Opinion on the results of the Risk Assessment of : 2-(2-methoxyethoxy)ethanol [111-77-3] 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. 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 LOELs or
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 (Hobson et al. al. 1986)
with 6 male guinea pigs per group, exposed 6
h/d, 5 d/w to 0, 40, 200 or 1000 mg/kg bw.
Marginal LOEL: 40 mg/kg bw, mild
periportal hepatocellular fatty changes
without increased liver weights. Focal
coagulation necrosis in the liver was observed
in all groups without dose-relationship. With
mid and high dose spleen weight reduction and
serum LDH increase were observed.
It should be noted that for rats in a
6-week
oral study the NOEL is 900 mg/kg bwt.
It is questionable therefore whether the LOEL
in the guinea pig study is the correct
starting point because the effects were
marginal, without liver weight increase and
contradictory to the oral and inhalative
studies with rats.
-
Inhalative exposure : Starting point
for the calculation is the 13-week study
(Miller et al. al. 1985) with rats (not
specified in text), exposed 46 mg/m3
6 h/d, 5 d/w to 0, 150, 490 or 1060 (highest
achievable concentration). NOEL: 1060
mg/m3 = 305 mg/kg.
A summary of the uncertainty factors used
and the OELs derived is given in the table:
| dermal
exposure | inhalative
exposure |
interspecies differences |
3.4 1)
x 3 |
3 |
intraspecies differences |
3 |
3 |
difference
between experimental conditions and
exposure pattern of the worker |
52) |
52) |
dose-response curve |
23 |
0.54) |
overall
factor |
3065) |
23 |
Calculated
HBORV |
40 mg/kg
/ 100 =
0.4 mg/kg =
28
mg/d (i.e. half a drop) |
1060
mg/m3 / 23 =
46 mg/m3(i.e. ca
400 mg/d) |
1) factor for allometric scaling
2) Standard factor 10, a factor 5 is
considered applicable, because no clear
conclusion can be drawn on extending exposure
times from semichronic to chronic
3) because LOEL is starting point
4) because NOEL may be much higher than
highest dose tested
5) reduced to 100 because factor for
difference between experimental conditions and
exposure pattern of the worker was considered
too conservative and effects were only
marginal
The OEL of 2-(2-methoxyethoxy)ethanol in
The Netherlands is 23 mg/m
3.
The HBORV calculated here is 46 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 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.
Especially in the case of the long-used and
well-investigated class of glycol others the
approach to use uncertainty factors without
considering 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 1.) the Risk
Assessment Report is of good quality.