# NIOSH Skin Notation (SK) Profiles

DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health 

# Propargyl Alcohol [CAS No. 107-19-7]ii Skin Notation Profiles | Propargyl Alcohol 

## This document is in the public domain and may be freely copied or reprinted.



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# Suggested Citation NIOSH [2014]. NIOSH skin notation profiles: propargyl alcohol. By Hudson NL, Dotson GS. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Con

trol and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-149. DHHS (NIOSH) Publication No. 2014-149 August 2014



### Safer • Healthier • PeopleTMSkin Notation Profiles | Propargyl Alcohol iii 

# Foreword As the largest organ of the body, the skin performs multiple critical functions, such as serving as the primary barrier to the external environment. For this reason, the skin is often exposed to potentially hazardous agents, including chemicals, which may contribute to the onset of a spec

trum of adverse health effects ranging from localized damage (e.g., irritant contact dermatitis and corrosion) to induction of immune-mediated responses (e.g., allergic contact dermatitis and pulmonary responses), or systemic toxicity (e.g., neurotoxicity and hepatoxicity). Under

standing the hazards related to skin contact with chemicals is a critical component of modern occupational safety and health programs. In 2009, the National Institute for Occupational Safety and Health (NIOSH) published Current Intelligence Bulletin (CIB) 61: A Strategy for Assigning New NIOSH Skin Notations [NIOSH 2009-147]. This document provides the scientific rationale and framework for the assignment of multiple hazard-specific skin notations (SK) that clearly distinguish between the systemic effects, direct (localized) effects, and immune-mediated responses caused by skin con

tact with chemicals. The key step within assignment of the hazard-specific SK is the determina

tion of the hazard potential of the substance, or its potential for causing adverse health effects as a result of skin exposure. This determination entails a health hazard identification process that involves use of the following:

• 

### Scientific data on the physicochemical properties of a chemical

• 

### Data on human exposures and health effects

• 

### Empirical data from in vivo and in vitro laboratory testing

• 

### Computational techniques, including predictive algorithms and mathematical models that describe a selected process (e.g., skin permeation) by means of ana

lytical or numerical methods. This Skin Notation Profile provides the SK assignments and supportive data for p ropargyl alco

hol. In particular, this document evaluates and summarizes the literature describing the hazard potential of the substance and its assessment according to the scientific rationale and framework outlined in CIB 61. In meeting this objective, this Skin Notation Profile intends to inform the audience—mostly occupational health practitioners, researchers, policy- and decision-makers, employers, and workers in potentially hazardous workplaces—so that improved risk-manage

ment practices may be developed to better protect workers from the risks of skin contact with the chemicals of interest.



### John Howard, M.D. Director, National Institute for Occupational Safety and Health Centers for Disease Control and PreventionSkin Notation Profiles | Propargyl Alcohol v 

# Contents Foreword

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii Abbreviations

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi Glossary

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viii Acknowledgments

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Introduction

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 General Substance Information:

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Purpose

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.3 Overview of SK Assignment

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2 Systemic Toxicity from Skin Exposure (SK: SYS)

. . . . . . . . . . . . . . . . . . . . . . 1 3 Direct Effects on Skin (SK: DIR)

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4 Immune-mediated Responses (SK: SEN)

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 5 Summary

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 References

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 

### Appendix: Calculation of the SI Ratio for Propargyl Alcohol

. . . . . . . . . . . . . . . 6 Overview

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Calculation

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Appendix References

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7vi Skin Notation Profiles | Dichloropropene 

