The Toxicologist - Society of Toxicology
The Toxicologist - Society of Toxicology
The Toxicologist - Society of Toxicology
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metabolism) was found to be 31.6 h. <strong>The</strong> average final fractions <strong>of</strong> administered<br />
dose recovered in urine as PI were 0.025% and 0.002%, for oral and dermal administration,<br />
respectively after 96 h. According to the model, when orally administered,<br />
PI rapidly hydrolyzes to phthalamic and phthalic acids such that only 0.04%<br />
<strong>of</strong> the PI found in the gastrointestinal tract is absorbed into the blood stream.<br />
Likewise, after dermal application, model predicts that only 7.4% <strong>of</strong> the applied<br />
Folpet dose crosses the epidermis. In the model, the PI initial metabolite <strong>of</strong> Folpet<br />
is formed in the dermis and further metabolized prior to reaching systemic circulation,<br />
such that only 0.125% <strong>of</strong> PI formed at the site-<strong>of</strong>-entry reaches systemic<br />
blood. Our mathematical model is in accordance with both measures <strong>of</strong> blood<br />
(R 2 =0.57 for dermal and R 2 =0.66 for oral) and urine (R 2 =0.98 for dermal and<br />
R 2 =0.99 for oral).<br />
1241 EVALUATION OF CARDIOVASCULAR DISEASE<br />
BIOMARKERS IN ADULT TOBACCO CONSUMERS: A<br />
COMPARISON BETWEEN THE NATIONAL HEALTH<br />
AND NUTRITION EXAMINATION SURVEY AND A<br />
SINGLE SITE CROSS-SECTIONAL STUDY.<br />
K. M. Marano, S. J. Kathman, B. A. Jones, B. G. Brown and M. F. Borgerding.<br />
RJ Reynolds Tobacco Co., Winston Salem, NC. Sponsor: C. Garner.<br />
Cardiovascular disease (CVD) physiological and biochemical markers <strong>of</strong> potential<br />
harm were compared in adult cigarette smokers, smokeless tobacco (chewing tobacco<br />
and snuff) consumers, and non-consumers <strong>of</strong> tobacco using data from the<br />
National Health and Nutrition Examination Survey (NHANES). A similar evaluation<br />
was then conducted in a subset <strong>of</strong> NHANES, which included male cigarette<br />
smokers, snuff consumers, and non-consumers <strong>of</strong> tobacco ages 26-49. <strong>The</strong>se two<br />
NHANES analyses were then compared with results from a single site, cross-sectional<br />
study <strong>of</strong> healthy U.S. male exclusive cigarette smokers, exclusive moist snuff<br />
consumers, and never consumers <strong>of</strong> tobacco ages 26-49. In both NHANES analyses<br />
and the cross-sectional study, median values for all markers were within normal<br />
clinical reference ranges. However, statistically significant differences were seen in<br />
some comparisons between the three tobacco consumption categories, which were<br />
generally consistent across the three data sets. Most differences were seen in cigarette<br />
smokers compared with non-consumers <strong>of</strong> tobacco (increases in white blood<br />
cells, neutrophils, monocytes, lymphocytes, fibrinogen, and C-reactive protein, and<br />
decreases in folate) and in cigarette smokers compared with smokeless tobacco consumers<br />
(increases in white blood cells, monocytes, and lymphocytes). In smokeless<br />
tobacco consumers compared with non-consumers <strong>of</strong> tobacco, only folate was statistically<br />
significantly different (decreased) in all analyses. In general, findings were<br />
consistent with the available published data <strong>of</strong> CVD biomarkers in smokeless tobacco<br />
consumers compared with non-consumers. Results additionally support previous<br />
reports <strong>of</strong> statistically significant differences in certain biomarkers <strong>of</strong> CVD in<br />
cigarette smokers and non-smokers.<br />
1242 AN ANALYSIS OF PERFLUOROCHEMICAL<br />
CONCENTRATIONS IN AMERICAN RED CROSS<br />
