agency failed to incorporate pharmaceutical uses of lindane into both the health and ecological risk assessments; (2) the Agency reduced the 10x child-protective factor to only 3x despite clear evidence of data gaps and of disproportionate susceptibility of fetuses and neonates to lindane toxicity; and (3) EPA failed to even respond to the fact (pointed out in our previous comments on the Lindane Draft Risk Assessment) that the Agency did not include consideration of the breast milk pathway in the exposure assessment.

Failure to Include Topical Use of Lindane for Lice and Scabies 

The Agency notes that over a thousand commenters informed EPA that the risk assessment of lindane would be incomplete without the inclusion of the pharmaceutical use of lindane as a lice and scabies treatment. The commenters are correct, and EPA should pay careful attention to these comments and take immediate steps to correct the problem. EPA should be well aware that the greatest exposure of children to lindane comes from direct application of the pesticide to their scalp or body for treatment of head lice or scabies. EPA should be aware that the greatest current discharges of lindane into the environment come from the 1.41 million applications per year of lindane shampoo, containing 1,320 pounds of active ingredient, discharged into the nations sewage systems.[1] EPA should also be aware that the Food Quality Protection Act (FQPA) was unanimously passed by Congress in order to prevent exactly this type of mischaracterization of health risks to children.

The FQPA amended the FFDCA to allow EPA to establish or leave in effect a tolerance for a pesticide chemical residue in or on a food only if she determines that the tolerance is safe.  FFDCA §408(b)(2)(A)(i)(emphasis added).  A tolerance can only be considered safe if the Administrator determines “that there is a reasonable certainty, that no harm will result from the aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.”  FQPA §408(b)(2)(A)(ii).  In making these determinations, special consideration must be given to the unique effects these pesticide residues may have on infants and children. FFDCA §408(b)(2)(C).  There is no exception in the FQPA for pesticides that are also used as pharmaceuticals. It is therefore patently obvious that EPA is ignoring the clear requirements of the FQPA in failing to consider the major use of lindane, and the major risk of lindane to children. Any tolerance set without determining that aggregate exposures to children, including pharmaceutical exposures, are safe, is illegal under the law. EPA cannot legally proceed to issue any final rules or tolerances based on a risk assessment that fails to even consider the main exposure pathway for children to lindane. The agencies response to the public “the Agency is still exploring this issue.” Is utterly unacceptable. The risk assessment should not proceed until this issue is addressed.

On November 5, 1979 (44 Federal Register, 63749), when EPA exempted lindane lice and scabies products from the requirements of the FIFRA, the situation has changed dramatically, most notably with passage of the Food Quality Protection Act of 1996 (FQPA). In light of the changes in law and science that have occurred in more than two decades since EPA gave up control of lindane, the Agency must either reassert its control over lice and scabies treatments under the FIFRA, or at least consider the human health and environmental impacts of these treatments in its current risk assessments. As lindane lice and scabies products dominate the human health and environmental risks of lindane, the risk assessments are meaningless without them.  Under the FIFRA, EPA has a statutory responsibility to ensure that pesticides are safe and effective for their intended uses and to prevent unreasonable adverse effects to man, other animals, and the environment from their usage (7 U.S.C. §136(bb), §136a(a), §136a(d)(2); §136d(b)).  By ignoring the risks posed by lindane lice and scabies treatments, EPA is not fulfilling its statutory responsibility. 

EPA also fails completely to address public comments and concerns about the enormous lindane discharges into public sewage systems due to pharmaceutical uses of this chemical, and the resultant contamination of surface waters. The Agency responds that it has funded two pollution prevention projects “to see if the pharmaceutical use of lindane can be altered or replaced with other treatments that are less persistent and/or less toxic to the environment. However, the Agency has not evaluated this release scenario to quantify the risk to human health or the environment.” Obviously EPA is not au courant with the pollution prevention projects that the Agency funded. EPA should know that the Region IX project has resulted in the complete ban of pharmaceutical uses of lindane in California. This ban was possible because there are ample choices of other treatments that can replace lindane for use against lice and scabies. In fact, there is no scientific dispute about the ready availability of alternatives. Most medical organizations no longer recommend lindane due to the significant risk of childhood poisonings. EPA must act quickly to evaluate the release scenario of lindane into water and quantify the risk to human health and the environment. It is insane for EPA’s Office of Pesticide Programs (OPP) to ignore this exposure pathway, while EPA’s Office of Water sets a limit of 19 ppt on lindane in water – a level that sanitation districts will violate unless OPP addresses the enormous problem of lindane discharges from pharmaceutical uses.

