| CAS no |
Syno-
nym |
Test |
Exposure route |
Species / model |
Conc. |
Exposure period |
Result/Effects |
NOAEL / LOAEL |
EPA DCN/Ref. |
| Octamethyltetracyclosiloxane |
| 556-67-2 |
D4 |
toxicokinetics, pharmacokinetics of 14C-D4 |
inhalation, nose only |
rat ( , ), Fisher 344, 50 ,/group |
7 and 700 ppm |
14 days, single, 6 hours/day (unlabelled D4); single 6 hour (14C-D4) |
level of absorption low and independent of gender and dose
distribution to most tissues
elimination via expired volatiles (parent) or metabolized via urine and faeces
rate of elimination of radioactivity in tissues was the same as from plasma except of fat
small dose-related effect on elimination on rats (more expired at the high dose compared to lower doses) suggesting saturation of metabolism at high doses |
not relevant |
86970000024
1996 |
| 556-67-2 |
D4 |
toxicokinetics, pharmacokinetics of 14C-D4 |
inhalation, nose only |
rat (), Fisher 344 |
7 and 700 ppm |
14 daily exposures to unlabelled D4 and a single exposure to 14C-D4 (day 15) at 7 and 700 ppm |
absorption and distribution mimicked single exposure results
rate of elimination of radioactivity in tissues was the same as from plasma except of fat and lung
small dose-related effect on elimination route on , rats (larger quantities eliminated via
lung, decreased quantities eliminated via faeces, urinary excretion constant at high compared to low dose) suggesting compensation of saturation effects through induction after repeated exposure |
no data |
86970000875
1997 |
| 556-67-2 |
D4 |
kinetics |
inhalation, nose only, vapour |
rat (), Fisher-344 (F-344) and Sprague-Dawley (SP) |
700 ppm |
single 6 hour exposure |
F-344 rats retained significantly higher amount of radioactivity (8.3+0.44%) than SD (5.9+0.26%)
excretion of radioactivity was similar in both strains in urine, faeces and expired volatiles
different concentration of radioactivity in fat over time
F rats showed a higher amount of radioactivity present as metabolites as compared to D4
kinetic difference suggest important biochemical differences leading to a decreased metabolism of D4 in female SP rats |
not relevant |
86010000010
2000 |
| 556-67-2 |
D4 |
kinetics, effect on immunological parameters, blood chemistry and pulmonary factors |
inhalation, mouthpiece and nasal exposure |
human |
10 ppm |
one hour |
mean deposition was 12%
peak plasma concentration was 78 ng/ml
rapid elimination from plasma after exposure termination (25 ng/ml; 6 hr and 4 ng/ml; 24 hr)
no effect on blood chemistry
no immunotoxic or proinflammatory/adjuvant effects |
not relevant |
86980000017
1997 |
| 556-67-2 |
D4 |
kinetics, 13C-D4 |
dermal |
human (3,3) |
1.4 g (), 1 g
() |
1, 2, 4, 6 and 24 hours |
D4 levels significantly elevated above baseline in blood and plasma at 1, 2, 4 and 6 hrs and in exhaled air at all time points
female subjects had significantly higher blood and plasma levels compared to male subjects |
not relevant |
86010000007
2000 |
| 556-67-2 |
D4 |
kinetics, pilot study to determine if inducing agents alter the metabolic profile of a single dose 14C-D4 |
oral gavage, i.p. and i.v. |
rat () |
pre-treatment: PB: 80 mg/kg i.p.; 3-MC: 30 mg/kg i.p.
14C-D4: 70 mg/kg i.v. or oral gavage |
pre-treatment: once per day for 4 consecutive days;
single administration of 14C-D4 the next day |
Phenobarbital but not 3-MC pre-treatment increases the amount and rate of urinary excretion
PB pre-treatment did not change urinary metabolic of D4 profíle
evidence that PB-inducible enzymes are involved in metabolism of D4 in rats |
not relevant |
86980000037
1997 |
| 556-67-2 |
D4 |
non-regulated study: identification of metabolites in urine (14C-D4) |
intravenously |
rat (,), Fisher 344 |
not stated |
no data |
ring opening and demethylation occurs (oxidation and hydrolysis)
major metabolites constituting 75 - 85% of the total radioactivity were dimethylsilanediol, methylsilanetriol
minor metabolites were tetramethyldisiloxane-1,3-diol [Me(2)Si(OH)-O-Si(OH)Me(2)], hexamethyltrisiloxane-1,5-diol [Me(2)Si(OH)-OSiMe(2)-OSi(OH)Me(2)], trimethyldisiloxane-1,3,3-triol [MeSi(OH)(2)-O-Si(OH)Me(2)], dimethyldisiloxane-1,1,3,3-tetrol [MeSi(OH)(2)-O-Si(OH)(2)Me], and dimethyldisiloxane-1,1,1,3,3-pentol [Si(OH)(3)-O-Si(OH)(2)Me].
