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Template Copyright 2014 © Clean Production Action
Content Copyright 2016 © ToxServices
GreenScreen® Version 1.2 Reporting Template – October 2014 GS-514
Limited license provided to EDF for posting via EDF’s website at https://www.edf.org/. Further copying, resale,
and distribution are expressly prohibited.
Benzyl Alcohol (CAS #100-51-6) GreenScreen® for Safer Chemicals (GreenScreen®)
Assessment
Prepared for:
Environmental Defense Fund
February 1, 2016
1367 Connecticut Ave., N.W., Suite 300
Washington, D.C. 20036
GreenScreen® Version 1.2 Reporting Template – October 2014 GS-514
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and distribution are expressly prohibited.
TABLE OF CONTENTS
GreenScreen® Executive Summary for Benzyl Alcohol (CAS #100-51-6) ............................................ i
Chemical Name ...................................................................................................................................... 1
GreenScreen® Summary Rating for Benzyl Alcohol ............................................................................. 2
Transformation Products and Ratings .................................................................................................... 3
Introduction ............................................................................................................................................ 3
GreenScreen® List Translator Screening Results ................................................................................... 4
PhysicoChemical Properties of Benzyl Alcohol .................................................................................... 5
Group I Human Health Effects (Group I Human) ................................................................................. 5
Carcinogenicity (C) Score .................................................................................................................. 5
Mutagenicity/Genotoxicity (M) Score ............................................................................................... 6
Reproductive Toxicity (R) Score ........................................................................................................ 8
Developmental Toxicity incl. Developmental Neurotoxicity (D) Score ............................................ 9
Endocrine Activity (E) Score ........................................................................................................... 10
Group II and II* Human Health Effects (Group II and II* Human) .................................................... 10
Acute Mammalian Toxicity (AT) Group II Score ............................................................................ 10
Systemic Toxicity/Organ Effects incl. Immunotoxicity (ST) .......................................................... 11
Group II Score (single dose) ......................................................................................................... 11
Group II* Score (repeated dose) ................................................................................................... 12
Neurotoxicity (N) ............................................................................................................................. 13
Group II Score (single dose) ......................................................................................................... 13
Group II* Score (repeated dose) ................................................................................................... 13
Skin Sensitization (SnS) Group II* Score ........................................................................................ 14
Respiratory Sensitization (SnR) Group II* Score ............................................................................ 16
Skin Irritation/Corrosivity (IrS) Group II Score ............................................................................... 16
Eye Irritation/Corrosivity (IrE) Group II Score ................................................................................ 17
Ecotoxicity (Ecotox) ............................................................................................................................ 18
Acute Aquatic Toxicity (AA) Score ................................................................................................. 18
Chronic Aquatic Toxicity (CA) Score .............................................................................................. 19
Environmental Fate (Fate) ................................................................................................................... 20
Persistence (P) Score ........................................................................................................................ 20
Bioaccumulation (B) Score .............................................................................................................. 21
Physical Hazards (Physical) ................................................................................................................. 21
Reactivity (Rx) Score ....................................................................................................................... 21
Flammability (F) Score..................................................................................................................... 21
References ............................................................................................................................................ 23
APPENDIX A: Hazard Benchmark Acronyms ................................................................................... 26
APPENDIX B: Results of Automated GreenScreen® Score Calculation for Benzyl Alcohol
(CAS #100-51-6) ........................................................................................................................... 27
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APPENDIX C: Pharos Output for Benzyl Alcohol (CAS #100-51-6) ................................................ 28
Licensed GreenScreen® Profilers ......................................................................................................... 32
TABLE OF FIGURES
Figure 1: GreenScreen® Hazard Ratings for Benzyl Alcohol ................................................................ 3
TABLE OF TABLES
Table 1: Physical and Chemical Properties of Benzyl Alcohol (CAS #100-51-6) ................................ 5
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GreenScreen® Executive Summary for Benzyl Alcohol (CAS #100-51-6)
Benzyl alcohol is a chemical that functions as a solvent, plasticizer, fragrance and flavoring
component, preservative, viscosity-controlling agent, and degreasing agent.
Benzyl alcohol was assigned a GreenScreen Benchmark™ Score of 2 (“Use but Search for Safer
Substitutes”). This score is based on the following hazard score combinations:
Benchmark 2e (“Moderate T (Group I Human)”)
o Moderate developmental toxicity (D)
Benchmark 2f (“Very High T (Ecotoxicity or Group II Human) or High T (Group II* Human)”)
o High Group II* Human (repeated dose neurotoxicity (Nr*) and skin sensitization (SnS*)
A data gap (DG) exists for endocrine activity (E). As outlined in CPA (2013) Section 12.2 (Step 8 –
Conduct a Data Gap Analysis to assign a final Benchmark score), benzyl alcohol meets requirements
for a GreenScreen® Benchmark Score of 2 despite the hazard data gaps. In a worst-case scenario, if
benzyl alcohol were assigned a High score for the data gap endocrine activity (E), it would be
categorized as a Benchmark 1 Chemical.
GreenScreen® Benchmark Score for Relevant Route of Exposure:
As a standard approach for GreenScreen® evaluations, all exposure routes (oral, dermal and
inhalation) were evaluated together, so the GreenScreen® Benchmark Score of 2 (“Use but Search for
Safer Substitutes”)is applicable for all routes of exposure.
GreenScreen® Hazard Ratings for Benzyl Alcohol
C M R D E AT SnS* SnR* IrS IrE AA CA P B Rx F
single repeated* single repeated*
L L L M DG M DG L M H H DG L H L L vL vL L L
Fate Physical
ST N
Group I Human Group II and II* Human Ecotox
Note: Hazard levels (Very High (vH), High (H), Moderate (M), Low (L), Very Low (vL)) in italics reflect estimated
(modeled) values, authoritative B lists, screening lists, weak analogues, and lower confidence. Hazard levels in
BOLD font are used with good quality data, authoritative A lists, or strong analogues. Group II Human Health
endpoints differ from Group II* Human Health endpoints in that they have four hazard scores (i.e., vH, H, M, and L)
instead of three (i.e., H, M, and L), and are based on single exposures instead of repeated exposures. Please see
Appendix A for a glossary of hazard acronyms.
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GreenScreen® Assessment for Benzyl Alcohol (CAS #100-51-6)
Method Version: GreenScreen® Version 1.21
Assessment Type2: Certified
Chemical Name: Benzyl Alcohol
CAS Number: 100-51-6
GreenScreen® Assessment Prepared By:
Quality Control Performed By:
Name: Zach Guerrette, Ph.D. Name: Bingxuan Wang, Ph.D., D.A.B.T.
Title: Toxicologist Title: Toxicologist
Organization: ToxServices LLC Organization: ToxServices LLC
Date: January 29, 2015 Date: Feb 4, 2015, Dec 4, 2015, Feb 1, 2016
Assessor Type: Licensed GreenScreen® Profiler Assessor Type: Licensed GreenScreen® Profiler
Name: Jennifer Rutkiewicz, Ph.D.
Title: Toxicologist
Organization: ToxServices LLC
Update Date: December 3, 2015
Assessor Type: Licensed GreenScreen® Profiler
Confirm application of the de minimus rule3: N/A (this assessment was conducted for the
theoretically pure substance)
Chemical Structure(s):
Also called:
Benzenemethanol; (Hydroxymethyl)benzene; alpha-Toluenol; Benzenecarbinol; Benzoyl alcohol;
Benzylicum; EINECS 202-859-9; Hydroxytoluene; Methanol, phenyl-; Phenolcarbinol;
Phenylcarbinol; Phenylcarbinolum; Phenylmethanol; Phenylmethyl alcohol (ChemIDplus 2015)
Chemical Structure(s) of Chemical Surrogates Used in the GreenScreen®:
In the absence of available data for the chemical of interest, ToxServices searched for a suitable
analog or class of analogs using guidance in the U.S. EPA’s procedure for identifying analogs (U.S.
1 Use GreenScreen® Assessment Procedure (Guidance) V1.2 2 GreenScreen® reports are either “UNACCREDITED” (by unaccredited person), “AUTHORIZED” (by Authorized
GreenScreen® Practitioner), “CERTIFIED” (by Licensed GreenScreen® Profiler or equivalent) or “CERTIFIED WITH
VERIFICATION” (Certified or Authorized assessment that has passed GreenScreen® Verification Program) 3 Every chemical in a material or formulation should be assessed if it is:
1. intentionally added and/or
2. present at greater than or equal to 100 ppm
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EPA 2010), ECHA’s read across assessment framework (ECHA 2015a) and OECD’s guidance on
grouping of chemicals (OECD 2014). Resources used for the surrogate search included the
ChemIDplus structural similarity search, OECD Toolbox, U.S. EPA’s Analog Identification
Methodology (AIM), and U.S. EPA’s Chemical Assessment Clustering Engine (ChemACE).
Surrogates were considered to be appropriate if they resemble the target in terms of molecular
structure and size, contain a substructure of functional group that may play a critical toxicological
role, share similar physicochemical properties (e.g. water solubility, partition coefficient), or have
common or similar precursors, metabolites, or breakdown products. Where surrogates are used to fill
data gaps or as supporting evidence, the use of a surrogate is clearly indicated for that endpoint.
Benzoic acid was identified as an appropriate surrogate to fill the Data Gap for reproductive toxicity.
As note by UNEP (2001), both benzyl alcohol and benzoic acid share a common metabolic pathway
(benzyl alcohol is oxidized to benzaldehyde and then benzoic acid) and are rapidly and completely
metabolized within 24 hours. Based on the shared metabolic pathways, benzoates including benzyl
alcohol and benzoic acid have similar toxicological profiles.
Benzoic acid (CAS# 65-85-0)
Identify Applications/Functional Uses (HSDB 2009):
1. Solvent
2. Plasticizer
3. Fragrance and flavoring component
4. Preservative
5. Viscosity-controlling agent
6. Degreasing agent
GreenScreen® Summary Rating for Benzyl Alcohol4: Benzyl alcohol was assigned a
GreenScreen Benchmark™ Score of 2 (“Use but Search for Safer Substitutes”). This score is
based on the following hazard score combinations:
Benchmark 2e (“Moderate T (Group I Human)”)
o Moderate developmental toxicity (D)
Benchmark 2f (“Very High T (Ecotoxicity or Group II Human) or High T (Group II* Human)”)
o High Group II* Human (repeated dose neurotoxicity (Nr*) and skin sensitization (SnS*)
A Data gap (DG) exists for endocrine activity (E). As outlined in CPA (2013) Section 12.2 (Step 8 –
Conduct a Data Gap Analysis to assign a final Benchmark score), benzyl alcohol meets requirements
for a GreenScreen® Benchmark Score of 2 despite the hazard data gaps. In a worst-case scenario, if
benzyl alcohol were assigned a High score for the data gap endocrine activity (E), it would be
categorized as a Benchmark 1 Chemical.
