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3.2.5.3	Potentially Exposed and Susceptible Subpopulation
Based on the weight of the scientific evidence, reduced fertility and developmental toxicity are the most
sensitive effects of NMP exposure. The lifestages of greatest concern for developmental effects are
pregnant women, the developing fetus, and women of childbearing age who may become pregnant.
Lifestages of concern for effects on reproductive health and fertility include men and women of
reproductive age as well as infants, children and adolescents. The results of one two-generation study in
rats (Exxon. 1991) indicate that in utero and postnatal developmental exposure to NMP may contribute
to risk of reduced fertility in adulthood. Other potential hazards of NMP identified in Section 3.2.3 may
be of concern for other lifestages.
Certain human subpopulations may be more susceptible to exposure to NMP than others. One basis for
this concern is that the enzyme CYP2E1 is partially involved in metabolism of NMP in humans and
there are large variations in CYP2E1 expression and functionality in humans (Ligocka et at.. 2003). The
variability in CYP2E1 in pregnant women could affect how much NMP reaches the fetus, which
typically does not express CYP2E1 (Mimes. 2007). Newborns and very young infants are particularly
susceptible to NMP exposure because they are metabolically immature. CYP2E1 is not fully expressed
in children until about 90-days of age (Johnsrud et at... 2003). The variability in CYP2E1 was identified
as an important uncertainty that was reflected in the calculation of the intraspecies uncertainty factor
(human variability). Pre-existing conditions affecting the liver may also impair metabolism of NMP in
some individuals. For example, fatty liver disease has been associated with reduced CYP function
(Fisher et at.. 2009).
Genetic variations or pre-existing conditions that increase susceptibility of the reproductive system, the
hepatic, renal, nervous, immune, and other systems targeted by NMP could also make some individuals
more susceptible to adverse health outcomes following consumer or workplace exposures. In addition,
people simultaneously exposed to other chemicals targeting these systems may also be more susceptible
to effects of NMP exposure.
While an uncertainty factor for interindividual variability provides some additional protection for
susceptible subpopulations, a lack of quantitative information on the extent to which any of these
specific factors increases risk precludes direct incorporation of these factors in the risk characterization.
3.2.5.4	Selection of Studies for Dose Response Assessment
EPA evaluated data from studies described above (Section 3.2.5.1) to characterize NMP's dose-response
relationships and select studies to quantify risks for specific exposure scenarios.
In order to select the most appropriate key studies for this analysis, EPA considered the relative merits
of the oral, inhalation and dermal animal studies, with respect to: (1) the availability of primary data for
statistical analysis; (2) the robustness of the dose-response analysis; and (3) the exposure levels at which
adverse effects were observed.
The selected key studies provided the dose-response information for the selection of points of departure
(PODs). EPA defines a POD as the dose-response point that marks the beginning of a low-dose
extrapolation. This point can be the lower bound on the dose for an estimated incidence or a change in
response level from a dose-response model {i.e., benchmark dose or BMD), a NOAEL or a LOAEL for
an observed incidence or change in level of response. PODs were adjusted as appropriate to conform to
the exposure scenarios derived in Section 2.4.
The key studies and endpoints selected for BMD modeling in support of POD derivation are listed
below. EPA performed additional BMD modeling on alternate endpoints that is described in more detail
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in the supplemental file, Risk Evaluation for n-Methylpyrrolidone (NMP), Benchmark Dose Modeling
Supplemental File. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2020e).
Studies Selectedfor BMD Modeling
For reduced fertility EPA selected the following study for dose response analysis:
•	Exxon (1991); high quality oral dietary study
For reduced fetal body weights EPA selected the following studies for dose-response analysis:
•	Becci (.1.982); medium quality dermal study
•	DuPont (.1.990); high quality inhalation study
•	Saillenfait (2002); high quality oral gavage study
•	Saillenfait (2003); high quality inhalation study
For fetal resorptions and increased fetal mortality EPA selected the following studies for dose-response
analysis:
•	Becci (.1.982); medium quality dermal study
•	Saillenfait (2002); high quality oral gavage study
•	Saillenfait (Saillenfait et al. 2003; Saillenfait et aL 2002); combined dose-response data from a high
quality oral gavage study and a high quality inhalation study
•	Sitarek et al. (2012); high quality oral gavage study
For stillbirth, EPA selected the following studies for dose-response analysis:
•	NMP Producers Group (1999b); high quality dietary study
•	NMP Producers Group (1.999c); high quality dietary study
•	Exxon (1.991); high quality dietary study
The Saillenfait et al. (2002) and Saillenfait et al. (2003) studies administered NMP via different routes
but were otherwise similar in study design, using the same exposure duration (GD 6-20) and the same
strain of rat (Sprague-Dawley); therefore, these studies were combined based on PBPK-derived internal
dose metrics. This expands the range of doses covered by the dose-response model. Also, a more robust
BMDL is likely, by virtue of using a model that is based on more data.
The relevance of reasonably available stillbirth data for acute versus chronic exposure scenarios is
unknown. While stillbirths could plausibly result from a single exposure, stillbirths in reasonably
available studies occur following repeated dietary exposures throughout gestation. EPA modeled dose-
response information for stillbirths in reasonably available studies as a reference point for derivation of
PODs for both acute and chronic exposures.
EPA guidance recommends a hierarchy of approaches for deriving PODs from data in laboratory
animals, with the preferred approach being PBPK modeling (\l ^ I'P \ 2012a). When data were
amenable, benchmark dose (BMD) modeling was used in conjunction with the PBPK models to estimate
PODs. For the studies for which BMD modeling was not possible (Sitarek et al.. llOt J; Becci et al..
1982). the NOAEL was used for the POD. Details regarding BMD modeling were described in the
supplemental file, Risk Evaluation for n-Methylpyrrolidone (NMP), Benchmark Dose Modeling
Supplemental File. Docket EPA-HQ-OPPT-2019-0236 (	s20e). Details regarding the PBPK
model can be found in Appendix J.
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Studies with only one exposure group (Hass et at.. 1995; Hass et at.. 1994) provide limited information
about the shape of the dose-response curve and could not be used for BMD modeling. Given the
concordance of effect levels in these studies with effect levels in other studies that had multiple exposure
groups, they were still seen as supportive of the dose-response relationship. Studies that did not report a
statistically significant effect for the endpoint being considered (Lee et at.. 198?) may help with dose
metric selection, but provide only limited information about the shape of the dose-response curve and
were not included in the dose-response assessment of that endpoint.
3.2.5.5 Derivation of Internal Doses
PBPK models for NMP in rats and humans (Appendix J) facilitate cross-species extrapolation of hazard
information. In this risk evaluation, EPA used a rat PBPK model to derive PODs based on internal doses
associated with health hazards in rats and used a human PBPK model to estimate internal doses (blood
concentrations) of NMP that may occur in humans under specific conditions of use. EPA calculated
risks by comparing internal doses predicted by the model in humans to PODs in units of internal doses
in rats. Internal doses are assumed to have consistent effects regardless of exposure route. EPA therefore
used the PBPK model to derive internal dose PODs based on the weight of the scientific evidence from
studies using different exposure routes. This section summarizes the toxicokinetics of NMP, the PBPK
models and dose metrics used to estimate internal doses in rats.
Toxicokinetic Parameters used in PBPK Modeling
NMP is well absorbed following inhalation, oral and dermal exposures (NMP Producers Group. 1995b).
In rats, NMP is distributed throughout the organism and eliminated mainly by hydroxylation to polar
compounds, which are excreted via urine. About 80% of the administered dose is excreted as NMP and
NMP metabolites within 24 hrs (WHO. 2001). The major metabolite is 5-hydroxy-N-methyl-2-
pyrrolidone (5-HNMP). Studies in humans show that NMP is rapidly biotransformed by hydroxylation
to 5-HNMP, which is further oxidized to N-methyl-succinimide (MSI); this intermediate is further
hydroxylated to 2-hydroxy-N-methylsuccinimide (2-HMSI). The excreted amounts of NMP metabolites
in the urine after inhalation or oral intake represented about 100% and 65% of the administered doses,
respectively (Akesson and Jonsson. 1997).
Dermal absorption of NMP has been extensively studied as it typically poses the greatest potential for
human exposure. Dermal penetration through human skin has been shown to be very rapid and the
absorption rate is in the range of 1-2 mg/cm2-hr. These values are 2- to 3-fold lower than those observed
in the rat. Prolonged exposures to neat NMP were shown to increase the permeability of the skin. Water
reduces the amount of dermal absorption (Pavan et at.. 2003) while other organic solvents (e.g., d-
limonene) can increase it (Huntingdon Life. 1998). The dermal penetration of 10% NMP in water is
100-fold lower than that of neat NMP, while dilution of NMP with d-limonene can increase the
absorption of NMP by as much as 10-fold. The dermal absorption of neat NMP under different
occlusion conditions indicated that dermal absorption 1 hour post-exposure was greatest under un-
occluded conditions (69%), followed by semi-occluded (57%) and occluded (50%t) conditions (OECD.
2007).
Dermal uptake of vapor NMP has been reported in toxicokinetic studies in humans. Bader et al. (2008)
exposed volunteers for 8 hrs to 80 mg/m3 of NMP. Exposure was whole body or dermal-only (i.e., with
a respirator). Excretion of NMP and metabolites was used to estimate absorption under different
conditions. The authors found that dermal-only exposures resulted in the excretion of 71 mg NMP
equivalents whereas whole-body exposures in resting individuals resulted in the excretion of 169 mg
NMP equivalents. Under a moderate workload, the excretion increased to 238 mg NMP equivalents.
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Thus, the authors estimated that the dermal absorption component of exposure from the air will be in the
range of 30% to 42% under whole-body exposure conditions to vapor.
Previously published PBPK models for NMP in rats and humans were adapted for use by EPA (see
Appendix J and U.S. EPA (2.015 c) for details of the PBPK model). The rat version of the model allows
for estimation of NMP time-courses in rat blood from inhalation, oral and dermal exposures. The human
version of the model, based on non-pregnant and pregnant women, also includes skin compartments for
portions of the skin in contact with NMP vapor and liquid and some of those details are described here
because it is an important component of human risk.
Analyzing the experimental studies of Akesson et al. (2004), the model yielded an average uptake of
2.1 mg/cm2-hr of neat NMP, but only 0.24 mg/cm2-hr of aqueous NMP (1:1 dilution in water).
Therefore, distinct values of the liquid permeability constant (PVL), 2.05xl0"3 cm/h and 4.78xl0"4 cm/h,
were identified from the experimental data. The appropriate value of PVL for neat versus diluted NMP
was used in the respective exposure scenarios in this assessment. Absorption also depends on the
partition coefficient (PC) skin:liquid equilibrium, PSKL, which was taken to be the skin:saline PC
reported by Poet et al. ( ), PSKL = 0.42 [no units] and assumed not to vary with dilution.
Predicted dermal uptake from liquid exposure is then a function of the liquid concentration, skin surface
exposed and duration of contact. The thickness of the liquid film does not factor directly into the
estimate. As a conservative estimate for user scenarios it is assumed that fresh material is constantly
depositing over the time of use such that the concentration on the skin remains essentially constant at the
formulation concentration. This is in contrast to simulations of experimental studies where the volume
placed on the skin at the start of the experiment is not replenished (Akesson et al.. 2004). in which case
the model tracks the amount of NMP remaining in the film and hence the changing concentration for
absorption from diluted NMP.
Penetration from vapor was estimated as part of model calibration using the Bader and van Thriel (2006)
inhalation data set. This report does not state how the subjects were dressed but the exposures were
conducted between late May and mid-June in Germany, so EPA assumed they wore short-sleeved shirts
and long pants. While there is no reason to expect that NMP vapors do not penetrate clothing, clothing
likely reduces uptake compared to open areas of skin. Since the fitted penetration constant (PV) is
multiplied by the skin surface area assumed to be exposed when calculating the penetration rate, these
cannot be uniquely determined from the toxicokinetic data. For the purpose of calibration and
subsequent modeling, it is assumed that the head, arms and hands are entirely exposed unless PPE is
worn. Together the fractional skin area exposed to vapor (SAVC) is 25% of the total skin surface area in
the absence of PPE or liquid dermal contact.
The skin:air PC, PSKA, was calculated from the measured skin:saline and blood:saline PCs reported by
Poet et al. (2010) and the blood:air PC specified in their model code: PSKA = 44.5. With these values of
SAVC and PSKA, the average permeation constant for vapor-skin transport was estimated as PV = 16.4
cm/h. These assumptions and the value of PV resulted in a prediction of 20% of a total uptake from air
(vapor) exposure via the dermal route. In contrast, Bader et al. (2008) measured 42% of total urinary
excretion occurring after only dermal exposure to vapors compared to combined inhalation and dermal
exposure under resting conditions. The discrepancy between the Bader et al. (2008) data and the current
model predictions could be because the subjects in Bader and van Thriel (2006). on which this model is
based, wore long-sleeved shirts, thereby reducing dermal absorption or due to the use of an idealized
model of inhalation uptake which could over-predict uptake by that route.
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For use scenarios in this assessment the air concentration in contact with the skin is assumed to be the
same as that available for inhalation with SAVC kept at 25% for consistency, except as specified in the
sections below when PPE is worn.
Rat Internal Doses for BMD
EPA used the validated PBPK models for extrapolating NMP doses across routes of exposure and from
animals to humans based on NMP-specific data (U.S. EPA. 2015c). An internal dose metric such as a
measure of toxicant concentration in the blood is expected to be a better predictor of response than the
applied dose (e.g., concentration in air) since it is closer to the site of the toxic effect (McLanahan et at..
2012). Further, a good internal dose metric should correlate with or be predictive of toxicity irrespective
of the route of exposure by which it occurs. However, this is only true if the metric is in fact a measure
of the likelihood of a toxic response or intensity of a toxic effect.
For NMP the existing toxicity data identified the parent (NMP) rather than the metabolites 5-hydroxy-N-
methyl-2-pyrrolidone (5-HNMP), N-methylsuccinimide (MSI) or 2-hydroxy-N-methylsuccinimide (2-
HMSI) as the proximate toxicant (Saillenfait et at.. 2007). Therefore, PBPK model-derived blood
concentrations of NMP were considered a better basis than applied dose for the dose-metric used in
extrapolation of health effects.
3.2.5.6 Points of Departure for Human Health Hazard Endpoints
PODs for Acute Exposure
Acute exposure was defined for workers as the exposure that occurs over the course of a single day. For
consumers, the acute exposure scenario was defined based on completion of a single project on a given
day. EPA selected increased post-implantation losses (including resorptions and fetal mortality) as the
most relevant endpoint for evaluating risks associated with acute exposure to workers and consumers.
For reference, EPA also modeled dose-response information for stillbirths in reasonably available
studies. While stillbirths could plausibly result from a single exposure, the relevance of the reasonably
available stillbirth data for acute exposure scenarios is not known. Since repeated dose studies were used
to investigate these hazard endpoints and the mode of action for NMP is uncertain, EPA assessed dose-
response with both the internal dose metrics of Cmax and AUC. Dose-response for these developmental
endpoints is based on Cmax and AUC maternal blood concentrations predicted by the PBPK model.
The Saillenfait et al. (2002); Saillenfait et al. (2003); Becci et al. (1982); Sitarek et al. (2012); Exxon
Exxc L) and NMP Producers Group (1999b. c) studies were selected for dose-response analysis.
The Saillenfait et al. studies measured post-implantation losses (i.e., resorptions and fetal mortality)
following oral (Saillenfait et al.. 2002) and inhalation (Saillenfait et al.. 2003) exposure to NMP. The
Saillenfait et al. oral and inhalation studies were similar in design and used the same exposure duration
(GD 6-20) and the same strain of rat (Sprague-Dawley). Higher internal serum doses of NMP (ranging
from 120 to 831 mg/L based on Cmax) were achieved in the oral study compared to the inhalation study
(internal doses ranged from 15 to 62 mg/L based on Cmax). Importantly, the dose-response relationship
between internal serum dose and post-implantation losses was comparable for both the oral and
inhalation studies conducted by Saillenfait et al. There was no significant evidence of a dose-response
relationship between the internal serum dose and post-implantation loss in the inhalation study or at
doses at the lower end of the dose-response in the oral exposure study. For these reasons, dose-response
data from the two Saillenfait et al. studies were combined to provide additional statistical power and
enhance confidence in the BMD modeling results, particularly in the low dose region of the response
curve. In addition to the combined analysis, dose-response data for post-implantation losses from the
Saillenfait et al. (2002) oral and inhalation (2003) studies were also modeled independently. However,
given the lack of a clear dose-response relationship for post-implantation loss in the inhalation study,
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EPA determined that it would be inappropriate to choose a BMDL from this study for use as a POD. For
the Saillenfait studies, EPA characterized dose-response for both post-implantation loss (including
resorptions and fetal mortality) and resorptions alone. While post-implantation loss in these studies is
driven primarily by resorptions, resorptions were not amenable to modeling whereas post-implantation
loss could be modeled as a dichotomous variable. A BMR of 1% for increased post-implantation losses
was used to address the relative severity of this endpoint (	1012a).
Table 3-10 summarizes the derivation of PODs for acute exposure based on post-implantation loss and
stillbirth in each of the studies selected for dose-response analysis. The PODs based on internal dose
(AUC and Cmax) were converted to an equivalent applied dose using the PBPK model. The calculated
equivalent administered doses are nearly the same as the NOAELs identified in each study
demonstrating consistency between the two methods for deriving PODs.
Table 3-10. Summary of Derivation of the PODs for Post-implantation Losses (Resorptions and
r.mlpoinl and
Reference



liMI)
KM 1)1.