no parent D4 present in urine |
no data |
8698000003286980000072
1997 |
| 556-67-2 |
D4 |
evaluation of D4 as inhibitor of human cytochrome P450 enzymes |
in vitro |
human liver microsomes from 7 individuals |
0.32 - 2.9 µM |
no data |
non competitive inhibitor of rat CYP2B1/2 (estimated Ki=0.11 mM)
non competitive inhibitor of human CYP2B6 (estimated Ki=3.6 mM)
competitive inhibitor of human CYP1A2 (estimated Ki=12 mM)
non competitive inhibitor of human CYP2D6 and CYP3A4/5 (estimated Ki=14 and 11 mM)
either competitive or non competitive inhibitor of CYP2C19 (estimated Ki=6.4 or 11 mM)
little or no capacity to inhibit rat CYP1A2 and human CYP2A6, CYP2C9 and CYP4A9/11 activity
activator of human CYP2E1
little or no capacity to to function as metabolism-dependent inhibitor of any of the P450 enzymes examined (except rat CYP1A1/2 and human CYP3A4/5 |
not relevant |
86990000017
1998 |
| 556-67-2 |
D4 |
in vitro dermal absorption, Flow-Through Diffusion Cell System |
in vitro percutaneous |
human skin |
neat D4 and formulated D4 (antiperspirant) |
24 hours |
0.50% of neat D4 absorbed (91.6% recovered from analysed sample)
0.49% of formulated D4 (103.2% recovered from analysed sample) |
not relevant |
86980000163
1998 |
| 556-67-2 |
D4 |
absorption potential |
oral gavage |
rat (,), Fisher 344 |
300 mg/kg 14C-D4 |
single
exposure |
carrier has an impact on absorption
peak levels of radioactivity delayed relative to parent D4
by 24 hr most of the radioactivity in blood could be attributed to metabolites
most of D4 absorbed from corn oil and neat D4 was metabolised and excreted via urine |
not relevant |
86980000184
1998 |
| 556-67-2 |
D4 |
physiologically based pharmacokinetic modelling (PBPK) |
inhalation |
human |
10 ppm 14C-D4 |
one hour during altering periods of rest and exercise |
hepatic extraction calculated from model parameters was 0.65 to 0.8 (clearance nearly flow-limited)
decreased retension of inhaled D4 during periods of exercise was explained by altered ventilation/perfusion characteristics and a rapid approach to steady-state conditions
high lipophilicity coupled with high hepatic and exhalation clearance
increased confidence in the utility of the model for predicting human tissue concentrations of D4 and metabolites during inhalation exposures |
not relevant |
Ready MB et al,
2003 |
| 556-67-2 |
D4 |
physiologically based pharmacokinetic modelling (PBPK) |
inhalation, dermal, oral, i.v. |
rat |
no data |
no data |
pharmacokinetics of D4 delivered by inhalation or dermal routes is similar, and is different from the i.v. or oral delivery route |
not relevant |
Sarangapani R et al
2003 |
| 556-67-2 |
D4 |
pharmacokinetics |
inhalation via mouthpiece |
human, 12 volunteers |
10 ppm |
one hour |
no changes in lung function
rapid non-linear blood clearance
mass transfer coefficient for D4 was 5.7×10-5 cm/s from lung air to blood |
no data |
Utel MJ et al
1998 |
| 556-67-2 |
D4 |
pharmacokinetics, PBPK modelling |
inhalation |
rat (,), Fisher 344 |
7, 70 and 700 ppm |
single exposure |
Despite its very high lipophilicity, D4 does not show prolonged retention because of high hepatic and exhalation clearance. |
no data |
Andersen ME et al
2001 |
| 556-67-2 |
D4 |
pharmacokinetics, pilot study |
inhalation, nose only |
rat (),Fisher 344 |
700 ppm,
14C-D4 |
6 hours |
radioactivity concentration highest in the lung tissue
max. conc. of radioactivity in blood, plasma or tissues observed at end of exposure period
rate of elimination of radioactivity from tissues the same as for plasma except for perirenal fat and lung
elimination routes: expired volatiles, renal or faecal excretion |
no data |
86960000517
1996 |
| 556-67-2 |
D4 |
percutaneous absorption, human skin / nude mouse model |