4 For inorganic chemicals with low human and ecotoxicity across all hazard endpoints and low bioaccumulation potential,
persistence alone will not be deemed problematic. Inorganic chemicals that are only persistent will be evaluated under the
criteria for Benchmark 4.
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Figure 1: GreenScreen® Hazard Ratings for Benzyl Alcohol
C M R D E AT SnS* SnR* IrS IrE AA CA P B Rx F
single repeated* single repeated*
L L L M DG M DG L M H H L L H L L vL vL L L
Fate Physical
ST N
Group I Human Group II and II* Human Ecotox
Note: Hazard levels (Very High (vH), High (H), Moderate (M), Low (L), Very Low (vL)) in italics reflect estimated
(modeled) values, authoritative B lists, screening lists, weak analogues, and lower confidence. Hazard levels in
BOLD font are used with good quality data, authoritative A lists, or strong analogues. Group II Human Health
endpoints differ from Group II* Human Health endpoints in that they have four hazard scores (i.e., vH, H, M, and L)
instead of three (i.e., H, M, and L), and are based on single exposures instead of repeated exposures. Please see
Appendix A for a glossary of hazard acronyms.
Transformation Products and Ratings:
Identify feasible and relevant fate and transformation products (i.e., dissociation products,
transformation products, valence states) and/or moieties of concern5
Benzyl alcohol is not likely to undergo hydrolysis as it lacks hydrolysable functional groups (HSDB
2009). Photodegradation of benzyl alcohol has been predicted as calculated rates indicate that 50%
photodegradation would occur after 1.3 to 3 days (UNEP 2001). No photodegradation products were
identified, but as very little is predicted to partition to air and the half-lives are short, any air
photodegradation products would not be considered to be feasible or relevant. In addition, because it
is readily biodegradable, biodegradation products are considered to be transient and are also not
considered to be relevant. Based on these findings, ToxServices concludes that the transformation
products do not modify the Benchmark Score for benzyl alcohol.
Introduction
Benzyl alcohol is used as a solvent, plasticizer, fragrance and flavoring component, preservative,
viscosity-controlling agent, and degreasing agent (HSDB 2009). It is produced via the hydrolysis of
benzyl chloride, catalytic reduction or Cannizzaro reaction of benzaldehyde, or hydrogenation of
benzoic acid. It can also be produced from toluene following oxidation to benzoic acid, esterification
with methanol and hydrogenation of methyl benzoate (HSDB 2009).
Benzyl alcohol is listed in Annex V, Section 34, of EC Regulation No. 1223/2009, and is approved
for use as a preservative in cosmetics sold in the European Union at a maximum use level of 1.0%.
Benzyl alcohol is listed in Annex III, Section 45 of EC Regulation No. 1223/2009 as a solvent,
perfuming, or flavoring agent that is acceptable for use in cosmetic products for purposes other than
inhibiting the development of microorganisms in the product (EC 2009). This purpose has to be
apparent from the presentation of the product. The CIR Expert Panel concluded that benzyl alcohol
is safe in the present practices of use and concentration in cosmetics evaluated by the panel, up to
10% (CIR 2014).
5 A moiety is a discrete chemical entity that is a constituent part or component of a substance. A moiety of concern is often the
parent substance itself for organic compounds. For inorganic compounds, the moiety of concern is typically a dissociated
component of the substance or a transformation product.
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ToxServices assessed benzyl alcohol against GreenScreen® Version 1.2 (CPA 2013) following
procedures outlined in ToxServices’ SOP 1.37 (GreenScreen® Hazard Assessment) (ToxServices
2013).
Preservative Spectrum of Effect:
As summarized below, benzyl alcohol displays moderate bacteriostatic and fungistatic activity, with
the best efficacy against gram-positive bacteria.
Benzyl Alcohol’s Preservative Spectrum of Effect
Microorganism Spectrum of Effect Reference
Gram-positive bacteria Good-Moderate Siegert 2014
Gram-negative bacteria Moderate Siegert 2014
Yeasts/Molds Moderate Siegert 2014
Head-space protection Yes Siegert 2014
GreenScreen® List Translator Screening Results
The GreenScreen® List Translator identifies specific authoritative or screening lists that should be
searched to identify GreenScreen® benchmark 1 chemicals (CPA 2012a). Pharos (Pharos 2015) is an
online list-searching tool that is used to screen chemicals against the List Translator electronically. It
checks all of the lists in the List Translator with the exception of the U.S. Department of
Transportation (U.S. DOT) lists (U.S. DOT 2008a,b) and these should be checked separately in
conjunction with running the Pharos query. The output indicates benchmark or possible benchmark
scores for each human health and environmental endpoint. The output for benzyl alcohol can be
found in Appendix B and a summary of the results can be found below:
Neurotoxicity
o Grandjean & Landrigan Neurotoxic Chemicals - Known to be neurotoxic in humans
Acute Mammalian Toxicity
o EC – CLP/GHS
o Associated with H302 – Harmful if swallowed
o Associated with H332 – Harmful if inhaled
o Associated with R20/22 - Harmful by inhalation and if swallowed
o GHS New Zealand – Category 6.1 D (oral and dermal) (equivalent to GHS Category
4) – acutely toxic
o Québec CSST - WHMIS Classifications - Class D2B - Toxic material causing other
toxic effects
Skin Sensitization
o GHS New Zealand Category 6.5B (contact) (equivalent to GHS Category 1) – contact
sensitizer
Eye Irritation
o GHS New Zealand Category 6.4A (equivalent to GHS Category 2A) – Irritating to
the eyes
Acute Aquatic Toxicity
o GHS New Zealand Category 9.1D (fish, crustacean) (equivalent to GHS Category 2-
3) – slightly harmful in the aquatic environment or are otherwise designed for
biocidal action.
Flammability
o Québec CSST - WHMIS Classifications - Class B3 - Combustible liquids
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When appropriate, HSNO classifications in New Zealand were converted to the corresponding GHS
classification (EPA 2012).
Physicochemical Properties of Benzyl Alcohol
Benzyl alcohol is a colorless liquid under standard temperature and pressure. It has a high vapor
pressure (0.094 mm Hg) indicating that it has the potential to exist in the vapor phase. It is very
soluble in water (at least 40,000 mg/L) and is more soluble in octanol than in water (log Kow of 1.05).
Its log Kow value indicates that it is not likely to bioaccumulate in the aquatic biota.
Table 1: Physical and Chemical Properties of Benzyl Alcohol (CAS #100-51-6)
Property Value Reference
Molecular formula C7-H8-O ChemIDplus 2015
SMILES Notation c1(ccccc1)CO ChemIDplus 2015
Molecular weight 108.139 g/mol ChemIDplus 2015
Physical state Liquid ECHA 2015b
Appearance Colorless ECHA 2015b
Melting point -15.4°C ECHA 2015b
Vapor pressure 7 Pa (0.053 mm Hg) at 20°C
0.094 mm Hg at 25°C
ECHA 2015b
ChemIDplus 2015
Water solubility 40,000 mg/L at 20°C
42,900 at 25°C
ECHA 2015b
ChemIDplus 2015
Dissociation constant pKa = 15.4 at 25°C ECHA 2015b
Density/specific gravity 1.04 g/cm3 at 22.5°C ECHA 2015b
Partition coefficient Log Kow = 1.05 at 20°C ECHA 2015b
Hazard Classification Summary Section6:
Group I Human Health Effects (Group I Human)
Carcinogenicity (C) Score (H, M, or L): L
Benzyl alcohol was assigned a score of Low for carcinogenicity based on the negative results for
tumor induction observed in two-year cancer bioassays in rats and mice. GreenScreen® criteria
classify chemicals as a Low hazard for carcinogenicity when negative data, no structural alerts, and
no GHS classification are available (CPA 2012b). Confidence in the score is high because it is based
on experimental data from well conducted studies in rats and mice.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
NTP 1989
o A 103-week carcinogenicity study (identified as GLP-compliant and OECD 451 in
ECHA 2015b) was performed with Fischer 344 rats (50/sex/dose group) administered
oral doses of benzyl alcohol (99% purity) in corn oil at 0, 200, or 400 mg/kg/day via
gavage five days a week. The equivalent doses for a 7-day/week exposure frequency
6 When original study reports were not available, ToxServices summarized study methodology, results, and study author
conclusions as reported in secondary sources. In cases where conclusions were not reported or where ToxServices interpreted the
results differently based on the information presented in the study summary, ToxServices’ conclusions are clearly stated.
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were 0, 143, and 286 mg/kg/day, respectively. At the end of the exposure period, the
surviving animals were sacrificed and evaluated for the presence of neoplastic lesions.
No treatment-related induction in the incidences of neoplastic lesions was observed in
this study.
o A 103-week carcinogenicity study (identified as GLP-compliant and OECD 451 in
ECHA 2015b) was performed with B6C3F1 mice (50/sex/dose group) administered oral
doses of benzyl alcohol (99% purity) in corn oil at 0, 100, or 200 mg/kg/day via gavage
five days a week. The equivalent doses for a 7-day/week exposure frequency were 0, 71,
and 143 mg/kg/day, respectively. At the end of the exposure period, the surviving
animals were sacrificed and evaluated for the presence of neoplastic lesions. No
treatment-related induction in the incidences of neoplastic lesions was observed in this
study.
ECHA 2015b
o Two additional studies were identified in the REACH dossier for benzyl alcohol (ECHA
2015b). However, they were assigned a reliability score of 4 (not assignable) and were
viewed by ToxServices as insufficient for inclusion in this assessment as these studies
were performed in vitro or involved an irrelevant exposure route (intraperitoneal).