# Abbreviations ACGIH American Conference of Governmental Industrial Hygienists CIB Current Intelligence Bulletin

cm 2 square centimeter(s) cm/hour centimeter(s) per hour DEREK Deductive Estimation of Risk from Existing Knowledge DIR skin notation indicating the potential for direct effects to the skin following contact with a chemical EC European Commission GHS G lobally Harmonized System for Classification and Labelling of Chemicals GPMT guinea pig maximization test IARC International Agency for Research on Cancer (IRR) subnotation of SK: DIR indicating the potential for a chemical to be a skin irritant following exposure to the skin k

aq coefficient in the watery epidermal layer k

p skin permeation coefficient k

pol coefficient in the protein fraction of the stratum corneum k

psc permeation coefficient in the lipid fraction of the stratum corneum LD 50 dose resulting in 50% mortality in the exposed population LD Lo dermal lethal dose LLNA local lymph node assay LOAEL lowest-observed-adverse-effect level logK OW base-10 logarithm of a substance’s octanol–water partition M molarity

m 3 cubic meter(s) mg milligram(s) mg/kg milligram(s) per kilogram body weight mg/m 3 milligram(s) per cubic meter mL milliliter(s) MW molecular weight NIOSH National Institute for Occupational Safety and Health NOAEL no-observed-adverse-effect level NTP National Toxicology Program OEL occupational exposure limit OSHA Occupational Safety and Health Administration REL recommended exposure limit RF retention factor SEN skin notation indicating the potential for immune-mediated reactions following exposure of the skin SI ratio ratio of skin dose to inhalation doseSkin Notation Profiles | Propargyl Alcohol vii SK skin notation S W solubility SYS skin notation indicating the potential for systemic toxicity following exposure of the skin USEPA United States Environmental Protection Agency μL microliter(s)viii Skin Notation Profiles | Propargyl Alcohol 

# Glossary Absorption



### — The transport of a chemical from the outer surface of the skin into both the skin and systemic circulation (including penetration, permeation, and resorption). Acute exposure



### — Contact with a chemical that occurs once or for only a short period of time. Cancer



### —Any one of a group of diseases that occurs when cells in the body become abnormal and grow or multiply out of control. Contaminant



### —A chemical that is (1) unintentionally present within a neat substance or mixture at a concentration less than 1.0% or (2) recognized as a potential carcinogen and present within a neat substance or mixture at a concentration less than 0.1%. Cutaneous (or percutaneous)



### — Referring to the skin (or through the skin). Dermal



### — Referring to the skin. Dermal contact



### — Contact with (touching) the skin. Direct effects



### — Localized, non-immune-mediated adverse health effects on the skin, including corrosion, primary irritation, changes in skin pigmentation, and reduction/ disruption of the skin barrier integrity, occurring at or near the point of contact with chemicals. Immune-mediated responses



### — Responses mediated by the immune system, including allergic responses. Sensitization



### —A specific immune-mediated response that develops following exposure to a chemical, which, upon re-exposure, can lead to allergic contact dermatitis (ACD) or other immune-mediated diseases such as asthma, depending on the site and route of re-exposure. Substance



### —A chemical. Systemic effects 

### —Systemic toxicity associated with skin absorption of chemicals after exposure of the skin.Skin Notation Profiles | Propargyl Alcohol ix 

# Acknowledgments This document was developed by the NIOSH Education and Information Division (Paul Schulte, Ph.D., Director). G. Scott Dotson, Ph.D., was the project officer for this document, assisted in great part by Naomi Hudson, Dr.P.H., MPH, Loren Tapp, M.D., and Aaron Sus

sell, Ph.D. The basis for this document was a report ( Toxicology Excellence for Risk Assessment [TERA] ) contracted by NIOSH and prepared by Bernard Gadagbui, Ph.D., and Andrew Ma

ier, Ph.D. For their contribution to the technical content and review of this document, special acknowl

edgment is given to the following NIOSH personnel: Denver Field Office Eric Esswein, M.Sc. Division of Applied Research and Technology Clayton B’Hymer, Ph.D. John Snawder, Ph.D. Mark Toraason, Ph.D. Division of Respiratory Disease Studies Gregory A. Day, Ph.D. Aleksander Stefaniak, Ph.D. Division of Surveillance, Hazard Evaluations, and Field Studies Matt Dahm, M.Sc. Todd Niemeier, M.Sc. Education and Information Division Devin Baker, M.Ed. Charles L. Geraci, Ph.D. Thomas J. Lentz, Ph.D. Richard Niemeier, Ph.D. Sudha Pandalai. M.D., Ph.D. Health Effects Laboratory Division Stacey Anderson, Ph.D. H. Fredrick Frasch, Ph.D. Vic Johnson, Ph.D. Michael Luster, Ph.D. Anna Shvedova, Ph.D. Paul Siegel, Ph.D. Berran Yucesoy, Ph.D. National Personal Protection Technology Laboratory Heinz Ahlers, M.Sc. Angie Shepherd For their contribution to the technical content and review of this document, special acknowl