percutaneous |
human skin |
neat and formulated D4 |
24 hours |
absorption of neat D4 was determined to be 1.09% |
not relevant |
86010000003
2000 |
| 556-67-2 |
D4 |
percutaneous absorption, 14C-D4, semi occlusive |
percutaneous |
rat (), Fisher-344 |
topical application at 10, 4.8, and 2 mg/cm² |
1, 6 and 24 hours |
average percentage of applied dose being absorbed was between 0.57 and 0.95% for all doses and all time points
significant decrease in per cent absorbed over time
washing exposed skin after 24 hrs decreased exposure |
not relevant |
86010000009
2000 |
| 556-67-2 |
D4 |
immunotoxicity |
oral gavage |
rat (,), Fisher, 10 (,) / group |
10, 30, 100, and 300 mg/kg |
28 days |
no alterations in NK cell activity, macrophage function, lymphocyte subpopulation
no alterations in humoral activity ()
dose-dependent increase in AFC-response ()
slight but dose-dependent increase in erythroid elements (,)
dose-dependent increase in liver weight and dose-dependent decrease in thymus weight (mostly )
systemic adsorption dependent on vehicle
D4 at doses between 10 and 300 mg/kg does not cause immune suppression (,) |
no data |
86980000072
1997 |
| 556-67-2 |
D4 |
non-regulated study;
immunotoxicity |
oral |
human |
12 mg |
two weeks |
no effects on studied immunological parameters or blood chemistry |
no data |
86990000015
1998 |
| 556-67-2 |
D4 |
immunotoxicity |
inhalation via mouthpiece |
human |
10 ppm |
one hour, reexposure after 3 months |
no immunotoxic or proinflammatory effects of respiratory exposure were observed |
no data |
Looney RJ et al
1997 |
| 556-67-2 |
D4 |
dose-response study |
inhalation, whole body |
rat (), Fisher 344 |
1, 7, 30, 70, 150, 300, 500, 700 and 900 ppm |
6 hours/day; 5 days |
dose-dependent increase in liver size and induction of PROD activity achieving a max response between 300 and 900 ppm
hepatic conc. of D4 may reach levels saturating CYP2B1/2 activity
induction of CYP2B1/2 enzymes is an early and sensitive biochemical response to D4 exposure in rat
max can be achieved following 5 days repeated inhalation of approx. 500 ppm D4
D4 is a Phenobarbital-like inducer of rat hepatic cytochrome P450 enzymes |
no data |
86990000029
1999 |
| 556-67-2 |
D4 |
subacute toxicity, pilot study on effects on liver size and hepatic enzyme induction |
inhalation, whole body |
rat (,), Fisher |
70 and 700 ppm |
28 days, 6 hours/day; 5 days/week |
dose and time dependent liver enlargement in rats, maximum by day 7
induction of several metabolizing enzymes, primarily CYP2B1
D4 induces hepatic cytochrome P450 enzymes
biochemical response similar to phenobarbital |
no data |
86970000723
1996 |
| 556-67-2 |
D4 |
subacute toxicity, effects on liver size and hepatic enzyme induction |
inhalation, whole body |
rat (,), Fisher 344 |
70 and 700 ppm |
28 days, 6 hours/day; 5 days/week |
rapid but revesible increase in liver size
induction of several metabolizing enzymes, primarily CYP2B1
D4 induces hepatic cytochrome P450 enzymes
biochemical response similar to phenobarbital |
no data |
86970000725
1997 |
| 556-67-2 |
D4 |
subacute toxicity; induction of rat hepatic microsomal cytochrome P450, UDP-glucoronosyltransferase, and epoxid hydrolase |
inhalation, whole body |
rat (,), Fisher 344 |
70 and 700 ppm |
28 days, 6 hours/day; 5 days/week |
D4 induces CYP enzymes and epoxide hydrolase in a manner similar to Phenobarbital - i.e. D4 is a PB-like inducer of hepatic microsomal enzymes in the Fisher 344 rat. |
no data |
McKim JM et al
1997 |
| 556-67-2 |
D4 |
subchronic toxicity |
inhalation |
albino rat (,), Fisher 344, 4 groups, 10 /10 / group |
=1000 ppm,
repeated dose (2.78, 5.13, 8.62 and 14.21 mg/l) |
20 days (), 21 days (), 6 hours/day; 5 days/week |
