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EC number: 266-582-5
CAS number: 67124-09-8
calculation of the DNELs is performed in accordance with the principles
given in ECHA (2008) “Guidance of Information Requirements and Chemical
Safety Assessment, Chapter R.8: Characterisation of dose
[concentration]-response for human health.”
1-(tert-dodecylthio)propan-2-ol, DNELs are needed for:
exposure by dermal route (local effects, workers and consumers),
exposure by oral route (systemic effects; only for consumers),
exposure by dermal route (systemic effects; workers and consumers),
exposure by inhalation routes (systemic effects; workers and consumers).
substance is not acutely toxic by dermal route of exposure, no DNEL for
acute systemic effects needs to be derived. A LD50 greater than 2000
mg/kg bw (OECD 434) is considered to be a NOAEL because no mortalities
and no systemic signs of toxicity were observed in treated animals
(Morris, 1991). Signs of slight dermal irritation were noted. Any risk
should be assessed qualitatively.
dermal DNEL for local effects is calculated because the test material is
a weak skin sensitizer in a LLNA study in rats (OECD 429) (Sanders,
2012). The DNEL is derived from the corrected NOAEL which was obtained
by conversion of EC3 value of 14.2 wt %. Such a DNEL can be used to
judge the remaining /residual likelihood of risks. However, the general
approach for assessing and controlling of risk of dermal sensitization
is qualitative (see Appendix III "Derivation of DNEL for skin
for inhalation (systemic and local) are not necessary since there is no
acute toxic hazard by inhalation.
systemic DNELs (dermal and inhalation) are derived from the results of
one-generation study in rats (OECD 415) (Thorsrud, 2002). Reproductive
toxicity was considered to be the most sensitive endpoint. These DNELs
ensure sufficient that reproductive toxicity effects in humans will not
occur. The dose level of 167 mg/kg bw was determined to be NOAEL for
parental toxicity and for developmental effects (see Discussion in
section 5.9.3 of CSR or refer to section 7.8. of IUCLID file).
long-term local DNEL (inhalation) is because there is no dose-response
and route-specific information on this endpoint. The substance is not
irritating/or sensitizing to respiratory system and does not pose a
hazard for humans by inhalation route of exposure (low vapour pressure
of 0.63 Pa). Long-term systemic DNEL covers sufficiently local effects.
long-term dermal DNEL for local effects is derived because the substance
is not irritating to skin and the systemic dermal DNEL is sufficient to
cover local effects.
qualitative approach in hazard assessment for eye and skin
irritation/corrosion is used because no dose descriptors are available
on these endpoints.
non-threshold endpoints (mutagenicity and carcinogenicity) no DNELs can
be derived because a No Observed Effect Level could not be established
from the relevant studies. Hence, the hazard characterization is based
on a qualitative approach.
available data for the different human health endpoints it is clear that
1-(tert dodecylthio) propan-2- exerts its effect by a threshold mode of
action. Thus, DNELs can be calculated for the different threshold
endpoints based on the most relevant dose descriptors per endpoint.
DNELs are derived based on the available toxicity data for the related
substances, reflecting the routes, duration and frequency of exposure.
DNELs are derived for workers and the general population. The general
population includes consumers and humans exposed via the environment.
noted in treated animals in the oral acute, sub-acute and in the
one-generation study point to the fact that the substance became
systemic available. The absorption by oral route is considered 100% and
assumed to be the same in rats and in humans due to the absence of route
specific information on rate of absorption. Dermal absorption of the
test susbtance is considered to be 50% (see Discussion in section 7.1.2.
"Dermal absorption" of the IUCLIF file and Appendix I in the CSR) and
assumed also to be equal in rats and in humans. A negligible absorption
by inhalation is assumed for the target chemical but in the absence of
information it is set to 100%.
dermal extrapolation is performed to derive long-term DNEL for systemic
effects. Since oral absorption was set to 100% and dermal to 50%, a
factor of 2 was used to adjust systemic available oral dose to the
systemic available dose resulting after dermal exposure (see Annex I
"Oral-to-dermal extrapolation" in the CSR). Oral-to-inhalation
extrapolation is performed to assess long-term inhalation effects in
humans. Due to the low vapour presure (0.63 Pa at 20°C), a low
bioavalability by inhalation route is considered for the target
chemical. Therefore, absorption rates by inhalation cannot be higher
than the absorption rates by oral route and assumed to be the same and
equal to 100% (realistic "worst-case") (see Annex II "Oral-to-inhalation
time differed in workers and in animals in the one-generation study.
Rats were exposed to the test substance per oral daily (5 days/week),
while workers are exposed 8h daily (5days/week). However, the dose
descriptor (the NOAEL of 167 mg/kg bw) was not adjusted to 8h exposure
because exposure time is not really relevant for the systemic dose.
in the respiratory volumes between experimental animals and humans were
used when an oral rat NOAEL from the sub-chronic dietary study in rats
was used to assess inhalation exposure in humans. 0.38 m³/kg/day is the
standard respiratory volumes in rats during 8h exposure. 6.7 and 10 m³
are standard respiratory volumes for workers under normal conditions and
by light activity, respectively.
of EC3 value to NOAEL
substance induced a dermal sensitization response with a calculated EC3
of 14.2 wt% and
the criteria as a weak dermal sensitizer (ECETOC Technical Report 87,
“Contact Sensitisation: Classification According to Potency”; Griem et
al., 2003). It is recognized that EC3 values is close enough to the
human NOAEL from human sensitization tests designed to confirm lack of
induction and therefore it can be used as a surrogate for the NOAEL
(ECHA Guidance R. 8, Appendix R.8 -10).
