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Initiation of Risk Assessments for Chemicals in Drinking Water (2005)

A. Requirements

The Calderon-Sher California Safe Drinking Water Act of 1996 requires the Office of Environmental Health Hazard Assessment (OEHHA) to post notices on its Web site of water contaminants for which it is initiating work, pursuant to development of a public health goal (PHG) for the chemical in drinking water. The law also describes the intent and general context of the PHGs. PHGs are concentrations of chemicals in drinking water that are not anticipated to produce adverse health effects following long-term exposures. These goals are non-regulatory in nature but are to be used as the health basis to update the state's primary drinking water standards (maximum contaminant levels, or MCLs) established by the California Department of Health Services (DHS) for chemicals subject to regulation.

The act requires PHGs to be developed for the approximately 85 chemicals for which state MCLs are presently available, and review and update of the risk assessments at least every five years. Other chemicals may be added to the list by legislative or interdepartmental request. Opportunities for public comment and peer review are provided.

B. Implementation
OEHHA has published 71 PHGs as of June 2005, although one of these evaluations, that for total chromium, has been rescinded. The technical support documents for the published PHGs are posted on the OEHHA Web site.

PHGs for all the other chemicals that have state MCLs are currently in preparation. Drafts for public comment on seven of these chemicals are posted on the OEHHA Web site, and are currently under peer review by the University of California. PHGs for the remaining chemicals with existing MCLs should be released for public review this year. A 45-day public comment period will be provided after posting, followed by a public workshop. The overall process includes scientific peer review arranged through the University of California, allotting time for revisions, further public comment, and preparing responses to comments.

OEHHA has prepared memoranda to DHS on the MCLs for “Gross alpha” and “Gross beta.” These MCLs are screening levels for radionuclides in drinking water, rather than regulatory standards for specific chemical entities. The memoranda discuss the relative risk from exposure to radioactivity derived from the various isotopes in the above categories, and are also posted on our Web site.

The PHG re-evaluation has been completed for thallium, inorganic mercury, and lindane. OEHHA concluded that no new information was available on these chemicals that would require significant changes to the PHG document. The re-reviews of several other chemicals which were announced in July 2004 are nearing completion.

Evaluation is now being initiated for another chemical for which a new MCL has been requested by the Department of Health Services, which therefore required preparation of a PHG. Re-review of earlier PHGs is being initiated for two additional chemicals. Comments are requested on each of these chemicals.

C. PHGs soon to be released for public review (initiation announced July 2001)

Draft documents for the following chemicals are nearing completion, and are planned for release for public review as soon as possible:

  • Hexavalent chromium
  • Dioxin
  • Molinate
  • Selenium
  • Styrene
  • Trihalomethanes

D. Initiation of risk assessments

Risk assessment is being initiated for the following chemical:

  • 1,2,3-Trichloropropane

1,2,3-Trichloropropane is being evaluated at the request of DHS, because of a pattern of increasing detections in California groundwater.
In addition, reviews are being updated for chemicals for which PHGs were prepared in the first years of our program, prioritized on the basis of availability of new data and significance as a drinking water contaminant. The following chemicals have been newly assigned for re-review:

  • 2,4-Dichlorophenoxyacetic acid
  • 1,2-Dichloroethane

A brief description of these chemicals is provided below. This announcement solicits the submission of pertinent information on these contaminants that could assist our office in preparing or updating the risk assessment and deriving a PHG.

Information submitted to OEHHA in response to this request should not be proprietary in nature, because all information submitted is a matter of public record. Information should be submitted by August 1, 2005 to:

PHG Project
Pesticide and Environmental Toxicology Section
Office of Environmental Health Hazard Assessment
P.O. Box 4010
Sacramento, California 95812-4010

All data submitted will be considered in the development of the PHG for these chemicals. The draft documents will be available for discussion in a public workshop and public comment will be solicited as described above in Section B. The final risk assessments will be utilized by DHS in potential revisions to the MCLs for the chemical in drinking water, as described in more detail on the DHS Web site.