reduced food consumption
reduced body weight and body weight gain
thymic atrophy
vaginal mucification
reduction in corpora lutea score |
no data |
86950000155
1995 |
| 556-67-2 |
D4 |
subchronic toxicity, range finding study for chronic study |
inhalation, nose only |
albino rat (,), Fisher 344, 4 groups, Gr.2, 3, 4: 20 /20 / group; Gr.5: 30 /30 / group |
=990 ppm, repeated dose (0.42, 1.48, 5.91 and 10.87 mg/l) |
3 months, 6 hours/day; 5 days/week |
slight reduction in body weight and food intake at 990 ppm.
slight dose related increase in abs. and rel. liver weight ( most sensitive)
slight reduction in thymus and ovarian weight in at the highest 2 doses
ovarian atrophy and vaginal mucification in
at 990 ppm |
no data |
86950000153
1995 |
| 556-67-2 |
D4 |
subchronic toxicity and splenic antibody cell response |
inhalation, whole body |
rat (,), Fisher |
7, 20, 60, 180 and 540 ppm |
28 days, 6 hours/day; 5 days/week |
statictically significant increase in liver weight and liver to body weight ( at 540 ppm; at 20-540 ppm)
no alterations in immune system AFC response |
no data |
86980000040
1997 |
| 556-67-2 |
D4 |
genetic toxicity, Ames test |
in vitro |
salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 |
maximum dose = 5 mg/plate with or without S9 |
no data |
no mutagenicity was detected in salmonella thyphimurium (negative) |
no data |
Vergnes JS et al
2000 |
| 556-67-2 |
D4 |
genetic toxicity, SCE assay |
in vitro |
chinese hamster ovary cells (CHO) |
=0.003 mg/ml with and without S9 |
no data |
no significant dose-related increases in chromosomal aberration frequencies (negative) |
no data |
Vergnes JS et al
2000 |
| 556-67-2 |
D4 |
genetic toxicity, chromosome abberations |
inhalation, whole body |
rat (,),
Sprague-Dawley |
700 ppm |
5 days, 6
hours/day |
No significant, treatment-related increases in chromosomal aberrations were detected (negative) |
no data |
Vergnes JS et al
2000 |
| 556-67-2 |
D4 |
single generation study (range-finding study for 2 gen. study) |
inhalation |
rat (,), Sprague-Dawley; 2 groups, 20 F0 /20 F0 / group |
70 and 700
ppm |
28 days, 6
hours/day |
treatment related reduction in mean body weight (,) shortly after exposure initiation
and late in gestation ()
statistically significant reduction in mean live litter size at 700 ppm accompanied by a decreased number of uterine implantations |
no data |
86960000398
1995 |
| 556-67-2 |
D4 |
reproductive toxicity, range-finding (test reproducibility of EPA, 3) |
inhalation, whole body |
rat (,), Sprague-Dawley; 2 groups, 22 F0 /22 F0 / group |
700 ppm |
=28 days, 6 hours/day |
treatment related reduction in mean body weight (,) shortly after exposure initiation and late in gestation ()
statistically significant reduction in mean live litter size at 700 ppm accompanied by a decreased number of corpora lutea and uterine implantations |
no data |
86970000023
1995 |
| 556-67-2 |
D4 |
reproductive toxicity, range-finding |
inhalation, whole body |
rat (), Sprague Dawley, 22 / group |
70, 300, 500, and 700 ppm |
6 hours/day for 70 at least days prior to mating |
maternal toxicity in F0 females at 300, 500 and 700 ppm
statistically significant reduction in mean live litter size and implantation site at 700 ppm |
no data |
86970000847
1997 |
| 556-67-2 |
D4 |
reproductive toxicity, range-finding study |
inhalation, whole body vapour |
rat (), Sprague-Dawley. 22 / group |
70, 300, 500, and 700 ppm |
6 hours daily for 70 days prior to mating |
increased liver and thyroid weights at 700 ppm
slight statistically insignificant reductions in pup survival (% per litter) at 700 ppm on PND 0 and during PND 0-4 interval
decrease in mean pup body weights on PND 1 and PND 4 at 700 ppm relative to control |