Mutagenicity/Genotoxicity (M) Score (H, M, or L): L
Benzyl alcohol was assigned a score of Low for mutagenicity/genotoxicity based on ToxServices not
classifying it as a genotoxicant under GHS criteria. GreenScreen® criteria classify chemicals as a
Low hazard for mutagenicity/genotoxicity when negative results, no structural alerts, and no GHS
classification are available (CPA 2012b). Confidence in the score is high because it is based on
experimental data for several well conducted studies.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
NTP Undated
o In vitro: A mouse lymphoma forward mutation assay (identified as GLP-compliant and
OECD 476 in ECHA 2015b) was equivocal for mutagenicity. L5178Y (TK+/TK-) cells
were tested at concentrations of 250-4,500 µg/mL in the presence of metabolic activation
and 156-5,000 µg/mL in the absence of metabolic activation. There was a statistically
significant increase in mutations at the thymidine kinase locus at a dose of 4,500 µg/mL
in the absence of metabolic activation. There were no statistically significant increases in
mutations at the thymidine kinase locus at all other dose levels. The study authors
concluded that the results “do not permit a definitive conclusion regarding the genetic
toxicity of benzyl alcohol.”
NTP 1984
o In vitro: An in vitro chromosomal aberration assay was positive for clastogenicity.
Chinese hamster ovary (CHO) cells were tested at concentrations of 50-5,000 µg/mL in
the presence of metabolic activation and 250-5,000 µg/mL in the absence of metabolic
activation. There was a statistically significant increase in chromosomal aberrations in
the presence of but not in the absence of metabolic activation.
o In vitro: An in vitro sister chromatid exchange (SCE) assay was weakly positive for
clastogenicity. CHO cells were tested at concentrations of 16-5,000 µg/mL in the
presence of metabolic activation and 16-1,600 µg/mL in the absence of metabolic
activation. There was a slight increase in the formation of SCEs seen in both the
presence and absence of metabolic activation.
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The significance of the SCE assay is controversial, and there is not complete
agreement in the toxicological community as to its ability to predict genotoxicity
(NSF 2011). Therefore, it is ToxServices’ opinion that this study not be given as
much weight as to determining the genotoxicity of benzyl alcohol.
NTP 1987
o In vivo: A sex-linked recessive lethal (SLRL) assay (identified as OECD 477 in ECHA
2015b) was found to be negative for mutagenicity. Drosophila melanogaster were given
doses of 5,000 ppm in food. There were no increases in SLRL mutations seen when
compared to control animals.
UNEP 2001
o In vitro: An Ames reverse mutation assay (identified as GLP-compliant, similar to
OECD 471 in ECHA 2015b) was negative for mutagenicity. Salmonella typhimurium
tester strains TA98, TA100, TA1535, and TA1537 at concentrations of benzyl alcohol
(99.9% purity) at 100-6,666 µg/plate in the presence and absence of metabolic activation.
There were no increases in histidine revertants seen in both the presence and absence of
metabolic activation.
o In vitro: A bacterial reverse mutation assay was negative for mutagenicity. An
Escherichia coli strain was tested at unknown concentrations in both the presence and
absence of metabolic activation. There were no increases in tryptophan revertants seen in
both the presence and absence of metabolic activation.
o In vivo: An in vivo mouse micronucleus assay conducted according to OECD 474 was
performed with ddY mice (6/dose group) administered intraperitoneal injections of
benzyl alcohol (purity not specified) at 50, 100, or 200 mg/kg. The animals were
sacrificed 24 hours after the injection and erythrocyte cells were isolated for the
evaluation of micronuclei. No increase in the frequency of micronuclei was observed
with treatment.
ECHA 2015b
o In vitro: Negative results for DNA damage were obtained in a DNA damage/repair
assay. Primary rat hepatocytes were exposed to benzyl alcohol (purity not specified) in
1% DMSO at 0, 1, 3, or 10 mM without metabolic activation. The highest concentration
of benzyl alcohol produced a positive result in the alkaline elution assay. However, the
cytotoxicity at this concentration was up to 100%. Therefore, authors stated that no
evidence of DNA damage/repair was observed in the absence of significant cytotoxicity.
o In vitro: Negative results for mutagenicity were obtained in an Ames test. S.
typhimurium tester strains TA 98 and TA 1535 were exposed to benzyl alcohol (purity
not specified) at 0.1 to 5.0 µmol/plate without metabolic activation. No increase in the
mutation frequency was observed with treatment in the absence of metabolic activation.
o In vitro: Negative results for clastogenicity were obtained in a chromosome aberration
test conducted in a manner similar to OECD 473 (no metabolic activation). Chinese
hamster lung (CHL) cells were exposed to benzyl alcohol (purity not specified) at 500-
2,000 µg/mL without metabolic activation. No increase in the frequency of chromosome
aberrations was observed with treatment in the absence of metabolic activation.
o In vitro: Negative results for mutagenicity were obtained in an Ames test. S.
typhimurium tester strains TA 92, TA, 94, TA 98, TA 100, TA 1535, and TA 1537 were
exposed to benzyl alcohol (purity not specified) at up to 10 µg/plate with metabolic
activation. No increase in the mutation frequency was observed with treatment in the
presence of metabolic activation.
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o In vivo: Positive results for genotoxicity were obtained in a Drosophila wing spot test.
Third instar larvae of Drosophila melanogaster trans-heterozygous for 2 genetic markers
were provided feed containing benzyl alcohol (99% purity) in water at 0.1 to 50 mM until
pupation. Wings of the emerging adult flies were scored for the presence of spots of
mutant cells formed via somatic mutations or mitotic recombination. The highest
concentration of benzyl alcohol produced an increase in the number of wing spots.
o In vivo: Negative results for clastogenicity were obtained in a mouse micronucleus test
conducted according to OECD 474. Male ddY mice (6/dose group) were administered
four intraperitoneal injections of benzyl alcohol (purity not specified) in saline at 100
mg/kg at 24-hour intervals. The animals were sacrificed 24 hours after the last injection
and bone marrow cells were isolation for evaluation of micronuclei. No increase in the
frequency of micronuclei was observed with treatment.
o Additional genotoxicity tests were identified in the REACH dossier for benzyl alcohol.
However, these tests were assigned reliability scores of 4 (not assignable). Therefore,
ToxServices did not include them in this assessment due to the availability of a large
dataset of well conducted and reported studies.
In summary, negative results for mutagenicity were obtained in three Ames tests and one
bacterial reverse mutation assay while positive results for mutagenicity were obtained in a mouse
lymphoma test without metabolic activation (negative results were obtained in the presence of
metabolic activation). Some evidence of chromosomal aberration induction was obtained in the
presence of, but not in the absence of, metabolic activation in one test and a second test found no
evidence of chromosome aberrations in the absence of metabolic activation. Slightly positive
induction of sister chromatid exchanges were obtained in an in vitro test with and without
metabolic activation while no evidence of DNA damage/repair was observed in the absence of
metabolic activation. While mixed results were obtained in vitro, two in vivo mouse
micronucleus tests and one SLRL test in drosophila produced negative results for clastogenicity
and mutagenicity, respectively. A positive result for mutagenicity was obtained in a drosophila
wing test but the relevance of this test to predict genotoxicity potential has not been established.
Based on the negative results obtained in standardized in vivo tests, ToxServices did not classify
benzyl alcohol as a genotoxicant under GHS criteria.
Reproductive Toxicity (R) Score (H, M, or L): L
Benzyl alcohol was assigned a score of Low for reproductive toxicity based on the lack of effects on
reproductive organs of mice and rats administered oral doses of benzyl alcohol for two years or
inhalation exposures for 4 weeks, and a lack of effects on fertility in a 4-generation reproductive
toxicity study in rats for the surrogate benzoic acid. GreenScreen® criteria classify chemicals as a
Low hazard for reproductive toxicity when negative data, no structural alerts, and no GHS
classification are available (CPA 2012b). The confidence in the score is high as it is based on a
functional evaluation of fertility and reproductive output for a strong surrogate with support from a
lack of histopathological changes to reproductive organs in repeated dose studies of benzyl alcohol.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
UNEP 2001
o Oral: A GLP-compliant, 103-week study conducted according to OECD 451 was
performed with male and female Fischer 344 rats (50/sex/dose) administered oral doses
of benzyl alcohol (99% purity) at 0, 200, or 400 mg/kg/day via gavage five days a week
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for 103 weeks. A NOAEL of 400 mg/kg/day was established, as there were no effects
observed on the testes or ovaries.
o Oral: A GLP-compliant 103-week study conducted according to OECD 451 was
performed with male and female B6C3F1 mice (50/sex/dose) were administered oral
doses of benzyl alcohol (99% purity) at 0, 100, or 200 mg/kg/day via gavage five days a
week for 103 weeks. A NOAEL of 200 mg/kg/day was established, as there were no
effects observed on the testes or ovaries.
ECHA 2015b
o Inhalation: A GLP-compliant repeated inhalation exposure test conducted according to
OECD 412 was performed with Sprague-Dawley rats (10/sex/dose group) administered
nose-only aerosol concentrations of benzyl alcohol (99.9% purity) at 0, 0.041, 0.102,
0.290, or 1.072 mg/L for 6 hours/day, 5 days/week for 4 weeks. The equivalent
concentrations for a 7-day/week exposure frequency are 0, 0.029, 0.073, 0.207, and 0.766
mg/L, respectively. No treatment-related effects were observed on the gross pathological
or histopathological observations of the reproduction organs. A reproductive toxicity
NOAEC of 1.072 mg/L was identified by the study authors.
Surrogate: Benzoic acid (CAS# 65-85-0)
UNEP 2001
o Oral: In a 4-generation reproductive toxicity study in rats, animals (40/sex/dose) were
administered 0.5 or 1% (reported by UNEP to be approximately 375 of 750 mg/kg/day)
benzoic acid (purity not stated) continuously in the diet. The first and second generations
were treated for a lifetime, the third generation was treated for 16 weeks, and the fourth
generation was treated until breeding. No further details were provided regarding the
treatment regimens or mating procedures. There was no evidence of systemic toxicity
based on valuations of weight, food efficiency, organ weights, and histopathology. There
were no effects on fertility or lactation. No additional details were provided. UNEP
identified a reproductive NOAEL of 750 mg/kg/day based on the lack of effects at the
highest dose tested. This study was considered by UNEP of high quality due to the
reputation of the investigators and because it was conducted according to a robust
protocol according to standards at the time.
Although no histopathological effects on reproductive tissues were seen in chronic studies, there
have been no studies evaluating effects of benzyl alcohol on mating and fertility. Therefore data
on the surrogate benzoic acid were also evaluated. Benzoic acid produced no effects on fertility
in a 4-generation study in rats. Therefore a score of Low was assigned.
Developmental Toxicity incl. Developmental Neurotoxicity (D) Score (H, M, or L): M
Benzyl alcohol was assigned a score of Moderate for developmental toxicity based on decreased pup
body weights observed in a mouse developmental toxicity test at a dose of 750 mg/kg/day.
