Document qd3Rdr7bGDQgx6B1L1VGrnBbn

May 3, 1995 Page 27 PESTICIDE & TOXIC CHEMICAL NEWS "We have to first confirm these health effects, and then see if they fit into a. v ^r.xu," Goldman remarked. "After that, we can develop an appropriate response," she said, In the consent agreement, DowElanco said it would: -- assist EPA by using its best efforts to review files of its parent companies for any information concerning health and environmental effects incidents for pesticide producer registered under F1FRA, which the company obtained as a consequence of its 1989 formation; --waive its right to request ajudicial or administrative hearing on the matter, and -- pay the penalty within 30 days, or pay the total civil penalty originally proposed in the complaint, $1,635 million. (*SPTCN 2712,15 pages, $8) 2-VINYL-l^-DIOXOLANE EXPOSURE LINKED TO RABBIT DEATHS IN SECTION 8(e) REPORT Rabbits exposed to 1,3-dioxolane, 2-ethenyl, also known as 2-vinyl-1,3-dioxolanc, died after displaying a variety of neurotoxic symptoms, according to TSCA Section 8(e) submission #8EHQ0495-13021, said Degussa Coip. The test substance was used undiluted and applied at 6.61 mg/kg, 66.1 mg/kg and 208.6 mg/kg on male and female rabbits, according to the study. The results were intoxication characterized by hypokinesia, decrease in muscle tone, loss ofrighting reflexes and salivation, which appeared about two hours after treatment and lasted until death. According to the study, deaths occurred between five and 24 hours after treatment, with the LD50 dose for males and females calculated at 25.1 mg/kg. In TSCA 8(e) submission #8EHQ-95-13426, Cytec Industries reported the results of a guinea pig maximization study conducted with acrylamide, 50% aqueous, by Stockhausen Laboratory for Toxicology in Germany. The results indicated a sensitization rate of 85%, indicative of a positive sensitization reaction, the submission said. (85PTCN 2716,2 pages, SS) J)j^VINYL CHLORIDE CANCER RISK LINKED TO EARLY-LIFE EXPOSURE A new quantitative cancer assessment on lifetime exposures to vinyl chloride in animals suggests that the risk of cancer depends on the age at exposure, with higher risks attributed to exposure at younger ages, said Environmental Protection Agency's V. James Cogliano at a recent toxicology meeting. Speaking at the April 25 Conference on Risk Assessment Issues for Sensitive Human Populations at Wright-Pattersoa Air Force Base in Ohio, Cogliano said newborn animal exposure studies demonstrate that a brief exposure can induce unseen tumors and higher incidence of apparent tumors following long-term exposure later in life. BFG41871 BFG 01383 Page 28 May 3,1995 PESTICIDE & TOXIC CHEMICAL NEWS Cogliano, chief; Carcinogen Assessment Statistics and Epidemiology Branch, EPA's Office of Research and Development, said new quantitative approaches reflecting early-life sensitivity have been developed to supplement conventional approaches to estimating the increased cancer risk from inhaling vinyl chloride. Vinvl Chloride Studies Mav Have Superfund Implications These studies may have implications for Superfund risk assessments as EPA must decipher the risk of inhaling vinyl chloride from nearby dumps, he said, as well as estimating early risks for other . chemicals. Cogliano told attendees of the Ohio meeting that studies on early-life effects of vinyl chloride exposure, especially in a species other than rats, would help resolve how the sensitive period corresponds with humans. But he encouraged more studies in young animals to identify other carcinogens that affect sensitive stages of development 'i When asked whether other chemicals had been tested, Cogliano replied that vinyl chloride was the first tested and that he would not expea to see a dramatic result with every chemical. "We think it could happen with other chemicals, but we have no data yet" he added. University ofMississippi's Harihara Mehendale also focused on young animals -- specifically, why early postnatal development rats were resistant to a deadly combination of chlordecone (CD) + CCI4 at individually nontoxic doses. Mehendale found that young tats responded faster to tissue injury than adults, and were less susceptible to acute exposure since they were more efficient in stimulating tissue repair. Mehendale focused on liver injury occurring in postnatally developing and adult male rats and found that prompt and exacting stimulation of tissue repair permitted efficient recovery from injury for the younger rats. Mehendale said that perhaps kidneys and lungs should be examined as well. Past research has focused on qualitatively defining causal relationships, but the U.S. Army-sponsored conference focused on the need to better define sources and calculate the magnitude of quantitative estimates of risk to sensitive populations. While the meeting showed a convergence on different methods in variability issues, "early efforts are just that in showing the feasibility of different analyses," said Dale Hattis, a research associate professor at Clark University's Center for Technology, Environment and Development. According to Hattis, there is pressure to better characterize uncertainties to determine whether population subgroups are being adequately protected and whether policymakers are getting the biggest bang for their buck. "There is a need in the current environment to count the bodies," he added. Documents flagged with a 8" " can be ordered through