no data |
86980000049
1997 |
| 556-67-2 |
D4 |
reproductive toxicity, range-finding study |
inhalation, whole body vapour |
rat (), Sprague-Dawley. 40 / group |
500 and 700 ppm |
6 hours daily for 70 days prior to mating |
toxicity demonstrated in F0 males at 700 ppm by clinical signs and reduces mean body weight gain and food consumption during the first week
no adverse effects on F1 pups at 500 and 700 ppm |
500 ppm (F0 toxicity)
700 ppm (F1) |
86980000061
1997 |
| 556-67-2 |
D4 |
reproductive toxicity |
inhalation, whole body vapour |
rat (), Sprague-Dawley, 4 groups, 24 / group |
70, 300, 500, and 700 ppm |
multiple exposure regimens during different phases of the reproduction cycle |
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 |
not relevant |
86980000153
1997 |
| 556-67-2 |
D4 |
reproductive toxicity |
inhalation, whole body |
rat () |
700 ppm |
6 hr/day, multiple or single day exposure |
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 |
no data |
86990000058
1999 |
| 556-67-2 |
D4 |
interim risk assessment of D4 reproductive effects - combination of reproductive toxicity studies with estimates of D4 intake in humans |
inhalation, whole body |
rat ( or ), Sprague-Dawley, 24 / group |
70, 300, 500, or 700 ppm |
6 hours/day, 7 days/week; 70 days prior to mating and continuing through PND 20 |
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 |
NOAEL (reproductive effects): 300 ppm |
86990000029
1999 |
| 556-67-2 |
D4 |
uterotrophic assay; estrogenic and antiestrogenic activity |
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)) |
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) |
4 consecutive days beginning on PND 18 (SP) or 21 (F-344), single dose once per day |
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 |
NOAEL (increased uterine weight: 100 mg/kg/day) |
84000000002
1999/2001 |
| 556-67-2 |
D4 |
estrogenicity |
in vitro |
human MCF-7 cell system |
exp. 1 and 2: 10µM D4 or 0.3 nM estradiol
exp. 3: 0.1 - 10 µM D4 or 0.3 nM estradiol |
exp. 1 and 2:24 or 48 hours |
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 |
no data |
86010000004
2000 |
| Decamethylcyclopentasiloxane |
| 541-02-6 |
D5 |
pharmacokinetics: metabolites of 14C-D5 and 14C-HMDS in urine |
oral and
intravenous |
rat (,), Fisher 344 |
no data |
no data |
major metabolites: Me(2)Si(OH)(2), HOMe(2)SiCH(2)OH, HOCH(2)Me(2)SiOSiMe(2)CH(2)OH, HOMe(2)SiOSiMe(2)CH(2)-OH, HOCH(2)Me(2)SiOSiMe(3), and Me(3)SiOH
no parent D5 was present in urine |
not relevant |
Drug metabolism and disposition, 2003 |
541-02-6
(evt. ud) |
D5 |
evaluation of D5 as a potential inhibitor of human cytochrome P450 enzymes |
in vitro |
human liver microsomes from 7 individuals |
0.04 - 3.5 µM |
incubation 0 - 15 min |
D5 appears to be a weak competitive inhibitor of human CYP3A4/5
D5 appears to be a strong reversible metabolism-dependent inhibitor of human CYP3A4/5
D5 has little or no capacity to function as a metabolism-dependent inhibitor of several subfamilies of rat and human cytochrome P450 enzymes. |
no data |
86010000008
2000 |
| 541-02-6 |
D5 |
dermatotoxicology |
in vitro |
percutaneous absorption, 14C-D5, rat skin, non occlusion |
6.4 mg/cm² 14C-D5 |
24 hours |
percentage of radioactivity found in the skin was 1.08% () and 1.46% () respectively
similar penetration profile for and |
not relevant |
86960000593
1996 |
| 541-02-6 |
D5 |
dermatotoxicology |
in vitro |
percutaneous absorption, 14C-D5, rat skin, non occlusion |
no data |
24 hours |
approx. 85% volatilized from skin surface
dose site contained 0.35% of administered dose
less than 1% of 14C recovered in urine and carcass
total absorbed was 0.8% with a total recovery of approx. 89% |
not relevant |
86970000009
1996 |