GreenScreen® criteria classify chemicals as a Moderate hazard for developmental toxicity when
limited or marginal evidence of developmental toxicity is observed in animals (CPA 2012b). The
confidence in the score is adjusted as the test used as the basis for the score only evaluated one dose
level and no effects were observed in a second test at a dose of 550 mg/kg/day.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
UNEP 2001
o Oral: Pregnant CD-1 mice (n=50) were administered doses of 750 mg/kg/day via gavage
on gestation days (GDs) 7-14. Pups were delivered and raised until postnatal day 3.
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Evaluations of maternal body-weight gain and mortality, mating, gestation, numbers of
live and dead pups per litter, total litter weight on days 1 and 2 post partum, litter weight
change between days 1 and 3 post partum, and pup survival were conducted. A maternal
and fetal LOAEL of 750 mg/kg/day was established based on a reduction in maternal
body weight on GD 18 and postnatal day 3 and decreased pup body weights on postnatal
days 1 and 3.
This study was identified as GLP-compliant in ECHA (2015).
o Oral: Pregnant mice (n = 50) were administered doses of 550 mg/kg/day via gavage on
GDs 6-15. A maternal and fetal NOAEL of 550 mg/kg/day was established, as there
were no treatment-related effects observed on maternal weight and weight gain, gestation
index, average number of live pups per litter, and postnatal survival and pup body weight
on days 0 and 3.
ECHA 2015b
o Additional developmental toxicity tests were identified in the REACH dossier for benzyl
alcohol. However, these tests were assigned reliability scores of 4 (not assignable).
ToxServices did not include them in this assessment as they were conducted in non-
mammalian species or no experimental details were provided.
Endocrine Activity (E) Score (H, M, or L): DG
Benzyl alcohol was assigned a score of Data Gap for endocrine activity based on the lack of data
identified for this endpoint.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
Not listed as a potential endocrine disruptor on the EU Priority List of Suspected Endocrine
Disruptors.
Not listed as a potential endocrine disruptor on the OSPAR List of Chemicals of Possible
Concern.
No data were identified for this endpoint.
Group II and II* Human Health Effects (Group II and II* Human)
Note: Group II and Group II* endpoints are distinguished in the v 1.2 Benchmark system. For
Systemic Toxicity and Neurotoxicity, Group II and II* are considered sub-endpoints and test data
for single or repeated exposures may be used. If data exist for single OR repeated exposures, then
the endpoint is not considered a data gap. If data are available for both single and repeated
exposures, then the more conservative value is used.
Acute Mammalian Toxicity (AT) Group II Score (vH, H, M, or L): M
Benzyl alcohol was assigned a score of Moderate for acute toxicity based on it being associated with
the EU Risk Phrase R20/22, GHS H-statements H302 and H332, and oral LD50 values of as low as
1,040 mg/kg. GreenScreen® criteria classify chemicals as a Moderate to High hazard for acute
toxicity when they are associated with the EU Risk Phrase R20/22, and a Moderate hazard when
associated with H302 and H332, or the oral LD50 values are between 300 and 2,000 mg/kg (CPA
2012b). Confidence in the score is high because it is based on authoritative listings supported by
data.
Authoritative and Screening Lists
o Authoritative:
EC – CLP/GHS
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Associated with H302 – Harmful if swallowed
Associated with H332 – Harmful if inhaled
Associated with R20/22 – Harmful by inhalation and if swallowed
o Screening:
GHS New Zealand – Category 6.1 D (oral and dermal) (equivalent to GHS
Category 4) – acutely toxic
o Other:
Québec CSST - WHMIS Classifications - Class D2B - Toxic material causing
other toxic effects
UNEP 2001
o Oral: LD50 values of 1,230-3,100 mg/kg (rat), 1,150- 1,580 mg/kg (mouse), and 1,040
mg/kg (rabbit) have been established for benzyl alcohol.
o Dermal: An LD50 value of 2,000 mg/kg has been established in rabbits.
o Inhalation: 4-hour nose-head only aerosol LC50 of greater than 4.178 mg/L have been
established in Wistar rats (identified as GLP-compliant and OECD 403 in ECHA 2015b).
ECHA 2015b
o Inhalation: 4-hour snout-only aerosol LC50 (CD (remote Sprague-Dawley origin) rat) =
greater than 5.4 mg/mL (GLP-compliant, OECD 403)
Systemic Toxicity/Organ Effects incl. Immunotoxicity (ST)
Group II Score (single dose) (vH, H, M, or L): DG
Benzyl alcohol was assigned a score of Data Gap for systemic toxicity (single dose) based on a lack
of adequate data for this endpoint.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
ECHA 2015b
o Oral: In an acute oral toxicity test that identified an oral LD50 of 1,620 mg/kg in male
Wistar rats, bloody eyes, sedation, side and prone-position, and a reduction in general
condition was observed in animals administered at least 1,254 mg/kg. No treatment-
related changes to body weight were observed. No data on gross pathological findings
were presented.
o Inhalation: In the acute inhalation toxicity test that identified a 4-hour LC50 value of
greater than 4,178 mg/L in Wistar rats, slight bradypnea (abnormally slow breathing rate)
and piloerection were observed at 4.78 mg/L. Approximately 3 hours after exposure the
breathing rate returned to normal and all rats were without symptoms on the first day
following exposure onwards. No treatment-related effects were observed on body
weights or gross pathological observations.
o Inhalation: In the acute inhalation toxicity test that identified a 4-hour LC50 value of
greater than 5.4 mg/mL in CD rats, no clinical signs of toxicity were observed with
treatment. Males exhibited a decrease in body weight gain relative to controls on the day
following treatment. No gross pathological changes were observed with treatment.
o Additional acute toxicity tests were identified in the REACH dossier for benzyl alcohol.
However, these tests were assigned reliability scores of 4 (not assignable) or did not
adequately identify the test substance used. ToxServices did not include them in this
assessment as experimental details were not provided.
Based on the weight of evidence, a Data Gap was assigned. Minor transient clinical signs
including effects on general condition, body weight, and respiration were not considered to be
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sufficient to assign a hazard classification based on a target organ effect. One oral study in rats
reported “bloody eyes” following exposure to 1,254 mg/kg. Similar effects were not observed in
the inhalation studies, or in subchronic oral studies that tested doses up to 800 mg/kg/day.
Chromodacryorrhea, a condition that resembles hemorrhaging from the eyes, is frequently
reported in rats, and is due to secretion of pigments in response to stress, pain, illness, or restraint
(Merck 2015). Considering the lack of similar effects on the eye in several subchronic oral
studies, the “bloody eyes” observed in the acute oral study are likely to be indicative of
chromodacryorrhea in response to stress rather than a targeted effect on the eye; however based
only on the single acute oral study with very limited study details reported, it is not possible to
exclude the possibility that it is the result of a systemic effect. In the absence of adequate data, a
Data Gap was assigned. Neurological effects such as sedation are considered under
neurotoxicity-single dose, below.
Group II* Score (repeated dose) (H, M, or L): L
Benzyl alcohol was assigned a score of Low for systemic toxicity (repeated dose) based on oral
NOAELs of at least 200 mg/kg/day in subchronic and chronic oral repeated dose studies.
GreenScreen® criteria classify chemicals as a Low hazard for systemic toxicity (repeated dose) when
oral NOAELs are greater than 100 mg/kg/day (CPA 2012b). Confidence in the score is high because
it is based on data from several well conducted studies.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
UNEP 2001
o Oral: A 13-week study (identified as GLP-compliant in ECHA 2015b) was conducted in
male and female F344/N rats. Animals (ten/sex/dose) were administered doses of 50,
100, 200, 400, and 800 mg/kg/day via gavage five days a week for 13 weeks. A NOAEL
of 400 mg/kg/day was established, based on clinical signs indicative of neurotoxicity
including staggering, respiratory difficulty, and lethargy.
o Oral: A 13-week study (identified as GLP-compliant in ECHA 2015b) was conducted in
male and female B6C3F1 mice. Animals (ten/sex/dose) were administered doses of 50,
100, 200, 400, and 800 mg/kg/day via gavage five days a week for 13 weeks. A NOAEL
of 200 mg/kg/day was established, based on reductions in relative weight gain in male
mice.
o Oral: A 103-week study (identified as GLP-compliant and OECD 451 in ECHA 2015b)
was conducted in male and female Fischer 344 rats. Animals (ten/sex/dose) were
administered doses of 200 and 400 mg/kg/day via gavage five days a week for 103
weeks. A NOAEL of 400 mg/kg/day was established, as there were no effects on body
weight gain, mortality, and compound-related non-neoplastic responses.
o Oral: A 103-week study (identified as GLP-compliant and OECD 451 in ECHA 2015b)
was conducted in male and female B6C3F1 mice. Animals (ten/sex/dose) were
administered doses of 100 and 200 mg/kg/day via gavage five days a week for 103
weeks. A NOAEL of 200 mg/kg/day was established, as there were no significant
treatment-related effects seen.
ECHA 2015b
o Inhalation: A GLP-compliant repeated inhalation exposure test conducted according to
OECD 412 was performed with Sprague-Dawley rats (10/sex/dose group) administered
nose-only aerosol concentrations of benzyl alcohol (99.9% purity) at 0, 0.041, 0.102,
0.290, or 1.072 mg/L for 6 hours/day, 5 days/week for 4 weeks. The equivalent
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concentrations for a 7-day/week exposure frequency are 0, 0.029, 0.073, 0.207, and 0.766
mg/L, respectively. The animals were evaluated for clinical signs of toxicity, body
weights, food consumption, hematology, clinical chemistry, organ weights, gross
pathology, and histopathology. No treatment-related effects were observed on these
parameters and the study authors identified a NOAEC of 1.072 mg/L (equivalent to 0.766
mg/L for a 7-day/week exposure frequency).
Neurotoxicity (N)
Group II Score (single dose) (vH, H, M, or L): M
Benzyl alcohol was assigned a score of Moderate for neurotoxicity (single dose) based on temporary
sedation and bradypnea (possible signs of narcotic effects) observed in some acute toxicity studies.
GreenScreen® criteria classify chemicals as a Moderate hazard for neurotoxicity (single dose) when
they cause transient narcotic effects that warrants a GHS category 3 classification (CPA 2012b).
Confidence level was reduced due to inconsistent observations across studies
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
Classified as a developmental neurotoxicant (Grandjean and Landrigan 2006, 2014).