>OI)





(Kxposure
Dose


Internal
Internal
Internal
Kqiiivalent
Diiralion/Uoiite)
Metric
Model»
liMU
Dose
Dose
Dose h
Oral Dose 11
Posl-implanlalion loss
(GD 6-20, oral, post-
implantation loss)
Saillenfait et al. (2002)
Cmax (mg/L
blood)
1 ,ou-
Probit
1%
RD
474
437
437
41S niu kg
bw/day
AUC (hr
mg/L
Log-
Probit
1%
RD
5010
4592
4592
419 mg/kg
bw/day

blood)



Post-implantation loss
(GD 6-20, oral and
Cmax (mg/L
blood)
Log-
probit
1%
RD
470
437
437
418 mg/kg
bw/day
inhalation) (Saillenfait
et al., (2003);
Saillenfait et al. (2002)
AUC (hr
mg/L
blood)
Log-
probit
1%
RD
4990
4590
4590
419 mg/kg
bw/day
Resorptions
(GD 6-20, oral, post-
implantation loss)
Saillenfait et al. (2002)
NOAEL
(Cmax,
mg/L
blood)
N/A
N/A
N/A
N/A
250 c
250 mg/kg
bw/day
Resorptions
(GD 6-15, dermal)
Becci et al. (1982)
NOAEL
(Cmax,
mg/L
blood)
N/A
N/A
N/A
N/A
662 d
612 mg/kg
bw/day
(oral)
237 mg/kg
bw/day
(dermal)
Embryo/fetal mortality
(GD1-PND1, oral)
NOAEL
(Cmax,
mg/L
blood)
N/A
N/A
N/A
N/A
265 e
264 mg/kg
bw/day
Stillbirth f
(SD rats, dietary
exposure throughout
NOAEL
(Cmax,
mg/L
blood)
N/A
N/A
N/A
N/A
142
147 mg/kg
bw/day
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Knripoinl mid
Ucl'crcncc



liMI)
KM 1)1.

»()D





(Kxposurc
Dose


1 iilermil
1 iilermil
lnlcrn;il
Kqiiivsilenl
Diirnlion/Koiilc)
Metric
Model11
liMU
Dose
Dose
Dose h
Orsil Dose"
gestation, lactation,
NOAEL






growth, pre-mating)
NMP Producers Grout)
'9b)
(AUC,
mg/L
blood)
N/A
N/A
N/A
N/A
2120
216 mg/kg
bw/day
Stillbirth f
(Wistar rats, dietary
exposure throughout
gestation, lactation,
growth, pre-mating)
NMP Producers Group
!9c)
Cmax (mg/L
blood)
Nlogistic
-ICC
1%
ER
429
58
58
62 mg/kg
bw/day
AUC (hr
mg/L
blood)
Nlogistic
-ICC
1%
ER
6440
855
855
96 mg/kg
bw/day
Stillbirth f







(SD Rats, dietary
exposure throughout
gestation, lactation,
growth, pre-mating)
Exxon(t°91)
AUC (hr
mg/L
blood)
Nlogistic
-ICC
1%
ER
6744
1183
1183
129 mg/kg
bw/day
ER = extra risk; RD = relative deviation






Complete documentation of BMD modeling is available in Risk Evaluation for n-Methylpyrrolidone (NMP), Benchmark
Dose Modeling Supplemental File. Docket EPA-HO-OPPT-2019-0236 (TJ.S. EPA. 2020e).
a Assuming daily oral gavage and initial BW 0.259 kg (i.e., the same experimental conditions as the Saillenfait et al.
(2002) study) for the purposes of comparison across the studies,
b Internal doses refer to maternal blood concentrations (as opposed to fetal blood concentrations which are not predicted by
the PBPK model).
0 BMD models were considered unacceptable due to uncertainty caused by lack of model fit; the internal serum dose is
based on a NOAEL of 250 mg/kg-bw/day.
d Dose-response data were not considered amenable to BMD modeling. The internal serum dose is based on a NOAEL of
237 mg/kg bw/day dermal exposure. An oral dose of 612 mg/kg bw/day, given on GD 6-20, is predicted to yield the same
peak concentration (662 mg/L).
e Dose-response data were not considered amenable to BMD modeling. The internal serum dose is based on a NOAEL of
450 mg/kg bw/day.
f The relevance of stillbirth for acute exposure is unclear, as these effects were only observed following exposure to NMP
throughout gestation. In addition, the effect was reported in dietary studies in which exposure occurs throughout the day
rather than through a single bolus (which would result in a greater peak exposure).
Post-implantation loss data from the Saillenfait et al. (2002) oral study and the pooled dataset from the
Saillenfait et al. oral and inhalation studies were amenable to BMD modeling, and BMDLs based on the
internal serum dose of NMP were calculated for both Cmax and AUC dose metrics. The calculated
BMDL for both the combined Saillenfait et al. studies and the Saillenfait et al. oral study alone was 437
mg/L (based on C max).
Neither the Becci study nor the Sitarek study were suitable for BMD modeling, hence the NOAEL was
used to derive PODs for these studies. The Becci et al. (1982) dermal study supports a NOAEL of 662
mg/L NMP based on increased resorptions, while the Sitarek et al. (2012) oral study supports a NOAEL
of 265 mg/L based on embryo/fetal mortality.
Stillbirth data from several two-generation reproductive studies were amenable to BMD modeling (NMP
Puxincers Group. 1999b. c; Exxon. 1991). BMD modeling for stillbirths identified at PNDO was
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conducted using both Cmax and AUC dose metrics, as it is unknown whether this effect is the result of a
single dose at a critical stage of development or is a result of repeated exposure to NMP. For the two-
generation reproductive study conducted with Sprague-Dawley rats (NMP Producers Group. 1999b). no
BMD models adequately fit the dataset and the NOAEL (i.e., 142 mg/L based on Cmax and 2,120 hr
mg/L based on AUC) was chosen as the POD. Alternatively, BMDLs of 58 mg/L (based on Cmax) and
855 hr mg/L (based on AUC) were derived for stillbirths from the NMP Producers Group (1999c) study
with Wistar rats, while a BMDL of 1,183 hr mg/L (based on AUC) was derived from the Exxon (1991)
study.
EPA selected the BMDL for post-implantation losses from the pooled dataset from the Saillenfait et al.
oral and inhalation studies as the basis for the acute POD. The BMDL of 437 mg/L for post-implantation
losses was considered more appropriate for use as the acute POD than the highest NOAEL of 265 mg/L
from the Sitarek et al. ( ) study for several reasons. First, as outlined in EPA guidance, the BMD
approach overcomes many of the limitations inherently associated with the NOAEL/LOAEL approach,
and thus is the preferred method for establishing a POD for use in risk assessment (	1012a).
Furthermore, dose-response data from the Saillenfait et al. oral and inhalation studies was combined to
provide additional statistical power and enhance confidence in the BMD modeling results, particularly in
the low dose region of the response curve. Finally, embryo/fetal mortality in the study by Sitarek et al.
occurred in a similar dose-range as post-implantation losses in the combined Saillenfait et al. oral and
inhalation studies (i.e., NOAELs for post-implantation losses and fetal mortality were 250 and 265
mg/L, respectively, and LOAELs were 669 and 531 mg/L, respectively).
Similarly, the BMDL of 437 mg/L for post-implantation losses was considered to be more appropriate as
the basis for the acute POD than the BMDL of 58 mg/L based on stillbirths identified at PNDO in the
two-generation reproductive study (N	:ers Group. 1999c) for several reasons. First, the cause
of the stillbirths was not determined and it is unknown whether stillbirths are the result of a single dose
at a critical stage of development or a result of repeated exposure to NMP throughout development, and
therefore it unknown whether stillbirths should be considered most relevant for acute or chronic
exposures. Additionally, stillbirths were reported in dietary studies in which exposure to NMP occurred
throughout the day rather than through a single bolus, which would result in a greater peak serum dose,
and thus AUC may be a more appropriate dose metric for stillbirths reported in dietary studies. Finally,
in reasonably available studies where it was reported, stillbirths occurred in a similar dose range as post-
implantation loss (LOAELs for stillbirths in dietary two-generation studies were all 500 mg/kg/day, the
same as the LOAEL for post-implantation loss in Saillenfait et al. (2002). Accordingly, EPA selected the
BMDL from the pooled Saillenfait et al. (2003; 2002) oral and inhalation studies as the POD for use as
the basis for calculating risk for acute NMP exposures.
The selected POD may be considered broadly relevant to both male and female exposures. As described
in Section 3.2.4, evidence from (Sitarek and Stetkiewicz. 2008) indicates that paternal exposure prior to
mating may decrease offspring viability. Though paternally-mediated effects on offspring are a well-
recognized phenomenon (U.S. EPA. 1996). this is the only reasonably available study that evaluates the
developmental effects of paternal NMP exposure alone. Several additional two-generation reproductive
studies reported increased stillbirths and decreased pup survival following both maternal and paternal
exposure to NMP; however, the relative contribution of each parental exposure was not determined. No
other studies have specifically explored the paternal contribution to developmental toxicity of NMP, and
the duration of paternal exposure required to have this effect is unknown. In the absence of further
characterization of the paternally-mediated effects of NMP, it is prudent to assume that the POD for
acute exposure may be relevant for males of reproductive age as well as pregnant women.
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EPA applied a composite uncertainty factor (UF) of 30 for the acute exposure benchmark MOE, based
on the following considerations:
•	An interspecies uncertainty/variability factor of 3 (UFa) was applied for animal-to-human
extrapolation to account for toxicodynamic differences between species. This uncertainty factor
is comprised of two separate areas of uncertainty to account for differences in the toxicokinetics
and toxicodynamics of animals and humans. In this assessment, the toxicokinetic uncertainty was
accounted for by the PBPK model as outlined in the RfC methodology (	lb). As
the toxicokinetic differences are accounted for, only the toxicodynamic uncertainties remain, and
an UFa of 3 is retained to account for this uncertainty.
•	A default intraspecies uncertainty/variability factor (UFh) of 10 was applied to account for
variation in sensitivity within human populations. The PBPK model did not account for human
toxicokinetic variability. Due to limited information on the degree that humans of varying
gender, age, health status, or genetic makeup might vary in the disposition of, or response to,
NMP a factor of 10 was applied.
PODs for Chronic Exposure
Chronic worker exposure was defined as exposure of 10% or more of a lifetime (	).
Repeated exposures over the course of a work week are anticipated during chronic worker exposure. The
most sensitive chronic endpoints were selected based on reproductive and developmental studies on
NMP. Adverse developmental outcomes from exposure during critical windows of development during
pregnancy can occur any time during the defined chronic worker exposure period. Reproductive toxicity
may be of concern for all workers of reproductive age. In addition to the reproductive and
developmental endpoints that serve as the basis for the POD, the POD is expected to be protective of
pregnant women and children as well as men and women of childbearing age.
Decreased male fertility, decreased female fecundity, decreased fetal body weight, and increased
stillbirths were selected as the endpoints of concern for chronic exposures. The Exxt	), Becci et
al. (1982). E. I. Dupont De Nemours & Co (1990). Saillenfait et al. (2002.). Saittemfait et al. (2003). and
NMP Producers Group (1999b. 1999c) studies were selected for dose-response analysis. The PBPK
model and BMD modeling were applied to these studies to calculate the BMDLs and PODs and BMD
modeling results are described in Risk Evaluation for n-Methylpyrrolidone (NMP), Benchmark Dose
Modeling Supplemental File. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2020e). Per BMD
Technical Guidance (	012a). an extra risk of 10% is recommended as the standard
benchmark response (BMR) for quantal data, because the 10% response is at or near the limit of
sensitivity in most cancer bioassays and in some non-cancer bioassays. For some endpoints, biological
and statistical considerations may warrant the use of a BMR lower than 10%. For reduced fertility, a
BMR of 10%) was used because there is no biological basis for lowering the BMR. A BMR of 5%
relative deviation was used for decreased fetal body weight because in the absence of knowledge as to
what level of response to consider adverse, it has been observed that 5% change relative to the control
mean is similar to statistically derived NOAELs in developmental studies (Kavtock et al. 1995). A
BMR of 1% extra risk was used for stillbirths to account for the severity of this endpoint (U.S. EPA.
2012a). For studies where data were not amenable to modeling, EPA applied NOAELs (in units of
internal dose) instead.
EPA considered combining fetal body weight data from the Saillenfait et al. (2002) and Saillenfait et al.
(2003) studies to provide a more extensive characterization of the dose-response curve across exposure
route. The Saillenfait et al. (2003) inhalation study observed a statistically significant decrease in fetal
body weights at an internal dose that corresponds to an oral dose lower than the NOAEL in the
Saillenfait et al. (2002) oral study. This implies that fetal body weights were more sensitive to inhalation
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exposures and this was not fully accounted for in the PBPK model. Therefore, datasets from the two
studies were not combined for this endpoint.
The results of benchmark dose modeling for fetal body weight and fertility endpoints are summarized in
Table 3-11. Internal doses for fetal body weight reflect maternal blood concentrations during gestation
and internal doses for fertility reflect blood concentrations in pups post-weaning. The PODs based on
internal dose (AUC) were converted to an equivalent applied dose using the PBPK model. The
calculated equivalent administered doses are nearly the same as the NOAELs identified in each study
(where reasonably available) demonstrating consistency between the two methods for deriving PODs.
Table 3-11. Summary of Derivation of the PODs for Reproductive and Developmental Effects
Following Chronic Exposure to NMP				
Endpoint and
Reference
Exposure
Duration/Route)
Selected
Model or
NOAEL
BMR
BIND
Internal
Dose AUC
(hrrng/L
blood)
BMDL
Internal
Dose AUC
(hr mg/L
blood)
P
OD
Internal
Dose AUC
(hr mg/L
blood)"
Equivalent
Applied Oral
Dose b
Fetal Body Weight
(GD 6-20, oral)
Exponential
3 c'd
5%
RD
1400
981
981
109 mg/kg
bw/day
Saillenfait et al. (2003)
(GD 6-20, inhalation)
Exponential
3 c
5%
RD
654
414
414
48 mg/kg
bw/day
3omt De
Exponential
3 c
5%
RD
315
223
223
27 mg/kg
bw/day
Nemours & Co (1990)
(preconception exposure,
GD 1 -20, inhalation)
Becci et 32)
(GD 6-15, dermal)
NOAEL=
237
mg/kg/dav 0
NA
NA
NA
2052
210 mg/kg
bw/day
Reduced Male Fertility
Exxc ) (Dietary
exposure throughout
gestation, lactation,
growth, pre-mating)
Log-
logistic
10%
ER
492"
34112
262 n
183 G
183
28 mg/kg
bw/day
Reduced Female Fecundity
Exxc ) (Dietary
exposure throughout
gestation, lactation,
growth, pre-mating)
Log-
logistic
10%
ER
862 11
420 G
401 fl
202 G
202
3 1 mg/kg
bw/day
Stillbirth
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Endpoint and
Reference
Exposure
Duration/Route)
Selected
Model or
NOAEL
BMR
BMD
Internal
Dose Al!C
(hr mg/L
blood)
BMDL
Internal
Dose AIJC
(hr mg/L
blood)
POD
Internal
Dose AIJC
(hr mg/L
blood)"
Equivalent
Applied Oral
Dose b
Stillbirth
(SD rats, dietary
exposure throughout
gestation, lactation,
growth, pre-mating)
NMP Producers Group
9b)
NOAEL=
160 mg/kg-
day g
N/A
N/A
N/A
2120
216 mg/kg
bw/day
Stillbirth
(Wistar rats, dietary
exposure throughout
gestation, lactation,
growth, pre-mating)
NMP Producers Grout)
9c)
Nlogistic -
ICC
1%
ER
6440
855
855
96 mg/kg
bw/day
Stillbirth
(SD Rats, dietary
exposure throughout
gestation, lactation,
growth, pre-mating)
Exxc )
Nlogistic -
ICC
1%
ER
6744
1183
1183
129 mg/kg
bw/day
RD = relative deviation; ER = extra risk
The POD selected for calculating risk of chronic NMP exposures is highlighted in bold. Complete documentation of BMD
modeling is available in Risk Evaluation for n-Methylpyrrolidone (NMP), Benchmark Dose Modeling Supplemental File.
DocketEPA-HO-OPPT-2019-0236 (US. EPA. 2020s).
a Internal doses for fetal body weight reflect maternal blood concentrations during gestation and internal doses for fertility
reflect blood concentrations in pups post-weaning (see discussion in Section 3.2.5.2).
' Assuming daily oral gavage CDs 6-20 and initial BVV 0.259 kg (i.e., the same experimental conditions as the Saillenfait et
al. (2002) studv) for the purposes of comparison across the studies.
0 Since standard models gave adequate results for all endpoints. non-standard models were not considered. Since fits to the
means were obtained using normal distribution models, lognormal models were not applied
•' For Saillenfait et al. (2002), the BMD and BMDL reported are from modeling the data with all the standard deviations set
equal to the maximum standard deviation across the groups.
e The data in Becci (Becci et al.. .1.982) were not amenable to BMD modelins. The mean weisht increased sraduallv from
the control to the middle dose group and then decreased significantly at the high dose group. This dose-response pattern is
essentially equivalent to one where only the highest dose has a response and thus the model estimates of the parameters
and BMDs would not be reliable. The internal serum dose is based on a NOAEL of 237 mg/kg bw/day dermal exposure.
f In the Exxon (1991) studv. each dam had two sets of matins ocriods. Each matins oeriod was analyzed separately: dl
indicates results for the first mating period and d2 indicates results from the second mating period. PODs for male fertility
and female fecundity in this study are calculated based on exposure levels in 50g rats immediately post-weaning.
gBMD modelins was attempted for stillbirth data reported in the NMP Producers Group (1999b) studv with Sprasue-
Dawley rats; however, no models adequately fit the dataset.
EPA selected the POD derived from decreased male fertility (183 hr mg/L) in a two-generation
reproductive study (Exxon. 1991) to be used in the calculation of risk estimates associated with chronic
exposures. This high-quality study identified the most sensitive reproductive endpoints and had a
significant dose-response relationship that was adequately modeled by the BMD model. The POD for
effects on reduced female fecundity in this study was very similar (202 hr mg/L) to the POD for effects
Page 265 of 576

