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TETRAHYDROFURAN
CASRN: 109999

Update: May 2014

Current Massachusetts Regulatory Limit
ORSGL = 0.6 mg/L

Federal Regulatory Limit
The U.S. EPA has not published an MCL for tetrahydrofuran.

Basis for Criteria
The ORSGL is based on an EPA IRIS RfD developed based on the two-generation reproductive study by Hellwig et al., (2002) presented below. The ORSGL assumes that a 70 kg adult ingests 2 L/day of water. A relative source contribution factor of 20% and a 10-fold uncertainty factor to account for potential carcinogenicity are incorporated into the final value.

RfD: 0.9 mg/kg/day (US EPA, 2012)
UF: 1000 (10 = interspecies; 10 = intraspecies; 10 = database variability)
MF: 1

Critical Effects
Tetrahydrofuran may cause irritation to the gastrointestinal tract with symptoms including nausea, vomiting and diarrhea, sore throat and abdominal pain. Liver or kidney injury may also occur.

In a 2-generation reproductive study in which rats were exposed to tetrahydrofuran in drinking water, dose-related decreases in body weight gain were consistently observed in both F1 and F2 generations pups and were accompanied by other developmental delays (i.e., delayed eye opening and increased incidence of sloped incisors) in the absence of significant maternal body weight changes or overt signs of toxicity (Hellwig et al., 2002). This study was used as the basis for the ORSGL. A benchmark dose [1] of 928 mg/kg/day identified by IRIS is the basis of the ingestion RfD as described above.

Cancer Assessment: In a two-year inhalation study, the National Toxicology Program (NTP, 1998) reported an increased incidence of renal tubule adenomas and carcinomas (statistically significant exposure-response trend) in male F344/N rats and an increased incidence of hepatocellular adenomas and carcinomas in female B6C3F1 mice (statistically significant trend). No evidence of carcinogenicity was observed in female rats or male mice. No other treatment-related increases in tumor incidence were observed. NTP concluded that the data provided some evidence of carcinogenicity in male rats and clear evidence of carcinogenicity in female mice. Based on this information and a lack of information via the oral or dermal routes to suggest that absorption does not occur via these routes, the U.S, EPA assumes that an internal dose of tetrahydrofuran will be achieved regardless of the route of exposure and thus designates tetrahydrofuran as having "suggestive evidence of carcinogenic potential".

Class
Organic

Analytical Information
PQL
: See method.

Analytical Methods
U.S. EPA Method 524.2

PQLs and analytical methods may have been updated since this guidance value was last revised. Updated analytical methods for drinking water and their associated PQLs may be found at http://www.epa.gov/safewater/methods/methods.html.

Other Regulatory Data
Any Health Advisories, Reference Doses (RfDs), cancer assessments or Cancer Potency Factors (CPFs) referenced in this document pertain to the derivation of the current guidance value. Updated information may be obtained from the following sources:

Health Advisories - The U.S. EPA provides guidance for shorter-term exposures for chemicals based on their non-cancer effects. Current health advisories may be more current than those used to derive MCLs and may be found at http://www.epa.gov/safewater/methods/methods.html.

RfDs, cancer assessments and CPFs - For specific information pertaining to derivation of drinking water criteria, consult the Federal Register notice that announces the availability of the most current guidance for that chemical. In addition, information on other current RfDs and CPFs as well as cancer assessments for specific chemicals may be found in the U.S. EPA Integrated Risk Information System (IRIS) at http://www.epa.gov/iris/. Please note that the information in IRIS may differ from that used in the derivation process as published in the Federal Register notice.

References

Chhabra, R.S., Elwell, M.R., Chou, B., Miller, R.A., and Renne, R.A. (1990).  Subchronic toxicity of tetrahydrofuran vapors in rats and mice. Fund. Appl. Toxicol. 14: 338-345.

Hellwig, J; Gembardt, C; Jasti, S. (2002) Tetrahydrofuran: two-generation reproduction toxicity in Wistar rats by continuous administration in the drinking water. Food Chem Toxicol 40(10):1515–1523.

Komsta, E., Chu, I., Secours, V.E., Valli, V.E. and Villeneuve, D.C. 1988. Results of a Short-Term Toxicity Study for Three Organic Chemicals Found in Niagara River Drinking Water. Bull. Environ. Contam. Toxicol. 41:515-522.

NTP (National Toxicology Program). June 1998. NTP Technical Report on the Toxicology and Carcinogenesis Studies of Tetrahydrofuran (CAS No. 109-99-9) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). TR-475. NIH Publication No. 98-3965. Public Health Service. National Institutes of Health (NIH).

U.S. EPA (U.S. Environmental Protection Agency). 2012. Integrated Risk Information System (IRIS). Washington, D.C. http://cfpub.epa.gov/ncea/iris/index.cfm (date accessed: May 2012).

 

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[1] The benchmark dose corresponds to the 95% lower confidence limit on the maximum likelihood estimate of the dose corresponding to a one standard deviation change from the control mean.  A one standard deviation change corresponds to 10% of an exposed population having larger decreases in body weight gain than the lowest 1% of the control group when the data follow a normal distribution.