ECHA 2015b
o Oral: In an acute oral toxicity test that identified an oral LD50 of 1,620 mg/kg in male
Wistar rats, sedation, side and prone-position, and a reduction in general condition was
observed in animals administered at least 1,254 mg/kg. No treatment-related changes to
body weight were observed. No data on gross pathological findings were presented.
o Inhalation: In the acute inhalation toxicity test that identified a 4-hour LC50 value of
greater than 4,178 mg/L in Wistar rats, slight bradypnea (abnormally slow breathing rate)
and piloerection were observed at 4.78 mg/L. Approximately 3 hours after exposure the
breathing rate returned to normal and all rats were without symptoms on the first day
following exposure onwards. No treatment-related effects were observed on body
weights or gross pathological observations.
o Inhalation: In the acute inhalation toxicity test that identified a 4-hour LC50 value of
greater than 5.4 mg/mL in CD rats, no clinical signs of toxicity were observed with
treatment. Males exhibited a decrease in body weight gain relative to controls on the day
following treatment. No gross pathological changes were observed with treatment.
o Additional acute toxicity tests were identified in the REACH dossier for benzyl alcohol.
However, these tests were assigned reliability scores of 4 (not assignable) or did not
adequately identify the test substance used. ToxServices did not include them in this
assessment as experimental details were not provided.
Group II* Score (repeated dose) (H, M, or L): H
Benzyl alcohol was assigned a score of High for neurotoxicity (repeated dose) based on symptoms of
gradual neurological deterioration observed in neonates benzyl alcohol poisoning, clinical signs of
neurotoxicity in animal studies at high doses, and being classified as a known neurotoxicant in
humans by Grandjean and Landrigan. GreenScreen® criteria classify chemicals as a Moderate to
High hazard for neurotoxicity (repeated dose) when they are classified as known neurotoxicant in
humans by Grandjean and Landrigan, and as a High hazard when classified to GHS category 1 (CPA
2012b). The confidence in the score is reduced due to insufficient human evidence and lack of
support from animal studies.
Authoritative and Screening Lists
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o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
Classified as a developmental neurotoxicant (Grandjean and Landrigan 2006, 2014).
UNEP 2001
o Benzyl alcohol poisoning in infants includes neurological symptoms (typically gradual
neurologic deterioration). No further details were identified.
o Oral: A 13-week study (identified as GLP-compliant in ECHA 2015b) was conducted in
male and female F344/N rats. Animals (ten/sex/dose) were administered doses of 50,
100, 200, 400, and 800 mg/kg/day via gavage five days a week for 13 weeks. A NOAEL
of 400 mg/kg/day was established, based on clinical signs indicative of neurotoxicity
including staggering, respiratory difficulty, and lethargy.
UIC Undated
o `Benzyl alcohol has been reported to cause fatal reactions “gasping syndrome” in
neonates when administered i.v. as a bacteriostatic agent in large volume or multi-dose
injectable products. The symptoms of gasping syndrome include severe metabolic
acidosis, neurologic deterioration and gasping respirations. This was believed to be due to
immature detoxification mechanisms in infants for benzyl alcohol and its metabolites
benzoic acid and hippuric acid. The syndrome was reversed in one surviving infant when
the exposure was discontinued, while in most other cases, it lead to mortality.
In summary, human case reports indicate that benzyl alcohol is capable of causing gasping
syndrome in neonates that includes symptoms of neurological deterioration when administered
intravenously. This route of exposure is not directly relevant to GreenScreen® evaluations, and
benzyl alcohol does not appear to be a specific neurological toxicant in humans (surviving infants
had reduced symptoms). In animals, neurological symptoms such as staggering, respiratory
difficulty and lethargy were observed only at high doses that do not warrant GHS classification.
It is not clear if infants are more sensitive than rodents to the neurological effects of benzyl
alcohol. According to GHS criteria, substances that produced significant toxicity in humans in
case reports or epidemiological studies (regardless of doses) are classified to category 1, while in
exceptional cases, human evidence can warrant category 2 classification when the weight of
evidence in humans is not sufficiently convincing for category 1 classification or the effect is not
severe, and available evidence from animals studies should be consistent with category 2
classification (UN 2013). Benzyl alcohol is classified as a known neurotoxicant in man by
Grandjean and Landrigan, which corresponds to a score of Moderate to High. ToxServices
conservatively classified benzyl alcohol to GHS category 1 based on human evidence, but
confidence level was reduced as no lasting neurological symptoms or neurological tissue
damages were known to be associated with benzyl alcohol administration in human infants.
Skin Sensitization (SnS) Group II* Score (H, M, or L): H
Benzyl alcohol was assigned a score of High for skin sensitization based on positive reactions in
humans, mixed results in animals, and the GHS New Zealand 6.5B classification (equivalent to GHS
Category 1). GreenScreen® criteria classify chemicals as a High hazard for skin sensitization when
they are classified as GHS Category 1A skin sensitizers (CPA 2012b). Confidence in the score is
high because it is based on experimental data in animals and humans, and the SCCNFP’s conclusion
that it is one of the 13 most frequently reported consumer allergens.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening:
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GHS New Zealand Category 6.5B (contact) (equivalent to GHS Category 1) –
contact sensitizer
ECHA 2015b
o A modified Draize test was performed with male and female Hartley guinea pigs (10
total, sex distribution not specified) administered dermal doses of benzyl alcohol (purity
not specified). The induction dose was performed with four intradermal injections of
0.25% benzyl alcohol (vehicle not specified) to shaved skin. After 14 days, the challenge
dose was applied as a combination of intradermal injection to one flank at 0.25% and
topical application to the other flank at 10% without coverage (open). The dermal
reactions were scored 24 hours after the challenge dose. A second challenge dose was
applied 7 days later using the same procedure. No positive skin reactions were observed
with treatment and the study authors concluded that benzyl alcohol was not sensitizing to
skin in this study.
o An open epicutaneous test was performed with Himalayan guinea pigs (4-6/dose group)
administered topical applications of 0.1 mL benzyl alcohol (purity not specified)
undiluted up to 3% (no further details available) daily for 21 days. Challenge doses were
applied on day 21 and day 35. Dermal reactions were evaluated 42, 48, and 72 hours
after the challenge dose. Positive skin reactions were observed following the challenge
dose. No further details were provided.
o A Freund's complete adjuvant (FCA) test was performed with Himalayan guinea pigs
(number and sex not specified) administered dermal doses of benzyl alcohol (purity not
specified). The induction doses were applied as intradermal injections of 0.05 ml
volumes of undiluted benzyl alcohol in a 50:50 mixture with FCA to the neck on days 0,
2, 4, 7, and 9 for a total dose of 250 mg. Controls were administered intradermal
injections of FCA alone. The challenge dose was applied as a topical application of
benzyl alcohol (concentration not specified) in petrolatum under occlusive dressing on
day 21 and day 35. Positive skin reactions were observed following the challenge dose.
No further details were provided.
o A Draize test was performed with Himalayan guinea pigs (number and sex not specified)
administered 0.05 mL intradermal injections of 0.1% benzyl alcohol (purity not
specified) in physiological saline. The induction doses were applied on day 0 and then on
9 alternate days for a total dose of 0.95 mg. The challenge doses were applied on days 35
and 49. Positive skin reactions were judged based on the mean diameter of the popular
reactions. No positive skin reactions were observed following the challenge dose. No
further details were provided.
o A guinea pig maximization test conducted according to OECD 406 was performed with
Himalayan guinea pigs (10/dose group, sex distribution not specified) administered
dermal doses of benzyl alcohol (purity not specified). The induction doses were
administered on day 0 as paired intradermal injections of 0.1 ml 5% methyl alcohol, 0.1
ml 5% emulsion of benzyl alcohol in FCA, and 0.1ml of FCA alone. On day 8, a 25%
solution of benzyl alcohol in petrolatum was applied to shaved skin under occlusive
dressing for 48 hours. The challenge dose was applied on day 21 as a sub-irritant
concentration (no further details provided) in petrolatum applied to the skin under
occlusive dressing for 24 hours. The dermal reactions were evaluated 24 and 48 hours
after removal of the dressing. No positive skin reactions were observed following the
challenge dose. No further details were provided.
SCCNFP 1999
o 5% Benzyl alcohol induced positive reactions in 0.5% of tested patients in Japan.
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o 5% Benzyl alcohol induced positive reactions in 3/20 patients as a fragrance ingredient.
o 5% Benzyl alcohol tested positive in 2/176 (1.2%) patients in a patch test as a fragrance
ingredient
o 10% Benzyl alcohol tested positive in 3/182 (1.6%) patients suspected of contact allergy
to cosmetics in a patch test with fragrance substances.
o Benzyl alcohol tested positive in 2/156 (1.3%) of patients with contact allergy to
cosmetic products.
o Benzyl alcohol tested positive in 3/578 (0.005%) subjects with sensitization reactions to
cosmetic products in a patch test.
o Benzyl alcohol tested positive in 4/242 (1.6%) patients with contact allergy from
different origins in a patch test.
o Benzyl alcohol is one of the most frequently reported and well-recognized consumer
allergens in the EU, according to existing knowledge (one of 13 allergens identified by
SCCNFP as being of most concern due to high frequency of sensitization reports).
Positive reactions for dermal sensitization were observed in an open epicutaneous test and a FCA
test while negative results were obtained in a guinea pig maximization test, Draize test, and
modified Draize test. These studies have insufficient detail regarding the percent of animals
having positive skin reactions. Positive patch tests were observed in humans and benzyl alcohol
is listed as one of the most frequently reported consumer allergens by SCCNFP. The GHS
criteria classify chemicals to category 1A when the frequency of occurrence for sensitization
reactions is high. Therefore, classification score of High was assigned for this endpoint.
Respiratory Sensitization (SnR) Group II* Score (H, M, or L): DG
Benzyl alcohol was assigned a score of Data Gap for respiratory sensitization based on a lack of
adequate data for this endpoint. Confidence level was reduced due to lack of direct measured data.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
UNEP 2001
o In the past several decades, no cases of health complaints, including sensitization
reactions have been reported in workers at manufacturing and application sites of benzoic
acid and its salts as well as benzyl alcohol.
Although there have been no case reports of respiratory sensitization to benzyl alcohol, in the
absence of challenge or animal studies, a lack of case reports was not considered to be sufficient
to assign a Low.