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on male fertility, making it highly relevant to both male and female reproductive endpoints. The broad
relevance of this endpoint for males and females ensures that this POD is directly applicable for all
chronic exposure scenarios considered in risk characterization. This POD selection is consistent with
EPA's Guidelines for Reproductive Toxicity Risk Assessment (	>96).
While reduced fertility was not consistently observed across all reasonably available studies, significant
reductions in fertility were reported in three high quality studies. The reduced male fertility and female
fecundity observed in the second generation of the Exxon study (1991) are particularly sensitive
endpoints. The biological plausibility of effects on male fertility and reproductive success is supported
by mechanistic evidence (discussed in Section 3.2.4.2) demonstrating that NMP competitively binds to
the testis-specific BRDT protein (Shortt et at.. 2014). a master regulator of epigenetic reprograming
during spermatogenesis (Jonathan Gaucher. 2012).
The selected chronic POD may be considered protective of reduced fetal body weight. The PODs
derived from effects on fetal body weight in two developmental inhalation exposure studies (Saillenfait
et at.. 200 , L Dupont De Nemours & Co. 1990) fall in an internal dose range (223 and 414 hr mg/L),
similar to the POD based on reduced fertility (183 hr mg/L), lending further support for the selected
POD. Both inhalation studies used whole body exposures where dermal absorption of NMP vapors
likely contributed to the toxicity. This is similar to human exposure scenarios; however, the unknown
differences between human and rat dermal absorption of NMP vapor adds uncertainty to values derived
from either of these studies alone. While the POD for the DuPont study was lower than the Saillenfait
study, the dose-response relationship in the DuPont study was not as robust as the Saillenfait study.
Lower variability in body weights was observed in the Saillenfait study than in the DuPont study. In the
DuPont study, statistically significant differences only occurred in the lowest and highest dose groups,
not the middle dose group. The Becci et; 2) study contributes to the weight of the scientific
evidence for developmental toxicity across exposure routes, but there are limitations in the dose-
response analysis for this study. The duration of dosing was shorter than for the Saillenfait studies and
the uncertainty regarding exposure duration and sampling time leads to uncertainty about recovery and
compensation. Furthermore, the dose-response data in Becci et al. (1982) were not amenable to BMD
modeling.
The selected chronic POD may also be considered protective of stillbirths associated with repeated-dose
exposure. Dose-response analysis of stillbirths reported following repeated-dose exposures throughout
gestation in the three two generation dietary studies identified PODs for chronic exposure ranging from
internal doses of 855-2,120 hr mg/L.
Dose-response modeling for alternate developmental endpoints show PODs in a similar internal dose
range to the key endpoints presented here. For example, BMD modeling of pup body weights at PND 21
reported by the NMP Producers Group (1999b) identified a BMDL of 100 hr mg/L. This endpoint was
not selected as the basis for POD derivation because there is uncertainty around the level of post-natal
exposure that occurs through lactation. Effects on post-natal body weight were reported at similar dose
levels as effects on fetal body weight. Other developmental endpoints, including reduced pup survival,
and delayed ossification were reported also at similar doses ranges as changes in fetal body weight
following repeated dose exposures. Dose-response modeling for several of these alternate endpoints is
described in more detail in the supplemental file, Risk Evaluation for n-Methylpyrrolidone (NMP),
Benchmark Dose Modeling Supplemental File. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2020e).
EPA applied a composite uncertainty factor (UF) of 30 for the chronic exposure benchmark MOE, based
on the following considerations:
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•	An interspecies uncertainty/variability factor of 3 (UFa) was applied for animal-to-human
extrapolation to account for toxicodynamic differences between species. This uncertainty factor
is comprised of two separate areas of uncertainty to account for differences in the toxicokinetics
and toxicodynamics of animals and humans. In this assessment, the toxicokinetic uncertainty was
accounted for by the PBPK model as outlined in the RfC methodology (1.5 .< j_\\ _ jM'JJb). As
the toxicokinetic differences are thus accounted for, only the toxicodynamic uncertainties
remain, and an UFa of 3 is retained to account for this uncertainty.
•	A default intraspecies uncertainty/variability factor (UFh) of 10 was applied to account for
variation in sensitivity within human populations. The PBPK model did not account for human
toxicokinetic variability. Due to limited information on the degree of humans of varying gender,
age, health status, or genetic makeup might vary in the disposition of, or response to, NMP a
factor of 10 was applied.
3.2.6 Summary of Human Health Hazards
Table 3-12 summarizes the hazard studies, health endpoints and UFs that are used for risk
characterization in this risk evaluation. The reported PODs reflect internal dose estimates (blood
concentrations) for comparison with internal dose estimates of human exposures from multiple routes
(e.g., inhalation and/or dermal).
Table 3-12. PODs Selected for Non-Cancer Effects from NMP Exposures
Kxposure
Dm ml ion
Tsir«et
System
Species
Dose
Metric
UMR
POD
I! fleet
I ncerliiinly
l-'sictors (I I s)
for
liciK'hniiirk
moi:
References
Diitii
Qunlilv
Score
Acute
Developmental
Rat
Cmax
(mg/L
blood)
1%
RD
437
mg/L
Post-
implantation
loss
(resorptions
and fetal
mortality)
UFa = 3
UFh = 10
Total UF = 30
Saillenfait
et al. 2003;
Saillenfait
et al.
(2002)
High
Chronic
Reproductive
Rat
AUC
(hr-
mg/L
blood)
10%
ER
183
hr-
mg/L
Decreased
Male
Fertility
UFa = 3
UFh = 10
Total UF = 30
Exxon
)
High
RD = relative deviation; ER= extra risk; UFA = interspecies UF; UFH = intraspecies UF.
Primary Strengths
There is a robust dataset for the critical reproductive and developmental effects that serve as the basis
for the PODs used in this risk characterization. The reasonably available studies demonstrate clear,
consistent effects on a continuum of reproductive and developmental endpoints following NMP
exposure across oral, inhalation, and dermal exposure routes. Each of the critical endpoints supporting
the PODs represents an adverse effect that is biologically relevant to humans. The acute POD based on
post-implantation loss reflects consistent observations across multiple high-quality studies using
multiple exposure routes. The chronic POD selected based on reduced fertility following exposure
across lifestages in a high-quality study is supported by other high-quality studies demonstrating
reduced fertility in males and females exposed only as adults. The biological plausibility of the effect on
male fertility is further supported by toxicokinetic evidence demonstrating that NMP reaches the testes
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and mechanistic evidence indicating thatNMP competitively binds BRDT, a testis-specific regulator of
epigenetic changes during spermatogenesis (discussed in Section 3.2.4.2). The POD derived from
reduced fertility is within close range (approximately a factor of two) of PODs derived from a
developmental endpoint (fetal body weight) that is consistently observed across studies, species, and
routes of exposure. The quality of the studies, consistency of effects, relevance of effects for human
health, coherence of the spectrum of reproductive and developmental effects observed and biological
plausibility of the observed effects of NMP contribute to the overall confidence in the PODs identified
based on reproductive and developmental endpoints.
The NMP PBPK models allow EPA to identify points of departure based on blood concentrations of
NMP that are associated with effects in animal models. Because the effects of NMP at a specific blood
concentration are independent of exposure route, a single internal dose POD can be applied to evaluate
risk from all routes of exposure. This eliminates the need for extrapolating hazard information across
exposure routes. The PBPK model also accounts for toxicokinetic information in rats and humans,
reducing a source of uncertainty associated with cross-species extrapolation.
Primary Limitations
While there is a large amount of animal data on reproductive and developmental effects of NMP, there
are not studies on reproductive and developmental toxicity of NMP in humans. Therefore, this risk
evaluation relies on the assumption that reproductive and developmental toxicity observed in animal
models is relevant to human health. It is unknown whether this assumption leads to an underestimation
or overestimation of risk.
Some potentially sensitive endpoints remain poorly characterized. For example, neurodevelopmental
effects were observed in response to a high dose exposure, but no NOAEL has been established for these
effects. In addition, there are limited data on the effects of NMP on sensitization and immunotoxicity,
endocrine effect, and cardiometabolic effects. If endpoints that are not well characterized are in fact
more sensitive to NMP than the endpoints that serve as the basis for the POD, this could lead to an
underestimation of risk.
For studies that identified developmental outcomes following pre- and/or postnatal exposures, maternal
toxicity was often also present. Although it has been demonstrated that NMP crosses the placenta, so
direct prenatal exposure to the offspring was likely, there were no studies that characterized the
interrelationship or contribution of maternal toxicity to offspring toxicity.
There is some uncertainty around which dose metrics are most appropriate for specific endpoints. For
example, there is uncertainty around whether stillbirths should be considered most relevant for acute or
chronic exposures. Stillbirths were reported in several of the reasonably available studies following
repeated-dose exposures (discussed in Section 3.2.4.1). It is unknown whether this effect was the result
of a single dose at a critical stage of development or a result of repeated exposure to NMP. In reasonably
available studies where it was reported, stillbirth occurred in a similar dose range as post-implantation
loss.
There are also some uncertainties associated with the specific endpoint used as the basis for the chronic
POD. The chronic POD is based on sensitive reproductive endpoints observed in a two-generation
reproductive study. Two of the subsequent studies that evaluated fertility in two-generation reproductive
studies reported developmental toxicity but found no significant effect on fertility at any dose tested.
Another two-generation study via inhalation deviated substantially from EPA and OECD guidelines and
had serious limitations due to uncertainties about the actual doses achieved, making it difficult to draw
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clear conclusions from the results. Although the critical effect is only observed in a single two-
generation study, it is supported by evidence in other high-quality studies of reduced fertility in male
and female rats exposed as adults. It is unclear whether this data limitation leads to an overestimation or
underestimation of risk.
In addition, because exposure in the key study occurred throughout gestation, lactation, post-weaning,
puberty and pre-mating, it is not possible to determine which exposure periods contributed to reduced
fertility. EPA therefore established a POD based on lifestage at which the lowest level of exposure
relative to body weight occurred. This assumption could result in up to a two-fold overestimation of risk
(see discussion in Section 3.2.5.2).
In inhalation studies, there is some uncertainty around the techniques used to generate NMP air
concentrations for animal exposures in some supporting studies considered in the weight of the scientific
evidence. Experimental conditions may have inadvertently resulted in the inclusion of aerosolized
particles in the exposure chamber in some inhalation exposure studies. NMP is hygroscopic; therefore,
variations in temperature, humidity and/or test protocol (e.g., the number of air changes, use of a spray
or nebulization technique to generate test atmospheres) may impact the NMP air saturation
concentration, resulting in condensation of NMP. Aerosol formation would result in increased dermal
and/or oral exposures (from grooming behavior) in addition to the intended inhalation exposure. The
two-generation inhalation study (Solomon et ai. 19c , * M Hipont De Nemours & Co. 1990) noted that
condensation observed on the chamber walls at the highest dose indicates that the actual air
concentrations of NMP were lower than the intended exposure. Nonetheless, higher test concentrations
and total body exposures to NMP were associated with adverse developmental effects in rats.
Overall Confidence
EPA has high confidence in the POD identified for evaluating risk from acute NMP exposure. The POD
is derived from developmental endpoints that are consistently observed in response to NMP across oral,
dermal and inhalation exposure routes. Application of the PBPK model reduces uncertainties associated
with extrapolation across species and exposure routes, further contributing to overall confidence in the
PODs.
EPA has medium confidence in the POD identified for evaluating risk from chronic NMP exposure. The
POD is informed by multiple endpoints that fall along a continuum of reproductive and developmental
effects. The fertility endpoint that serves as the quantitative basis for the POD is supported by evidence
from multiple studies, but is not consistently replicated across studies. Application of the PBPK model
reduces uncertainties associated with extrapolation across species and exposure routes, further
contributing to overall confidence in the PODs.
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4 RISK CHARACTERIZATION
4.1 Environmental Risk
4.1.1 Risk Estimation Approach
The environmental risk of NMP is characterized by calculating risk quotients or RQs (
Bamthouse et at.. 1982.). The RQ is defined as:
RQ = Environmental Concentration / Effect Level
An RQ equal to 1 indicates that the exposures are the same as the concentration that causes effects. If the
RQ is above 1, the exposure is greater than the effect concentration. If the RQ is below 1, the exposure
is less than the effect concentration. The Effect Levels and COCs used to calculated RQs are identified
in Section 3.1.2 and in Table 4-1, respectively.
Frequency and duration of exposure also affects the potential for adverse effects in aquatic organisms.
Therefore, the number of days that the chronic COC was exceeded was also calculated using E-FAST as
described in Section 2.3.2. The days of exceedance modeled in E-FAST are not necessarily consecutive
and may occur sporadically throughout the year. Facilities with an RQ > 1 for the acute exposure
scenario or an RQ > 1 and 20 days or more of exceedance for the chronic exposure scenario would
suggest the potential for environmental risks posed by NMP. The 20-day exceedance time frame was
derived from partial life cycle tests (e.g., daphnid chronic and fish early life stage tests) that typically
range from 21 to 28 days in duration.
Table 4-1. Concentrations of Concern (COCs) for Environmental Toxicity
Knviron menial Toxicity
Mosl Sensitive Species
COCs
Acute Toxicity, aquatic organisms
48-Hour aquatic
invertebrates
100,000 |ig/L
Chronic Toxicity, aquatic
organisms
21-Day aquatic invertebrates
1,770 ng/L
EPA used estimated acute and chronic exposure concentrations of NMP in surface water (Section 2.3.2)
and acute and chronic COCs (Section 3.1.2) to evaluate the risk of NMP to aquatic species. Table 4-2
and Table 4-3 summarize the RQs and days of exceedance used to characterize risk to aquatic organisms
from acute and chronic exposures to NMP. In Table 4-2 RQ values are reported for the top ten direct and
indirect dischargers reporting to the TRI in 2015. Table 4-3 shows RQ values to the nine direct
dischargers and top ten indirect dischargers reporting to the TRI in 2018. Based on these values (acute
RQs all < 1, and chronic RQs < 1 or RQ > 1 but < 20 days of exceedance) risk to aquatic organisms
from acute or chronic exposure pathways was not indicated. As previously stated, an RQ below 1
indicates that the exposure concentrations of NMP is less than the concentration that would cause an
effect to organisms in aquatic exposure pathways. The chronic COC was exceeded in 2015 at one
location in Oregon (RQ = 1.1), but exceedance was predicted to occur for less than 20 days.
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Table 4-2. Calcnlated Risk Quotients (RQs) for XATP Bused Top Facility Dischargers Reported in 201 TRT data

