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EC number: 609-530-2
CAS number: 38172-91-7
Based on the physicochemical properties and the results obtained
in the toxicity tests, fractions of the reaction mass will be absorbed
via the GI tract and become systemically available.
Uptake into the systemic circulation following dermal exposure is
very limited due to high water solubility of the substance at room
temperature. Also, based on the high water solubility and the results
obtained in the respective toxicological investigation, it is unlikely
that relevant amounts of the reaction mass will become systemically
bioavailable via inhalation.
After becoming bioavailable, it is assumed that the substance and
its metabolites will circulate within the blood stream and will finally
be transported to the liver where Phase I and Phase II metabolism may
occur. Ultimately the metabolism products will be excreted via the
kidney in the urine or by exhalation as CO2.
Based on its BCF values neither the constituents of the reaction
mass nor its potential metabolism products are considered to be
1 Physico-Chemical Data on 2-Propyn-1-ol compound with
The organic reaction product composed of 2-Propyn-1-ol compound
with methyloxirane appears as a clear colourless liquid at standard
ambient temperature and pressure. Depending on the degree
of polymerisation the molecular weight of the reaction product will be
found in the range of 114.5 to 230.31 g/mol. At standard ambient
pressure, the melting point is minus 22°C while the boiling point was
determined to be at 101.8°C. The
reaction product is very miscible with water soluble as
indicated by the measured water solubility value of 1000 g/L
empirically measured logPow was found to be 0.0 at 24°C (shake flask
method). A BCF value of 3.162 L/kg wet-weight was calculated using
EPIWIN. The substance has a vapour pressure of 0.43 hPa
2 Toxicokinetic analysis of 2-Propyn-1-ol compound with
Due to the very high water solubility and the low logPow of the
reaction product, systemic uptake via passive diffusion is limited
within the gastro intestinal (GI) tract. However, water soluble
chemicals will readily dissolve into the GI fluids which in turn enhance
the contact with the intestinal mucosa. Considering that the smaller a
molecule, the more easily it may be taken up, reaction products with a
molecular weight below 200 g/mol, which is the case for the majority of
the UVCB, may pass through aqueous pores or may be carried through the
epithelial barrier by the bulk passage of water.
With regards to toxicological data on the reaction product, an
acute oral systemic toxicity study in rats determined the LD50 for male
animals to be 464 mg/kg bw and for female animals to be higher than 464
mg/kg bw. For animals that died during the study, observed adverse
effects included general congestion, bloody ulcerations in the glandular
stomach and a yellow brown discoloration of the liver. Animals scarified
after the end of the study did not show any pathological findings. Here,
it remains unclear if these effects are caused by systemic toxicity of
if they can be regarded as secondary effects caused by the local
irritation of the glandular stomach. More detailed information relating
to the bioavailability of the reaction product into systemic circulation
following oral intake can be derived from a subacute combined repeated
dose toxicity study with the reproduction and developmental toxicity
screening test (OECD 422) and an oral 90-day repeated dose toxicity
study (OECD 408). Here, results of the post mortem investigation
revealed that the organ weights of kidney and liver were increased in
both males and females at the high doses levels of 125 mg/kg bw/day
(OECD 422) and 150 mg/kg bw/day (OECD 408) respectively. These effects
provide evidence that the reaction product or its metabolites reaches
the systemic circulation following oral administration. In the OECD 408
study, histopathological changes in the liver and kidneys were noted and
the observed effects were considered to be adverse. In addition effects
on the body weights of the animals and on hematology and clinical
chemistry were observed in the OECD 408 study at 150 mg/kg bw/day.
Overall, based on the physicochemical properties and the results
obtained from the oral toxicity testing it can be assumed that the
reaction product or its metabolites becomes systemically available
following oral intake.
Based on the high water solubility of the reaction product, dermal
uptake is negligible. Its is commonly known that substances with a water
solubility above 10 g/L and a logPow value of ≤ 0 are too hydrophilic to
cross the lipid rich environment of the stratum corneum. These
assumptions, based on the physicochemical properties, are further
supported by results achieved from an acute dermal toxicity study with
the 2-Propyn-1-ol compound with methyloxirane performed on rats (OECD
402). During this study, no systemic effects were observed and the LD50
was determined to be > 2000 mg/kg bw (limit dose). Also, no skin
irritation potential and no immunological response were observed in a
irritation test on rabbit skin (OECD 404) and Murine Local Lymph Node
Assay (LLNA) (OECD 429) respectively.
