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CERHR Monograph: Potential Human ��������������������������� �������������������������������������������� ����������������������������������� ��������������������� NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Propylene Glycol March 2004 NIH Publication No. 04-4482 Table of Contents Preface .............................................................................................................................................v Introduction .................................................................................................................................... vi NTP Brief on Propylene Glycol .......................................................................................................1 References ........................................................................................................................................4 Appendix I. NTP-CERHR Ethylene Glycol / Propylene Glycol Expert Panel Preface ..............................................................................................................................I-1 Expert Panel ......................................................................................................................I-2 Appendix II. Expert Panel Report on Propylene Glycol ............................................................. II-i Table of Contents ........................................................................................................... II-iii Abbreviations ...................................................................................................................II-v List of Tables ................................................................................................................ II-viii List of Figures ................................................................................................................ II-ix Preface .............................................................................................................................II-x Chemistry, Usage and Exposure ......................................................................................II-1 General Toxicological and Biological Effects ................................................................II-11 Developmental Toxicity Data .........................................................................................II-50 Reproductive Toxicity Data ............................................................................................II-69 Summaries, Conclusions and Critical Data Needs ........................................................II-74 References ......................................................................................................................II-77 Appendix III. Public Comments on Expert Panel Report on Propylene Glycol American Chemistry Council ........................................................................................ III-1 iii [This page intentionally left blank] iv Preface The National Toxicology Program (NTP) the chemical is hazardous to humans. The panel established the NTP Center for the Evaluation also identifies areas of uncertainty and where of Risks to Human Reproduction (CERHR) additional data are needed. The CERHR expert in 1998. The CERHR is a publicly accessible panels use explicit guidelines to evaluate the resource for information about adverse repro- scientific literature and prepare the expert panel ductive and/or developmental health effects reports. Expert panel reports are made public associated with exposure to environmental and comments are solicited. and/or occupational chemicals. The CERHR is located at the National Institute of Environmen- Next, the CERHR prepares the NTP-CERHR tal Health Sciences (NIEHS) of the National monograph. The NTP-CERHR monograph Institutes of Health and Dr. Michael Shelby is includes the NTP brief on the chemical eval- the director.1 uated, the expert panel report, and all public comments. The goal of the NTP brief is to pro- The CERHR broadly solicits nominations of vide the public, as well as government health, chemicals for evaluation from the public and regulatory, and research agencies, with the private sectors. The CERHR follows a formal NTP’s interpretation of the potential for the process for review and evaluation of nominated chemical to adversely affect human repro- chemicals that includes multiple opportunities ductive health or children’s health. The NTP- for public comment. Chemicals are selected for CERHR monograph is made publicly available evaluation based upon several factors including electronically on the CERHR web site and in the following: hard copy or CD-ROM from the CERHR. • potential for human exposure from use and occurrence in the environment 1 Information about the CERHR is available on the • extent of public concern web at <http://cerhr.niehs.nih.gov> or by contact- • production volume ing the director: • availability of scientific evidence for repro- NIEHS, P.O. Box 12233, MD EC-32, ductive and/or developmental toxicity. Research Triangle Park, NC 27709 919-541-3455 [phone] The CERHR convenes a scientific expert panel 919-316-4511 [fax] that meets in a public forum to review, discuss, [email protected] [email] and evaluate the scientific literature on the Information about the NTP is available on the web selected chemical. Public comment is invited at <http://ntp-server.niehs.nih.gov> or by contact- prior to and during the meeting. The expert panel ing the NTP Office of Liaison and Scientific Re- produces a report on the chemical’s reproduc- view at the NIEHS: tive and developmental toxicities and provides [email protected] [email] its opinion of the degree to which exposure to 919-541-0530 [phone] v Introduction In 1999, the CERHR Core Committee, an advi- throughout the evaluation process. sory committee composed of representatives from NTP member agencies, recommended The NTP has prepared an NTP-CERHR mono- propylene glycol and ethylene glycol for expert graph for propylene glycol. This monograph panel review. Propylene glycol was selected includes the NTP brief on propylene glycol, because it is a high production volume chemi- a list of the expert panel members (Appendix cal and there is widespread human exposure. I), the expert panel’s report on propylene gly- Ethylene glycol is the subject of a separate col (Appendix II), and all public comments monograph. received on the expert panel’s report on propyl- ene glycol (Appendix III). The NTP-CERHR Propylene glycol is used as a chemical inter- monograph is intended to serve as a single, col- mediate in the manufacture of unsaturated lective source of information on the potential polyester resins, and is found in cosmetics, for propylene glycol to adversely affect human personal care products, pharmaceuticals, food, reproduction or development. Those interested liquid detergents, deicing fluids, antifreeze/ in reading this monograph may include indi- engine coolant, paints, coatings, and tobacco viduals, members of public interest groups, and products. Propylene glycol also is used in the staff of health and regulatory agencies. production of plasticizers, 2-methylpiperazine, 1,2-propylene diamine, hydroxylated poly- The NTP brief included within this monograph ester, polyester-type fluorescent resin matrix, presents the NTP’s interpretation of the potential and polyether polyols. for exposure to propylene glycol to cause adverse reproductive or developmental effects in people. As part of the evaluation of propylene glycol, It is based on information about propylene glycol the CERHR convened a panel of scientific provided in the expert panel report, the public experts (Appendix I) to review, discuss, and comments, and additional scientific information evaluate the scientific evidence on the potential available since the expert panel meetings. reproductive and developmental toxicities of The NTP brief is intended to provide clear, the chemical. There was a public meeting of balanced, scientifically sound information on the CERHR Ethylene Glycol/Propylene Glycol the potential for propylene glycol exposures to (EG/PG) Expert Panel on February 11-13, result in adverse health effects on development 2003. The CERHR received public comments and reproduction. vi NTP Brief on Propylene Glycol NTP Brief NTP What is Propylene Glycol? can occur through its use in food and tobacco Propylene Glycol (PG) is a small, hydroxy- products and in prescription and over-the- substituted hydrocarbon with the chemical counter medicines. PG is rapidly degraded in formula C3H8O2 and the structure shown in water; no information was located on PG levels Figure 1. in drinking water. Figure 1. Chemical structure of PG There is limited information on average U.S. exposure levels and no information on exposure OH levels due to dermal contact was noted. The av- erage U.S. daily intake of PG from food prod- H3C CH CH2 OH ucts is estimated at 34 mg/kg bw/day for a 70 kg PG is used as a chemical intermediate in the person. [NOTE: mg/kg bw/day=milligrams per production of unsaturated polyester resins. kilogram of body weight per day.] Since PG has PG is used in liquid detergents, deicing fluids, GRAS status and may not be listed as a specific antifreeze/engine coolant, paints and coatings. ingredient in some foods, dietary intake based PG is one of the chemicals ‘generally recognized upon product labeling could result in an under- as safe’ (GRAS) by the U.S. Food and Drug estimation of intake. PG is also an ingredient in Administration and is used in foods, cosmetics,
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