edgment is given to the following CDC personnel: Office of Surveillance, Epidemiology and Laboratory Services/Epidemiology and Analysis Program Office Barbara Landreth, M.A.x Skin Notation Profiles | Propargyl Alcohol In addition, special appreciation is expressed to the following individuals for serving as inde

pendent, external reviewers and providing comments that contributed to the development or Frank A Barile, Ph.D., St. John’s University , College of Pharmacy, Queens, NY Phillip L. Williams, Ph.D., CIH, The University of Georgia, College of Public Health, Athens, GA G. Frank Gerberick, Ph.D., The Procter and Gamble Company, Cincinnati, OH Dori Germolec, Ph.D., National Toxicology Program, National Institute for Environmental Health Sciences, Research Triangle, NC Ben Hayes, M.D., Ph.D., Division of Dermatology, Vanderbilt School of Medicine, Nashville, TN Jennifer Sahmel, M.Sc., CIH, ChemRisk, Boulder, CO James Taylor, M.D., Industrial Dermatology, The Cleveland Clinic, Cleveland, OHSkin Notation Profiles | Propargyl Alcohol 1 

# 1 Introduction
1.1 General Substance Information

Chemical: Propargyl Alcohol CAS No: 107-19-7 Molecular weight ( MW ): 56.1 Molecular formula: C 3 H 3 OH Structural formula: Synonyms: 1-Propyn-3-ol; 2-Propyn-1-ol; 2-Propynyl alcohol Uses: Propargyl alcohol is used primarily as a corro sion inhibitor, chemical reagent and interme

diate [ACGIH 2001].



### Table 1. Summary of the SK assignment for propargyl alcohol Skin notation Critical effect Data available SK: SYS (FATAL) Acute toxicity Limited animal data 

## 1.2 Purpose This skin notation profile presents (1) a brief summary of epidemiological and toxicological data associated with skin contact with propar

gyl alcohol and (2) the rationale behind the hazard-specific skin notation (SK) assign

ment for propargyl alcohol. The SK assign

ment is based on the scientific rationale and logic outlined in the Current Intelligence Bul

letin (CIB) 61: A Strategy for Assigning New NIOSH Skin Notations [NIOSH 2009]. The summarized information and health hazard assessment are limited to an evaluation of the potential health effects of dermal exposure to propargyl alcohol. A literature search was conducted through April 2014 to identify in

formation on propargyl alcohol, including but not limited to data relating to its toxicokinet

ics, acute toxicity, repeated-dose systemic tox

icity, carcinogenicity, biological system/func

tion–specific effects (including reproductive and developmental effects and immunotox

icity), irritation, and sensitization. Informa

tion was considered from studies of humans, animals, or appropriate modeling systems that are relevant to assessing the effects of dermal exposure to propargyl alcohol. 

## 1.3 Overview of SK Assignment Propargyl alcohol is potentially capable of causing numerous adverse health effects fol

lowing skin contact. A critical review of avail

able data has resulted in the following SK assignment for propargyl alcohol: SK: SYS (FATAL) . Table 1 provides an overview of the critical effects and data used to develop the SK assignment for propargyl alcohol. 

# 2 Systemic Toxicity from Skin Exposure (SK: SYS)
No toxicokinetic data were identified that evaluated the potential of propargyl alcohol to be absorbed through the skin of humans following dermal exposure. Dix et al. [2001] investigated the disposition of propargyl al

cohol in male rats following dermal exposure.2 Skin Notation Profiles | Propargyl Alcohol The authors applied radiolabeled propargyl alcohol in an ethanol solution at the target dose of ~5 milligrams per kilogram (mg/kg) under non-occlude conditions to the backs of test animals for a 6-hour exposure period. When adjusted for body weight, the applied dose corresponded to applied doses of ~1.25 mg/rat. The reported results indicated that only 4.3% of the applied dose was absorbed through the skin that up to 85% of the applied dose was unavailable for dermal absorption because of the volatile nature of propargyl al

