No. 1031 - Miljøstyrelsen

106
CAS no Synonym
Test Exposure
route
556-67-2 D4 reproductive toxicity inhalation,
whole body
vapour
556-67-2 D4 reproductive toxicity inhalation,
whole body
556-67-2 D4 interim risk assessment
of D4 reproductive
effects -
combination of reproductive
toxicity
studies with estimates
of D4 intake
in humans
556-67-2 D4 uterotrophic assay;
estrogenic and antiestrogenic
activity
inhalation,
whole body
Species / model Conc. Exposure
period
rat (♀), Sprague-
Dawley, 4 groups,
24 / group
70, 300, 500, and
700 ppm
multiple exposure
regimens
during different
phases of
the reproduction
cycle
rat (♀) 700 ppm 6 hr/day,
multiple or
single day
exposure
rat (♀ or ♂), Sprague-Dawley,
24 /
group
oral immature rat (♀),
Fisher and Sprague-Dawley,
6
groups, 12
♀/group, 12 control
groups (estrogenic
effect: EE,
DES-DP and CE;
antiestrogenic
effect: D4 +EE))
556-67-2 D4 estrogenicity in vitro human MCF-7 cell
system
Decamethylcyclopentasiloxane
70, 300, 500, or
700 ppm
D4: 250, 500 and
1000 mg/kg/day;
EE: 1, 3, 10 and 30
µg/kg/day; DES-
DP: 0.5, 1.5, 5, and
15 µg/kg/day; CE:
10, 35, 75 and 175
mg/kg/day;
D4+EE: 500
mg/kg/day (D4)+1,
3, 10 and 30
µg/kg/day (EE)
exp. 1 and 2: 10µM
D4 or 0.3 nM
estradiol
exp. 3: 0.1 - 10 µM
D4 or 0.3 nM
estradiol
6 hours/day, 7
days/week; 70
days prior to
mating and
continuing
through PND
20
4 consecu-tive
days beginning
on PND
18 (SP) or 21
(F-344), single
dose once per
day
exp. 1 and 2:24
or 48 hours
Result/Effects NOAEL /
LOAEL
effects on intrauterine survival following exposure from 3 days
prior to mating until gestation day 3 were similar to effects
following exposure from 28 days prior to mating until gestation
day 19
no effects on intrauterine survival when exposure was terminated
3 days prior to mating indicating reversibility of these
effects
pre-mating phase: reduced pregnancy rate, effects on mean
body weight gain, reduced food consumption and/or reduced
no. of mean corpora lutea and implantation sites, increased
no. of small implantation sites and reduced mean uterine
weight for different treatment regimes
post-mating phase: toxicity only expressed in a single group
by reduced mean body weight gain and food consumption
estimated ADI’s for a hypothetical woman using several
products and working in a silicone product manufacturing
were 0.158 or 0.145 mg/kg/day for dermal and inhalation
exposure
ADI’s for persons exposed to D4 in food were highest for
children one year of age or younger: approx. 0.002 mg/kg/day
Margins of Safety or Exposure (MOE) > 100
Vast majority of MOE’s > 10,000 for workers, consumers, and
the general public exposed to background levels of D4
MOE’s considered acceptable to support the safety of D4 for
use in its intended applications
weakly estrogenic (dose-related increase in uterine weight and
epithelial cell height) in both SP and F-344 rats
weak antiestrogenic properties by partially blocking EE induced
uterine weight increases (competitive inhibition of
estrogen receptor binding or D4 acting as a partial estrogen
agonist)
estrogenic and antiestrogenic effects of D4 were several orders
of magnitude less potent than EE, and many times less
potent than the weak phytoestrogen CE
D4 appears to have estrogenic potential at 0.1 - 10 µM seen
as early as 15 min post exposure reaching maximal induction
at 6-24 hours
results suggest that D4 can elicit an estrogenic effect that is
dose-dependent with no significant anti-estrogenic activity
EPA DCN/Ref.
not relevant 86980000153
1997
no data 86990000058
1999
NOAEL (reproductive
effects): 300
ppm
NOAEL (increaseduterine
weight:
100
mg/kg/day)
86990000029
1999
84000000002
1999/2001
no data 86010000004
2000