A threshold for skin sensitization can be
defined as EC3 concentration (%), which is converted into dose per skin
area (in µg/cm²):
EC3[%] x ρ
x 250 [µg/cm²/%]
= EC3[µg/cm²] = NOAEL
ρ is density of the liquid, 250 factor is calculated by converting 25 µL
(applied to the mouse ear in a standard LLNA protocol) into µg/cm².
[%] x ρ x 250 [µg/cm²/%] = 14.2 x 0.91 x 250 = 3230.5 [µg/cm²]
of the oral NOAEL into dermal NOAEL (long-term exposure - systemic
dermal NOAEL = oral rat NOAEL x (ABS oral-rat/ABS dermal-human) = 167
mg/kg bw x (100%/50%) = 334 mg/kg bw. There is no information available
on oral absorption in rat and in human therefore it is assumed to be the
same and equal 100% (worst case). Low dermal absorption potential (50%)
is considered for the target substance. (see Annex I "Oral-to-dermal
of the oral NOAEL into inhalation NOAEC (long-term exposure - systemic
NOAEC = oral rat NOAEL x (1/0.38m³) x (ABS oral-rat/ABS inh-human) x
(6.7/10)m³ = 167 mg/kg bw x (1/0.38m³) x (100%/100%) x (6.7/10)m³ =
294.4 mg/m³. A low bioavalability by the inhalation route is considered
for the taget substance.
of assessment factors and calculation of DNELs:
assessment factors have been applied to the correct starting point to
obtain the endpoint specific DNELs. Assessment factors (AFs) correct
uncertainties and variability within and between species in the effect
species-specific default assessment factor of 4 for allometric scaling
for rats is applied in case of usage of oral NOAEL to derive dermal
differences factor of 1 is applied in case of derivation of acute dermal
DNEL for local effects using EC3 value from sensitization study because
skin sensitization is local immunological effect (see Appendix III
"Derivation of DNEL for skin sensitization");
allometric scaling factor is applied in case of oral-to-inhalation
assessment factors of 2.5 is applied for remaining interspecies
differences in toxicodynamics between rat and human. In case of DNEL for
dermal sensitization, no factor for remaining differences have been
applied since toxicokinetic and toxycodynamic by sensitization response
are the same across mammalian species (Api, 2006; Basketter, 2000,
listed in Appendix III).
factor of 5 is applied for workers for all endpoints and for all
factor of 2 was applied for duration of exposure (one –generation
study). Males were exposed 119 days to test material; females were
exposed 14 days before mating, throughout the gestation (21 days) and
lactation (21 days) resulting in 56 days (exposure duration is between
sub-acute and sub-chronic). "Compounds, such as most industrial
chemicals, that have relatively short-hilf lives, are not reactive to
tissue components and do not deplete essential elements, might
have NOAEL in 28-day studies close to those for chronic studies" is
mentioned in the ECETOC Technical Report No.86 "Derivation of Assessment
Factors for Human Health Risk Assessment". Based on the toxicity pattern
of test substance, the NOAEL of 167 mg/kg bw obtained in the
one-generation study is expected to be close to one of subchronic
duration and therefore the assessment factor of 2 is considered
related to dose response:
factor of 3 was used in case of using EC3 value for the derivation of
DNEL for dermal sensitization. Two independent studies were conducted on
this substance, and the test material is shown to be weak sensitizer
of whole data base:
assessment factor for uncertainties to the quality of the data base is
regarded to be 1.
exposure – local effects (dermal)
sensitization= 3230.5 µg/cm²÷(1 x 1 x 5 x 3 x 1) = 215.4 µg/cm²
where AFs are: 1 -interspecies, 1 - remaining interspecies differences,
5 - intraspecies, 3 – dose response, 1 - quality of data base.
exposure - systemic effects (dermal)
systemic= 334 mg/kg bw ÷ (4 x 2.5 x 5 x 2 x 1) = 3.34 mg/kg bw.
AFs are: 4 - interspecies, 5 - intraspecies, 2.5 - remaining
interspecies differences in toxicodynamics between rat and human, 2 -
duration of exposure (one-generation study), 1- quality of data base.
exposure - systemic effects (inhalation)
systemic= 294.4 mg/m³ ÷ (2.5 x 5 x 2 x 1) = 11.8 mg/m³. AFs are:
2.5 - remaining interspecies differences, 5 - intraspecies, 2 - duration
of exposure (one-generation study), 1 - quality of data base.
principles of the DNEL calculation for the general population are the
same as already described for workers. However, there are additional
considerations or deviations for:
of the starting point:
(absorption by oral route)
oral absorption in rats and in humans is assumed to be the same since no
information for oral absorption for target chemical in rats and in
humans is available.
differences in the respiratory volumes under normal conditions and by
light activity in humans were taken into account.
of assessment factors:
higher assessment factor of 10 (in place of 5 for workers) for
intraspecies variation/differences of human population was used.
of endpoint-specific DNEL for general population
conversion of the repeated oral rat NOAEL into inhalation NOAEC was
performed as follows:
inhalation NOAEC = oral rat NOAEL x (1/1.15 m³/kg bw/day x (ABS
oral-rat/ABS inhal-human),where 1.15 is standard respiratory volume
(m³/kg bw) of rats during 24 h exposure, ABS is absorption (values are
the same as described for workers).
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