Acute Kxposnre Scenario
Chronic Kxposnrc Scenario


Stream N.MP

Stream N.MP

# Davs


Concentration

Concentration

C hronic ('()('
l-'acilitv
State
(Jig/'-)
UQ
(MS/I.)
UQ
Kxceeded
Direct Discharger Facilities
Fortran Industries
NC
2.2E+02
2.2E-03
1.1E+01
6.1E-03
0
Spruance Plant
VA
1.2E+02
1.2E-03
5.8E+00
3.2E-03
0
GlobalFoundries
VT
4.4E+01
4.4E-04
2.1E+00
1.2E-03
0
American Refining Group
PA
8.5E+00
8.5E-05
4.0E-01
2.3E-04
0
Essex Group, Fort Wayne
IN
5.6E+00
5.6E-05
2.7E-01
1.5E-04
0
BASF Corp
MI
1.1E-03
1.1E-08
4.9E-04
2.8E-07
0
Indirect Discharger Facilities
Koch Membrane
MA
N/A
N/A
6.0E+01
3.4E-02
0
Pall Corp.
FL
N/A
N/A
8.8E+02
5.0E-01
0
Air Products
MO
N/A
N/A
6.4E+02
3.6E-01
0
GVS; GE Healthcare: Westborough
POTW
MA
N/A
N/A
8.6E+02
4.9E-01
0
Intel, Aloha; Intel, Ronler Acres:
OR
N/A
N/A
2.0E+03
1.1E+00

Rock Creek STP, Hillsboro POTW
z
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Table 4-3. Calculated Risk Quotients (RQs) Tor \A1~P Bused on Top Facility Dischargers Reported in 201S TRT data

Acute Kxposnre Scenario
Chronic Kxposnrc Scenario


Stream N.MP

Stream N.MP

# Davs


Concentration

Concentration

Chronic COC
l-'acilitv
Stale
(ng/l.)
UQ
(MS/I.)
UQ
Kxceeded
Direct Discharger Facilities
Fortran Industries,
NC
6.2E+00
6.2E-05
2.5E-01
1.4E-04
0
Spruance Plant,
VA
1.2E+02
1.2E-03
4.9E+00
2.8E-03
0
GlobalFoundries
VT
7.3E+01
7.3E-04
3.4E+00
1.9E-03
0
BASF, Mcintosh
AL
7.6E+00
7.6E-05
2.9E-01
1.6E-04
0
American Refining Group
PA
4.2E+00
4.2E-05
1.7E-01
9.6E-05
0
Essex Group, Fort Wayne
IN
2.3E+02
2.3E-03
9.2E+00
5.2E-03
0
GlobalFoundries
NY
4.9E+01
4.9E-04
2.3E+00
1.3E-03
0
BASF Corp
MI
6.2E-03
6.2E-08
5.4E-04
3.1E-07
0
Essex Group Franklin
IN
3.0E+01
3.0E-04
1.4E+00
7.9E-04
0
Indirect Discharger Facilities
Koch Membrane
MA
N/A
N/A
9.0E+01
5.1E-02
0
Pall Corp.
FL
N/A
N/A
8.1E+02
4.6E-01
0
Air Products
MO
N/A
N/A
4.3E+02
2.4E-01
0
GVS; GE Healthcare: Westborough
POTW
MA
N/A
N/A
1.0E+03
5.7E-01
0
Intel, Aloha; Intel, Ronler Acres:
OR
N/A
N/A
1.0E+03
5.8E-01
0
Rock Creek STP, Hillsboro
Veolia ES Technical Solutions, LLC
NJ
N/A
N/A
2.8E+01
1.6E-02
0
Intel Corp
AZ
N/A
N/A
0.0E+00
0.0E+00
0
Caterpillar, Inc
IL
N/A
N/A
8.6E-01
4.9E-04
0
Cree, Inc
NC
N/A
N/A
2.2E+01
1.2E-02
0
Pall Filtration
CA
N/A
N/A
3.6E+01
2.0E-02
0
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4.1.2 Assumptions and Key Uncertainties for the Environment
In the NMP Problem Formulation ( .	• ) and this RE, EPA completed a screening level
evaluation of environmental risk using inherently conservative assumptions. The analysis was completed
using estimated concentrations of NMP in the aquatic environment as described in Section 2.3.2 and
compared those acute and chronic exposure estimates to conservative measures of acute and chronic
hazard (COCs) as described in Section 3.1.2. However, there is uncertainty associated with the acute and
chronic COCs identified for aquatic receptors. First, more acute duration toxicity data were reasonably
available in the literature compared to chronic duration data. For the chronic fish endpoint, an acute to
chronic ratio (ACR) approach was used to extrapolate a chronic toxicity value for NMP based on the
reported acute values. Using a single value of 10 to extrapolate from acute to chronic hazard for species
in the aquatic compartment is consistent with existing EPA methodology for the screening and analysis
of industrial chemicals (U.S. EPA, 2012e). While this value is routinely used by EPA to assess the
hazard of new industrial chemicals, there is uncertainty regarding using a single ACR value to estimate
chronic hazards across species and chemicals. Therefore, EPA is less certain of chronic hazard values
than the acute hazard values. Second, AFs were used to calculate the acute and chronic COCs for NMP.
AFs account for differences in inter- and intra-species variability, as well as laboratory-to-field
variability and are routinely used within TSCA for assessing the hazard of new industrial chemicals
(with very limited environmental test data). There is some uncertainty associated with the use of
standardized AFs used the hazard assessment. EPA in the NMP Problem Formulation (U.S. EPA.
2018c) did not conduct any further analyses on pathways of exposure for terrestrial receptors as
described in Section 2.5.3.1 of the NMP Problem Formulation and further described in Section 2.2 and
2.3 of this risk evaluation.
4.2 Human Health Risk
The human health risks associated with NMP conditions of use identified in Section 1.4 are discussed
below. Specific information regarding the methodologies used to derive exposure estimates, including
related assumptions and data limitations or uncertainties can be found in Section 2.4; an overview of the
potential human health hazards, including key and supporting studies is presented in Section 3.2.
4.2.1 Risk Estimation Approach
An overview of the approach to quantifying occupational and consumer risks for the evaluated
conditions of use for NMP is shown in Figure 4-1. To evaluate the human health risks of NMP, EPA
first evaluated acute and chronic exposures to NMP for workers and ONUs (Section 2.4.1), and acute
exposures to NMP for consumer users and consumer bystanders (Section 2.4.2). For workers and ONUs,
EPA evaluated the dermal (worker only), inhalation, and vapor-through-skin exposure routes. For
consumers and bystanders, EPA evaluated dermal (user only), inhalation, vapor-through-skin, and oral
(child users only) exposure routes. As discussed in Section 2.4, EPA used reasonably available exposure
data from models and measured concentrations to estimate occupational and consumer exposure to NMP
for all conditions of use. Dermal and inhalation exposure parameters and concentrations of NMP were
used as input parameters for a validated human PBPK model, which was used to predict the human
internal serum dose {i.e., Cmax (mg/L) or AUC (hr mg/L)) of NMP for combined routes of exposure {i.e.,
inhalation, dermal, vapor-through-skin). The internal human serum dose for each condition of use was
then compared to the rat internal serum dose point of departure (POD), which was calculated using a
validated rat PBPK model and benchmark dose modeling as described in Section 3.2.
To evaluate non-cancer risks, margins of exposure (MOEs) for acute and chronic exposure were
calculated using Equation 4-1. The MOE is the ratio of the non-cancer POD divided by a human exposure
dose. MOEs allow for the presentation of a range of risk estimates.
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EPA interpreted the MOE risk estimates for each use scenario in reference to benchmark MOEs.
Benchmark MOEs are the total UF for each non-cancer POD. The MOE estimate was interpreted as a
human health risk if the MOE estimate was less than the benchmark MOE {i.e., the total UF). On the
other hand, the MOE estimate indicated negligible concerns for adverse human health effects if the
MOE estimate was equal to or exceeded the benchmark MOE. Typically, the larger MOE, the more
unlikely it is that a non-cancer adverse effect would occur.
Rat PBPK Model
BMD Modeling
Dermal &
Inhalation Inputs
CEM Dose
Estimate
(mg/kg-day)
Acute
Exposure
Chronic
Exposure
Dermal &
Inhalation Inputs
Dermal &
Inhalation Inputs
Acute
Exposure
Human PBPK
Internal Dose
(("max. mg/L)
Human PBPK
Internal Dose
(AUC, hr mg/L)
Human PBPK
Internal Dose
(Cmax, mg/L)
Oral
(mouthing)
Inhalation, dermal
(worker only),
vapor-through-skin
Inhalation, dermal
(worker only),
vapor-through-skin
Inhalation, dermal,
vapor-through-skin
Dose-Response Assessment
Workers & Occupational
Non-Users
Users & Bystanders
Rat Internal Dose PODs
(BMDLs, mg/L)
Internal Dose
Cmax (mg/L; acute exposure) &
AUC (hr mg/L; chronic exposure)
Consumer Exposure Assessment
Occupational Exposure Assessment
Developmental &
Reproductive Toxicity
Endpoints:
Post-implantation losses
(acute exposures)
Decreased male fertility
(chronic exposures)
Margin of Exposure (MOE)
Rat Internal Dose POD
Human Internal Dose
Figure 4-1. Schematic of Analysis Plan for Quantifying Occupational and Consumer Risks of
NMP.
Equation 4-1. Equation to Calculate Non-Cancer Risks Following Acute or Chronic Exposures
Using Margin of Exposures
Non — cancer Hazard value (POD)
M0E =	 H^ Exposure 	
Where:
MOE = Margin of exposure (unitless)
(POD) = internal dose (Cmax, mg/L or AUC hr mg/L)
Human Exposure = internal dose exposure estimate
(Cmax, mg/L or AUC hr mg/L) from occupational or consumer
exposure assessment. Cmax was used for acute exposure scenarios
and the AUC was used for chronic exposure scenarios.
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In this risk characterization, peer-reviewed PBPK models for NMP in rats and humans (Appendix J)
allow EPA to estimate internal doses (blood concentrations) that may occur in humans and compare
these to PODs based on internal doses associated with health hazards in rats. MOEs are calculated by
dividing PODs in units of internal blood concentrations in rats by human blood concentrations expected
for specific exposure scenarios. For characterization of risks from acute exposures, PODs and human
exposure estimates are in terms of maximum blood concentrations (Cmax) while for risks from chronic
exposures, they are in terms of average daily exposure (AUC).
The PBPK models facilitate integration of exposure and hazard information across exposure routes. For
each exposure scenario, the PBPK model is used to aggregate simultaneous inhalation and dermal
exposures into a single human internal dose. The relative contribution of inhalation and dermal exposure
routes varies across exposure scenario. The PBPK models also allow the risk characterization to
incorporate information about toxicokinetics. Internal doses predicted by the model account for internal
exposure that remains after external exposure has ceased, reflecting the rate of metabolism and
elimination. Toxicokinetic information captured in rat and human models reduces toxicokinetic
uncertainty associated with interspecies extrapolation.
Table 4-4 and Table 4-5 summarize the use scenarios, populations of interest and toxicological
endpoints used to evaluate risk for acute and chronic exposures for workers and acute exposure for
consumers, respectively.
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Table 4-4. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Occupational Risks Fo
lowing Acute and Chronic Exposures to NMP
Populations and
Toxicological
Approach
Occupational I s
e Scenarios of NMP
Population of
Interest and
Exposure Scenario:
Users:
Adults and youth of both sexes (>16 years old) exposed to NMP during
product use in a workday, typically 8 or 12 hours a'b
Occupational Non-users:
Adults and youth of both sexes (>16 years old) indirectly exposed to NMP
while in the vicinity of product use.
Health Effects of
Concern,
Concentration and
Time Duration
Acute Non-Cancer Health
Effects:
Developmental toxicity (post-
implantation loss)
Hazard Values (POD): 437 mg/L
(Cmax blood concentration)
Chronic Non-Cancer Health Effects:
Reproductive toxicity (reduced
fertility)
Hazard Values (POD): 183 hr mg/L
(AUC blood concentration)
Uncertainty Factors
(UF) used in Non-
Cancer
Margin of Exposure
(MOE) Calculations
UFs for Acute Hazard:
Total UF = 30 (10X UFh * 3X UFa) c
UFs for Chronic Hazard:
Total UF = 30 (10X UFh * 3X UFa) c
a It is assumed that there is no substantial buildup of NMP in the body between exposure events due to NMP' s short
biological half-life (~2.5 hours).
b EPA expects that the users of NMP-based products and exposed non-users are generally adults, but younger individuals
may be users and exposed non-users.
0 UFH = intraspecies UF; UFA= interspecies UF
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Table 4-5. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Consumer Risks Following Acute Exposures to NMP	
Populations and Toxicological
Approach
Consumer I se Scenarios of NMP
Population of Interest and
Exposure Scenario:
Users:
Adults of both sexes (>16 years old) typically exposed to NMP a'b
Bystanders:
Individuals of any age indirectly exposed to NMP while being in the rest
of the house during product use (see Section 2.4.2 for more information).
Health Effects of Concern,
Concentration and Time
Duration
Non-Cancer Health Effects:
Developmental toxicity (post-implantation loss).
Hazard Values (POD): 437 mg/L (Cmax blood concentration)
Uncertainty Factors (UF) used
in Non-Cancer
Margin of Exposure (MOE)
Calculations
Total UF = 30 (10X UFh * 3X UFa) c
11 It is assumed that there is no substantial buildup of NMP in the body between exposure events due to NMP's short biological
half-life (~2.5 hours).
b EPA expects that the users of these products are generally adults, but younger individuals may be users of NMP-based paint
strippers.
0 UFh= intraspecies UF; UFA= interspecies UF
4.2,2 Risk Estimation for Worker Exposures for Occupational Use of NMP
The risk characterization was performed using internal dose estimates derived from PBPK modeling of
occupational exposures based on reasonably available monitoring data. PBPK modeling allowed EPA to
estimate internal doses integrating inhalation, dermal, and vapor through skin exposures, which further
allowed EPA to evaluate acute and chronic risks from aggregate exposure to NMP for each condition of
use. The following sections (Sections 4.2.2.1 through 4.2.2.17) present risk estimates of acute and
chronic inhalation, dermal, and vapor through skin exposures for workers following occupational use of
NMP in each condition of use. Risk estimates for occupational non-users are shown in Section 4.2.3.
Risks shown in this section are calculated based on occupational exposure estimates summarized in
Table 2-73 and hazard points of departure summarized in Table 3-12. MOEs calculated for acute and
chronic occupational exposures for each condition of use are summarized in Table 4-6 through Table
4-39. MOE values below the benchmark MOE of 30 (described in Section 3.2.5.6) are indicated with
bold and shaded grey.
For each occupational exposure scenario, EPA calculated risk based on a glove protection factor of 1,
which corresponds to no glove usage or use of gloves that are not protective against NMP. EPA also
calculated risks based on glove protection factors of 5, 10, and 20 based on exposure modeling described
in Section 2.4.1 and in the Supplemental Excel File on Occupational Risk Calculations (
2.02.0s). As indicated in Table 2-3, use of protection factors above 1 is valid only for glove materials that
have been tested for permeation against the NMP-containing liquids associated with the condition of
use. More information on glove materials for protection against NMP is in Appendix F. For each
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occupational exposure scenario, EPA also calculated risk based on use of a half mask air-purifying
respirator (APF of 10). For most occupational exposure scenarios the primary route of exposure to NMP
was via the dermal route, and respirator use had minimal impact on internal dose estimates and
subsequent risk calculations (see Table 4-55 for a comparison of MOEs with and without respirator use).
For this reason, risk calculations for respirator use are not shown in Sections 4.2.2.1 - 4.2.2.17, but are
shown for select occupational exposure scenarios in Table 4-55 and are fully summarized in the
Supplemental Excel File on Occupational Risk Calculations (U.S. EPA. 2020s).
As described in Section 2.4.1, EPA calculated alternate exposure estimates for some occupational
exposure scenarios based on alternate assumptions about contact durations, monitoring times, or other
input parameters. Risks calculated for these alternate "what-if' exposure scenarios are shown in the
Supplemental Excel File on Occupational Risk Calculations (U.S. EPA. 2020s).
4.2.2.1 Manufacturing of NMP
Table 4-6. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Manufacturing				
Health Kndpoint
Acute POD.
(m»/l.)
Kxposure
l.e\el '
moi:
Benchmark
moi:
( Total I I )
No
(iloM'S
(iloM'S
PI 5
(iloM'S
l»l 10
(ilOM'S
PI 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
5.3
32
65
133
30
High-End
1.1
10
23
49
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
Table 4-7. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Manufacturing				
Health Kndpoint
Chronic
POD. Al C
(lir m»/l.)
Kxposure
l.e\el '
moi:
Benchmark
moi:
( Total I 1)
No
(iloM'S
(ihncs
PI 5
(ihncs
PI 10
(ihncs
PI 20
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.4
2.8
6.0
12
30
High-End
0.04
0.6
1.3
2.9
MOEs < 30 are indicated in bold and shaded grey
11 Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
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occupational air concentrations for both the loading of NMP into bulk containers and into drums. For
modeling of these air concentrations, EPA attempted to address variability in input parameters by
estimating both central tendency and high-end parameter values. Additionally, for modeling of air
concentrations during the loading of drums, EPA used Monte Carlo simulation to capture variability in
input parameters. EPA expects the duration of inhalation and dermal exposure to be realistic for loading
activities, as these durations are based on the length of time required to load NMP into specific container
sizes (i.e., tank trucks, rail cars, and drums).
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the loading
activities toward the true distribution of durations for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario. Skin surface areas
for actual dermal contact are uncertain. The glove protection factors, based on the ECETOC TRA model
as described in Section 2.4.1.1, are "what-if' assumptions and are uncertain. EPA is uncertain of the
accuracy of emission factors used to estimate fugitive NMP emissions and thereby model NMP air
concentrations. The representativeness of the modeling results toward the true distribution of inhalation
concentrations for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.2 Repackaging
Table 4-8. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Importation and Repackaging			
Health Kndpoint
Acute POD.
C„,;,x (mji/l.)
Kxposuiv
I.CM'I '
moi:
Benchmark
moi:
( Total I I )
No
(iloM'S
(iloM'S
PI 5
(iloM'S
l»l 10
(ilOM'S
PI 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
5.3
32
65
133
30
High-End
1.1
10
23
49
MOEs < 30 are indicated in bold and shaded grey
11 Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
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Table 4-9. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Importation and Repackaging 		
Health Kndpoinl
Chronic
POD. A! C
(lir nig/I.)
Exposure
l.e\el '
moi:
Benchmark
moi:
( Total I 1)
No
Cloxcs
(ihnes
l»l 5
(ihnes
l»l 10
(ihnes
l»l 20
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.4
2.8
6.0
12
30
High-End
0.04
0.6
1.3
2.9
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational inhalation exposure concentrations for both the unloading of NMP from bulk containers
and from drums. For modeling of these air concentrations, EPA attempted to address variability in input
parameters by estimating both central tendency and high-end parameter values. Additionally, for
modeling of air concentrations during the loading of drums, EPA used Monte Carlo simulation to
capture variability in input parameters. EPA expects the duration of inhalation and dermal exposure to
be realistic, as the durations are based on the length of time to load NMP into specific container sizes
{i.e., tank trucks, rail cars, and drums).
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the unloading
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario. Skin surface areas
for actual dermal contact are uncertain. The glove protection factors, based on the ECETOC TRA model
as described in Section 2.4.1.1, are "what-if' assumptions and are uncertain. EPA is uncertain of the
accuracy of the emission factors used to estimate fugitive NMP emissions and thereby to model NMP air
concentrations. The representativeness of the modeling results toward the true distribution of inhalation
concentrations for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
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4.2.2.3 Chemical Processing, Excluding Formulation
Table 4-10. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Chemical Processing (Excluding Formulation)		
Health Knilpoint
Acute POD.
Kxposure
l.e\el '
MOI!
Benchmark
moi:
( Total I 1)
No
(iloxes
(ilo\es
PI 5
(ilo\es
PI 10
Chnes
PI 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
5.3
32
65
133
30
High-End
1.1
10
23
49
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
Table 4-11. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Chemical Processing (Excluding Formulation)		
Health Knclpoint
Chronic
POD. Al C
(lir m»/l.)
Exposure
l.e\el
moi:
Benchmark
moi:
( Total I 1)
No
(ihnes
(ihncs
PI 5
(ihncs
PI 10
(ihncs
PI 20
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.4
2.8
6.0
12
30
High-End
0.04
0.6
1.3
2.9
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational inhalation exposure concentrations for both the unloading of NMP from bulk containers
and from drums. For modeling of these air concentrations, EPA attempted to address variability in input
parameters by estimating both central tendency and high-end parameter values. Additionally, EPA used
Monte Carlo simulation to capture variability in input parameters. EPA expects the duration of
inhalation and dermal exposure to be realistic, as the duration is based on the length of time to load
NMP into drums.
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the unloading
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario. Skin surface areas
for actual dermal contact are uncertain. The glove protection factors, based on the ECETOC TRA model
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as described in Section 2.4.1.1, are "what-if" assumptions and are uncertain. EPA is uncertain of the
accuracy of the emission factors used to estimate fugitive NMP emissions and thereby to model NMP air
concentrations. The representativeness of the modeling results toward the true distribution of inhalation
concentrations for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.4 Incorporation into Formulation, Mixture, or Reaction Product
Table 4-12. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Formulations, Mixtures, or Reaction Products	
Health Kndpoint
Acute I'OI).
(nig/l.)
Kxposure
I.C\cl '
moi:
lien chili ark
moi:
( l olal I I )
No
(Jo\cs
(ihnes
PI 5
(ihnes
l»l 10
(ihnes
l»l 20
Liquid - Unloading drums
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
5.3
32
65
133
30
High-End
1.1
10
23
49
Liquid - Miscellaneous (Maintenance, analytical, loading)
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
91
459
906
1,757
30
High-End
1.1
10
23
49
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
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Table 4-13. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Formulations, Mixtures, or Reaction Products	
Health Kndpoinl
Chronic
POD. At C
(lir ing/L)
Kxposure
Lcm'I '
moi:
lien chili ark
moi:
(Total I 1)
No
(iloM'S
(ilo\cs
PI 5
(ilo\cs
PI 10
(ihnes
l»l 20
Liquid - Unloading drums
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.4
2.8
6.0
12
30
High-End
0.04
0.6
1.3
2.9
Liquid - Miscellaneous (Maintenance, analytical, loading)
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
8.4
43
84
163
30
High-End
0.04
0.6
1.4
2.9
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational inhalation exposure concentrations for the unloading of NMP from drums. For modeling of
these air concentrations, EPA attempted to address variability in input parameters by estimating both
central tendency and high-end parameter values. Additionally, EPA used Monte Carlo simulation to
capture variability in input parameters. EPA expects the duration of inhalation and dermal exposure to
be realistic, as the duration is based on the length of time to load NMP into drums. EPA assessed worker
inhalation exposure during maintenance, bottling, shipping, and loading of NMP using directly
applicable monitoring data, which is the highest of the approach hierarchy, taken at an adhesive
formulation facility. The data quality rating for the monitoring data used by EPA is high. EPA expects
the duration of inhalation and dermal exposure to be realistic for the unloading of drums, as the duration
is based on the length of time to load NMP into drums.
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the assessed
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario (NMP concentration
is lower in the formulated products). Skin surface areas for actual dermal contact are uncertain. The
glove protection factors, based on the ECETOC TRA model as described in Section 2.4.1.1, are "what-
if' assumptions and are uncertain. EPA estimated worker inhalation exposure concentration during the
loading of NMP in solid formulations using EPA's OSHA PEL for PNOR model ( EPA, 2015a).
which is the lowest approach on the hierarchy. EPA did not use these inhalation exposure concentrations
Page 283 of 576