E. Descriptions of chemicals or substances for review initiation:

1,2,3-TRICHLOROPROPANE

1,2,3-Trichloropropane (TCP) is a chlorinated alkane that has been used as a cleaning and degreasing agent and as a chemical intermediate, and is classed as a high production volume chemical. It also occurs as a byproduct in the production of other chlorinated compounds such as epichlorohydrin and has been detected in groundwater, especially in association with waste sites (ATSDR, 1992; CDHS, 2005). Synonyms are allyl trichlorhydride and trichlorohydrin. The California Department of Health Services established a notification level of 0.005 mg/L for TCP in 1999 based on it causing cancer in laboratory animals (CDHS, 2005). No MCL has been promulgated for this chemical.

TCP is rapidly absorbed from the gastrointestinal tract, metabolized and excreted. TCP metabolites have been detected bound to DNA, RNA and proteins in rats. TCP was positive for mutagenic activity in both bacterial and mammalian cells in the presence of metabolic activation (IARC, 1995).

The administration of TCP by gavage yielded tumors in a number of tissues in male and female rats and mice at low doses (NTP, 1993). IARC classified TCP as a probable human carcinogen (Group 2A based on sufficient evidence of carcinogenicity in experimental animals and inadequate evidence in humans (IARC, 1995). The National Toxicity Program (NTP) classified TCP as reasonably anticipated to be a human carcinogen based on sufficient evidence of malignant tumor formation at multiple sites in multiple species in experimental animals (NTP, 2004), and it was listed as a carcinogen under Proposition 65 in 1999 (OEHHA, 2005).
Other effects observed in experimental animals include inflammation, degeneration and other histopathological changes in nasal cavity, lung, liver, and kidney; decreased body weight gains; alterations in serum enzymes associated with hepatic and renal toxicity; and decreased red cell mass. Reproductive toxicity has also been observed in laboratory animals.

The review of this chemical should give special consideration to exposure of infants and children because of its potent carcinogenicity and its detection in California drinking water.

Selected References

CDHS (2005). 1,2,3-Trichloropropane: notification level and monitoring results. California Department of Health Services.

IARC (1995). 1,2,3-Trichloropropane. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Volume 63. International Agency for Research on Cancer, Lyon, France, pp. 223–244.

Johannsen F, Levinskas G, Rusch G, Terrill J, Schroeder R (1988). Evaluation of the subchronic and reproductive effects of a series of chlorinated propanes in the rat. I. Toxicity of 1,2,3-trichloropropane. J Toxicol Environ Health 25:299–315.

La DK, Lilly PD, Anderegg RJ, Swenberg JA (1995). DNA adduct formation in B6C3F1 mice and Fischer-344 rats exposed to 1,2,3-trichloropropane. Carcinogenesis 16:1419–1424.

La DK, Schoonhoven R, Ito N, Swenberg JA (1996). The effects of exposure route on DNA adduct formation and cellular proliferation by 1,2,3-trichloropropane. Toxicol Appl Pharmacol 140(1):108–114.

Mahmood NA, Overstreet D, Burka LT (1991). Comparative disposition and metabolism of 1,2,3-trichloropropane in rats and mice. Drug Metab Dispos 19:411–418.

Mirsalis J, Tyson CK, Beck J, Loh F, Steinmetz K, Contreras C, Austere L, Martin S, Spalding J (1983). Induction of unscheduled DNA synthesis (UDS) in hepatocytes following in vitro and in vivo treatment. Environ Mutagen 5:482.

NTP (1993). Toxicology and carcinogenesis studies of 1,2,3-trichloropropane (CAS No. 96-18-4) in F344/N rats and B6C3F1 mice (gavage studies). U.S. Department of Health and Human Services, National Toxicology Program, Research Triangle Park, NC. pp. 1–345 (NTP TR 384, December 1993).

NTP (2004). 11th report on carcinogens. National Toxicology Program, U.S. Department of Health and Human Services, Public Health Service. Accessed at: http://ehp.niehs.nih.gov.

OEHHA (2005). Chemicals known to the state to cause cancer or reproductive toxicity. Office of Environmental Health Hazard Assessment, Sacramento, CA.

Villeneuve D, Chu I, Secours VE, Cote MG, Plaa GL, Valli VE (1985). Results of a 90-day toxicity study on 1,2,3- and 1,1,2-trichloropropane administered via the drinking water. Science Tot Environ 47:421–426.