| 541-02-6 |
D5 |
subacute toxicity |
inhalation,
whole body |
rat (,), Fisher 344, 4 groups, 15 / 15 / group |
10, 25, 75 and 160 ppm |
28 days, 6 hours/day; 7 days/week |
no adverse effects on body weight, food consumption or urinalysis
no alteration of humoral immunity
minor transient changes in haematological serum chemistry and organ weight
increase in liver to body weight (,) at 160 ppm, but not after recovery
increase in thymus to body weight () at 160 ppm, but not after recovery |
NOEL (histopathological changes): 10 ppm; NOEL (systemic toxicity: 75 ppm, NOEL (immunosuppression): 160 ppm |
86970000385
1996 |
| 541-02-6 |
D5 |
subacute toxicity |
inhalation |
albino rat (,), Fisher 344, 4 groups, 10 / 10 ) / group |
0.44, 0.65, 1.50, and 2.27 mg/l |
20 days (), 21 days (), 6 hours/day; 5 days/week |
no D5 related effects |
250 ppm |
86950000174
1995 |
| 541-02-6 |
D5 |
subacute toxicity, liver enlargement |
inhalation, whole body |
rat (), Fisher 344 |
160 ppm |
28 days, 6 hours/day; 7 days/week |
similar enzyme induction profile as D4 but lower magnitude (less effective)
induction of hepatic phase I and II metabolising enzymes (nearly identical to that following exposure to 70 and 700 ppm D4 and to Phenobarbital)
liver enlargement (liver to body weight change) only slightly less than after exposure to 700 ppm D4 and considerably greater than following exposure to 70 ppm D4
although enzyme induction and proliferation of the smooth ER may contribute to cellular hypertrophy other mechanisms are also involved |
no data |
86980000020
1997 |
| 541-02-6 |
D5 |
subchronic toxicity |
inhalation, nose only |
rat (,), Fisher 344 |
0 (30 ,) 26 (20 ,), 46 (20 ,), 86 (20 ,) and 224 (30 ,) ppm Recovery gr. : 0 (10 ,) and 224 (10 ,) ppm |
three months, 6 hrs/day, 5 days/week |
primary target organ following D5 inhalation is the lung
nose-only D5 vapour inhalation provides minimal changes in the lung similar in incidence and severity to spontaneously occurring changes in control animals
no histopathological finding in the liver |
no data |
Burns LA et al
1997 |
| 541-02-6 |
D5 |
subchronic
toxicity |
inhalation |
albino rat (,), Fisher 344, 4 groups, 20 / 20 ) / group, 30 in the high dose group |
0.44, 0.75, 1.33, and 3.53 mg/l |
13 weeks, 6 hours/day; 5 days/week |
minor reduction in body weight gain
possible mild effect on the liver (elevated gamma-glutamyltransferase activitet)
slight increase in absolute and relative liver weight () at 250 ppm
no histopathological findings |
no data |
86950000154
1995 |
| 541-02-6 |
D5 |
reproductive toxicity, two-generation |
inhalation, whole body |
rat
(,),Sprague-Dawley, 30 / 30 / group |
30, 70 and 160 ppm |
6 hours/day; at least 70 days prior to mating |
no parental toxicity observed in F0 and F1
no effects on reproductive performance (F0 and F1)
no neonatal toxicity (F1 and F2)
no F2 developmental neurotoxicity |
NOAEL (parental tox., reproductive tox., neonata tox., and developmental neurotox.: 160 ppm |
86990000032
1999 |
| 541-02-6 |
D5 |
reproductive toxicity, single generation, range-finding study |
inhalation, whole body |
rat (,), Sprague-Dawley, 2 groups of F0, 22 / 22 / group |
26 and 132 ppm |
min. 28 days, 6 hours/day |
total litter loss in 2 dams at 132 ppm (significance uncertain)
no effects on reproductive parameters
no significant toxicological findings |
no data |
86970000006
1996 |
| 541-02-6 |
D5 |
chronic toxicity and
carcinogenicity (not finalised) |
inhalation |
rat (,), Fisher 344,
60 / 60 / group |
10, 40 and 160 ppm |
two years, 6 hrs/day, 5 days/week |
the preliminary results show that female rats exposed to the highest concentration of D5 exhibited a statistically significant increase of uterine tumours.