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for the PBPK modeling because the PBPK model does not account for solids and because both the
inhalation and dermal exposure potential are captured within other occupational exposure scenarios.
EPA is uncertain of the accuracy of the emission factors used to estimate fugitive NMP emissions and
thereby to model NMP air concentrations. For the maintenance, bottling, shipping, and loading of liquid
NMP, the monitoring data consists of only 7 data points from 1 source. The representativeness of the
modeling and the monitoring data toward the true distribution of inhalation concentrations for these
occupational exposure scenarios is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.5 Metal Finishing
Table 4-14. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
Health Kndpoint
Acute I'OI).
C111;„ (mji/l.)
Kxposurc
Le\el
moi:
lien chili ark
moi:
( Total I 1)
No
(iloM'S
(iloM'S
l»l 5
(iloM'S
l»l 10
(iloM'S
l»l 20
Spray application
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
2.7
143
288
573
30
High-End
1.7
14
31
64
Dip application
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
27
142
281
550
30
High-End
1.7
14
31
65
Brush application
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
27
135
258
466
30
High-End
1.7
14
31
64
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration (unless specified otherwise), 1-hand dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction. High-end means worst-case air concentration (unless specified
otherwise), 2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction.
Page 284 of 576

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Table 4-15. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Metal Finishing 			
Health Kndpoinl
Chronic
POD. At C
(lir m»/L)
Kxposure
I.CM'I '
moi:
lien chili ark
moi:
(l olal I 1)
No
(iloM'S
(ihncs
PI 5
(ihncs
PI 10
(iloM'S
PI 20
Spray application
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
2.4
13
27
53
30
High-End
0.1
0.8
1.8
3.8
Dip application
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
2.4
13
26
51
30
High-End
0.1
0.8
1.8
3.8
Brush application
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
2.4
12
24
43
30
High-End
0.1
0.8
1.8
3.8
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration (unless specified otherwise), 1-hand dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction. High-end means worst-case air concentration (unless specified
otherwise), 2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. To estimate inhalation exposure during spray application, EPA used surrogate
monitoring data, which is in the middle of the approach hierarchy, including 26 data points. These data
have a data quality rating of high. To estimate inhalation exposure during dip application, EPA used
surrogate monitoring data for dip cleaning, which is in the middle of the approach hierarchy, including
data from 5 sources. These data have data quality ratings of medium to high. To estimate inhalation
exposure during brush application, EPA used modeled data from the RIVM report (RIVM. 2013). which
has a data quality rating of high. The use of modeling is in the middle of the approach hierarchy. EPA
used durations associated with inhalation monitoring data to estimate duration of inhalation and dermal
exposure during spray application.
Primary Limitations
For occupational exposure scenarios other than spray application, EPA did not find exposure duration
data and assumed a high-end of 8 hours because the surrogate data or modeled values are 8-hour TWA
values. EPA assumed a mid-range of 4 hours for central tendency exposure duration. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed activities toward the true distribution of duration for all worker activities in this occupational
exposure scenario is uncertain. Due to lack of data, EPA could not calculate central tendency and high-
end NMP concentration in metal finishing products and used the low-end and high-end of the NMP
Page 285 of 576

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concentration range reported in 2016 CDR. Skin surface areas for actual dermal contact are uncertain.
The glove protection factors, based on the ECETOC TRA model as described in Section 2.4.1.1, are
"what-if' assumptions and are uncertain. The reasonably available monitoring data for spray application
is from 1996. The extent to which these data are representative of current worker inhalation exposure
potential is uncertain. The worker activities associated with the surrogate data used to assess worker
inhalation exposure during dip application are not detailed for all sample points. The modeled inhalation
exposure concentration during roller/brush application was obtained from RIVM (2013) and not
generated by EPA. For all occupational exposure scenarios, representativeness of the monitoring data,
surrogate monitoring data, or modeled data toward the true distribution of inhalation concentrations for
this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.6 Application of Paints, Coatings, Adhesives and Sealants
Table 4-16. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Application of Paints, Coatings, Adhesives and Sealants		
Health Knclpoint
Acule I'OI).
(m»/l.)
Kxposure
1 .e\ el '
moi:
Benchmark
moi:
(Total I 1)
No
(ihnes
(ihnes
l»l 5
(ihnes
l»l 10
(ihnes
l»l 20
Spray application
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
1,395
6,070
10,424
16,249
30
High-End
14
81
161
311
Roll / curtain application
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
1,445
7,110
13,919
26,699
30
High-End
14
83
169
342
Dip application
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
1,261
4,182
5,872
7,359
30
High-End
14
81
164
323
Roller / brush and syringe / bead application
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
890
1,780
2,030
2,182
30
High-End
14
81
162
313
MOEs < 30 are indicated in bold and shaded grey2,182
a Central tendency means: typical air concentration (unless specified otherwise), 1-hand dermal (445 cm2 surface area
Page 286 of 576