Volp RF, Sipes IG, Falcoz C, Carter DE, Gross JF (1984). Disposition of 1,2,3-trichloropropane in the Fischer 344 rat: Conventional and physiological pharmacokinetics. Toxicol Appl Pharmacol 75:8–17.

World Health Organization (2003). 1,2,3-Trichloropropane, Concise International Chemical Assessment Document 56. Accessed at: http://www.who.int/ipcs/
publications/cicad/en/cicad56.pdf.

2,4-DICHLOROPHENOXYACETIC ACID (2,4-D)

2,4-Dichlorophenoxyacetic acid (2,4 D) is an alkylchlorophenoxy herbicide commonly used to control a variety of broad-leaf weeds (while sparing grasses) in agricultural, nonagricultural (e.g. residential turf, right-of way), forestry, and aquatic sites. It has been widely used in consumer products for weed control on lawns, formulated as an ester, an aqueous solution of the amine salt, or as a wettable powder.
For this review, the medical literature was searched, concentrating primarily on articles published since the first review, published in 1997. Those articles that appeared to have the potential to affect the regulatory level were retrieved. Among these, the most significant animal studies were the acute, subchronic and chronic toxicity studies (Charles et al., 1996a,b; Paulino et al., 1996) identified in the previous review. The report on chronic tests by Charles et al. (1996a) provides cancer bioassays in rats and mice. These studies were conducted by Dow Chemical Company at the request of U.S. EPA to investigate doses of 2,4-D higher than those in the previous studies (Dow, 1983).

A major factor in the present review is whether the health of sensitive subpopulations is being adequately protected, considering both new data and the strengthened emphasis on protection of infants and children required under AB2342 (2004). There is some concern about the potential for adverse effects on neurological development in infants and children, combined with the extra exposure potential of infants and children from the use of 2,4-D on lawns. Comments on these aspects are particularly welcomed.

Selected References
Atanassov K (1992). Effect of the herbicide Schpritshormit (Na salt of 2,4-D chlorophenoxyacetic acid) on the karotype of the domesticated rabbit. Animal Sci 29:54-61.

Beasley VR, Arnold EK, Lovell RA, Parker AJ (1991). 2,4-D toxicosis. I: A pilot study of 2,4-dichlorophenoxyacetic acid and dicamba- induced myotonia in experimental dogs. Vet Hum Toxicol 33:435-440.

Bortolozzi A, Ferri A, Garcia G, Evangelista de Duffard AM (1995). Developmental neurotoxicity of the herbicide 2,4-dichlorophenoxyacetic acid. Neurotoxicology 16 (4):764.

Charles JM, Bond DM, Jeffries TK, Yano BL, Stott WT, Johnson DA, Cunny HC, Wilson RD, Bus JS (1996a). Chronic dietary toxicity/oncogenicity studies on 2,4-dichlorophenoxyacetic acid in rodents. Fund App Toxicol 33:166-172.

Charles JM, Cunny HC, Wilson RD, Bus JS (1996b). Comparative subchronic studies on 2,4-dichlorophenoxyacetic acid, amine and ester in rats. Fund Appl Toxicol 33:161-165.

Charles JM, Dalgard DW, Cunny HC, Wilson, RD, Bus, JS (1996c). Comparative subchronic and chronic dietary toxicity studies on 2,4-dichlorophenoxyacetic acid, amine and ester in the dog. Fund Appl Toxicol 29:78-85.

DPR (2004). Summary of Toxicology Data, 2,4-D. Department of Pesticide Regulation, California Environmental Protection Agency, Sacramento, CA. Accessed at: www.cdpr.ca.gov/docs/toxsums/pdfs/636.pdf. Last updated 2/24/2000.

Duffard R., Garcia G, Rosso S, Bortolozzi A, Madariaga M, di Paolo O, Evangelista de Duffard AM, et al. (1996). Central nervous system myelin deficit in rats exposed to 2,4-dichlorophenoxyacetic acid throughout lactation. Neurotoxicol Teratol 18:691-696.

Hoar SK, Blair A, Holmes FF, et al. (1986). Agricultural herbicide use and risk of lymphoma and soft tissue sarcoma. JAMA 256:1141-1147.