cohol. In addition, Dix et al. [2001] indicated that it is unlikely that humans would receive a significant internal dose of propargyl alco

hol following dermal exposure unless the skin was in contact with liquid propargyl for a pro

longed period. However, Dix et al. [2001] did not evaluate the potential of propargyl alcohol to be dermally absorbed under occluded con

ditions. Due to the volatility of the chemical, the amount of propargyl alcohol that was der

mally absorbed could have differed compared to the study using non-occluded conditions. For example, Vernot et al. [1977] measured skin absorption toxicity under occluded con

ditions, and reported findings that propargyl alcohol was acutely fatal at relatively low dos

es. Additionally, Dix et al. [2001] were using very low concentrations in the dermal absorp

tion studies of propargyl alcohol. At concen

trations as low as of 8 mg/kg, Dow Chemi

cal Company [1957] reported no toxicity, but exposures to a 1.58% solution of propargyl alcohol in Dowanol 50B at 15.8 mg/kg or 31.6 mg/kg in rabbits was fatal. The potential of propargyl alcohol to pose a skin absorption hazard was also evaluated, with use of a pre

dictive algorithm for estimating and evaluat

ing the health hazards of dermal exposure to substances [NIOSH 2009]. The evaluation method compares an estimated dose accumu

lated in the body from skin absorption and an estimated dose from respiratory absorption associated with a reference occupational ex

posure limit. On the basis of this algorithm, a ratio of the skin dose to the inhalation dose (SI ratio) of 247 was calculated for propargyl alcohol. An SI ratio of ≥0.1 indicates that skin absorption may significantly contribute to the overall body burden of a substance [NIOSH 2009]; therefore, propargyl alcohol is consid

ered to be absorbed through the skin follow

ing dermal exposure. Additional information on the SI ratio and the variables used in its calculation are included in the appendix. No human dermal lethal concentration (LD Lo ) estimates were identified. A dermal LD 50 value (the dose resulting in 50% mortal

ity in the exposed animals) of 88 mg/kg was reported in an acute toxicity study using three female albino New Zealand rabbits per dose [Vernot et al 1977]. Propargyl alcohol was ap

plied under occluded conditions using gauze patches to keep the compound in contact with the skin under a latex rubber film [Vernot et al. 1977]. In another study, Dow Chemical Company [1957] reported that dermal appli

cation of a 1.58% solution of propargyl alco

hol in Dowanol 50B at doses of 15.8 mg/kg or 31.6 mg/kg for 24 hours was lethal to 1 of 2 rabbits exposed, while 8 mg/kg produced no toxicity. Signs of toxicity observed includ

ed diarrhea and hyperemia [Dow Chemical Company 1957]. Dix et al. [2001] reported no deaths in rats that received ~1.25 mg of propargyl alcohol in an ethanol solution to their backs for 6-hour exposure periods under non-occluded conditions. Because the report

ed acute dermal LD 50 values for rabbits are lower than the critical dermal LD 50 value of 200 mg/kg that identifies chemical substances to be considered fatal when in contact with the skin [NIOSH 2009], propargyl alcohol is considered acutely fatal following dermal exposure. No epidemiological studies or human case reports or repeat-dose, subchronic or chronic dermal toxicity studies in animals were identi

fied that evaluated the potential of propargyl alcohol to cause systemic toxicity following dermal exposure. No standard toxicity or spe

cialty studies were identified that evaluated biological system/function specific effects (in

cluding reproductive and developmental ef

fects and immunotoxicity) following dermal exposure to propargyl alcohol.Skin Notation Profiles | Propargyl Alcohol 3 

### Table 2. Summary of the carcinogenic designations * 

### for propargyl alcohol by numerous governmental and nongovernmental organizations Organization Carcinogenic designation NIOSH [2005] No designation NTP [2011] No designation USEPA [2012] No designation European Parliament [2008] No designation IARC [2012] No designation EC [2014] † No designation ACGIH [2001] No designation ACGIH = American Conference of Governmental Industrial Hygienists; EC = European Commission, Joint Research, Institute for

Health and Consumer Protection; IARC = International Agency for Research on Cancer; NIOSH = National Institute for Occu

pational Safety and Health; NTP = National Toxicology Program; USEPA = United States Environmental Protection Agency. *The listed cancer designations were based on data from nondermal (such as oral or inhalation) exposure rather than dermal exposure. † Date accessed.