ADULT BLOOD DONORS, 2000 TO 2010.<br />
G. W. Olsen 1 , D. C. Mair 2 , C. C. Lange 3 , M. E. Ellefson 3 and W. K. Reagen 3 .<br />
1 Medical, 3M Company, St. Paul, MN, 2 North Central Region, American Red Cross,<br />
St. Paul, MN and 3 Environmental Laboratory, 3M, St. Paul, MN.<br />
In 2000, the 3M Company voluntarily began phase out production <strong>of</strong> perfluorooctanesulfonyl-based<br />
products that were used as surfactants, paper and packaging<br />
treatments and surface protectants after perfluorooctanesulfonate (PFOS,<br />
C8F17SO3-) was reported in human populations and the environment. <strong>The</strong> majority<br />
<strong>of</strong> the manufacture phase-out was accomplished by the end <strong>of</strong> 2000. Between<br />
2000-2001 and 2006 an approximate 60% decline in PFOS concentrations was<br />
observed across 6 American Red Cross blood donation centers representing Boston,<br />
MA., Charlotte, N.C., Hagerstown, MD., Los Angeles, CA., Minneapolis-St. Paul,<br />
MN., and Portland, OR. An approximate 25% decline was observed for perfluorooctanoate<br />
(PFOA, C7F15COO-). <strong>The</strong> present study extends these trend statistics<br />
an additional four years as the length <strong>of</strong> time since the phase-out is nearly twice<br />
the reported mean half-life <strong>of</strong> serum elimination for PFOS <strong>of</strong> approximately 5<br />
years. In the summer <strong>of</strong> 2010, 600 plasma samples were collected from 300 male<br />
and 300 female American Red Cross anonymous blood donors between the ages <strong>of</strong><br />
20-69 at the same six locations. Sample extraction is accomplished using protein<br />
precipitation. <strong>The</strong> final eluates are analyzed for PFOS, perfluroohexanesulfoante<br />
(PFHxS, C6F13SO3-), perfluorobutanesulfonate (PFBS, C4F9SO3-), and a homologous<br />
series <strong>of</strong> perfluorocarboxylates from perfluorobutyrate (PFBA,<br />
266 SOT 2011 ANNUAL MEETING<br />
C3F7COO-) through perfluorododecanoate (PFDA, C11F23COO-), using highperformance<br />
liquid chromatography interfaced with a triple-quadrupole mass spectrometer.<br />
Quantification is accomplished using matrix-matched extracted calibration<br />
curves in combination with isotopically-labeled internal standards and<br />
surrogates.<br />
1243 PLASTICIZER MIGRATION FROM TOYS AND CHILD<br />
CARE ARTICLES.<br />
M. A. Dreyfus and M. A. Babich. U.S. Consumer Product Safety Commission,<br />
Bethesda, MD.<br />
Dialkyl phthalates, including diisononyl phthalate (DINP), have been used as plasticizers<br />
in children’s products made from polyvinyl chloride (PVC), such as teethers<br />
and toys. Children may be exposed when handling or mouthing PVC products because<br />
plasticizers are not covalently bound. <strong>The</strong> Consumer Product Safety<br />
Improvement Act <strong>of</strong> 2008 (CPSIA) prohibited the use <strong>of</strong> certain phthalates in child<br />
care articles and children’s toys. Thus, manufacturers have changed to other plasticizers<br />
or non-PVC plastics. However, the potential health risks <strong>of</strong> alternative plasticizers<br />
have not been evaluated. CPSC staff purchased 63 children’s products comprising<br />
129 components before the phthalate regulations took effect. Plastics<br />
identified by FTIR included PVC, polypropylene, polyethylene, and ABS. Of the<br />
129 components tested, 38 were PVC. Plasticizers identified by GC-MS in the 38<br />
PVC components included acetyltributyl citrate (ATBC) (20); di(2-ethylhexyl)<br />
terephthalate (DEHT) (14); 1,2-cyclohexanedicarboxylic acid diisononyl ester<br />
(DINCH) (13); 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB) (9); di(2<br />
ethyhexyl) phthalate (DEHP) (1); and DINP (1). Most tested components contained<br />