HSDB (1996). 2,4-D. Hazardous Substances Data Bank, Micromedex, Inc. pp. 94-97.
IRIS (2004). 2,4-Dichlorophenoxyacetic acid (2,4-D), last updated 05/05/1988. Integrated Risk Information System, U.S. Environmental Protection Agency, Washington, DC. Accessed at: http://www.epa.gov/iris.

Kelly SJ, Guidotti TL (1989). Phenoxyacetic acid herbicides and chlorophenols and the etiology of lymphoma and soft-tissue neoplasms. Publ Health Rev 1989/90, 17:1-37.

Knopp D, Sciller F (1992). Oral and dermal application of 2,4-dichlorophenoxyacetic acid sodium and dimethylamine salts to male rats: Investigation on absorption and excretion as well as induction of hepatic mixed-function oxidase activities. Arch Toxicol 66 (3):170-174.

Leiss JK, Savitz DA (1995). Home pesticide use and childhood cancer: A case-control study. Am J Publ Health 85(2):249-252.
Liu RC, Hahn C, Hurtt ME (1996). The direct effect of hepatic peroxisome proliferators on rat Leydig cell function in vitro. Fundam Appl Toxicol 30:102-108.

Moody RP, et al. (1990). Dermal absorption of the phenoxy herbicides 2,4-D, 2,4-D amine, 2,4-D isooctyl, and 2,4-T in rabbits, rats, rhesus monkey, and humans: A cross-species comparison. J Toxicol Environ Health 29:237-245. Also see Moody RP, et al. Errata. J Toxicol Environ Health 32(1):107, 1991.

Munro IC, Carlo GL, Orr JC, Sund KG, Wilson RM, Kennepohl E, Lynch BS, Jablinske M, Lee NL (1992). A comprehensive, integrated review and evaluation of the scientific evidence relating to the safety of the herbicide 2,4-D. J Am Coll Toxicol 11:559-664.

Paulino CA, Guerra JL, Oliveira GH, Palermo-Neto J (1996). Acute, subchronic and chronic 2,4-dichlorophenoxyacetic acid (2,4-D) intoxication in rats. Vet Hum Toxicol 38(5):348-352.

Pavlica M, Papes D, Nagy N (1991). 2,4-Dichlorophenoxyacetic acid causes chromatin and chromosome abnormalities in plant cells and mutations in cultured mammalian cells. Mut Res 263:77-81.

Pelletier O, et al. (1989). Disposition of 2,4-dichlorophenoxyacetic acid dimethylamine salt by Fisher 344 rats dosed orally and dermally. J Toxicol Environ Health 28:221-234.

Pilinskaya MA (1974). Cytogenetic effect of the herbicide 2,4-D on human and animal chromosomes. Tsitol Genet 8:202-206.

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

Seiler JP (1979). Phenoxyacids as inhibitors of testicular DNA synthesis in male mice. Bull Environ Contam Toxicol 21:89-92.

Turkula TE, Jaha SM (1985). Increased rates of sister chromatid exchanges induced by the herbicide 2,4-D. J Heredity 76:213-214.

Turkula TE, Jahal SM (1987). Induced clastogenicity in white rats by the herbicide 2,4-D. Cytologia 52:181-275.

U.S. EPA (1999). Transport of lawn-applied 2,4-D from turf to home: Assessing the relative importance of transport mechanisms and exposure pathways. U.S. Environmental Protection Agency, Washington, D.C. EPA/600/R-99/040.

U.S. EPA (2004). Memorandum. 2,4-D. HED’s Human Health Risk Assessment for the Reregistration Eligibility Decision (RED) Revised to Reflect Error-only Comments from Registrants. U.S. Environmental Protection Agency, Washington, D.C.

WHO (1984). Environmental Health Criteria 29: 2,4-Dichlorophenoxyacetic Acid (2,4-D). World Health Organization, Geneva, p. 99.

Zahm SH, Weisenburger DD, Babbitt PA, et al. (1990). A case-control study of non-Hodgkin’s lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska. Epidemiology 1:349-356.