Although data were not identified to deter

mine the potential for propargyl alcohol to be carcinogenic following dermal exposure, other agencies or organizations have evaluated the carcinogenicity potential of the substance via alternative exposure pathways. Table 2 sum

marizes carcinogenic designations of multiple governmental and nongovernmental organi

zations for propargyl alcohol. Although the single toxicokinetic data iden

tified for propargyl alcohol in rats suggested that the chemical has limited potential to be absorbed through the skin (i.e., percent ab

sorption is less than 10%), this was a non-oc

cluded test, which would not be predictive of absorption following continuous or repeated skin contact. Two acute toxicity studies [Dow Chemical Company 1957; Vernot et al 1977] * were identified that indicated propargyl alco

hol is potentially fatal when in contact with skin. While detailed methods for the dermal application of propargyl alcohol were not avail

able for the Dow Chemical Company [1957], the study conducted by Vernot et al. [1977] reported detailed methods and the study was

*References in bold text indicate studies that serve

as the basis of the SK assignments. consistent with OECD principals. Therefore, on the basis of the data for this assessment, propargyl alcohol is assigned the SK: SYS (FA

TAL) notation. 

# 3 Direct Effects on Skin (SK: DIR)
No human or animal in vivo studies for cor

rosivity or in vitro tests for corrosivity of propargyl alcohol using human or animal skin models or in vitro tests for skin integrity using cadaver skin were identified. Application of 15.8 mg/kg or 31.6 mg/kg of a 1.58% propar

gyl alcohol solution in Dowanol 50B for 24 hours was reported to cause moderate edema in dermally-exposed rabbits [Dow Chemi

cal Company 1957]. Rowe and McCollister [1982] reported from unpublished data from the Dow Chemical Company, that when ap

plied to the skin of rabbits, the undiluted ma

terial caused some superficial necrosis, a 10% solution caused edema, and a 1% solution did not cause any adverse skin effect. The struc

ture activity relationship model, Deductive Estimation of Risk from Existing Knowledge ( DEREK ), predicted propargyl alcohol to be negative for skin irritation.4 Skin Notation Profiles | Propargyl Alcohol 

### Table 3. Summary of previous skin hazard designations for propargyl alcohol Organization Skin hazard designation NIOSH [2005] [skin]: Potential for dermal absorption OSHA [2014]* [skin]: Potential for dermal absorption ACGIH

[2001] [skin]: Based on evidence of skin penetration of propargyl alcohol, with subsequent mortality, in treated rabbits EC [2014]* R24: Harmful if in contact with skin R34: Cause burns ACGIH = American Conference of Governmental Industrial Hygienists; EC = European Commission, Joint Research, Institute

for Health and Consumer Protection; NIOSH = National Institute for Occupational Safety and Health; OSHA = Occupational Safety and Health Administration. *Date accessed. Insufficient data are available to assess the potential of propargyl alcohol to cause skin corrosion. Review of the available information that demonstrates the ability of propargyl al

cohol to cause irritation described as moder

ate edema in rabbits [Dow Chemical Com

pany 1957] is insufficient to assign propargyl alcohol is the SK: DIR notation. 

# 4 Immune-mediated Responses (SK: SEN) No occupational exposure studies or hu

man patch tests or predictive tests in animals (guinea pig maximization tests, Buehler test, murine local lymph node assays, etc.) were identified that evaluated the potential of the propargyl alcohol to cause skin sensitization. DEREK predicted propargyl alcohol to be a skin sensitizer. Lack of data precludes evalu

ation of the skin sensitization potential of propargyl alcohol. Therefore, on the basis of the data for this assessment, propargyl alcohol is not assigned the SK: SEN notation. 

