Opinion on the results of the Risk Assessment of : 2-(2-butoxyethoxy)ethanol [112-34-5] carried out in the framework of Council Regulation (EEC)793/93 on the evaluation and control of the risks of existing substances - Opinion expressed at the 6th CSTEE plenary meeting, Brussels, 27 November 1998
1. The
conclusions of the Risk Assessment Report are
not justified
1.1 Occupational
Exposure Levels should not be derived in Risk
Assessment Reports. However, the Rapporteur
derives Health Based Occupational Reference
Values (HBORV; i.e. safe levels for exposure
to chemicals at the workplace) from animal
studies by applying uncertainty factors.
Variability between species and between
individuals undoubtedly exist, but the
magnitudes of the respective uncertainty
factors are not scientifically justified or
rather arbitrary (see
General Comment).
1.2 The
HBORVs for dermal and
inhalative exposure are derived from NOELs
obtained from animal experiments, and applying
uncertainty factors which are scientifically
not justified.
The starting point for the calculation is
the 13-week study (Auletta et al. al. 1993)
with rats, exposed 6 h/d, 5 d/w to 0, 200, 600
or 2000 mg/kg bw. NOEL systemic :
³2000 mg/kg bw, erythema concentration
dependent. Applying an overall - uncertainty
factor of five a dermal HBORV of 37 mg/kg is
derived.
The starting point for the calculation is
the 13-week study (BASF 1992) with rats,
exposed 6 h/d, 5 d/w to 0, 13, 40 or 94 mg/m
3.
NOEL
³
94 mg/m
3
A summary of the uncertainty factors used
and derived OELs is given in the table:
| dermal
exposure | inhalative
exposure |
interspecies differences |
4 1)
x 3 |
3 |
intraspecies differences |
3 |
3 |
difference
between experimentalconditions and
exposure pattern of the worker |
32) |
22) |
dose-response curve |
0.53 |
1 |
confidence
in database |
1 |
24) |
overall
factor |
54 |
36 |
Calculated
HBORV |
2000
mg/kg / 54 =
37 mg/kg =2592 mg/d |
94 mg/m3
/ 23 =
2.6 mg/m3(i.e. ca 20 mg/d) |
1) factor for allometric scaling
2) Standard factor 10, a factor 3 (2) is
considered applicable, because no clear
conclusion can be drawn on extending exposure
times
from semichronic to chronic
3) because NOEL may be much higher than
highest dose tested
4) because in a 5-week study a NOEL of 37
mg/m
3 was obtained, LOEL 117 mg/m
3
It is unclear why different factors for
"difference between experimental conditions
and exposure pattern of the worker" were used
(see also RAR 2-(2-methoxyethoxy)ethanol
factor = 5!). All studies were 13-week
studies.
It is unclear why for "dose-response curve"
for inhalative exposure in contrast to dermal
exposure 0.5 was not used, because this was
also the highest concentration tested.
It is not reasonable to introduce a factor
of 2 for "confidence in database" for
inhalative exposure because the NOEL was 94
mg/m
3 and should be used.
OELs in The Netherlands 50 mg/m
3,
in Germany 100 mg/m
3. The HBORV
proposed here is 2.6 mg/m
3.
1.3 General Comment
The HBORVs derived in the reports suggest,
that 2-(2-methoxyethoxy)ethanol is about 100
times more toxic than
2-(2-butoxyethoxy)ethanol via the dermal route
and on the other hand about 20 times less
toxic via inhalation. Again, this discrepancy
cannot be explained scientifically.
These discrepancies stem from the use of
uncertainty factors without taking into
account the whole database on glycol ethers.
Moreover, some of the factors are obviously
arbitrary. Especially in the case of the
long-used and well-investigated class of
glycol ethers the approach to use uncertainty
factors without taking into account structure
activity relations is not appropriate.
Regarding established OELs for other glycol
ethers such as ethoxyethanol and
methoxyethanol, the calculated values for
dermal exposure to 2-(2-methoxyethoxy)ethanol
and for inhalative exposure to
2-(2-butoxyethoxy)ethanol are unrealistically
low.
2. Except the conclusions (see l.) the Risk
Assessment Report is of good quality.