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exposed), and central tendency NMP weight fraction. High-end means worst-case air concentration (unless specified
otherwise), 2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction.
Table 4-17. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Application of Paints, Coatings, Adhesives and Sealants		
Health Kndpoinl
Chronic
POD. At C
(lir m»/L)
Kxposure
I.CM'I '
moi:
lien chili ark
moi:
(l olal I 1)
No
(iloM'S
(ihncs
PI 5
(ihncs
PI 10
(iloM'S
PI 20
Spray application
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
130
567
976
1,530
30
High-End
0.8
4.8
9.6
19
Roll / curtain application
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
134
661
1,294
2,485
30
High-End
0.8
4.9
10
20
Dip application
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
118
394
556
700
30
High-End
0.8
4.8
9.8
19
Roller / brush and syringe / bead application
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
84
169
194
209
30
High-End
0.8
4.8
9.6
19
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration (unless specified otherwise), 1-hand dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction. High-end means worst-case air concentration (unless specified
otherwise), 2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from 79 values from a variety of data sources with data quality
ratings ranging from medium to high. The spread of the 79 values of weight fraction was more
pronounced than other OESs, leading to a larger than average difference of central tendency and high-
end exposures; however, this data set is stronger than average and reduces uncertainties. To estimate
inhalation exposure during spray application, EPA used directly applicable personal monitoring data, the
highest of the approach hierarchy, including 26 data points. These data have a data quality rating of
high. To estimate inhalation exposure during roll/curtain application, EPA used modeling, which is in
the middle of the approach hierarchy. To estimate inhalation exposure during dip application, EPA used
surrogate monitoring data for dip cleaning, which is in the middle of the approach hierarchy, including
data from 5 sources. These data have data quality ratings of medium to high. To estimate inhalation
Page 287 of 576

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exposure during roller / brush and syringe/bead application, EPA used modeled data from the RIVM
report (RIVM. 2013). which has a data quality rating of high. The use of modeling is in the middle of
the approach hierarchy. EPA used durations associated with short-term inhalation monitoring data to
estimate duration of inhalation and dermal exposure during spray application.
Primary Limitations
For occupational exposure scenarios other than spray application, EPA did not find exposure duration
data and assumed a high-end of 8 hours because the surrogate data or modeled values are 8-hour TWA
values. EPA assumed a mid-range of 4 hours for central tendency exposure duration. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed activities toward the true distribution of duration for all worker activities in this occupational
exposure scenario is uncertain. Skin surface areas for actual dermal contact are uncertain. The glove
protection factors, based on the ECETOC TRA model as described in Section 2.4.1.1, are "what-if'
assumptions and are uncertain. The reasonably available monitoring data for spray application is from
1996 and the surrogate monitoring data used in the model for roll / curtain application is from 1994 or
earlier. The extent to which these data are representative of current worker inhalation exposure potential
is uncertain. The worker activities associated with the surrogate data used to assess worker inhalation
exposure during dip application are not detailed for all sample points. The modeled inhalation exposure
concentration during roller / brush application was obtained from RIVM (2013) and not generated by
EPA. For all occupational exposure scenarios, representativeness of the monitoring data, surrogate
monitoring data, or modeled data toward the true distribution of inhalation concentrations for this
occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
Page 288 of 576

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4.2.2.7 Recycling and Disposal
Table 4-18. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational
Health Kndpoint
Acute POD.
(m»/l.)
Kxposure
l.e\el '
moi:
Benchmark
moi:
( Total I 1)
No
(iloxes
(ilo\es
PI 5
(ilo\es
PI 10
Chnes
PI 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
6.8
40
82
165
30
High-End
1.1
10
23
49
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
Table 4-19. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Health Endpoint
Chronic
POD. Al C
(lir inji/L)
Exposure
Le\el;|
moi:
Benchmark
moi:
(Total LI")
No
Clo\es
(ihncs
PI 5
(ihncs
PI 10
(ihncs
PI 20
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.5
3.6
7.5
15
30
High-End
0.04
0.6
1.3
2.9
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
Modeling, in the middle of the approach hierarchy, was used to estimate occupational inhalation
exposure concentrations for both the unloading of NMP from bulk containers and from drums. For
modeling of these air concentrations, EPA attempted to address variability in input parameters by
estimating both central tendency and high-end parameter values. Additionally, for modeling of air
concentrations during the unloading of drums, EPA used Monte Carlo simulation to capture variability
in input parameters. EPA expects the duration of inhalation and dermal exposure to be realistic for the
unloading activities, as the durations are based on the length of time to unload NMP from specific
container sizes (i.e., tank trucks, rail cars, and drums).
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the unloading
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. EPA did not find NMP concentration data and assumed waste NMP may contain
very little impurities and be up to 100% NMP. Skin surface areas for actual dermal contact are
uncertain. The glove protection factors, based on the ECETOC TRA model as described in Section
2.4.1.1, are "what-if' assumptions and are uncertain. For the modeling of NMP air concentrations, EPA
Page 289 of 576

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is uncertain of the accuracy of the emission factors used to estimate fugitive NMP emissions and thereby
estimate worker inhalation exposure concentration. The representativeness of the modeling results
toward the true distribution of inhalation concentrations for this occupational exposure scenario is
uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.8 Removal of Paints, Coatings, Adhesives and Sealants
Table 4-20. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
Health Kndpoint
Acute POD.
C„,;,x (m»/L)
Kxposure
l.e\el '
moi:
Benchmark
moi:
( l olal I 1)
No
(Jo\cs
(ihnes
PI 5
(ihnes
l»l 10
(ihnes
PI 20
Miscellaneous removal
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
70
182
226
257
30
High-End
4.4
27
51
85
Graffiti removal
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
55
280
546
1,036
30
High-End
7.7
49
99
196
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: mid-range or mean air concentration, 1-hand dermal (445 cm2 surface area exposed), and central
tendency NMP weight fraction. High-end means high-end air concentration, 2-hand dermal (890 cm2 surface area exposed),
and high-end weight NMP fraction.
Page 290 of 576

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Table 4-21. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Health Kndpoinl
Chronic
POD. At C
(lir m»/L)
Exposure
l.e\el '
moi:
Benchmark
moi:
(Total I I )
No
(Jo\cs
(ilo\cs
PI 5
(ilo\cs
PI 10
(ihnes
l»l 20
Miscellaneous removal
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
6.4
17
21
24
30
High-End
0.2
1.6
3.0
5.1
Graffiti removal
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
5.0
26
51
96
30
High-End
0.4
2.9
5.9
12
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: mid-range or mean air concentration, 1-hand dermal (445 cm2 surface area exposed), and central
tendency NMP weight fraction. High-end means high-end air concentration, 2-hand dermal (890 cm2 surface area exposed),
and high-end weight NMP fraction.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from a variety of data sources with data quality ratings
ranging from medium to high. To estimate inhalation exposure during miscellaneous paint and coating
removal, EPA used directly applicable personal monitoring data, the highest of the approach hierarchy,
including data from three studies. These data have a data quality rating of high. To estimate inhalation
exposure during graffiti removal, EPA used directly applicable personal monitoring data, the highest of
the approach hierarchy, including 25 data points. These data have a data quality rating of high. EPA
used durations associated with inhalation monitoring data to estimate duration of inhalation and dermal
exposure during miscellaneous paint and coating removal.
Primary Limitations
For graffiti removal, EPA did not find data other than 8-hour TWA values. EPA assumed a high-end
exposure duration equal to 8 hours and a central tendency exposure duration of 4 hours, which is the
mid-range of a full shift. The representativeness of the assumed estimates of duration of inhalation and
dermal exposure for the assessed activities toward the true distribution of duration for all worker
activities in this occupational exposure scenario is uncertain. The glove protection factors, based on the
ECETOC TRA model as described in Section 2.4.1.1, are "what-if' assumptions and are uncertain. The
short-term inhalation exposure concentrations for miscellaneous removal are based on data from 1993
and the extent to which these data are representative of current worker inhalation exposure potential is
uncertain. For graffiti removal, EPA used the minimum, mean, and maximum air concentrations
reported by one literature source for 25 datapoints. EPA did not have these 25 data points with which to
calculate 50th and 95th percentile values. The representativeness of the monitoring data toward the true
distribution of inhalation concentrations for this occupational exposure scenario is uncertain.
Page 291 of 576

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Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.9 Other Electronics Manufacturing
Table 4-22. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Other Electronics Manufacturing 		
Health Knilpoint
Acute POD.
(m»/l.)
Exposure
l.e\el '
moi:
Benchmark
moi:
( Total I 1)
No
(Jo\cs
(ilo\es
PI 5
(ilo\es
PI 10
Chnes
l»l 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
27
137
266
494
30
High-End
1.1
9.6
21
42
MOEs < 30 are indicated in bold and shaded grey
11 Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration, 2-
hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
Table 4-23. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Other Electronics Manufacturing		
Health Knclpoint
Chronic
POD. Al C
(lir m»/l.)
Kxposure
Le\el '
moi:
lien cli in ark
moi:
( Total I 1)
No
(ilo\es
(ihncs
PI 5
(ihncs
PI 10
(ihncs
PI 20
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
2.4
13
25
46
30
High-End
0.04
0.5
1.2
2.5
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from OSHA data (OSHA. 2017). which has a data quality
rating of high. EPA used directly applicable inhalation monitoring data, which is the highest of the
approach hierarchy, to estimate worker inhalation exposure during one electronics manufacturing
operation. These data have a data quality rating of high.
Page 292 of 576

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Primary Limitations
The OSHA data (OSHA.. 2017) monitoring data were provided as 8-hour TWA values. EPA assumed 8
hours as the high-end duration of liquid contact and mid-range of 4 hours as the central tendency
duration of liquid contact. The representativeness of the estimates of duration of inhalation and dermal
exposure for the assessed activity toward the true distribution of duration for all worker activities in this
occupational exposure scenario beyond capacitor, resistor, coil, transformer, and other inductor
manufacturing is uncertain. Skin surface areas for actual dermal contact are uncertain. The glove
protection factors, based on the ECETOC TRA model as described in Section 2.4.1.1, are "what-if'
assumptions and are uncertain.
The OSHA data (OSHA. 201?) monitoring data only include capacitor, resistor, coil, transformer, and
other inductor manufacturing. The representativeness of the monitoring data for capacitor, resistor, coil,
transformer, and other inductor manufacturing toward the true distribution of inhalation concentrations
for all worker activities in this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.10 Semiconductor Manufacturing
Table 4-24. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
Health Kndpoint
Acule l»OI>.
C„,.n (lll»/l.)
Kxposure
l.e\el '
moi:
Benchmark
moi:
( Total I 1)
No
(ihnes
(ihnes
l»l 5
(ihnes
l»l 10
(ihnes
PI 20
Container handling, small containers
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
23
125
252
504
30
High-End
2.3
21
47
98
Container handling, drums
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
48
253
508
1,020
30
High-End
2.3
21
46
97
Fab worker (75% body coverage)
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
1,013
4,916
9,461
17,586
30
High-End
198
988
1,925
3,646
Maintenance
Page 293 of 576

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Health Kndpoint
Acme POD.
(m»/l.)
Exposure
l.e\el '
moi:
Benchmark
moi:
(Total I I )
No
(iloM'S
(iloM'S
PI 5
(iloM'S
PI 10
(iloM'S
PI 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
48
252
508
1,020
30
High-End
0.6
7.9
19
43
Virgin NMP truck unloading
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
5.3
31
63
125
30
High-End
1.1
10
23
48
Waste truck loading
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
6.8
40
81
165
30
High-End
1.5
13
29
61
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration, 2-
hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
Table 4-25. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Semiconductor Manufacturing 		
Health Kndpoinl
Chronic
POD. AI (
(lir m»/L)
Kxposure
I.CM'I '
moi:
lien cli m ark
moi:
( Total I 1)
No
(ihnes
(ihnes
PI 5
(ihnes
PI 10
(ihnes
PI 20
Container handling, small containers
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
1.5
8.7
18
35
30
High-End
0.1
0.9
2.1
4.3
Container handling, drums
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
3.3
18
36
72
30
High-End
0.1
0.9
2.0
4.3
Fab worker (75% body coverage)
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
71
346
667
1,242
30
High-End
8.7
44
85
161
Maintenance
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
3.3
18
36
72
30
High-End
0.02
0.3
0.8
1.9
Page 294 of 576

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Health Kndpoinl
Chronic
POD. At (
(lir ing/L)
Kxposure
I.CM'I '
moi:
lien chili ark
moi:
(l olal I 1)
No
(iloM'S
(ilo\cs
PI 5
(ilo\cs
PI 10
(iloM'S
PI 20
Virgin NMP truck unloading
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.4
2.8
5.8
11
30
High-End
0.04
0.6
1.3
2.8
Waste truck loading
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.5
3.6
7.4
15
30
High-End
0.1
0.7
1.7
3.6
MOEs < 30 are indicated in bold and shaded grey2,182
11 Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from the data provided by SIA (2019c). which has a data
quality rating of high. EPA used directly applicable inhalation monitoring data, which is the highest of
the approach hierarchy, to estimate worker inhalation exposure during a variety of semiconductor
manufacturing tasks. These data have a data quality rating of high.
Primary Limitations
The SIA (2019c) monitoring data were provided as 8-hour or 12-hour TWA values. EPA assumed 8 or
12 hours as the high-end duration of liquid contact and mid-range of 4 or 6 hours as the central tendency
duration of liquid contact. The representativeness of the estimates of duration of inhalation and dermal
exposure for the assessed activities toward the true distribution of duration for all worker activities in
this occupational exposure scenario is uncertain. Skin surface areas for actual dermal contact are
uncertain. The glove protection factors, based on the ECETOC TRA model as described in Section
2.4.1.1, are "what-if' assumptions and are uncertain.
The majority of the data points in SIA (2019c) were non-detect for NMP and, for these samples, EPA
used the LOD/2 to calculate central tendency and high-end inhalation exposure concentration values
4). The extent to which the use of LOD/2 accurately represents the actual inhalation
concentrations is uncertain. The representativeness of the SIA monitoring data for semiconductor
manufacturing toward the true distribution of inhalation concentrations for all worker activities in this
occupational exposure scenario is uncertain. The uncertainty in the representativeness of the data may
result in either overestimation or underestimation of exposures, depending on the true distribution of
inhalation concentrations.
Page 295 of 576

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Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.11 Printing and Writing
Table 4-26. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Printing and Writing 			
Health Knilpoinl
Acute POD.
(nig/l.)
Exposure
l.e\el ' ''
moi:
Benchmark
moi:
(Total I 1)
No
(iloM'S
(iloM'S
PI 5
(iloM'S
PI 10
(iloM'S
PI 20
Printing a
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
575
2,812
5,452
10,267
30
High-End
158
802
1,598
3,164
Writing b
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
470,210
2,357,1
26
NA
NA
30
High-End
470,210
2,357,1
26
NA
NA
MOEs < 30 are indicated in bold and shaded grey
aFor printing, central tendency means: central tendency (50th percentile) air concentration, 1-hand dermal (445 cm2 surface
area exposed), and central tendency NMP weight fraction. High-end means worst-case (95th percentile) air concentration, 2-
hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction.
b For writing, central tendency means: dermal exposure over 1 cm2 surface area exposed [incidental contact] and central
tendency NMP weight fraction. High-end means dermal over 1 cm2 surface area exposed [incidental contact], and high-end
weight NMP fraction. EPA expects inhalation exposure to NMP during writing is negligible.
Page 296 of 576