# 5 Summary
No human data were identified that char

acterized the toxicological effects of der

mal exposure to propargyl alcohol. A single toxicokinetic study for propargyl alcohol in rats suggested that the chemical has limited potential to be absorbed through the skin (i.e., percent absorption is less than 10%) because of the highly volatility nature of the chemical [Dix et al. 2001]. Two acute toxicity studies [Dow Chemical Company 1957; Vernot et al 1977] were identified that indicated propar

gyl alcohol is potentially fatal when in con

tact with skin. While a description the study protocol, more specifically the dermal appli

cation method, was not included in the Dow Chemical Company [1957] study, Vernot et al. [1977] provided a sufficient description of the study protocol, which was consistent with OECD principals. The findings of these studies indicate that deaths may occur after acute dermal exposure to low concentrations of propargyl alcohol. Review of the available information that demonstrates the ability of propargyl alcohol to cause irritation described as moderate edema in rabbits [Dow Chemi

cal Company 1957] is insufficient to assign propargyl alcohol the SK: DIR notation. In

sufficient information was identified to assess the potential of propargyl alcohol to act as a skin sensitizer. Therefore, on the basis of these assessments, propargyl alcohol is assigned a composite skin notation of SK: SYS (FA

TAL). Table 3 summarizes the skin hazard designa

tions for propargyl alcohol previously issued by NIOSH and other organizations. The equiva

lent dermal designations for propargyl alco

hol, according to the Global Harmonization System (GHS) of Classification and LabelingSkin Notation Profiles | Propargyl Alcohol 5 of Chemicals, are Acute Toxicity Category 3 (Hazard statement: Toxic in contact with the skin) and Skin Corrosi on Category 1B (Haz

ard statement: Causes severe skin burns and eye damage) [ European Parliament 2008]. 

# References
Note : Asterisks (*) denote sources cited in text; daggers ( † ) denote additional resources. *ACGIH (American Conference of Governmen

tal Industrial Hygienists) [2001]. Propargyl alcohol. In: Documentation of threshold limit values and biological exposure indices 7th ed., Vol. 3. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. *Dix KJ, Coleman DP, et al. [2001]. Disposition of propargyl alcohol in rat and mouse after in

travenous, oral, dermal and inhalation exposure. Xenobiotica 31 :357–375. *Dow Chemical Company [1957]. Range finding skin absorption tests on propargyl alcohol. By Olson KJ. Midland, MI: Dow Chemical Com

pany. On file with the U.S. Environmental Pro

tection Agency under TSCA Section 8D. OTS #0510183.*EC (European Commission) [ND]. Prop2-yn-1-ol. In: EINICS (European Inven

tory of Existing Commercial Chemical Sub

stances), http://esis.jrc.ec.europa.eu/. Accessed: 04-29-14. *European Parliament, Council of the European Union [2008]. Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, label

ing and packaging of substances and mixtures, amending and repealing Directives 67/548/ EEC and 1999/45/EC, and amending Regu

lation (EC) No 1907/2006. OJEU, Off J Eur Union L353:1–1355, http://eurex.europa.eu/ LexUriServ/LexUriServ.do?uri=OJ:L:2008:35 3:0001:1355:EN:PDF. Accessed: 04-29-14. †Faucher JA. [1977]. Sorption of organic com

pounds by human skin. Union Carbide Corpo

ration, Tarrytown, New York. Cosmet. Toilet

ries 92 :61–62. *IARC (International Agency for Research on Cancer) [2012]. Agents reviewed by the IARC monographs. In: IARC monographs on the evaluation of carcinogenic risks to humans, http://monographs.iarc.fr/ENG/Monographs/ PDFs/index.php. Accessed: 04-29-14. *NIOSH [2005]. Propargyl alcohol. In: NIOSH pocket guide to chemical hazards. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Pre

vention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publica

tion No. 2005-149, http://www.cdc.gov/niosh/ npg/. Accessed: 04-29-14. *NIOSH [2009]. Current intelligence bulletin 61: a strategy for assigning new NIOSH skin notations. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National In

