Inert Ingredients of Pesticide Products

LIST 2.  POTENTIALLY TOXIC INERTS/HIGH PRIORITY FOR TESTING

    The changes made and the reasons for the changes are explained below.

Additions to List -1

    Di-(2-ethylhexyl)adipate and methyl-formamide (DMF) were moved to List 1 from Lists 3 and 2 respectively.  Based on a National Toxicology Program bioassay, positive results for oncogenicity were indicated for di-(2-ethyl-hexyl)adipate: This chemical caused increased incidences of hepatocellular carcinomas in female mice, and thus meets one of the criteria for categorization as a List 1 inert.

    For dimethylformamide (DMF), hepatotoxicity has been reported at very low doses in animal studies and it is commonly observed in case reports of industrial exposure. Developmental toxicity has also been reported to occur in animal studies in the literature. In addition, recent reports of clusters of testicular cancer associated with human exposure to DMF have added to the weight of evidence which supports upgrading this compound from List 2 to List 1.

Additions to List 2

    Based on data available at the time of the April 27, 1987, FR Notice, monochlorobenzene was determined to be an oncogen as well as an ecotoxin. For these reasons, it was placed on List 1. The EPA Science Advisory Board has reviewed the oncogenicity data on monochlorobenzene and concluded that it is a class D oncogen, i.e., not classifiable. EPA scientists have reevaluated the ecotoxicity data and concluded that monochlorobenzene does not meet List 1 ecotoxicity triggers. Because of these determinations, monochlorobenzene is being moved from List 1 to List 2 and is now considered as a high priority for testing.

    Methyl ethyl ketoxime has been moved from List 3 to List 2 because of its close structural relationship to acetoxime, which has been reported as being carcinogenic in preliminary tests and is also positive in a mouse lymphoma test. Methyl ethyl ketoxime has been proposed for testing under section 4 of the Toxic Substances Control Act.

Additions to Lists 3 and 4

    To accommodate revision of the lists, EPA has decided to subdivide List 4 into two parts. The previous list 4, representing inerts generally recorded as safe, has become List 4A, and a new List 4B has been created. List 4B is composed of inerts for which EPA has sufficient information to reasonably conclude that the current use pattens in pesticide products will not adversely affect public health and the environment. List 4B inerts in formulations proposed for new use pattems which cause signifcant increases in exposure will receive further scrutiny.

    Two inerts, gammabutyrolactone and dioctyl sodium sulfosuccinate (DSS), are being removed from List 2 because EPA now has a complete human health effects data base indicating that they do not meet the criteria for List 1 and that their current use in pesticides should not adversely affect human health.

    The placement of gammabutyrolactone on List 2 was based on structural analogy to the known oncogen, betabutyrolactone. Further review indicates this analogy is inappropriate. In addition, a review of toxicity data for gammabutyrolactone, including acute and subchronic data, developmental toxicy, mutagenicity, and oncogenicity indicates a low order of toxicity. Thus EPA has decided to remove gammabutyrolactone from List 2 and add it to List 4B because current use pattems pose minimal risk for human health. Because gammabutyrolactone has not been adequately tested for ecotoxicity, however, it is being placed on List 3 for these effects. EPA decided to list the inert on two lists to reflect the different degree of knowledge the Agency has about the inert's various effects. EPA considered it appropriate to place the inert on List 4B because it has sufficient information about human health effects, and to also place it on List 3 to reflect inadequate information concerning the ecotoxicity of this inert.

    DSS was placed on List 2 because of developmental and reproductive toxicity concerns as well as ecotoxicity concern for surfactants. Data have now been reviewed for these effects, and indicate a low order of toxicity. Thus, DSS is added to List 4B for nonadverse effects on human health. Because of limited ecotoxicity testing, however, DSS remains on List 3 (unknown toxicity) for these effects.

Deletions From All Lists

    Further investigation of ethylene thiourea, carbon disulfide, and 1,1-dimethylhydrazine (UDMH, the impurity in Alar, which is in Special Review), has revealed that these are only impurities, not intentionally added inerts. Furthermore, betabutyrolactone, benzene, dichlorvos, 1, 2-dimethylhydrazine, pentachlorophenol and sodium pentachlorophenate, dinitro-o-cresol, dinitrophenol, ethyl methyl phenylglycidate, formaldehyde and paraformaldehyde, hexachlorophene, mercury oleate, 2-nitropropane, 1,2-dichloropropane, and thiourea are not now used as inerts in any pesticide products. Therefore, these chemicals have been removed from all lists of inert ingredients and are not currently cleared for use as inerts in any pesticide product. Thus, in the event a registrant or applicant purposes to include one of these chemicals as an inert ingredient in a pesticide product, EPA will consider the chemical a new inert.

    Impurities in registered products are contaminants from the manufacturing process for the active ingredient, rather than intentionally added inert ingredients. The presence and toxicity of impurities is routinely evaluated during the normal Agency review processes. Impurities are identified in the product chemistry review, and would probably have been presented as part of the test material, during testing considered for support of the registration. Thus, it is not appropriate to subject impurities to the Inerts Strategy.

    As discuss in the April 22, 1987 Notice, registrants with products containing List 1 inert ingredients must amend their product registrations by adding the following statement to the label:

This product contains the toxic inert ingredient (name of inert).

    The wording should be placed in close proximity to the ingredients statement in a type size comparable to other front panel text. Since dimethylformamide and di-(2-ethylhexyl) adipate have been added to List 1, registrants of products containing these inerts are required to submit applications to amend their product labels not later than May 22. 1990. Products containing one or more of these inert ingredients released for shipment after May 22, 1991 must have the amended label in place.

    Registrants of products containing dimethylformamide have already received a Data Call-In. All registrants have either voluntarily cancelled or committed to reformulate the product. Most reformulations have been received: a few time extensions were granted to allow for necessary testing of the reformulated product.

    A Data Call-In for di-(2-ethylhexyl) adipate will be issued at the same time as for diethylhexylpthalate since the uses are similar and we expect to find them in the same types of products. Data Call-ins for other original List 1 inerts were mailed in March 1989.

Stocks of Old Formulations

    Registrants are encouraged to substitute or remove any List 1 or List 2 inert ingredient from their products by submiting a new Confidential Statement of Formula as a proposed amendment to the registration. The April 22, 1987 Policy statement did not address provisions governing the sale of stock of old formulations. If a registrant reformulates its product to replace a List 1 or List 2 inert ingredient with a less toxic inert, EPA has determined that some limit on continued sale of stock of the old formulation is appropriate.

    Once a registrant submits the revised formulation, registrants may manufacture only the old formulation, properly labeled as containing a toxic inert as described above, until EPA accepts the new formulation. Stocks of the old formulation, bearing the required labeling, may be released for shipment by the registrant for a period not to exceed twelve months from the date EPA accepts the new formulation. Products already in channels of trade (retailers, distributors, dealers) are not subject to this limitation.

Dated: October 10, 1989.
Douglas D. Campt,
Director, Office of Pesticide Programs.
(FR Doc. 89-27213 Filed 11-21- 89: 8:45am)
BILLING CODE 6560-60-M