Documenti Express by calling 202-544-1980. BFG 01384 BFG41872 May 3, 1995 Page 29 PESTICIDE & TOXIC CHEMICAL NEWS According to Hams, it is unlikely that the same factor of 10 rule is appropriate for all different kinds of noncancer risks and different kind of agents, despite the need for relatively straightforward and standardized treatment of variability in toxic risks. Sociodemogranhic factors Affect Susceptibility to Chemicals Ken Sexton of the University of Minnesota's School of Public Health noted how sociodemographic variables, such as class and race, can affect exposure-related and susceptibilityrelated attributes which, in turn, can lead to the well-documented disparities in health status among populations. "There has been a surprising lack ofresearch" in occupational and environmental studies on this issue, said Sexton, who helped launch EPA's National Human Exposure Assessment Survey, an interagency initiative to conduct exposure surveillance ofAmericans. 1 Sexton defined individuals and groups at potentially greater risk when they are exposed above a health-related benchmark, more susceptible to the effects of exposure, or both. Too much regulation also can render groups more susceptible to risk, Sexton said. Increasing regulation can affect socioeconomic status, in turn adversely affecting health, he said. The congressional debate on risk assessment is raising important questions, such as the impact of cumulative risk, comparative risk and total risk, and bringing together epidemiology and toxicology into "one sphere," he said. Multiple Chemical Sensitivity Syndrome Explored How multiple chemical sensitivity is defined will determine how many people are affected, said Claudia Miller, who for the past two years has been involved with Houston Veterans Affairs' Regional Referral Center for GulfWar veterans. Miller outlined an emerging theory on chemical sensitivity. The idea that it "may be a mechanism for disease posits that a broad spectrum of chronic illnesses, ranging from asthma and migraine to depression and chronic fatigue, may be the consequences ofenvironmental chemical exposures," she said. First, an initial exposure event interacts with a susceptible individual, causing loss of tolerance to everyday, low-level chemicals. Miller said, adding that substances then trigger symptoms that perpetuate the iiw*. Seventy-one percent of Gulf War veterans surveyed said they have chemical intolerances, Miller said. David Oberstreet, research associate professor, University ofNorth Carolina at Cbapel Hill, presented finding* on his research on Flinders Sensitive Line rats, which are selectively bred to be more sensitive to organophosphate diisopropylfluorophosphate. These rats showed similar symptoms to MCS humans, including depression and reduced activity and appetite, he said. BFG 01385 BFG41873 V hi I. * a.. & MO <0 ' 9 UJ .k Q aVcOoi 5tb3 fifi w O 00 tr 45> S C <r-> -UN 2d ' 3d 39;U-l 3EGN-ENU-ohFE-*CFL i `n --Lb uu ^55 > - s^Q<i^^.-8135 I Existing Chemicals r'.Zd/ ATSDR Chemicals Added to MTL FMX F.PA is adding 12 chemicals to the Master Testing List in response to a request for testing by the Agency for Toxic Substances and Disease Registry (ATSDR). The chemicals are: benzene, lieryllium, chloroethane, chromium, cyanide, di (2crhythcxyl) phthaiate, mercury, methylene chloride, tecrachloroethyienc, toluene, trichloroethyl ene. and vinyl chloride. ATSDR is required to identify the hazardous substances most commonly found at Superfund sites, prepare toxicological pro files, and identify priority data needs for those substances. ATSDR is also required to initiate a research program to meet the oriority data needs it identifies. In October 1992, ATSDR requested F.PA to use its authorities under TSCA and FIFRA to fill some of the data needs it identified on 37 chemicals. In its response to ATSDR, EPA agreed to develop a test rule under section 4 of TSCA to obtain data on 12 of the chemi cals, but noted that a TSCA test rule would not be an appropriate mechanism for obtaining data on the other 25 chemicals. Before initiating rulemaking, EPA is inviting manufacturers of the 12 chemicals listed in the following table to submit testing plans and enter into consent agreements for testing. EPA intends to issue a test rule in late 1994 for any of the 12 substances which are not covered by a consent order or a voluntary esting agreement. Chemical Mercury Vinyl chloride Benzene Tichloroethylene Chromium Tetrachloroethyiene Cyanide Beryllium Toluene Methylene chloride Chloroethane I Testing to be Proposed 1 Immunotoxicity oral Chronic oral 1 Reproductive oral 1 Acute oral : Reproductive inhalation Developmental inhalation 1 , Subchronic oral Neurotoxicity oral -i Subchronic oral Neurotoxicity oral Acute oral Reproductive oral immunotoxicity oral Reproductive inhalation Neurotoxicity inhalation immunotoxicity inhalation Developmental inhalation Acute inhalation Subchronic inhalation Developmental inhalation Fate In soil Acute inhalation Subchronic inhalation with reproductive and pulmonary pathology Developmental inhalation ! mmuotoxicity inhalation B'oavailability Fate in air Comparative Pharmacokinetics immunotoxicity oral Subchronic oral immunotoxicity oral Developmental oral Neurotoxicity oral Comparative Pharmacokinetics immunotoxicity oral BFG41875 12 CHEMICALS IN PROGRESS BFG 01387 Ii *S<M. \ aJ oO T\aj^Ac^, OUs>w i9W O.S. 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