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Table 4-27. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Printing and Writing			
Health Kndpoinl
Chronic
POD. At C
(lir ing/L)
Kxposure
moi:
lien chili ark
moi:
(Total I 1)
No
(iloM'S
(ilo\cs
PI 5
(ilo\cs
PI 10
(Jo\cs
l»l 20
Printing3
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
53
261
507
957
30
High-End
9.4
48
95
188
Writing b
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
116,016
578,404
NA
NA
30
High-End
116,016
578,404
NA
NA
MOEs < 30 are indicated in bold and shaded grey
a For printing, central tendency means: central tendency (50th percentile) air concentration, 1-hand dermal (445 cm2 surface
area exposed), and central tendency NMP weight fraction. High-end means worst-case (95th percentile) air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction.
bFor writing, central tendency means: dermal exposure over 1 cm2 surface area exposed [incidental contact] and central
tendency NMP weight fraction. High-end means dermal over 1 cm2 surface area exposed [incidental contact], and high-
end weight NMP fraction. EPA expects inhalation exposure to NMP during writing is negligible.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
For printing activities, EPA assessed dermal exposure to central tendency and high-end NMP weight
fractions, calculated as the 50th and 95th percentiles, respectively, from a variety of data sources with
data quality ratings of high. For writing activities, EPA assessed dermal exposure to 1 to 2% NMP based
on one writing product identified in the Use and Market Profile for n-Methylpyrrolidone (ABT. 2017).
For worker dermal exposure during writing, EPA determined the skin surface area dermally exposed to
writing ink using a literature source with a data quality rating of high. To estimate worker inhalation
exposure during printing, EPA used surrogate monitoring data, which is in the middle of the approach
hierarchy. These data include 48 samples and have a data quality rating of high. EPA used durations
associated with inhalation monitoring data to estimate duration of inhalation and dermal exposure during
printing activities.
Primary Limitations
For writing, EPA did not find exposure duration data and assumed a high-end of 8 hours based on the
length of a full shift and a central tendency of 4 hours based on the mid-range of a shift. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed printing and writing activities toward the true distribution of duration for all worker activities in
this occupational exposure scenario is uncertain. For printing, skin surface areas for actual dermal
contact are uncertain. The glove protection factors, based on the ECETOC TRA model as described in
Section 2.4.1.1, are "what-if' assumptions and are uncertain. The surrogate monitoring data used to
estimate occupational inhalation exposure during printing is from 1983. The extent to which these data
are representative of current worker inhalation exposure potential is uncertain. The representativeness of
Page 297 of 576

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the surrogate monitoring data toward the true distribution of inhalation concentrations for this
occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.12 Soldering
Table 4-28. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Soldering 				
Health Kndpoint
Acute POD.
(m»/l.)
Kxposure
l.e\el '
moi:
Benchmark
moi:
( Total I I )
No
(iloM'S
(iloM'S
PI 5
(iloM'S
PI 10
(iloM'S
PI 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
1,285
2,030
2,182
2,268
30
High-End
400
1,398
2,024
2,608
MOEs < 30 are indicated in bold and shaded grey
11 Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
Table 4-29. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Soldering				
Health Kndpoint
Chronic
POD. Al C
(lir nig/I.)
Kxposurc
l.e\el '
moi:
Benchmark
moi:
( Total I I )
No
(iloM'S
(ihncs
PI 5
(ihncs
PI 10
(ihncs
PI 20
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
122
194
209
217
30
High-End
24
84
123
159
MOEs < 30 are indicated in bold and shaded grey
11 Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed worker dermal exposure to 1 - 2.5% NMP based on one soldering product identified in
the Use and Market Profile for NMP (WY 201 ').
Page 298 of 576

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Primary Limitations
EPA did not find inhalation monitoring data specific to this use and used modeled data for the bush
application of a substance containing NMP as surrogate. The representativeness of this modeled data
towards this use is uncertain. EPA did not find reasonably available data on actual duration of liquid
contact and assumed a high-end of 8 hours based on the length of a full shift and a central tendency of 4
hours based on the mid-range of a shift. The representativeness of the assumed estimates of duration of
inhalation and dermal exposure toward the true distribution of duration for all worker activities in this
occupational exposure scenario is uncertain. Skin surface areas for actual dermal contact are uncertain.
The glove protection factors, based on the ECETOC TRA model as described in Section 2.4.1.1, are
"what-if' assumptions and are uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.13 Commercial Automotive Servicing
Table 4-30. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
Health Kndpoint
Acute POD.
(inii/l-)
Exposure
l.e\el
moi:
Benchmark
moi:
( Total I I )
No
(iloM'S
(iloM'S
PI 5
(iloM'S
PI 10
(ilOM'S
PI 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
651
1,207
1,347
1,430
30
High-End
28
111
169
227
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: central tendency (50th percentile) air concentration, 1-hand dermal (445 cm2 surface area exposed),
and central tendency NMP weight fraction. High-end means high-end (95th percentile) air concentration, 2-hand dermal
(890 cm2 surface area exposed), and high-end weight NMP fraction.
Table 4-31. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Health Kndpoint
Chronic
POD. Al C
(lir m»/l.)
Exposure
l.e\el
moi:
Benchmark
moi:
( Total I 1)
No
(iloxes
(ihncs
PI 5
(ihncs
PI 10
(ihncs
PI 20
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
62
115
129
137
30
High-End
1.6
6.7
10
14
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: central tendency (50thpercentile) air concentration, 1-hand dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction. High-end means high-end (95th percentile) air concentration, 2-
hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction.
Page 299 of 576

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EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from a variety of data sources with data quality ratings of
high. Modeling, in the middle of the approach hierarchy, was used to estimate occupational inhalation
exposure concentrations. For modeling of these air concentrations, EPA attempted to address variability
in input parameters by estimating both central tendency and high-end parameter values. Additionally,
EPA used Monte Carlo simulation to capture variability in input parameters. EPA expects the duration
of inhalation and dermal exposure to be realistic, as the duration is based on the length of time to
conduct aerosol degreasing of automotive brakes.
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the aerosol
brake degreasing activities toward the true distribution of duration for all worker activities in this
occupational exposure scenario is uncertain. Skin surface areas for actual dermal contact are uncertain.
The glove protection factors, based on the ECETOC TRA model as described in Section 2.4.1.1, are
"what-if' assumptions and are uncertain. For the modeling of NMP air concentrations, EPA used aerosol
product use rate and application frequency from one literature source (GARB. 2000) on brake servicing.
The extent to which this is representative of other aerosol degreasing applications involving NMP is
uncertain. The representativeness of the modeling results toward the true distribution of inhalation
concentrations for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.14 Laboratory Use
Table 4-32. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Laboratories
Health Kndpoint
Acute POD.
(inii/l-)
Exposure
I.C\cl
moi:
Benchmark
moi:
( Total I I )
No
(iloM'S
(iloM'S
PI 5
(iloM'S
PI 10
(ilOM'S
PI 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
5.3
32
65
133
30
High-End
1.1
10
23
48
MOEs < 30 are indicated in bold and shaded grey
11 Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
Page 300 of 576

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Table 4-33. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Laboratories
Health Endpoinl
Chronic
POD. A! C
(hi- in&'L)
Exposure
Level11
MOE
lien cli in ark
MOE
(Total LF)
No
Cloves
Chncs
PF 5
Chncs
PF 10
Chnes
PF 20
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.4
2.8
6.0
12
30
High-End
0.04
0.6
1.3
2.9
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed occupational inhalation exposure using directly applicable personal monitoring data,
which is the highest of the approach hierarchy, from one source with a data quality rating of medium.
EPA also used a modeled inhalation exposure concentration value, which is in the middle of the
approach hierarchy, from RIVM ( ). This data has a data quality rating of high. EPA determined
central tendency exposure duration from the inhalation monitoring data. EPA expects the central
tendency duration of inhalation and dermal exposure to be realistic, as the duration is task-based.
Primary Limitations
EPA assumed a high-end duration of liquid contact of 8 hours based on the length of a full shift. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed activities toward the true distribution of duration for all worker activities in this occupational
exposure scenario is uncertain. EPA did not find NMP concentration data and assumed workers may be
exposed to up to 100% NMP since NMP is a carrier chemical, and carrier chemical concentrations may
be very high. Skin surface areas for actual dermal contact are uncertain. The glove protection factors,
based on the ECETOC TRA model as described in Section 2.4.1.1, are "what-if' assumptions and are
uncertain.
The monitoring data used for central tendency worker inhalation exposure is only one data point from a
1996 industrial hygiene report. The extent to which these data are representative of current worker
inhalation exposure potential is uncertain. The modeled high-end inhalation exposure concentration was
obtained from RIVM (20! 3) and not generated by EPA. The representativeness of the monitoring data
and modeled exposure toward the true distribution of inhalation concentrations for this occupational
exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
Page 301 of 576

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health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.15 Lithium Ion Cell Manufacturing
Table 4-34. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Lithium Ion Cell Manufacturing 		
Health Kndpoinl
Acule POD.
(nig/l.)
Kxposure
l.e\el '
moi:
Benchmark
moi:
(Total I 1)
No
(Jo\cs
(ihnes
PI 5
(ihnes
PI 10
(ihnes
PI 20
Container handling, small containers
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
4.1
27
58
119
30
High-End
0.6
8.0
19
43
Container handling, drums
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
23
125
254
511
30
High-End
0.6
7.9
19
43
Cathode coating
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
27
134
253
450
30
High-End
8.1
46
84
139
Cathode mixing
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
27
139
272
514
30
High-End
8.3
51
102
195
Research and development
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
27
143
287
570
30
High-End
1.1
10
23
48
Miscellaneous additional activities
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
26
131
245
426
30
High-End
1.1
10
22
48
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: central tendency (50th percentile) air concentration (for virgin NMP truck unloading and waste
truck loading, EPA scaled a single 8-hour TWA value to a 4-hour TWA values), 1-hand dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction. High-end means high-end (95th percentile) air concentration (for
virgin NMP truck unloading and waste truck loading, EPA used a single 8-hour TWA value), 2-hand dermal (890 cm2
surface area exposed), and high-end weight NMP fraction.
Page 302 of 576

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Table 4-35. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Lithium Ion Cell Manufacturing		
Health Kndpoinl
Chronic
POD. At C
(lir mg/L)
Kxposure
I.CM'I '
moi:
lien chili ark
moi:
(l olal I 1)
No
(iloM'S
(ihncs
PI 5
(ihncs
PI 10
(iloM'S
PI 20
Container handling, small containers
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.2
1.9
4.0
8.3
30
High-End
0.02
0.3
0.8
1.9
Container handling, drums
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
1.5
8.8
18
36
30
High-End
0.02
0.3
0.8
1.9
Cathode coating
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
2.4
12
23
42
30
High-End
0.4
2.7
5.0
8.4
Cathode mixing
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
2.4
13
25
48
30
High-End
0.5
3.0
6.1
12
Research and development
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
2.4
13
27
53
30
High-End
0.04
0.6
1.3
2.9
Miscellaneous additional activities
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
2.3
12
23
40
30
High-End
0.04
0.6
1.3
2.8
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: central tendency (50th percentile) air concentration (for virgin NMP truck unloading and waste
truck loading, EPA scaled a single 8-hour TWA value to a 4-hour TWA values), 1-hand dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction. High-end means high-end (95th percentile) air concentration (for
virgin NMP truck unloading and waste truck loading, EPA used a single 8-hour TWA value), 2-hand dermal (890 cm2
surface area exposed), and high-end weight NMP fraction.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from the data provided by Lithium Ion Cell Manufacturers'
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Coalition (LICM. 2020a) which has a data quality rating of high. EPA used directly applicable
inhalation monitoring data, which is the highest of the approach hierarchy, to estimate worker inhalation
exposure during a variety of lithium ion cell manufacturing tasks. These data have a data quality rating
of high.
Primary Limitations
The Lithium Ion Cell Manufacturers" Coalition (LICM. 2020a) monitoring data were provided as 8-hour
or 12-hour TWA values. EPA assumed 8 or 12 hours as the high-end duration of liquid contact and mid-
range of 4 or 6 hours as the central tendency duration of liquid contact. The representativeness of the
estimates of duration of inhalation and dermal exposure for the assessed activities toward the true
distribution of duration for all worker activities in this occupational exposure scenario beyond
semiconductor manufacturing is uncertain. Skin surface areas for actual dermal contact are uncertain.
The glove protection factors, based on the ECETOC TRA model as described in Section 2.4.1.1, are
"what-if' assumptions and are uncertain.
The representativeness of the monitoring data for lithium ion cell manufacturing toward the true
distribution of inhalation concentrations for all worker activities in this occupational exposure scenario
is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
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4.2.2.16 Cleaning
Table 4-36. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
of NMP in Cleaning 				
Health Kndpoint
Acule POD.
(m»/l.)
Exposure
1 .e\ el '
moi:
Benchmark
moi:
(Total I I )
No
(iloxes
(ihncs
PI 5
(ihncs
PI 10
(ihncs
PI 20
Dip cleaning
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
8.8
50
102
206
30
High-End
1.1
10
23
49
Spray / wipe cleaning
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
90
451
885
1,697
30
High-End
1.1
10
23
50
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: central tendency (50th percentile) air concentration, 1-hand dermal (445 cm2 surface area exposed),
and central tendency NMP weight fraction. High-end means high-end (95th percentile) air concentration, 2-hand dermal
(890 cm2 surface area exposed), and high-end weight NMP fraction.
Table 4-37. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Cleaning
Health Kndpoint
Chronic
POD. At C
(lir mg/l.)
Exposure
1 .e\ el
moi:
Benchmark
MOE
( Total I I )
No
(Jo\cs
(ihncs
PI 5
(ihncs
PI 10
(ihncs
PI 20
Dip cleaning
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
0.7
4.5
9.4
19
30
High-End
0.04
0.6
1.3
2.9
Spray / wipe cleaning
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
8.3
42
82
158
30
High-End
0.04
0.6
1.4
3.0
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: central tendency (50thpercentile) air concentration, 1-hand dermal (445 cm2 surface area exposed),
and central tendency NMP weight fraction. High-end means high-end (95th percentile) air concentration, 2-hand dermal
(890 cm2 surface area exposed), and high-end weight NMP fraction.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from a variety of data sources with data quality ratings
ranging from medium to high. To estimate inhalation exposure during dip cleaning, EPA used directly
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applicable monitoring data, which is in the highest of the approach hierarchy, including data from 5
sources. These data have data quality ratings ranging from medium to high. To estimate inhalation
exposure during spray / wipe application, EPA used directly applicable monitoring data, which is in the
highest of the approach hierarchy, including data from 4 sources. These data have data quality ratings
ranging from medium to high.
Primary Limitations
EPA did not find reasonably available data on actual duration of liquid contact and assumed a high-end
of 8 hours based on the length of a full shift and a central tendency of 4 hours based on the mid-range of
a shift. The representativeness of the assumed estimates of duration of inhalation and dermal exposure
for the assessed cleaning activities toward the true distribution of duration for all worker activities in this
occupational exposure scenario is uncertain. Skin surface areas for actual dermal contact are uncertain.
The glove protection factors, based on the ECETOC TRA model as described in Section 2.4.1.1, are
"what-if' assumptions and are uncertain.
The worker activities associated with the monitoring data used to assess inhalation exposure during dip
cleaning and spray/wipe cleaning were not detailed for all samples. Where EPA could not determine the
type of cleaning activities associated with a data point, EPA used the data in the estimates for both dip
and spray/wipe cleaning. For both occupational exposure scenarios, the representativeness of the
monitoring data toward the true distribution of inhalation concentrations for this occupational exposure
scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.2.17 Fertilizer Application
Table 4-38. Non-Cancer Risk Estimates for Acute Worker Exposures Following Occupational Use
Health Kndpoint
Acute I'OI).
C111;„ (mji/l.)
Kxposure
Le\el
moi:
Benchmark
moi:
( Total I 1)
No
(Jo\cs
(ihncs
l»l 5
(ihncs
l»l 10
(ilo\es
l»l 20
DEVELOPMENTAL
EFFECTS
Post-implantation Loss
437
Central
Tendency
2,892
3,210
3,246
3,264
30
High-End
149
628
1,032
1,519
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
Page 306 of 576

