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EC number: 208-754-4
CAS number: 540-72-7
Rapid and complete oral absorption and low dermal absorption; predominantly extracellular distribution; rapid excretion of unchanged compound via urine. No bioaccumulation potential.
For the evaluation of Sodium thiocyanate use
is made of a category approach on the principle that for salts of
thiocyanic acid that are readily dissociable in water, the toxicity is
driven by SCN-, whereas the cation (NH4+, Na+, or K+) does not play a
role of importance for the hazard evaluation, except possibly for local
effects where ammonium ion might not be representative for the K or Na
Therefore, in case data is lacking for
Sodium thiocyanate for a specific endpoint, use is made from
cross-reading where possible from Ammonium or potassium thiocyanate.
Dose levels are then converted based on the difference of molecular
weight between these salts, to make them equivalent on the basis of the
amounts of thiocyanate.
Thiocyanates are of low acute toxicity.
There are many acute oral LD50 values reported in literature for the
ammonium, sodium and potassium thiocyanate salts, that are all within
the same range falling in the category of 300-2000 mg/kg bw (GHS Cat
IV). There is no large species difference, although possibly dogs are
more sensitive. Also information on acute toxicity via other routes of
application, including i.p., s.c. and i.v. in various species, indicate
a similar level of acute toxicity compared to oral. This indicates that
oral absorption is complete, and that following absorption by any route
the distribution over the extracellular volume is the same. (Except for
i.v. administration, where KSCN is about 5 times more toxic, which is
caused by the toxicity of the potassium for the heart.)
Acute dermal toxicity is low, with an LD50
available for KSCN > 2000 mg/kg bw. There is no information on
Local effects to skin and eyes are mediated
by the cation. In vivo eye irritation studies in rabbits have shown
Ammonium and Sodium thiocyanate to result to severe effects on the eyes
requiring classification as severe eye irritant Cat.1. Studies on rabbit
skin have shown Ammonium thiocyanate to be not irritating to skin. This
results was confirmed byin vitrotesting using RhE (Episkin). Also
Sodium thiocyanate was shown not to be irritating to skin in this test
Thiocyanates are not sensitising as
indicated by a LLNA with NaSCN.
For repeated dose, there is a standard
90-day oral gavage study in rats with NH4SCN resulting to a NOAEL of 20
mg/kg bw/day, based on changes in haematological and clinical chemistry
parameters seen at 100 mg. Mortality was observed at 500 mg/kg bw/day.
Dogs seem to be more sensitive as dose levels of potassium and sodium
thiocyanate of 100 mg/kg bw per day caused a progressive loss of weight,
apathy, head droop, ataxia, and ultimate death. Dogs receiving about 20
mg NaSCN or KSCN/kg bw per day for 12 weeks were in excellent condition
There are many studies on thiocyanate but
generally they only focus on thyroid function. Studies indicate that
hypothyroidy from thiocyanate exposures depend on iodide status. Effects
are fully reversible after ceasing exposures or with additional iodide
For reproduction toxicity limited data is
available. Again, the available studies focus on the possible goitrogen
effects of thiocyanate. A 2-generation study with fixed dose levels in
the food leading to exposures of 100-1000 mg/kgbw for the females,
resulted to hypothyroidy of these animals, but did not results in overt
reproduction toxicity as judged by the normal body weights of the pups.
Although a standard guideline study for the
assessment of reproduction toxicity is lacking and thus no firm
conclusion regarding the NOAEL for reproduction toxicity can be made (a
NOAEL on its own would basically also not be very informative as levels
would also depend on iodine and thiocyanate levels in used feed),
indications are that at levels not leading to hypothyroidy, reproduction
toxicity is unlikely. Classification for reproduction toxicity is
therefore not indicated, and further studies are not expected to lead to
additional relevant information.
Toxicokinetics, metabolism and
There are no OECD guideline or GLP reports
available from studies on dermal and gastro-intestinal absorption,
distribution, metabolism and excretion.
However based on the available literature
and reviews by WHO (1993), DECOS (2003) and the RMM DAR from the KSCN
PPP dossier (2008) a basic toxicokinetic assessment can be performed.
For the full assessment please refer to section 13 of this IUCLID5 file
and section 5.1 of the attached chemical safety assessment.
Based on the available data on animals and
humans the following conclusions can be drawn.