EPA Must Retain the Full 10x Margin of Safety to Protect Children from Lindane

EPA’s stated rationale for reducing the 10x FQPA margin of safety to 3x is deeply flawed. EPA gives six reasons for reducing the FQPA safety factor. Each of these reasons is either incorrect or irrelevant to the question before the Agency. They are discussed and refuted below:

1)      “The toxicology data base is complete”

EPA repeatedly mentions that lindane has shown endocrine disrupting effects in numerous studies submitted to EPA and in the open literature. Rather than regulating lindane as an endocrine disruptor, however, EPA states the intention to require future studies on the endocrine disrupting effects of lindane through the Endocrine Disruptor Screening and Testing Program. This statement of intention amounts to an acknowledgement that there are significant data gaps in the toxicology database for lindane. If there were no data gaps, there would be no need for endocrine disruptor testing. In addition, as detailed below, EPA itself admits that lindane may be transformed in the environment into the even more toxic isomer, b-HCH, and the Agency asserts that the issue is still unresolved (discussed in greater detail below). This is an extremely important data gap that must be addressed or filled by using the full 10x factor. Thus it is incorrect for EPA to say that the database is complete.

2)      “Available data provide no indication of increased susceptibility in rats from in utero exposure to lindane in the prenatal developmental study.”

This statement is misleading and manipulative. EPA uses three rat studies to assess fetal risk: a prenatal developmental study, a reproductive toxicity study, and a developmental neurotoxicity study. While it is true that there was no clear evidence of increased susceptibility in the first study, the other two both clearly show qualitative, and in one case, quantitative increased susceptibility in the fetus. If EPA is purporting to use a weight-of-evidence approach to assessing the scientific literature, the evidence clearly supports the disproportionate susceptibility of the fetus to the toxic effects of lindane. Furthermore, biologic plausibility also supports fetal susceptibility due to the various neurotoxic and endocrine disrupting modes of action of this chemical in the fetus and neonate. Finally, the one study that purported to fail to demonstrate increased fetal susceptibility – the rat developmental study – is the least sensitive of the studies at detecting functional abnormalities. In addition, there were increased skeletal malformations compared to controls at all doses tested. The facts that the study lacked statistical power to detect an effect on skeletal development, and lacked the sensitivity to address functional endpoints are not be sufficient reason to reduce the FQPA factor. Reducing the FQPA safety factor based on one study flies in the face of the weight of scientific evidence and the mode of action of this pesticide.

3)      “The offspring effects seen in the developmental neurotoxicity study were the same as those seen in the two-generation reproduction study.”

Even if it were true, this statement would be irrelevant to the question before the Agency. The more important issue is that both of these studies clearly showed disproportionate vulnerability in the fetus. In addition, this statement is incorrect. The developmental neurotoxicity study showed increased motor activity and decreased motor activity habituation as compared to controls. These endpoints are important because they are indicative of the same type of CNS stimulation seen in human children who have been exposed to lindane. Although full-blown seizures were not observed in this particular study, these effects are along the continuum of CNS kindling and behavioral alterations that have been observed in humans. These effects were seen in the offspring in the absence of maternal toxicity. It should go without saying that CNS hyperexcitability in the offspring at doses non-toxic to the mother is indicative of a serious and very disturbing risk to the fetus, infant, and child.

4)      “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.”

This rationale is rather pathetic in light of the examples presented in our comments showing that the Agency completely omits numerous exposure pathways from the risk assessment. The adequacy of the exposure data should be reconsidered after the agency evaluates and includes the data on exposure to pharmaceutical lindane, pet products, lindane in breast milk, lindane in fish, and historical residues of lindane.

5)      “Although the developmental toxicity study in rabbits was classified unacceptable, the HIARC concluded that a new study is not required.”

This rationale is also irrelevant to the decision about the 10x FQPA factor. Whether or not a new rabbit study is needed, there are obvious data gaps due to incomplete information about endocrine disrupting effects.

6)      “There are currently no residential uses.”

This is the strangest of the six reasons for abandoning the FQPA margin of safety. Most members of the public would consider direct application of lindane to a child’s skin (or to the skin of a household pet) to be a residential use. Failure to acknowledge this use of lindane has a Byzantine strangeness that baffles logic. Clearly there are residential uses. EPA must include them and must use the full 10x FQPA margin of safety because of these household uses and because none of the six justifications for abandoning the 10x holds up to logic or scientific scrutiny.

EPA’s Confusion About Human Testing Policies

In Appendix B, page 3, HED responds to comments about the numerous reports of childhood poisonings related to lindane. The response asserts “However, current Agency policy is that a regulatory decision cannot be made based on a human endpoint until a final policy regarding the ethical aspect of the use of human studies for regulatory purposes is issued.” Obviously HED is confused about the difference between purposeful dosing of human subjects with toxic pesticides, and reports of poisonings collected by Poison Control Centers, FDA, and EPA due to current uses of the chemical in commerce. The industry practice of paying ‘volunteers’ to drink pesticide potions is quite rightly under review for ethical and scientific reasons, and such studies should not be used to support regulatory decisions. The collection of data on ongoing childhood poisonings from lindane that is sold today in commerce is an essential function of Poison Control Centers and is required by law of FDA and EPA. These data can and should form the foundation of regulatory decisionmaking. It is difficult for this commenter to comprehend how EPA could be so confused as to conflate these two obviously different types of information on human health effects.