stitute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2009-147, http://www.cdc.gov/niosh/docs/2009-147/ pdfs/2009-147.pdf. Accessed: 04-29-14. *NTP [2011]. Report on Carcinogens. Twelfth Edition; U.S. Department of Health and Hu

man Services, Public Health Service. National Toxicology Program, http://ntp.niehs.nih.gov/ ntp/roc/twelfth/roc12.pdf . Accessed 04-29-14. *OSHA [ND]. Propargyl alcohol. In: Sampling and analytical methods, http://www.osha.gov/ dts/sltc/methods/organic/org097/org097.html. Accessed: 04-29-14. * Rowe V; McCollister S.B. [1982]. Alcohols. In: Clayton GD and Clayton FE editors. Patty’s Industrial Hygiene and Toxicology, 3 rd Rev. ed., Vol. 2C, Toxicology. New York. John Wiley & Sons; 1982. p. 4671–4673. *USEPA [2012]. Integrated Risk Information System: propargyl alcohol. In: Integrated Risk Information System, http://www.epa.gov/ncea/ iris/subst/0468.htm. Accessed: 04-29-14.Skin Notation Profiles | Propargyl Alcohol 7 

# Appendix: Calculation of the SI Ratio for Propargyl Alcohol This appendix presents an overview of the SI ratio and a summary of the calculation of the SI ratio for propargyl alcohol. Although the SI ratio is considered in the determination of a substance’s hazard potential following skin contact, it is intended only to serve as support

ive data during the assignment of the NIOSH SK. An in-depth discussion on the rationale and calculation of the SI ratio can be found in Appendix B of the Current Intelligence Bul

letin (CIB) 61: A Strategy for Assigning New NIOSH Skin Notations [NIOSH 2009]. 

## Overview The SI ratio is a predictive algorithm for esti

mating and evaluating the health hazards of skin exposure to substances. The algorithm is designed to evaluate the potential for a sub

stance to penetrate the skin and induce sys

temic toxicity [NIOSH 2009]. The goals for incorporating this algorithm into the pro

posed strategy for assigning SYS notation are as follows: 1. Provide an alternative method to evalu

ate substances for which no clinical re

ports or animal toxicity studies exist or for which empirical data are insufficient to determine systemic effects. 2. Use the algorithm evaluation results to determine whether a substance poses a skin absorption hazard and should be la

beled with the SYS notation. The algorithm evaluation includes three steps: 1. determining a skin permeation coeffi

cient ( k p ) for the substance of interest, 2. estimating substance uptake by the skin and respiratory absorption routes, and 3. evaluating whether the substance poses a skin exposure hazard. The algorithm is flexible in the data require

ment and can operate entirely on the basis of the physicochemical properties of a substance and the relevant exposure parameters. Thus, the algorithm is independent of the need for biologic data. Alternatively, it can function with both the physicochemical properties and the experimentally determined permeation coefficient when such data are available and appropriate for use. The first step in the evaluation is to deter

mine the k p for the substance to describe the transdermal penetration rate of the substance [NIOSH 2009]. The k p , which represents the overall diffusion of the substance through the stratum corneum and into the blood capil

laries of the dermis, is estimated from the compound’s molecular weight ( MW ) and base-10 logarithm of its octanol–water par

tition coefficient (log K OW

). In this example, k p is determined for a substance with use of Equation 1. A self-consistent set of units must be used, such as outlined in Table A1. Other model-based estimates of k p may also be used [NIOSH 2009]. 

### Equation 1: Calculation of Skin Permeation Coefficient ( k p 

### )

aq pol psc p 

## k k k k 1 1 1

+ + =

where k psc is the permeation coefficient in the lipid fraction of the stratum corneum, k pol is the coefficient in the protein fraction of the stratum corneum, and k aq is the coefficient in the watery epidermal layer. These components are individually estimated by log k psc

= −1.326 + 0.6097 × log K ow − 0.1786 × MW 0.5 k pol

= 0.0001519 × MW −0.5 k aq = 2.5 × MW −0.5 The second step is to calculate the biologic mass uptake of the substance from skin ab

sorption (skin dose) and inhalation (inhala

tion dose) during the same period of exposure.8 Skin Notation Profiles | Propargyl Alcohol The skin dose is calculated as a mathematical product of the k p , the water solubility ( S W ) of the substance, the exposed skin surface area, and the duration of exposure. Its units are mil

ligrams (mg). Assume that the skin exposure continues for 8 hours to unprotected skin on the palms of both hands (a surface area of 360 square centimeters [cm 2 ]). 