Skin Irritation/Corrosivity (IrS) Group II Score (vH, H, M, or L): L
Benzyl alcohol was assigned a score of Low for skin irritation/corrosivity based on experimental data
indicating that it does not warrant GHS classification as a skin irritant. GreenScreen® criteria
classify chemicals as a Low hazard for skin irritation/corrosivity when negative data, no structural
alerts, and no GHS classification are available (CPA 2012b). Confidence in the score is high because
it is based on experimental data form well conducted studies.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
ECHA 2015b
o A GLP-compliant dermal irritation test conducted according to OECD 404 was
performed with New Zealand White rabbits (3 total, sex not specified) administered
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topical applications of 0.5 mL undiluted benzyl alcohol (99.99% purity) to shaved skin
under semi-occlusive dressing for 4 hours. An observation period of 7 days followed the
exposure period. The dermal reactions were evaluated at 24, 48, and 72 hours after the
start of the exposure period. The mean erythema score for two of the animals was 0/4,
while the mean score for the third animal was 0.7/4. The mean edema score was 0/4. All
dermal irritation effects were fully reversible within 72 hours.
Based on the results of this study, ToxServices did not classify benzyl alcohol as
a dermal irritant under GHS criteria. GHS guidance (UN 2013) requires that a
chemical produce mean scores of ≥ 1.5 for erythema or edema in at least 2 of 3
tested animals from grades at 24, 48, and 72 hours.
o A dermal irritation test was performed with New Zealand White rabbits (1/sex/dose
group) administered topical applications of 0.5 mL undiluted benzyl alcohol (purity not
specified) to the skin under semi-occlusive dressing for 24 hours. An observation period
of 7 days followed the exposure period. The dermal reactions were evaluated at 24, 48,
and 72 hours after the start of the exposure period. The mean erythema and edema scores
were 0/4.
Based on the results of this study, ToxServices did not classify benzyl alcohol as
a dermal irritant under GHS criteria. GHS guidance (UN 2013) requires that a
chemical produce mean scores of ≥ 1.5 for erythema or edema in at least 2 of 3
tested animals from grades at 24, 48, and 72 hours.
o Additional skin irritation tests were identified in the REACH dossier for benzyl alcohol.
However, these tests were assigned reliability scores of 4 (not assignable) and were not
conducted according to validated methods or were reported with insufficient details could
not be assessed or were in vitro tests that would not be weighed as heavily as the well
conducted in vivo studies. Therefore, ToxServices did not include them in this
assessment.
Eye Irritation/Corrosivity (IrE) Group II Score (vH, H, M, or L): H
Benzyl alcohol was assigned a score of High for eye irritation/corrosivity based on experimental data
indicating that it meets criteria for classification as a Category 2A eye irritant under GHS criteria,
which is in agreement with the classification from GHS New Zealand.. GreenScreen® criteria
classify chemicals as a High hazard for eye irritation/corrosivity when chemicals are classified as
GHS Category 2A eye irritants (CPA 2012b). Confidence in the score is high because it is based on
experimental data.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening:
GHS New Zealand Category 6.4A (equivalent to GHS Category 2A) – Irritating
to the eyes
ECHA 2015b
o A GLP-compliant eye irritation test conducted according to OECD 405 was performed
with New Zealand White rabbits (3 total, sex not specified) administered ocular
instillations of 0.1 mL undiluted benzyl alcohol (99.99% purity). The eyes were rinsed
after 24 hours and the animals were observed for 21 days. The mean corneal score was
1/4, the mean iris score was 0/2 for two of the animals while the third animal had a mean
score of 0.3/2, the mean conjunctival score was 2/3, and the mean chemosis score was
0.7/4 for two of the animals and 1/4 for the third animal. The chemosis effects were fully
reversible within 7 days, and the corneal and conjunctival effects were fully reversible by
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21 days at the latest. The study authors concluded that benzyl alcohol was irritating to
the eyes.
Based on the results of this study, ToxServices classified benzyl alcohol as a
Category 2A ocular irritant according to GHS guidelines. GHS criteria (UN
2013) classify chemicals as Category 2A ocular irritants if they produce corneal
opacity scores of ≥ 1, iritis scores of ≥ 1, conjunctival redness scores of ≥ 2,
and/or chemosis scores of ≥ 2 in at least 2 of 3 animals tested at 24, 48, and 72
hours after instillation, and the effects being fully reversible within 21 days.
o An eye irritation test was performed with New Zealand White rabbits (2 total, sex not
specified) administered ocular instillations of 0.1 mL undiluted benzyl alcohol (purity not
specified). An observation period of 7 days followed the instillation. The ocular effects
were evaluated at 1, 24, and 48 hours and 7 days. In both animals the mean corneal score
was 1/4, the iris score ranged from 0-1 (max 2), and the conjunctival score ranged from
0-2 (max 3). One animal had a chemosis score that ranged from 0-1 (max 4) while the
other had a chemosis score that ranged from 0-2 (max 4). All ocular irritation effects
with the exception of the corneal irritation resolved within 7 days. The study authors
concluded that benzyl alcohol causes superficial corrosion of the cornea and was
moderately irritating to the eye.
ToxServices could not assign a classification to benzyl alcohol based on the
results of this test as the mean ocular irritation values were not available for 24,
48, and 72 hours.
o A GLP-compliant ocular irritation test conducted according to OECD 405 was performed
with New Zealand White rabbits (3 total, sex not specified) administered ocular
instillations of 0.1 mL undiluted benzyl alcohol (99.98% purity). An observation period
of 18 days followed the instillation. One animal was sacrificed on day 10 of the study for
ethical reasons; the animal displayed soft feces and hypoactivity although the study
authors state that these clinical signs were not attributed to the treatment. For the two
remaining animals, the mean corneal score was 2/4, the mean iris score was 1/2, the mean
conjunctival score was 2.5/3, and the chemosis score was 3/4 for one animal and ranged
from 1-2 out of 4 for the other animal. The corneal effects were fully reversible within
18 days while the other ocular irritation effects were reversible within 11 days. The study
authors concluded that benzyl alcohol was irritating to the eyes.
Based on the results of this study, ToxServices classified benzyl alcohol as a
Category 2A ocular irritant according to GHS guidelines. GHS criteria (UN
2013) classify chemicals as Category 2A ocular irritants if they produce corneal
opacity scores of ≥ 1, iritis scores of ≥ 1, conjunctival redness scores of ≥ 2,
and/or chemosis scores of ≥ 2 in at least 2 of 3 animals tested at 24, 48, and 72
hours after instillation, and the effects being fully reversible within 21 days.
o Additional eye irritation tests were identified in the REACH dossier for benzyl alcohol.
However, these tests were assigned reliability scores of 4 (not assignable) and were
reported with very limited details. Therefore, ToxServices did not include them in this
assessment given the availability of well conducted and reported studies.
Ecotoxicity (Ecotox)
Acute Aquatic Toxicity (AA) Score (vH, H, M, or L): L
Benzyl alcohol was assigned a score of Low for acute aquatic toxicity based on acute aquatic toxicity
values greater than 100 mg/L in fish, aquatic invertebrates and algae. GreenScreen® criteria classify
chemicals as a Low hazard for acute aquatic toxicity when acute aquatic toxicity values are greater
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than 100 mg/L (CPA 2012b). Confidence in the score is high because it is based on experimental
data from several studies.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening:
GHS New Zealand Category 9.1D (fish, crustacean) (equivalent to GHS Category
2-3) – slightly harmful in the aquatic environment or are otherwise designed for
biocidal action.
UNEP 2001
o 48-hour LC50 (Leuciscus idus, ide) = 646 mg/L (DIN 38412 Teil 15)
o 24-hour mobility EC50 (Daphnia magna) = 400 mg/L (DIN 38412 Teil 11)
o 48-hour mobility EC50 (Daphnia magna) = 360 mg/L
ECHA 2015b
o 96-hour LC50 (Pimephales promelas, fathead minnow) = 460 mg/L (non-GLP-compliant,
EPA OPP 72-1)
o 96-hour LC50 (Oryzias latipes, Japanese rice fish) = greater than 100 mg/L (OECD 203)
o 48-hour mobility EC50 (Daphnia magna) = 230 mg/L (GLP-compliant, OECD 202)
o 24-hour mobility EC50 (Daphnia magna) = 55 mg/L (DIN 38412 Teil 11)
o 72-hour growth rate EC50 (Pseudokirchnerella subcapitata, green algae) = 770 mg/L
(GLP-compliant, OECD 201)
o 72-hour area under growth curve EC50 (P. subcapitata, green algae) = 500 mg/L (GLP-
compliant, OECD 201)
o 96-hour cell growth LOAEC (Scenedesmus sp.) = 640 mg/L
o Additional acute aquatic toxicity tests were identified in the REACH dossier for benzyl
alcohol. However, these tests were assigned reliability scores of 3 (not reliable) or 4 (not
assignable). ToxServices did not include them in this assessment as they were provided
with very limited details or did not involve exposures similar to those upon which GHS
criteria are based.
All the reported L/EC50 values are above 100 mg/L except one 24-hour mobility EC50 of 55 mg/L
in daphnia reported in a study conducted according to DIN 38412 Teil 11. Another study
following the same protocol reported a 24-hour mobility EC50 of 400 mg/L in daphnia. The
standard test duration for acute toxicity studies in daphnia is 48 hours, and good quality 48h EC50
values are identified to be 230 and 360 mg/L in two studies in daphnia. Therefore, the weight of
evidence indicates that benzyl alcohol is not highly toxic to aquatic invertebrates. In addition, the
L/EC50 values for fish and algae are > 100 mg/L which corresponds to a Low.
Chronic Aquatic Toxicity (CA) Score (vH, H, M, or L): L
Benzyl alcohol was assigned a score of Low for chronic aquatic toxicity based on the most
conservative chronic aquatic toxicity value of 51 mg/L. GreenScreen® criteria classify chemicals as
a Low hazard for chronic aquatic toxicity when chronic aquatic toxicity values are greater than 10
mg/L (CPA 2012b). Confidence in the score is high because it is based on experimental data.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
ECHA 2015b
o 21-day reproduction NOEC (Daphnia magna) = 51 mg/L (GLP-compliant OECD 211)
o 72-hour growth rate and area under growth curve NOEC (P. subcapitata, green algae) =
310 mg/L (GLP-compliant, OECD 201)
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A score of Low was assigned based on the NOEC values for daphnia and algae, which are much
greater than the guidance value of 10 mg/L. Although there are no chronic toxicity data for fish,
available acute data (presented above) do not indicate that fish are more sensitive than
invertebrates and plants.