EPA Fails to Include Exposure to b-HCH

In the response to public comment in Appendix B, page 6, EPA responds, “HED believes the available data do not support significant isomerization of lindane (gamma-HCH) to beta-HCH in the environment.”  In the risk assessment itself (p.9), EPA expresses much more uncertainty than in the response to comments: “lindane can possibly transform to the alpha and beta isomers of hexachlorocyclohexane by biological and phototransformation, although this issue remains to be conclusively resolved.” Furthermore, in the response to public comments in Appendix D, page 3, EFED asserts that “it appears that there is a high possibility of the formation of b-HCH under some circumstances.”  The Agency must address this issue in light of the evidence in the peer-reviewed scientific literature.[2] [3] In particular, we suggest that HED and EFED scientists talk with each other about this specific point. Resolution of this question is of substantial public health and environmental importance. The beta-isomer of HCH is the most persistent and bioaccumulative form. As much as 90 percent of HCH detected in human tissues and breast milk is the b form of HCH.[i]  EPA must reconsider its position in light of the available evidence and the major implications of isomerization, and should include a risk assessment for b-HCH exposures as a result of lindane use. If the Agency feels that it is unable to make a decision about whether or not to include b-HCH, then it must acknowledge this problem as a major source of uncertainty in the risk assessment and account for the data gap by requiring data collection to address this important question, and increasing the FQPA safety factor to the full 10x.

Failure to Include Breast Milk Exposures

EPA completely failed to address a major concern raised in our previous comments: the fact that the Agency omitted consideration of the breast milk pathway in the exposure assessment. We would like to know why the agency failed to even acknowledge this concern in its response to public comments. We are also deeply concerned that EPA failed to add the breast milk pathway in the revised risk assessment. It is not acceptable to ignore public comments, and even less acceptable to fail to include a major exposure pathway to children as required under the FQPA.

It is bizarre that the EPA document could admit that, “the milk:plasma concentration ratio for lindane indicates a much more efficient excretion of the compound in milk…The presence of lindane in mammalian milk exposes nursing offspring during critical periods of post-natal development (Dalsenter et al. 1997).” (p. 12 of Lindane RED Chapter: Environmental Fate and Ecological Risk Assessment) Yet at the same time, EPA fails to include a nursing infant scenario in the risk assessment. This omission is particularly egregious because lindane is known to bioaccumulate to higher levels in breast milk, and because the nursing infant is at higher risk from the neurotoxic and endocrine disrupting effects of this chemical. Failure to include the breast milk exposure pathway is a violation of §408(b)(2)(D)(vi) of the FFDCA.

Worker Risks are High and Underestimated

EPA’s failure to combine risks to workers from dermal exposures and inhalation exposures to lindane defies logic. It is a slap in the face of sound science to assume that the same chemical when inhaled has completely different toxicity than when it penetrates the skin, yet that it EPA’s current misguided policy. It should be obvious to any scientist or toxicologist that such an approach makes no sense. It is patently obvious that an individual exposed to lindane via both skin and lungs is getting an additive dose of that chemical. It is also obvious that in worker populations such combined exposures are highly likely, and even inevitable.

Persisting in the policy of considering each of these exposures separately guarantees that EPA will seriously underestimate real-world exposures to human beings that are handling this chemical on the job. That knowledge is particularly sobering in light of the fact that this split risk assessment still found serious worker risks. NRDC is deeply concerned that workers (including pregnant and lactating women) may be exposed to dangerous levels of this chemical. It is not appropriate for EPA to get dermal and inhalation levels just below dangerous thresholds and claim that the risk assessment provides adequate protection of worker health and safety. Mitigation measures must bring levels of exposure low enough that workers who inhale this chemical and get it on their skin are still protected from health effects. The Ministry of Agriculture, Fisheries and Food in the United Kingdom ordered that all uses of lindane for seed treatment be stopped in 1999 after determining that "the level of exposure of those treating seeds with lindane is considered to be above acceptable levels."[ii] We believe that seed treatment poses unacceptable health risks to workers, and that the EPA risk assessment, despite efforts to obfuscate the truth by separating dermal and inhalation exposures, demonstrates a serious health risk that must be addressed.

NRDC is incorporates by reference all our prior comments on the Lindane Draft Risk Assessment dated October 29, 2001, as we believe that EPA has failed to address any of our concerns in the revised risk assessment. Failure to include the major exposure pathways to lindane is an affront to the scientific database on this chemical and is in contravention of the plain language of the Federal Food, Drug and Cosmetic Act as amended by the Food Quality Protection Act of 1996. On reviewing the literature on lindane’s persistence, bioaccumulation in the environment and in human tissues, and toxicity, we do not believe that this chemical can safely be registered for use in the United States. We are particularly concerned about the disproportionate risks to certain subpopulations, including fetuses, breastfeeding infants, subsistence fishing communities, and workers. We will continue to monitor EPA regulatory activities involving lindane and will not stand by while the Agency tramples the clear requirements of FQPA.