these preliminary findings may indicate that there is a potential carcinogenic hazard associated with D5 |
no data |
EPA, August 2003 |
| Hexamethyldisiloxane |
| 107-46-0 |
HMDS |
metabolites of 14C-D5 and 14C-HMDS in urine |
oral and
intravenous |
rat (,), Fisher 344 |
no data |
no data |
major metabolites: Me(2)Si(OH)(2), MeSi(OH)(3), MeSi(OH)(2)OSi(OH)(3), MeSi(OH)(2)OSi(OH)(2)Me, MeSi(OH)(2)OSi(OH)Me(2), Me(2)Si(OH)OSi(OH)Me(2), Me(2)Si(OH)OSiMe(2)OSi(OH)Me(2), nonamethylcyclopentasiloxanol, and hydroxymethylnonamethylcyclopentasiloxane
no parent HMDS was present in urine
metabolites of the linear siloxane are structurally different from that obtained for cyclic siloxane except for the commonly present Me(2)Si(OH)(2). |
not relevant |
Drug metabolism and disposition, 2003 |
| 107-46-0 |
HMDS |
acute toxicity |
inhalation, whole body |
albino rat (,), Fisher 344,
3 groups, 5 and 5 / group |
1,067; 14,050 and 16,659 ppm (mean values) |
4 hours, obs. 14 days |
LC50 = 15,956 ppm |
10,067 ppm |
86970000724
1997 |
| 107-46-0 |
HMDS |
subacute toxicity |
inhalation, nose only |
albino rat (,), Fisher 344,
5 groups, 10 and 10 / group |
Gr.1: 0 mg/l, Gr.2: 0.9 ± 0.2 mg/l; Gr.3: 3.4 ± 0.4 mg/l; Gr 4.: 12.7 ± 0.8 mg/l and Gr.5: 59.2 ± 8.6 mg/l |
one month, 6 hrs/day, 5 days/week |
the incidence and severity of focal inflammatory lesions in the lungs was moderately increased in Gr. 5 animals (,)
increase in incidence and severity of renal tubule regeneration in male rats of Gr. 4 and 5.
hyaline droplet accumulation, protein casts and granular casts were present in kidneys in several gr. 5 males
minimal hepatocellular hypertrophy was evident in males of Gr. 4 and 5 and one female in Gr.5 and a slight increase in pigment accumulation in bile ducts in Gr.5 males |
no data |
86980000041
2001 |
| 107-46-0 |
HMDS |
subchronic toxicity |
inhalation, whole body |
rat (,), Fisher 344,
6 groups, 20 and 20 / group |
Gr.1: 0 mg/l, Gr.2: 0.33 mg/l; Gr.3: 1.3 mg/l; Gr 4.: 4.0 mg/l, Gr.5: 10.0 mg/l and Gr6: 33.3 mg/l |
13 weeks, 6 hrs/day, 5 days/week |
test related effects in kidneys of males at 4.0, 10.0 and 33.3 mg/l (at 4.0 mg/l, increased incidence and severity of tubular regeneration; at 10 and 33.3 mg/l increased incidence and severity of tubular regeneration with tubular hyaline casts |
NOAEL= 1.3 mg/l () and 33.0 mg/l () |
86980000182
1998 |
| 107-46-0 |
HMDS |
subchronic toxicity |
inhalation, whole body |
rat (,), Fisher 344, 6 groups, 20 / 20 / group |
50, 200, 600, 1500, and 5000 ppm (nominal) |
13 weeks, 6 hours/day; 5 days/week |
no treatment-related signs of clinical toxicity or mortality, statistically significant effects upon body weight gain or food consumption, ophthalmoscopic changes, gross macroscopic necropsy findings, or organ weight changes were noted
histological lesions in the kidney apparently consistent with male rat-specific alpha-2-urinary globulin nephropathy were observed in male rats exposed to 593, 1,509, and 5,012 ppm of HMDS, accompanied by slightly increased plasma urea and creatinine concentrations |
not stated |
Cassidy SL et al
2001 |
| 107-46-0 |
HMDS |
subchronic toxicity |
inhalation,
nose only |
albino rat (,), Fisher 344,
5 groups, 30 and 30 / group or 20 and 20 / group |