Environmental Fate (Fate)
Persistence (P) Score (vH, H, M, L, or vL): vL
Benzyl alcohol was assigned a score of Very Low for persistence based on it meeting the 10-day
biodegradation window in the OECD 301 A test. GreenScreen® criteria classify chemicals as a Very
Low hazard for persistence when they partition primarily to soil and water and meet the 10-day
biodegradation window in ready biodegradation tests (CPA 2012b). Confidence in the score is high
because it is based on several well conducted biodegradation tests.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
ECHA 2015b
o A ready biodegradability test (GLP status unknown) conducted according to OECD 301
C (Modified MITI Test) was performed with activated sludge (adaptation not specified)
exposed to benzyl alcohol (purity not specified) at 100 mg/L for 14 days. At the end of
the exposure period, the level of degradation was 92-96%. The study authors concluded
that benzyl alcohol was readily biodegradable in this test.
o A ready biodegradability test (GLP status unknown) conducted according to OECD 301
A (DOC Die Away Test) was performed with sewage (predominantly domestic,
adaptation not specified) exposed to benzyl alcohol (purity not specified) at 20 mg/L
based on organ carbon content for 21 days. The level of degradation was 92-94% after 7
days, 94-96% after 14 days, and 95-97% after 21 days. The study authors concluded that
benzyl alcohol was readily biodegradable in this test. ToxServices concluded that benzyl
alcohol met the 10-day biodegradation window in this test.
o A ready biodegradability test (GLP status unknown) conducted according to OECD 301
D (Closed Bottle Test) was performed with adapted, activated sludge exposed to benzyl
alcohol (purity not specified) at greater than 2 and less than 5 mg/L for 28 days. At the
end of the exposure period, the level of degradation was 95% based on theoretical oxygen
demand (ThOD). The study authors concluded that benzyl alcohol was readily
biodegradable in this test.
o U.S. EPA 2012
The BIOWIN modeling Ready Biodegradable Predictor indicates that benzyl
alcohol is expected to be readily biodegradable (see Appendix D). Fugacity
modeling predicts 64.8% will partition to soil with a half-life of 30 days, 34%
will partition to water with a half-life of 15 days, and 1.03% will partition to air
with a half-life of 11.2 days hours.
o Additional biodegradation tests were identified in the REACH dossier for benzyl alcohol.
However, these tests evaluated the anaerobic degradation or inherent biodegradability of
benzyl alcohol or were not conducted according to or comparable to guideline protocols
and thus could not be compared to GHS criteria. Given the availability of several well
conducted ready biodegradation studies producing positive results, ToxServices did not
include them in this assessment.
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Bioaccumulation (B) Score (vH, H, M, L, or vL): vL
Benzyl alcohol was assigned a score of Very Low for bioaccumulation based on an estimated BCF of
0.31 and a measured log Kow of 1.05. GreenScreen® criteria classify chemicals as a Very Low hazard
for bioaccumulation when BCF values are no greater than 100 and log Kow values are no greater than
4.0 (CPA 2012b). Confidence in the score is high because it is based on an experimental log Kow
value.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
UNEP 2001
o Benzyl alcohol does not bioaccumulate, with an estimated bioconcentration factor (BCF)
of 0.31.
ECHA 2015b
o Benzyl alcohol has a log Kow value of 1.05 at 20°C in a shake-flask and HPLC method
test.
Physical Hazards (Physical)
Reactivity (Rx) Score (vH, H, M, or L): L
Benzyl alcohol was assigned a score of Low for reactivity based on reports that it is not oxidizing
and an HMIS rating that it is not explosive, self-reactive, or otherwise reactive. GreenScreen®
criteria classify chemicals as a Low hazard for reactivity when no GHS classifications are available
for any of the reactivity sub-endpoints (CPA 2012b). The confidence in the score is adjusted as it is
not based on data or authoritative lists.
Authoritative and Screening Lists
o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening: Not listed on any authoritative lists for this endpoint.
ECHA 2015b
o Benzyl alcohol does not contain any functional groups associated with explosive or
oxidizing properties.
Sigma-Aldrich 2014
o A material safety data sheet for benzyl alcohol states that it has a reactivity rating of 0
from the National Fire Protection Association (NFPA) (“Normally stable, even under fire
exposure conditions, and is not reactive with water”) (NFPA 2012) and Hazardous
Materials Identification System (HMIS) (“Materials that are normally stable, even under
fire conditions, and will not react with water, polymerize, decompose, condense, or self-
react. Non-explosives”) (Paint.org 2015).
Based on the MSDS identified above stating that benzyl alcohol is nonreactive and the
conclusion in the REACH dossier that it lacks functional groups associated with oxidative and
explosive properties, ToxServices did not classify benzyl alcohol as a reactive chemical based on
GHS criteria (UN 2013).
Flammability (F) Score (vH, H, M, or L): L
Benzyl alcohol was assigned a score of Low for flammability based on its measured flash points of
94-101°C GreenScreen® criteria classify chemicals as a Low hazard for flammability when they are
not classifiable under GHS as a flammable liquid based on a flash point of greater than 93°C (CPA
2012b). Confidence in the score is high because it is based on experimental data.
Authoritative and Screening Lists
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o Authoritative: Not listed on any authoritative lists for this endpoint.
o Screening:
Québec CSST - WHMIS Classifications - Class B3 - Combustible liquids
ECHA 2015b
o A flash point of 100.4°C was identified for benzyl alcohol in an open cup test.
o A flash point of 94°C was identified for benzyl alcohol (method not reported).
UNEP 2001
o A flash point of 101°C was identified for benzyl alcohol in a closed cup test (DIN
51758).
Based on the above data, ToxServices did not classify benzyl alcohol as a flammable liquid under
GHS criteria (UN 2013). GHS criteria specify that flammable liquids have flash points of no
greater than 93°C. WHMIS class B3 includes combustible materials that must be heated before
catching fire (at 37.8ºC – 93.3ºC). The measured flash point of greater than 100ºC does not
warrant a WHMIS B3 classification, and it was not clear how Environment Canada came to this
classification. Therefore, ToxServices relied on experimental data rather than the screening list
for this endpoint.
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References
ChemIDplus. 2015. Entry for Benzyl alcohol (CAS #100-51-6). United States National Library of
Medicine. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/100-51-6.
Clean Production Action (CPA). 2012a. List Translator. Dated February 2012. Available at:
http://www.greenscreenchemicals.org/.
Clean Production Action (CPA). 2012b. The GreenScreen® for Safer Chemicals Version 1.2
Criteria. Dated: November 2012. Available at: http://www.greenscreenchemicals.org/.
Clean Production Action (CPA). 2013. The GreenScreen® for Safer Chemicals Chemical Hazard
Assessment Procedure. Version 1.2 Guidance. Dated August 31, 2013. Available at:
http://www.greenscreenchemicals.org/.
Cosmetic Ingredient Review (CIR). 2014. CIR Compendium.
Environmental Protection Authority (EPA). 2009. Correlation between GHS and New Zealand
HSNO Hazard Classes and Categories Information Sheet. Third Revised Edition. Available
at: http://www.epa.govt.nz/Publications/hsnogen-ghs-nz-hazard.pdf.
European Chemicals Agency (ECHA). 2015a. Read-Across Assessment Framework (RAAF).
Available: http://echa.europa.eu/documents/10162/13628/raaf_en.pdf.
European Chemicals Agency (ECHA). 2015b. REACH Dossier for Benzyl Alcohol (CAS #100-51-
6). Available at: http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d9b1369-7454-687c-
e044-00144f67d249/DISS-9d9b1369-7454-687c-e044-00144f67d249_DISS-9d9b1369-7454-687c-
e044-00144f67d249.html.
European Union (EU). 2009. Regulation (EC) No. 1223/2009 of the European Parliament and of the
Council of 30 November 2009 on cosmetic products. Recast. Official Journal of the European Union.
L342/39. Dated December 22, 2009.
Grandjean, P. and P.J. Landrigan. 2006. Developmental neurotoxicity of industrial chemicals.
Lancet 368: 2167-2178.
Grandjean, P. and P.J. Landrigan. 2014. Neurobehavioral effects of developmental toxicity. The
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Hazardous Substances Data Bank (HSDB). 2009. Entry for Benzyl Alcohol (CAS #100-51-6).
HSDB Number 46. Last revision date April 20, 2009. United States National Library of Medicine.
Available at: http://toxnet.nlm.nih.gov/newtoxnet/hsdb.htm.
The Merck Veterinary Manual. 2015. Mice and Rats as Pets. Available:
http://www.merckvetmanual.com/mvm/exotic_and_laboratory_animals/rodents/mice_and_rats_as_p
ets.html.
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and distribution are expressly prohibited. Page 24 of 32
National Fire Protection Association (NFPA). 2012. NFPA 704: Standard System for the
Identification of Hazards of Materials for Emergency Response. Available at:
http://www.nfpa.org/codes-and-standards/free-access
National Toxicology Program (NTP). Undated. Benzyl alcohol mouse lymphoma assay. Study
Number 464779. National Institute of Environmental Health Sciences, Department of Health and
Human Services. Available at: http://tools.niehs.nih.gov/cebs3/ntpViews/?studyNumber=002-
01714-0009-0000-4.
National Toxicology Program (NTP). 1984. Benzyl alcohol in vitro cytogenetics assays. Study
Number 944840. National Institute of Environmental Health Sciences, Department of Health and
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01714-0002-0000-7 and http://tools.niehs.nih.gov/cebs3/ntpViews/?studyNumber=002-01714-0001-
0000-6.
National Toxicology Program (NTP). 1987. Benzyl alcohol sex linked recessive lethal assay. Study
Number 419402. National Institute of Environmental Health Sciences, Department of Health and
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01714-0008-0000-3.
National Toxicology Program (NTP). 1989. NTP Technical Report on the Toxicology and
Carcinogenesis Studies of Benzyl Alcohol (CAS No. 100-51-6) in F344/N Rats and B6C3F1 Mice
(Gavage Studies). NTP TR 343, NIH Publication No. 89-2599. National Institutes of Health, Public
Health Service, U.S. Department of Health and Human Services. Available at:
http://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr343.pdf.
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http://www.paint.org/component/docman/cat_view/49-hmis.html.
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Analysis of the need for appropriate consumer information and identification of consumer allergens.
SCCNFP/0017/98 Final. Available at: www.expub.com.
Siegert, W. 2014. Approved Preservatives for Cosmetics. Berlin: Schülke & Mayer GmbH.