Overall, the results from the dermal toxicity and sensitisation
testing do not suggest that toxicological relevant amounts of the
reaction product are absorbed and become systemically available and
consequently support the assumptions based on the substance’s
Considering the vapour pressure and the resulting low volatility,
it cannot be completely ruled out that fractions of the substance can be
inhaled when handled at room temperature. However, vapours of very
hydrophilic substances are retained in the mucus and are thus not
available for systemic absorption. Furthermore, results obtained from thein
vivoinhalation toxicity testing support the assumption that even if
the substance becomes bioavailable following inhalation, no toxicity
effects are to be expected. More specifically, no systemic toxicological
effects related to the test substance were noted in an acute inhalation
toxicity tests on rats (comparable to OECD 403). The respective LC50 was
determined to be greater than 5.1 mg/L based on reweighing of the test
material. This concentration was the maximum achievable vapour
concentration for the test material.
Once absorbed it is expected that the reaction products and its
metabolites are distributed within the blood stream. Here the transport
efficiency to the body tissues is limited by the rate at which the
highly water soluble substances cross cell membranes. More specifically,
access to the central nervous system or the testes is likely to be
restricted by the blood-brain and blood-testes barriers (Rozman and
Klaassen, 1996). The results observed in the subacute and subchronic
toxicity studies provide evidence that a transport to the liver and
Based on the low BCF value, the reaction product has a negligible
potential to bioaccumulate in the human body.
Based on the chemical structure, the main components of the
UVCB (sumformula: C6H10O2) most likely will undergo ether cleavage by
addition of H2O in the strong acidic environment of the stomach or by
Phase I enzymes once taken up into the body. This will lead to two
metabolites, namely Prop-2-yn-1-ol (CAS # 107-19-7) and Propane-1,2-diol
(CAS # 57-55-6). Propane-1,2-diol is converted by alcohol dehydrogenase
to lactaldehyde by a NAD-dependent reaction. Lactaldehyde is then
further metabolized to lactate which is a good substrate for
Prop-2-yn-1-olmetabolism in rats and mice was examined by
identifying urinary metabolites following oral administration of
radiolabelled test substance. In male Sprague-Dawley rats, 56 % of the
radioactivity administered was excreted in the urine within 96 hours.
The highest concentration was observed in the first 24 -hour urine. The
main metabolites were 2-propynoic acid,
3-(carboxymethylthio)-2-propenoic acid, and 3-[[2-(acetylamino)-2-
accounting for 27, 20, 20, and 15 %, respectively, of the total
radioactivity excreted in the urine during the first 24 hours
post-administration. From the results, it was suggested that the
metabolism of Propargyl alcohol in rats involves oxidation into
2-propynoic acid and multiple glutathione additions to the carbon-carbon
triple bond yielding numerous metabolites. In mice, about 60 % of the
radiolabel administered was excreted in the urine by 96 hours. The
highest concentration was observed in the first 24-hour urine. The main
metabolites were (E + Z)-3-[(2-amino-2-carboxyethyl)thio]-2-propenoic
3-[(2-formylamino-2-carboxyethyl)thio]-2-propenoic acid accounting for
41, 17, 15, and 13 %, respectively, of the total radioactivity excreted
in the urine during the first 24 hours post-administration. The data
suggested that metabolism of Propargyl alcohol in mice involves
glucuronide conjugation to form 2-propyn-1-ol glucuronide as well as
oxidation into 2-propynal which undergoes either multiple glutathione
additions or oxidation into 2-propynoic acid (only ca. 2 %). Comparison
of rat and mice data indicates quantitative and qualitative differences
in formation of glucuronide conjugates and of 2-propynoic acid and
metabolites derived from glutathione. In addition, extensive
enterohepatic recycling of metabolites via the bile is also evident
based on available data. In addition, metabolism via other Phase I
enzymes is also possible together with Phase II conjugation reactions
that may occur which covalently link an endogenous substrate to the
reaction product itself or to its Phase I metabolites in order to
ultimately facilitate excretion of the other components of the UVCB.
Based on the expected biotransformation reactions, molecular size
and water solubility, it is most likely that the final metabolites are
excreted via the urine or via exhalation of CO2. Fractions of the
chemical which are not absorbed within the GI tract will be readily
excreted via the faeces.
(2008), Guidance on information requirements and chemical safety
assessment, Chapter R.7c: Endpoint specific guidance.
Marquardt H., Schäfer S. (2004). Toxicology. Academic Press,,, 2nd
Mutschler E., Schäfer-Korting M. (2001) Arzneimittelwirkungen.
Lehrbuch der Pharmakologie und Toxikologie. Wissenschaftliche
Rozman K.K., Klaassen C.D. (1996) Absorption, Distribution, and
Excretion of Toxicants. In Klaassen C.D. (ed.) Cassarett and Doull's
Toxicology: The Basic Science of Poisons. McGraw-Hill, New York.
G., Metzler M. (1978) Biotransformation organischer Fremdsubstanzen.
Thieme Verlag, Stuttgart.
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