### Equation 2: Determination of Skin Dose Skin dose

= k p × S w × Exposed skin surface area × Exposure time

= k p (cm/hour) × S w (mg/cm 3 ) × 360 cm 2 × 8 hours The inhalation dose (in mg) is derived on the basis of the occupational exposure limit (OEL) of the substance—if the OEL is de

veloped to prevent the occurrence of systemic effects rather than sensory/irritant effects or direct effects on the respiratory tract. Assume a continuous exposure of 8 hours, an inhala

tion volume of 10 cubic meters (m 3 ) inhaled air in 8 hours, and a factor of 75% for reten

tion of the airborne substance in the lungs during respiration (retention factor, or RF). 

### Equation 3: Determination of Inhalation Dose Inhalation dose = OEL × Inhalation volume × RF = OEL (mg/m 3 ) × 10 m 3 × 0.75 The final step is to compare the calculated skin and inhalation doses and to present the result as a ratio of skin dose to inhalation dose (the SI ratio). This ratio quantitatively indi

cates (1) the significance of dermal absorp

tion as a route of occupational exposure to the substance and (2) the contribution of dermal uptake to systemic toxicity. If a substance has an SI ratio greater than or equal to 0.1, it is considered a skin absorption hazard. 

## Calculation Table A1 summarizes the data applied in the previously described equations to determine the SI ratio for propargyl alcohol. The calcu

lated SI ratio was 247 is greater than the cut

off point of 0.1. On the basis of these results, propargyl alcohol is predicted to represent a skin absorption hazard. 

## Appendix References NIOSH [2005]. NIOSH pocket guide to chemical hazards. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Dis

ease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2005–149, http:// www.cdc.gov/niosh/npg/. Accessed: 04-29-14. NIOSH [2009]. Current intelligence bulletin 61: a strategy for assigning new NIOSH skin notations. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National In

stitute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2009-147, http://www.cdc.gov/niosh/docs/2009-147/ pdfs/2009-147.pdf. Accessed: 04-29-14. SRC [2009]. Interactive PhysProp database demo, http://www.srcinc.com/what-we-do/databas

eforms.aspx?id=386 . Accessed: 04-29-14.Skin Notation Profiles | Propargyl Alcohol 9 

### Table A1. Summary of data used to calculate the SI ratio for propargyl alcohol
Variables used in calculation Units Value Skin permeation coefficient

Permeation coefficient of stratum corneum lipid path( k psc ) cm/hr 1.2734 × 10 -3 Permeation coefficient of the protein fraction of the stra

tum corneum ( k pol

) cm/hr 2.0286 × 10 -5 Permeation coefficient of the watery epidermal layer ( k aq ) cm/hr 0.3337 Molecular weight ( MW ) * amu 56.07 Base-10 logarithm of its octanol–water partition coeffi

cient (Log K ow ) * None -0.38 Calculated skin permeation coefficient ( k p ) cm/hr 1.2887 × 10 -3 Skin dose

Water solubility ( S w ) * mg/cm 3 1000 Calculated skin permeation coefficient ( k p ) cm/hr 1.2887 × 10 -3 Estimated skin surface area (palms of hand) cm 2 360 Exposure time hr 8 Calculated skin dose mg 3711.38 Inhalation Dose

Occupational exposure limit (OEL) † mg/m 3 2 Inhalation volume m 3 10 Retention factor (RF) None 0.75 Inhalation dose mg 15 Skin dose–to–inhalation dose (SI) ratio None 247.43

* Variables identified from SRC [2009]. † The OEL used in calculation of the SI ratio for propargyl alcohol was the NIOSH recommended exposure limit (REL) [NIOSH 2005].