Sigma-Aldrich. 2014. Safety Data Sheet for Benzyl Alcohol (CAS #100-51-6). Product Number
80708. Version 5.9. Revision date July 31, 2014. Available at:
http://www.sigmaaldrich.com/catalog/product/fluka/80708?lang=en®ion=US.
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ToxServices. 2013. SOP 1.37: GreenScreen® Hazard Assessments. Dated: April 24, 2013.
University of Illinois at Chicago (UIC). Undated. Drug information updates. Benzyl alcohol
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http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.
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APPENDIX A: Hazard Benchmark Acronyms
(in alphabetical order)
(AA) Acute Aquatic Toxicity
(AT) Acute Mammalian Toxicity
(B) Bioaccumulation
(C) Carcinogenicity
(CA) Chronic Aquatic Toxicity
(D) Developmental Toxicity
(E) Endocrine Activity
(F) Flammability
(IrE) Eye Irritation/Corrosivity
(IrS) Skin Irritation/Corrosivity
(M) Mutagenicity and Genotoxicity
(N) Neurotoxicity
(P) Persistence
(R) Reproductive Toxicity
(Rx) Reactivity
(SnS) Sensitization- Skin
(SnR) Sensitization- Respiratory
(ST) Systemic/Organ Toxicity
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APPENDIX B: Results of Automated GreenScreen® Score Calculation for Benzyl Alcohol (CAS #100-51-6)
Ca
rcin
og
enic
ity
Mu
tag
enic
ity
/Gen
oto
xic
ity
Rep
rod
uct
ive
To
xic
ity
Dev
elo
pm
enta
l T
ox
icit
y
En
do
crin
e A
ctiv
ity
Acu
te T
ox
icit
y
Sk
in S
ensi
tiza
tio
n*
Res
pir
ato
ry S
ensi
tiza
tio
n*
Sk
in I
rrit
ati
on
Ey
e Ir
rita
tio
n
Acu
te A
qu
ati
c T
ox
icit
y
Ch
ron
ic A
qu
ati
c T
ox
icit
y
Per
sist
ence
Bio
acc
um
ula
tio
n
Rea
ctiv
ity
Fla
mm
ab
ilit
y
S R * S R * * *
Inorganic
Chemical?
Chemical
NameCAS# C M R D E AT STs STr Ns Nr SNS* SNR* IrS IrE AA CA P B Rx F
No Benzyl Alcohol 100-51-6 L L L M DG M DG L M H H DG L H L L vL vL L L
a b c d e f g
No No No No No
No No No No Yes Yes No
STOP
STOP
a b c d e f g h i j bm4End
Result
Yes Yes Yes Yes Yes 2
Final
GreenScreen®
Benchmark Score
1Benzyl Alcohol 2
GreenScreen® Score Inspector
Table 1: Hazard Table
Group I Human Group II and II* Human Ecotox Fate Physical
Sy
stem
ic T
ox
icit
y
Neu
roto
xic
ity
Table 2: Chemical Details
Table 3: Hazard Summary Table Table 6
Benchmark Chemical Name
Preliminary
GreenScreen®
Benchmark Score
Chemical Name
Table 4
2
3
4
22
Note: Chemical has not undergone a data gap
assessment. Not a Final GreenScreenTM
Score
After Data gap Assessment
Note: No Data gap Assessment Done if Preliminary
GS Benchmark Score is 1.4
Table 5: Data Gap Assessment Table
Datagap Criteria
3
Benzyl Alcohol
1
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APPENDIX C: Pharos Output for Benzyl Alcohol (CAS #100-51-6)
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APPENDIX D: EPISuite Modeling Results for Benzyl Alcohol (CAS #100-51-6)
CAS Number: 100-51-6
SMILES : OCc(cccc1)c1
CHEM : Benzenemethanol
MOL FOR: C7 H8 O1
MOL WT : 108.14
------------------------------ EPI SUMMARY (v4.11) --------------------------
Physical Property Inputs:
Log Kow (octanol-water): 1.05
Boiling Point (deg C) : ------
Melting Point (deg C) : -15.40
Vapor Pressure (mm Hg) : 0.053
Water Solubility (mg/L): 40000
Henry LC (atm-m3/mole) : ------
Log Octanol-Water Partition Coef (SRC):
Log Kow (KOWWIN v1.68 estimate) = 1.08
Log Kow (Exper. database match) = 1.10
Exper. Ref: HANSCH,C ET AL. (1995)
Boiling Pt, Melting Pt, Vapor Pressure Estimations (MPBPVP v1.43):
Boiling Pt (deg C): 205.65 (Adapted Stein & Brown method)
Melting Pt (deg C): -5.43 (Mean or Weighted MP)
VP(mm Hg,25 deg C): 0.0535 (Mean VP of Antoine & Grain methods)
VP (Pa, 25 deg C) : 7.14 (Mean VP of Antoine & Grain methods)
MP (exp database): -15.2 deg C
BP (exp database): 205.3 deg C
VP (exp database): 9.40E-02 mm Hg (1.25E+001 Pa) at 25 deg C
Water Solubility Estimate from Log Kow (WSKOW v1.42):
Water Solubility at 25 deg C (mg/L): 6.36e+004
log Kow used: 1.05 (user entered)
melt pt used: -15.40 deg C
Water Sol (Exper. database match) = 4.29e+004 mg/L (25 deg C)
Exper. Ref: YALKOWSKY,SH & DANNENFELSER,RM (1992)
Water Sol Estimate from Fragments:
Wat Sol (v1.01 est) = 32322 mg/L
ECOSAR Class Program (ECOSAR v1.11):
Class(es) found:
Benzyl Alcohols
Henrys Law Constant (25 deg C) [HENRYWIN v3.20]:
Bond Method : 2.17E-007 atm-m3/mole (2.20E-002 Pa-m3/mole)
Group Method: 4.66E-008 atm-m3/mole (4.72E-003 Pa-m3/mole)
Exper Database: 3.37E-07 atm-m3/mole (3.41E-002 Pa-m3/mole)
For Henry LC Comparison Purposes:
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User-Entered Henry LC: not entered
Henrys LC [via VP/WSol estimate using User-Entered or Estimated values]:
HLC: 1.885E-007 atm-m3/mole (1.910E-002 Pa-m3/mole)
VP: 0.053 mm Hg (source: User-Entered)
WS: 4E+004 mg/L (source: User-Entered)
Log Octanol-Air Partition Coefficient (25 deg C) [KOAWIN v1.10]:
Log Kow used: 1.05 (user entered)
Log Kaw used: -4.861 (exp database)
Log Koa (KOAWIN v1.10 estimate): 5.911
Log Koa (experimental database): None
Probability of Rapid Biodegradation (BIOWIN v4.10):
Biowin1 (Linear Model) : 0.9829
Biowin2 (Non-Linear Model) : 0.9878
Expert Survey Biodegradation Results:
Biowin3 (Ultimate Survey Model): 3.1422 (weeks )
Biowin4 (Primary Survey Model) : 3.8261 (days )
MITI Biodegradation Probability:
Biowin5 (MITI Linear Model) : 0.5370
Biowin6 (MITI Non-Linear Model): 0.7077
Anaerobic Biodegradation Probability:
Biowin7 (Anaerobic Linear Model): 0.7025
Ready Biodegradability Prediction: YES
Hydrocarbon Biodegradation (BioHCwin v1.01):
Structure incompatible with current estimation method!
Sorption to aerosols (25 Dec C)[AEROWIN v1.00]:
Vapor pressure (liquid/subcooled): 7.07 Pa (0.053 mm Hg)
Log Koa (Koawin est ): 5.911
Kp (particle/gas partition coef. (m3/ug)):
Mackay model : 4.25E-007
Octanol/air (Koa) model: 2E-007
Fraction sorbed to airborne particulates (phi):
Junge-Pankow model : 1.53E-005
Mackay model : 3.4E-005
Octanol/air (Koa) model: 1.6E-005
Atmospheric Oxidation (25 deg C) [AopWin v1.92]:
Hydroxyl Radicals Reaction:
OVERALL OH Rate Constant = 8.2541 E-12 cm3/molecule-sec
Half-Life = 1.296 Days (12-hr day; 1.5E6 OH/cm3)
Half-Life = 15.550 Hrs
Ozone Reaction:
No Ozone Reaction Estimation
Fraction sorbed to airborne particulates (phi):
2.46E-005 (Junge-Pankow, Mackay avg)
1.6E-005 (Koa method)
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Note: the sorbed fraction may be resistant to atmospheric oxidation
Soil Adsorption Coefficient (KOCWIN v2.00):
Koc : 21.46 L/kg (MCI method)
Log Koc: 1.332 (MCI method)
Koc : 12.43 L/kg (Kow method)
Log Koc: 1.094 (Kow method)
Experimental Log Koc: 1.1 (database)
Aqueous Base/Acid-Catalyzed Hydrolysis (25 deg C) [HYDROWIN v2.00]:
Rate constants can NOT be estimated for this structure!
Bioaccumulation Estimates (BCFBAF v3.01):
Log BCF from regression-based method = 0.104 (BCF = 1.271 L/kg wet-wt)
Log Biotransformation Half-life (HL) = -1.5888 days (HL = 0.02578 days)
Log BCF Arnot-Gobas method (upper trophic) = 0.167 (BCF = 1.47)
Log BAF Arnot-Gobas method (upper trophic) = 0.167 (BAF = 1.47)
log Kow used: 1.05 (user entered)
Volatilization from Water:
Henry LC: 3.37E-007 atm-m3/mole (Henry experimental database)
Half-Life from Model River: 1808 hours (75.32 days)
Half-Life from Model Lake : 1.981E+004 hours (825.3 days)
Removal In Wastewater Treatment:
Total removal: 1.91 percent
Total biodegradation: 0.09 percent
Total sludge adsorption: 1.80 percent
Total to Air: 0.02 percent
(using 10000 hr Bio P,A,S)
Level III Fugacity Model:
Mass Amount Half-Life Emissions
(percent) (hr) (kg/hr)
Air 1.03 11.2 1000
Water 34 360 1000
Soil 64.8 720 1000
Sediment 0.0929 3.24e+003 0
Persistence Time: 424 hr
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Licensed GreenScreen® Profilers
Benzyl Alcohol GreenScreen® Evaluation Prepared by:
Zach Guerrette, Ph.D.
Toxicologist
ToxServices LLC
Benzyl Alcohol GreenScreen® Evaluation QC’d by:
Bingxuan Wang, Ph.D.
Toxicologist
ToxServices LLC