1,2-DICHLOROETHANE (1,2-DCA)

1,2-Dichloroethane (1,2-DCA), also known as ethylene dichloride, is primarily used in the production of vinyl chloride, 1,1,1-trichloroethane, trichloroethylene, perchloroethylene, and other industrial chemicals. It is also used as a solvent in cleaning and degreasing industries, a grain fumigant, and is a constituent in varnish removers and scouring compounds. The PHG, published in 1999, is based on carcinogenicity, specifically, hemangiosarcomas in male rats from a chronic oral bioassay conducted by the National Cancer Institute in 1978. 1,2-DCA has been identified by U.S. EPA as a probable human carcinogen (B2) and is listed under Proposition 65 as a chemical known to the state to cause cancer. The California Department of Health Services reports that between 1984 and 2001, 1,2-DCA was detected in 123/15,350 water samples analyzed for this chemical. Between 1984 and 2000, the MCL was exceeded 119 times; between 1994 and mid-2002, it was exceeded 59 times. 1,2-DCA is one of the most commonly exceeded organic MCLs in California.

Little new toxicological data appear to be available on 1,2-DCA. Animal studies show that 1,2-DCA ingestion can cause mild-to-moderate transient lung injury; ethanol exposure can increase the hepatotoxic effects of 1,2-DCA; and oral exposure to 1,2-DCA can result in renal toxicity. The mouse bone marrow genotoxicity assay is weakly sensitive to 1,2-DCA exposure, but sister chromatid exchange frequencies were significantly increased in workers exposed to a low concentration of 1,2-DCA in air. The authors express concern about the genotoxicity potential of 1,2-DCA.

Animal reproductive studies do not suggest a potential for birth defects, although there is an epidemiology study suggesting an association of cardiac defects with exposure to 1,2-DCA in drinking water. The potential effects of 1,2-DCA in infants, children, and other sensitive populations need further evaluation. The risk assessment on this significant drinking water pollutant should be given a high priority to ensure that the PHG remains appropriate for protection of public health, including sensitive subpopulations.

Selected References

Bove FJ, Fulcomer MC, Klotz JB, Esmart J, Dufficy EM, Savrin JE (1995). Public drinking water contamination and birth outcomes. Am J Epidemiol 141(9):850-62..

Bowler RM, Gysens S, Hartney C (2003). Neuropsychological effects of ethylene dichloride exposure. Neurotoxicology 24(4-5):553-62.

Cheng TJ, Chou PY, Huang ML, Du CL, Wong RH, Chen PC (2000). Increased lymphocyte sister chromatid exchange frequency in workers with exposure to low level of ethylene dichloride. Mutat Res 470(2):109-14.

Cottalasso D, Domenicotti C, Traverso N, Pronzato M, Nanni G (2002). Influence of chronic ethanol consumption on toxic effects of 1,2-dichloroethane: glycolipoprotein retention and impairment of dolichol concentration in rat liver microsomes and Golgi apparatus. Toxicology 178(3):229-240.

Crebelli R, Carere A, Leopardi P, Conti L, Fassio F, Raiteri F, Barone D, Ciliutti P, Cinelli S, Vericat JA (1999). Evaluation of 10 aliphatic halogenated hydrocarbons in the mouse bone marrow micronucleus test. Mutagenesis 14(2):207-15.
IARC (1999). 1,2-Dichloroethane. International Agency for Research on Cancer. Monogr Eval Carcinog Risks Hum71 Pt 2:501-29.
Morel G, Ban M, Hettich D, Huguet N (1999). Role of SAM-dependent thiol methylation in the renal toxicity of several solvents in mice. J Appl Toxicol 19(1):47-54.

Morris J (2000). Small-time polluter, big-time problems. Did Keil Chemical cause childhood cancer? US News World Rep Feb 28; 128(8):57-8.
National Toxicology Program (2002). 1,2-Dichloroethane (ethylene dichloride). Rep Carcinog 10:88-90.

Salovsky P, Shopova V, Dancheva V, Yordanov Y, Marinov E (2002). Early pneumotoxic effects after oral administration of 1,2-dichloroethane. J Occup Environ Med 44(5):475-80.

Toyo'oka T, Tanabe J, Jinno H (2001). Determination of rat hepatocellular glutathione by reversed-phase liquid chromatography with fluorescence detection and cytotoxicity evaluation of environmental pollutants based on the concentration change. Biomed Chromatogr 15(4):240-7.