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EC number: 252-104-2
CAS number: 34590-94-8
document entitled "P-series glycol ethers DNELs overview" attached to
this endpoint summary for a full overview of the DNELs.
for the Toxicodynamic factor (TkD)
the P-series glycol ethers there are toxicity studies on several
different species (rat, rabbit, mouse, guinea pig, monkey, etc.). Where
comparable studies are available for the same substance in two or more
different species it is clear that there is little difference in the
NOELs. For example, for PM there are 90-day repeated dose toxicity
studies in rats, rabbits, and mice. The NOEC in each study is 1000 ppm.
For DPM there are 28 to 31 week inhalation studies in rats, monkeys,
rabbits and guinea pigs. The NOEC for each species is 300 ppm. Based on
the consistency in NOELs between species it appears that adjusting for
Allometric scaling when deriving the DNELs would be sufficient to
address any potential inter species differences. As such it is
considered justified to use a factor 1 for the ‘toxicodynamic
for the Duration factor
2011 publication of Batke et al. (2011)an
analysis of the RepDose database to derive appropriate assessment
factors for extrapolating a NOEL from a shorter to a longer term study
was presented. The study determined that in many cases the default
factors proposed by ECHA are unnecessarily conservative and that in the
case of rapidly metabolised substances that do not have the potential to
bioaccumulate and have a minimal toxicological fingerprint, lower
factors can be used to extrapolate from shorter to longer durations. The
data available on the P-series glycol ethers indicates that they are
rapidly and extensively metabolised and have no potential for
bioaccumulation. As such it is considered justified to use the
assessment factors proposed by Batke et al. (2011).
M; Escher S; Hoffmann-Doerr S; Melber C; Messinger H; Mangelsdorf I
(2011).Evaluation of time extrapolation factors based on the database
Intraspecies Assessment Factor
to the ECHA guidance document, where scientific justification exists,
one can deviate from the default ECHA assessment factors used in DENL
derivation. In deriving DNELS, the assessment factor chosen for
Intraspecies variability (worker and general population) has been taken
from the ECETOC technical report no, 110 as an alternative to the ECHA
default. The ECETOC working group performed a detailed assessment of the
many publications available on human variability as it pertains to risk
assessment. As a consequence of this assessment it was determined that
in the majority of cases a factor of 3 for worker or 5 for general
population is sufficient to address Intraspecies variability.
Specifically considering the p-series glycol ethers, they have a low
order of toxicity, with key effects primarily limited to adaptive
effects in the liver and kidney (likely associated with either enzyme
induction or alpha 2u-globulin formation). These substances also
demonstrate very little variability in effect levels and target organs
when tested in multiple species and for multiple durations (sub-acute to
chronic). As such it is considered that the lower assessment factors
proposed by ECETOC should adequately address the Intraspecies
variability within the risk assessment.
DNELs have been derived for:
systemic, long term
Systemic, long term
The EU-Scientific Committee for Occupational Exposure Limits
(SCOEL) established an OEL of 50 ppm based on the NOEC of 200 ppm from
the 90-day repeated dose inhalation study in rats. This is equivalent to
308 mg/m3. In accordance with the ECHA guidance on DNELs (R8)
this OEL will be used as DNEL for long-term inhalation.
DNEL = 308 mg/m3
Starting point for DNEL derivation: 13-week repeated dose dermal
toxicity study in rabbits; NOAEL for systemic effects of 2850 mg/kg
No adjustment is made for inter-species bioavailability (rabbit
Total factor = 10.08
No factor used for ‘other differences’
DNEL =283 mg/kg bw/day
DNELS have been derived for:
systemic, long term
systemic, long term
For the DNEL calculation the dose descriptor used was the
worker-DNEL-long term for the inhalation route (50 ppm). This was
corrected for the differences in duration of exposure between worker and
consumer (24h per day, 7 days per week vs. 8hr per day, 5 days per week)
and the intra-species differences (worker vs. general population), a
factor of 2.
DNEL = 37 mg/m3
Duration adjustment has been made to correct for exposure
differences between the study animals (5 days/week) and general
population (7 days/week).
Modified starting point = 2035 mg/kg bw/day
Population variability: 5
Total factor = 16.8
DNEL = 121 mg/kg bw/day
Starting point for DNEL derivation: 28-day repeated dose oral
toxicity study in rats; NOAEL of 1000 mg/kg bw/day.
No adjustment made for inter-species bioavailability (rats vs.
population variability: 5
Total factor = 28
No additional factor is used for ‘other differences’. The Duration
factor of 1.4 is used rather than the factor of 3.4 proposed by Batkeet
al.(2011) when extrapolating from a short term repeated dose
toxicity study to a chronic exposure. This is justified because the
NOECs from repeated dose inhalation studies do not significantly differ
when comparing the short term and long term studies. As such, the
duration appears to have minimal effect on the DNEL.
DNEL = 36 mg/kg bw/day
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