The compound is rapidly and almost
completely absorbed after oral exposure. In humans the distribution of
thiocyanate in the body is predominantly extracellular. The majority of
the thiocyanate entering the body is rapidly excreted as compound via
urine. Small amounts are excreted in the expired air as CO2 or HCN or
are taken up in the one-carbon pool via formic acid. Studies in humans
have shown that thiocyanate can be transported to the foetus.
Dermal absorption is considered to be low
based on the general notion that salts of ionic substances are not
easily absorbed via skin. The estimated log Kow value (KOWWIN v1.67) is
-2.52 for sodium thiocyanate, and in general with a logPow <-1 no
dermal absorption is taken into account.
Comparing the oral LD50 of around 500 mg/kg
bw, with the dermal LD50 is > 2000 mg/kg (showing no mortality) confirms
lower absorption rates via dermal route.
The rate of absorption will be low, but in
case only very small amounts are deposited on the skin, a relative
larger fraction of the deposited amount will be absorbed. On the other
hand, when a large amount /volume is deposited, the low rate of
absorption makes that the actual absorbed amounts as fraction of the
exposure is very low.
There is one study from literature on KSCN
in human subjects indicating a dermal absorption of 10.15% ± 6.60% of
the administered dose.(Feldmann RJ, Maibach HI., 1970, Absorption of
some organic compounds through the skin in man, Invest Dermatol.
54(5):399-404.). This involves exposure of very small amount of
radiolabelled material, and consequently the reported absorbed fraction
is relatively high. (4 µg KSCN/cm2, total surface 13 cm2,
skin not washed for 24 hrs; observations for 5 days). The study
concluded to an absorption rate of 10.15% ± 6.60% of the administered
dose, with a maximum rate of 0.1%/hr seen between day 3 and 4.
Considering that this study represents the worst case condition (low
amounts very long exposure times) the dermal absorption is set at 10%.
Physical-chemical properties of thiocyanates
indicate a low likelihood for exposure via inhalation, with a boiling
point > 300 °C and low vapour pressure (< 1.33 x 10-8 Pa; read-across
from KSCN). Furthermore thiocyanates are very hygroscopic, and inhalable
particles are not available and will generally also not be formed during
handling and use of the substance.
Thiocyanate can also be formed in the body
by transsulfurization, which entails the transference of sulphur by
mercaptopyruvate, thiosulphate and other sulphur sources to cyanide. A
key role in detoxicfication of cyanide is played by the enzyme
rhodanese, which catalyses the reaction of thiosulphate with cyanide to
thiocyanate and sulphite.
Thiocyanate is secreted by the mammary and
salivary glands and the gastric mucosa. This secretion is functional as
the compound serves in mammals as a substrate for the peroxidase in
milk, saliva and gastric juice. Excessive amounts of thiocyanate are
excreted in the urine. With a normal renal function the half life for
the elimination is 2 to 5 days.
For the general population the average daily
intake of thiocyanates through food via natural sources is estimated to
be between 10-14 mg/day (0.17-0.23 mg/kgbw/day). Natural background
serum concentrations of thiocyanate found are 33.5 ± 25.4 µM for
non-smokers and 111.2 ± 92.1 µM smokers (Tsuge, 2000), and after diner
levels up to 160 µM of serum were seen (Eminedoki, 1994). 160 µM SCN-
compares to 12 mg NH4SCN/L.Also evaluations have been performed as
to the possible beneficial effects of physiological intake levels of in
total of 100 mg NaSCN/day and use as feed additive (Weuffen, 2003). This
publication also lists values of various background levels of
thiocyanates in surface waters, drink water, air, food and body fluids.
The most consistent and most critical effect
of thiocyanate is the inhibition of the thyroid function through
competitive inhibition of the uptake by iodine.
Goiter endemics were reported to develop
when the critical urinary iodine/ SCN− ratio decreases below 3 µg iodine
per mg SCN−. Iodine supplementation completely reverses the goitrogenic
influence of SCN−. (Erdoğan MF, 2003, BioFactors 19;107–111)
SCN− is also generated from cigarette
smoking as a detoxifying product of cyanide.
In the absence of severe iodine deficiency
or iodine excess, adverse thyroidal effects occur with chronic serum
thiocyanate concentrations ≥200 µmol/L whereas non-adverse effects are
observed with concentrations in the range of 65–85 µmol/L. No adverse or
non-adverse effects are observed at serum concentrations below 50
µmol/L, even among sensitive subpopulations. (Gibbs JP, 2006,
Hum.Ecol.Risk Assess. 12:1;157-173)
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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