multiple plasticizers. Total plasticizer concentrations ranged from 2.5 to<br />
58%. Migration rates were measured by the Joint Research Centre method to estimate<br />
oral exposure when the articles are mouthed. Migration rates (micrograms/10<br />
cm 2 /min) were: ATBC (range 0.8 to >15); TXIB (0.9—11.3), DINCH (0.4—7.3);<br />
and DEHT (0.1—3.6). Migration rates did not correlate well with plasticizer concentration.<br />
Wipe sampling was used to estimate the amount <strong>of</strong> plasticizer that<br />
could be transferred to skin. Plasticizer release ranged from 490 (ATBC) to 32,000<br />
(DINP) micrograms per 100 cm 2 . This study was performed to assist a Chronic<br />
Hazard Advisory Panel (CHAP) convened by the CPSC, as directed in the CPSIA,<br />
“to study the effects on children’s health <strong>of</strong> all phthalates and phthalate alternatives<br />
as used in children’s toys and child care articles.” This work has not been reviewed or<br />
approved by, and does not necessarily represent the views <strong>of</strong>, the Commission.<br />
1244 RESIDENTIAL EXPOSURE MODELING FOR OZONE-<br />
GENERATING AIR CLEANERS.<br />
M. A. Babich, K. R. Carlson and T. A. Thomas. U.S. Consumer Product Safety<br />
Commission, Bethesda, MD.<br />
Some portable residential indoor air cleaners generate ozone either intentionally or<br />
as a byproduct <strong>of</strong> operation. Acute and chronic health effects have been linked to<br />
ozone inhalation exposure. <strong>The</strong> U.S. Food and Drug Administration established an<br />
ozone emission limit <strong>of</strong> 50 ppb for medical devices. Underwriters Laboratories<br />
(UL) has incorporated the 50 ppb limit into a voluntary standard for emissions<br />
from portable household air cleaner products (UL 867). UL 867 allows a maximum<br />
steady-state concentration <strong>of</strong> 50 ppb [0.099 mg/cm 3 ] in a 30 m 3 test chamber<br />
with a net apparent decay rate <strong>of</strong> 1.33 h. -1 CPSC staff used modeling to evaluate<br />
the adequacy <strong>of</strong> UL 867 to maintain ozone at “acceptable” levels (≤ 50 ppb)<br />
during normal conditions <strong>of</strong> air cleaner use in a residential setting. <strong>The</strong> maximum<br />
source strength allowed by UL 867 was estimated to be approximately 4 mg/h. <strong>The</strong><br />
concentration <strong>of</strong> ozone in a simulated room or house was then estimated by using<br />
one, two, and multiple zone models, a source strength <strong>of</strong> 4 mg/h, and various input<br />
factors (air exchange rate, ambient concentration, deposition velocity, room volume,<br />
and surface to volume ratio). Modeled ozone concentrations ranged from<br />
7.73 to 37.4 ppb for six out <strong>of</strong> seven one-zone scenarios. In the seventh “worstcase,”<br />
one-zone scenario, reduced infiltration rates, room volume, deposition velocity,<br />
ratio <strong>of</strong> total surface area to envelope surface area, and increased ambient ozone<br />
yielded an estimated ozone concentration <strong>of</strong> 79.8 ppb. In another exercise, probabilistic<br />
estimation <strong>of</strong> ozone concentrations for one-zone and two-zone models<br />
ranged from 6.3 to 28 ppb (averages) when using source strengths < 19.8 mg/h. At<br />
a source strength <strong>of</strong> 4 mg/h, approximately 99.9 percent <strong>of</strong> the estimated cases had<br />
ozone concentrations <strong>of</strong> less than 50 ppb for both the one-zone and two-zone models.<br />
Under reasonably foreseeable conditions <strong>of</strong> use, ozone concentrations <strong>of</strong> ozone<br />
do not exceed 50 ppb when derived from air cleaners that meet the UL 867 voluntary<br />
standard. This work has not been reviewed or approved by, and does not necessarily<br />
represent the views <strong>of</strong>, the Commission.