Gr.1: 0 mg/l, Gr.2: 0.14 ± 0.02 mg/l; Gr.3: 0.73 ± 0.2 mg/l; Gr 4: 3.42 ± 0.49 mg/l and Gr.5: 13.64 ± 1.47 mg/l |
three months, 6 hrs/day, 5 days/week |
no treatment related deaths, clinical signs, effect on body weight, food consumption, or hematology or clinical biochemistry parameters
multifocal, subpleural, subacute to subchronic interstitial inflammation in lungs of all groups. After the recovery period an increase of these finding were still seen in Gr.5
slightly increased incidence and severity of testicular tubular atrophy in Gr.5 males
slightly increased incidence of proteinaceous casts and severity of tubular regeneration in the kidneys in Gr.5 males |
no data |
86980000048
1997 |
| 107-46-0 |
HMDS |
reproductive toxicity, one generation |
inhalation |
rat (,), Crl:CD®(SD)IGS BR,
4 groups, 24 and 24 / group |
Gr.1: 0 ppm, Gr.2: 100 ppm Gr.3: 1030 ppm and Gr 4: 5000 ppm |
6 hrs/day, 28 consecutive days prior to mating |
all F0 animals survived
transient effect on body weight gain and food consumption at 5000 ppm
slight but not statistically significant effect on postnatal pup survival for the 500 ppm group |
not stated |
86010000010
2000 |
| 107-46-0 |
HMDS |
uterotrophic assay; estrogenic and antiestrogenic activity |
oral |
immature rat (), Sprague-Dawley |
HMDS: 600 and 1200 mg/kg/day;
EE: 3 µg/kg/day; HMDS+EE: 1200 mg/kg/day + 3 µg/kg/day (EE) |
4 consecutive days beginning on PND 18 (SP), single dose once per day |
no measurable effect on uterine weight when tested as an agonist
when co-administered together with EE HMDS produced a slight, but statistically significant reduction in absolute uterine weight |
not stated |
84000000002
2001 |
| Combined |
540-05-9, 556-67-2, 541-02-6,
540-97-6, and 107-50-6, or LMWS |
D3, D4, D5, D6, and D7 or LMWS |
kinetics, distribution |
subcutaneous |
mice (), CD-1 |
Gr.1: 250 mg LMW cyclosiloxane mixture;
Gr.2: DMPS-V |
single exposure |
low molecular weight silicones persist in the organs of mice for at least one year after a single s.c. injection
every organ examined (10 different) accumulated silicones
individual cyclosiloxanes show different retention in tissues
D5 and D6 appear to persist longer than D4
high levels of cyclosiloxanes in ovaries and moderately high in uterus |
not relevant |
Subbarao VK et al |
556-67-2,
541-02-6,
107-46-0 |
D4, D5, D6 |
exposure assessment, interim, establishment of average daily dose (ADD) |
inhalation, dermal, oral |
human, workers, consumers, general public |
three year analysis of potential exposure |
Various exposures |
women are typically exposed to a greater diversity of personal care products
individuals who are exposed from several sources seem to get the highest exposure
female siloxane workers who use siloxane products high in D4 content and resides in the vicinity of a plant using these materials could experience a total base case ADD
exposure for most other persons is smaller
ADD: 0.71 (D4), 0.23 (D5), and 0.09 (D6) mg/kg/day
occ. exposure, female workers: 0.5252 mg/kg/day
consumers: 0.4784 mg/kg/day
general public: 0.0217 mg/kg/day (residents in vicinity of a silicone plant) |
not relevent |
1998 |
Mucification: A change produced in the vaginal mucosa of spayed experimental animals following stimulation with oestrogen; characterised by the formation of tall columnar cells secreting mucus.