October 29, 2001

 

Public Information and Records Integrity Branch

Information Resources and Services Division (7502C)

Office of Pesticide Programs

Environmental Protection Agency

1200 Pennsylvania Ave., NW

Washington, D.C. 20460

 

Attn: Docket control number OPP-34239                                                                         

 

Dear Sir or Madam:

 

The 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.

 

(1) 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.

 

(1)(a) 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 Act. 

 

The 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).

 

Other 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. 

 

(1)(b) 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.

 

(1)(c) 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.

 

(1)(d) 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 lindane.

 

There 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.

 

Finally, 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 exposure assessment.

 

(2) 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).

 

Therefore, 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 children.

 

(3) 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).

(4) 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 not justified. 

 

(5) 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 Assessment). 

 

The 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 you.

 

References

 

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 binding to GABA(A) receptors in fetal rat brainstem.  Dev Neurosci 20(1): 34-41.

 

Beard, A., Bartlewski, P., Chandolia, R., et al., 1999. Reproductive and endocrine function in rams exposed to the organochlorine pesticides lindane and pentatchlorophenol from conception. J. Reproduction and Fertility 115(2): 303-314.

 

Beard, A., Rawlings, N., 1998.  Reproductive effects in mink (Mustela vison) exposed to the pesticides lindane, carbofuran, and pentachlorophenol in a multigeneration study.  J. Reprod Fertil 113(1): 95-104.

 

Chadwick, R. and Freal, J., 1972. Comparative acceleration of lindane metabolism to chlorophenols by pretreatment of rats with lindane or with DDT and lindane.  Food Cosmet Toxicol. 10: 789-95.

 

Dalsenter, P., Faqi, A., Webb, J., et al., 1997.  Reproductive toxicity and toxicokinetics of lindane in the male offspring of rats exposed during lactation.  Human and Experimental Toxicology 16(3): 146-53.

 

Dalsenter, P., Faqi, A., Webb, J., et al., 1996.  Reproductive toxicity and tissue concentration of lindane in adult male rats.  Human and Experimental Toxicology 15(5): 406-10.

 

Davis, J., Brownson, R., Garcia, R., 1992.  Family pesticide use in the home, garden, orchard, and yard.  Arch. Env. Contam. Toxicol.  22(3): 260-66.

 

Dikshith, T., Datta, K., Kushwah, H., et al., 1978.  Histopathological and biochemical changes in guinea pigs after repeated dermal exposure to benzene hexachloride.  Toxicology 10:55-66.

                     

Drug Topics, 1998.  Picky, Picky.  Seeking alternatives to a lousy situation.  August 3, 1998. 

 

EFED, 2001, Environmental Fate and Effects Division, RED Chapter for Lindane, USEPA, Office of Prevention, Pesticides and Toxic Substances, Washington, D.C. (Memorandum, August 1, 2001).

 

FDA, 2000.  Food and Drug Administration Total Diet Study.  Summary of residues found ordered by food market baskets 91-3 to 99-1 (26 baskets), September 2000.

 

Ginsburg, C., Lowry, W., Reisch, J., 1977.  Absorption of lindane in infants and children.  J. Pediatrics 91: 998-1000.

 

Handbook of Pediatric Environmental Health.  1999.  American Academy of Pediatrics, Committee on Environmental Health.  R. Etzel and S. Balk, Editors, Elk Grove Village, Il., page 194.

 

Hanig, J., Yoder, P., Krop, S., 1976. Convulsions in weanling rabbits after a single topical application of 1% lindane.  Toxicol. Appl. Pharm.  38: 463-69.

 

Heil, A., 2001.  Personal Communication with J. Schreiber.

 

Lahiri, P., Mandal, A., Sircar, S., et al., 1990.  Insecticides and impaired reproductive success: Studies on lindane toxication.  Impacts of Environment on Animals and Aquaculture, Eds. S. Manna and B. Jana, pages 291-296. 

 

Lindane. Org., 2001.  Background on the use of lindane to treat head lice and scabies.

 

Pages, N., di Blasi-Bouvet, S., Schlatter, J., et al., 2000.  Hormone disruptive effects of residual doses of lindane in male rats exposed at prenatal and postnatal periods.  Hun Exp Toxicol 19(8): 479.

 

Physicians Desk Reference, 2001.  Medical Economics Company, Inc., Montvale NJ.

 

Rawlings, N., Cook, S., Waldbillig, D., 1998.  Effects of the pesticides carbofuran, chlorpyrifos, dimethoate, lindane, trillate, trifluralin, 2,4-D, and pentachlorophenol on the metabolic endocrine and reproductive endocrine system in ewes.  J. Toxicol Environ Health 54(1): 21-36.

 

Rivera, S., Rosa, R., Martinez, E., et al., 1998.  Behavioral and monoaminergic changes after lindane exposure in developing rats.  Neurotoxicol and Teratology 20(2): 155-160.