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Table 4-39. Non-Cancer Risk Estimates for Chronic Worker Exposures Following Occupational
Use of NMP in Fertilizer Application			
Health Knilpoinl
Chronic
POD. A! C
(lir nig/I.)
Exposure
l.e\el '
moi:
Benchmark
moi:
( Total I 1)
No
(Jo\cs
(ihnes
l»l 5
(ihnes
l»l 10
(ihnes
l»l 20
REPRODUCTIVE
EFFECTS
Decreased Fertility
183
Central
Tendency
279
307
311
313
30
High-End
8.9
38
62
92
MOEs < 30 are indicated in bold and shaded grey
a Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to 0.1 to 7% NMP, based on data from public comments and literature,
which have data quality ratings of high. EPA assessed occupational inhalation exposure during fertilizer
application using a modeled inhalation exposure concentration value, which is in the middle of the
approach hierarchy, from RIVM ( ). This data has a data quality rating of high.
Primary Limitations
EPA did not find reasonably available data on actual duration of liquid contact and assumed a high-end
of 8 hours based on the length of a full shift and a central tendency of 4 hours based on the mid-range of
a shift. The representativeness of the assumed estimates of duration of inhalation and dermal exposure
toward the true distribution of duration for all worker activities in this occupational exposure scenario is
uncertain. Skin surface areas for actual dermal contact are uncertain. The glove protection factors, based
on the ECETOC TRA model as described in Section 2.4.1.1, are "what-if' assumptions and are
uncertain. The modeled inhalation exposure concentration was obtained from RIVM (2013) and not
generated by EPA. The representativeness of the modeled exposure toward the true distribution of
inhalation concentrations for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoint and POD selected for risk characterization of acute exposure and medium confidence in the
health endpoint and POD selected for risk characterization of chronic exposure. Section 3.2.6 describes
the justification for this confidence rating.
4.2.3 Risk Estimation for Exposures to NMP for Occupational Non-Users (ONUs)
Table 4-40 presents the risk estimates for chronic inhalation exposures to ONUs for reproductive effects.
A human PBPK model (described in Appendix J) was used to calculate internal NMP exposure
estimates for ONUs. Duration-based NMP air concentrations, which are used for worker and ONU
exposure estimates, assure that the PBPK model accounts for the full amount of inhalation and vapor-
through-skin exposure. Unlike workers, ONUs are not assumed to be exposed via dermal contact with
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liquid NMP because they do not have direct dermal contact with liquid chemicals, see Section 2.4.1.1.
ONUs are not assumed to be wearing a respirator. EPA expects that ONUs are exposed to lower air
concentrations than workers since they may be further from the emission source than workers. Examples
of ONUs include supervisors, managers, and other employees that may be in the production areas but do
not perform tasks that result in direct dermal contact with NMP.
Calculated MOE values that are below the benchmark MOE (30), indicate a risk concern (shown in bold
and shaded grey). EPA analyzed the highest acute exposure scenario for ONUs, paint removers -
miscellaneous stripping, calculating an 8 hr TWA air concentration of 64 mg/m3, resulting in a peak
blood concentration of 1.53 mg/L. Based on an acute POD of 437 mg/L, the acute MOE for the ONUs
with the highest acute exposure is 285, well above the benchmark MOE of 30. Therefore, EPA did not
further analyze ONU risks from acute exposure for additional COUs.
Table 4-40. ONU Risk Estimates based on Adverse Reproductive Effects (Decreased
Fertility) from Chronic NMP Exposures			
Occupation
-------
Occupation
-------
Occupation
-------
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for all of the occupational exposure scenarios for ONUs is medium. EPA assigns the same confidence
level for PBPK inputs for both workers and ONUs because lower surface areas for liquid contact for
ONUs have higher certainty, but air concentrations experienced by ONUs have lower certainty. These
factors cannot be quantified and are assumed to offset one another in determining ONU confidence level
using worker confidence level as a starting point.
The studies that support the health concerns for adverse developmental effects following acute exposure
and adverse reproductive effects following chronic exposure are described above in Section 3.2. Overall,
EPA has high confidence in the health endpoint and POD selected for risk characterization of acute
exposure and medium confidence in the health endpoint and POD selected for risk characterization of
chronic exposure. Section 3.2.6 describes the justification for this confidence rating.
Page 311 of 576
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4.2.4 Risk Estimation for Acute Exposures from Consumer Use of NMP
The following sections present the risk estimates for acute dermal and inhalation exposures following
consumer use of NMP in each condition of use. Risk estimates that indicate risk relative to the
benchmark MOE (i.e., non-cancer MOEs that are below the benchmark MOE of 30) are highlighted by
shading the cell.
4.2.4.1 Adhesives and Sealants
Table 4-41. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Adhesives and Sealants
Kxposure
Scenario
Health Effect.
Kiidpoint and Study
POD (peak
hlood
concentration.
mg/1.)
W omen
Childhearing
A go r.xposure.
Peak lilood
Concentration.
( „l:,\ (lllg/1.)
moi:
Benchmark
MOE
( Total I I )
Low Weight
Fraction
Adhesives and
Sealants
Medium Intensity
Use
DL\LLOPMLM.YL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
0.011
38,758
30
Low Weight
Fraction
Adhesives and
Sealants
High Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
0.070
6,248
30
High Weight
Fraction
Adhesives and
Sealants
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
4.084
107
30
High Weight
Fraction
Adhesives and
Sealants
High Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
18.628
23
30
One MOE calculated using a high-end estimate for acute exposure to consumers from the use of NMP -
containing adhesives is below the benchmark MOE (30); MOE High Intensity Use = 23.
Overall Confidence
The adhesives scenarios and the sealants scenarios are based on corresponding publicly available
consumer product data, specifically the weight fractions and the amount of product used and duration of
use from consumer survey data. EPA has a high confidence in these parameters for representing the
adhesives and sealants consumer use scenarios.
Page 312 of 576
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EPA has a high confidence in the Consumer Exposure Model (CEM), its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical and chemical properties. The emission rate used in CEM for the adhesives
scenario and sealants scenario was estimated since product-specific emission from chamber studies was
not reasonably available. EPA has high confidence in the emission rate estimate based on physical and
chemical properties.
The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by CEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a high confidence in the input parameters estimating the adhesive scenario and the sealants
scenario.
The studies that support the health concerns for adverse developmental effects following acute exposure
and adverse reproductive effects following chronic exposure are described above in Section 3.2. Overall,
EPA has high confidence in the health endpoint and POD selected for risk characterization of acute
exposure described above in Section 3.2. Section 3.2.6 describes the justification for this confidence
rating.
4.2.4.2 Adhesives Removers
Table 4-42. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
the Removal of Adhesives
Kxposure
Scenario
Health Kfleet.
Kndpoint and Study
POD (peak
hlood
concentration,
ing/l.)
W omen
Childhearing
Age Kxposure.
Peak lilood
Concentration.
( „l:,\ (lllg/L)
moi:
Benchmark
MOE
( Total I I )
Adhesives
Removers
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
437
1.292
338
30
Adhesives
Removers
High Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
5.957
73
30
All MOEs calculated using high-end estimates for acute exposure to consumers from use of NMP -
containing adhesive removal products are above the benchmark MOE (30).
Overall Confidence
The adhesives remover scenario is based on corresponding publicly available consumer product data,
specifically the weight fractions and the amount of product used and duration of use from consumer
Page 313 of 576
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survey data. EPA has a high confidence in these parameters for representing the adhesives remover
consumer use scenarios.
EPA has a high confidence in the Consumer Exposure Model (CEM), its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical and chemical properties. The emission rate used in CEM for the adhesive
remover scenario was estimated since product-specific emission from chamber studies was not
reasonably available. EPA has high confidence in the emission rate estimate based on physical and
chemical properties.
The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by CEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a high confidence in the input parameters estimating the adhesives remover scenario.
The studies that support the health concerns for adverse developmental effects following acute exposure
described above in Section 3.2. Overall, EPA has high confidence in the health endpoint and POD
selected for risk characterization of acute exposure. Section 3.2.6 describes the justification for this
confidence rating.
Page 314 of 576
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4.2.4.3 Auto Interior Liquid and Spray Cleaners
Table 4-43. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Auto Interior Liquid and Spray Cleaners 				
Kxposure
Scenario
Health K fleet.
Kndpoinl and Study
POD (peak
hlood
concentration.
m«/l.)
W omen
Childhearing
Age Kxposure.
Peak lilood
Concentration.
(		 (nig/I.)
moi:
Benchmark
MOI.
(Total 11)
Auto Interior
Liquid Cleaner
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002.)
437
0.256
1,710
30
Auto Interior
Liquid Cleaner
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
4.356
100
30
Auto Interior
Spray Cleaner
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
0.093
4,676
30
Auto Interior
Spray Cleaner
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al (2002)
437
0.184
2,381
30
All MOEs calculated using high-end estimates for acute exposure to consumers from the use of NMP -
containing auto interior (liquid and spray) cleaners are above the benchmark MOE (30).
Overall Confidence
The auto interior liquid cleaner scenario and the auto interior spray cleaner scenario are based on
corresponding publicly available consumer product data, specifically the weight fractions and the
amount of product used and duration of use from consumer cleaner/degreaser survey data. EPA has a
medium to high confidence in these parameters for representing the auto interior liquid cleaner scenario
and the auto interior spray cleaner consumer use scenarios.
EPA has a high confidence in the Consumer Exposure Model (CEM), its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical and chemical properties. The emission rate used in CEM for the auto
interior liquid cleaner scenario and the auto interior spray cleaner scenario was estimated since product-
Page 315 of 576
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specific emission from chamber studies was not reasonably available. EPA has high confidence in the
emission rate estimate based on physical and chemical properties.
The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by CEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a medium to high confidence in the input parameters estimating the auto interior liquid cleaner
scenario and the auto interior spray cleaner scenario.
The studies that support the health concerns for adverse developmental effects following acute exposure
and adverse reproductive effects following chronic exposure are described above in Section 3.2. Overall,
EPA has high confidence in the health endpoint and POD selected for risk characterization of acute
exposure described above in Section 3.2. Section 3.2.6 describes the justification for this confidence
rating.
4.2.4.4 Cleaners/Degreasers, Engine Cleaner/Degreaser and Spray Lubricant
Table 4-44. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Cleaners/Degreasers, Engine Cleaner/Degreaser and Spray Lubricant			



W omen





Childbcaring




POD (peak
Age Kxposure.




blood
Peak lilood

Benchmark

Health Kfleet.
concentration.
Concentration.

moi:
Kxposure Scenario
Kndpoint and Study
mg/l.)
C		 (mg/l.)
moi:
(Total IT')

DLYLLOPMLM.YL





EFFECTS




Cleaners/Degreasers
Increased Post-




Medium Intensity
Use
implantation Losses
Saillenfait et al.
(2003); Saillenfait et





al. (2002)
437
1.034
423
30

DEVELOPMENTAL





EFFECTS




Cleaners/Degreasers
High Intensity Use
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et





al. (2002)
437
13.40
33
30

DEVELOPMENTAL




Engine
Cleaner/Degreaser
Medium Intensity
Use
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.




(2003); Saillenfait et





al. (2002)
437
1.682
260
30
Engine
Cleaner/Degreaser
DEVELOPMENTAL




High Intensity Use
EFFECTS
437
16.46
27
30
Page 316 of 576
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Kxposurc Seciiiirio
llcsillh Kfleet.
Knripoinl niul Study
POD (pesik
blood
eoneenlmlion.
ing/l.)
W omen
('hiklhesiring
Age Kxposurc.
Peak mood
Concent ml ion.
CnuxOllg/l.)
MOK
ISeneli 111:1 r k
MOK
(Total I I )

Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
al (2002)




Spray Lubricant
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
al. (2.002)
437
0.332
1,316
30
Spray Lubricant
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
al (2002)
437
2.853
153
30
One MOE calculated using a high-end estimate for acute exposure to consumers from the use of NMP -
containing engine cleaners/degreasers is below the benchmark MOE (30); MOE High Intensity Use =
27.
Overall Confidence
The cleaner/degreaser scenario and the engine cleaner/degreaser scenario are based on corresponding
publicly available consumer product data, specifically the weight fractions and the amount of product
used and duration of use from consumer survey data. EPA has a high confidence in these parameters for
representing the cleaner/degreaser and engine cleaner/degreaser consumer use scenarios.
EPA has a high confidence in the Consumer Exposure Model (CEM), its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical and chemical properties. The emission rate used in CEM for the
cleaner/degreaser scenario and engine cleaner/degreaser scenario was estimated since product-specific
emission from chamber studies was not reasonably available. EPA has high confidence in the emission
rate estimate based on physical and chemical properties.
The difference in MOE between the medium-intensity and high-intensity use scenarios for the engine
cleaner/degreaser is the result of the unique combination of longer duration of use, higher weight
fraction, and greater mass used that results in significantly higher NMP air concentration. The inhalation
exposure combined with the dermal exposure results in the high-intensity use MOE below 30.
Page 317 of 576
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The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by CEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a high confidence in the input parameters estimating the cleaner/degreaser scenario and the
sealants scenario.
The studies that support the health concerns for adverse developmental effects following acute exposure
described above in Section 3.2. Overall, EPA has high confidence in the health endpoint and POD
selected for risk characterization of acute exposure. Section 3.2.6 describes the justification for this
confidence rating.
4.2.4.5 Paints and Arts and Craft Paint
Table 4-45. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Paint and Arts and Craft Paint
Kxposure
Scenario
Health KITect.
Kndpoint and Study
POD (peak
hlood
concenl ration,
ing/l.)
Women
Childhearing
Age Kxposure.
Peak lilood
Concentration.
('mux (lllg/l <)
moi:
Benchmark
MOE
(Total IT')
Paints
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
0.374
1,169
30
Paints
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
1.422
307
30
Arts and Crafts
Paints
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
0.071
6,139
30
Arts and Crafts
Paints
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
0.222
1,970
30
All MOEs calculated using high-end estimates of acute exposure to consumers from the use of NMP-
containing paints (including those used in arts and crafts) are above the benchmark MOE (30).
Page 318 of 576
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Overall Confidence
The paint and the arts and crafts paint scenarios are based on corresponding publicly available consumer
product data, specifically the weight fractions and the amount of product used and duration of use from
consumer survey data. EPA has a high confidence in these parameters for representing the paint and arts
and crafts paint scenarios.
EPA has a high confidence in the Consumer Exposure Model (CEM), its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical and chemical properties. The emission rate used in CEM for the paint and
arts and crafts paint scenarios was estimated since product-specific emission from chamber studies was
not reasonably available. EPA has high confidence in the emission rate estimate based on physical and
chemical properties.
The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by CEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a high confidence in the input parameters estimating the paint and arts and crafts paint
scenarios.
The studies that support the health concerns for adverse developmental effects following acute exposure
described above in Section 3.2. Overall, EPA has high confidence in the health endpoint and POD
selected for risk characterization of acute exposure. Section 3.2.6 describes the justification for this
confidence rating.
4.2.4.6 Stains, Varnishes, Finishes (Coatings)
Table 4-46. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Stains, Varnishes, Finishes (Coatings) 				
Kxposure
Scenario
Health K fleet.
Kmlpoint and Study
POD (peak
hlood
concentration,
ing/l.)
Women
Chiklhearing
Age Kxposure.
Peak Blood
Concentration.
C		 (m«/l.)
moi:
Benchmark
MOI.
(Total 11)
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
0.341
1,283
30
High Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
1.947
224
30
All MOEs calculated using high-end estimates of acute exposure to consumers from the use of NMP -
containing stains, varnishes and finishes (coatings) are above the benchmark MOE (30).
Page 319 of 576
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Overall Confidence
The stains, varnishes and finishes (coatings) scenarios are based on corresponding publicly available
consumer product data, specifically the weight fractions and the amount of product used and duration of
use from consumer survey data. EPA has a high confidence in these parameters for representing the
stains, varnishes and finishes (coatings) scenarios.
EPA has a high confidence in the Consumer Exposure Model (CEM), its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical and chemical properties. The emission rate used in CEM for the stains,
varnishes and finishes (coatings) scenarios was estimated since product-specific emission from chamber
studies was not reasonably available. EPA has high confidence in the emission rate estimate based on
physical and chemical properties.
The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by CEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a high confidence in the input parameters estimating the stains, varnishes and finishes
(coatings) scenarios.
The studies that support the health concerns for adverse developmental effects following acute exposure
described above in Section 3.2. Overall, EPA has high confidence in the health endpoint and POD
selected for risk characterization of acute exposure. Section 3.2.6 describes the justification for this
confidence rating.
4.2.4.7 Paint Removers
Table 4-47. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Paint Removers
Kxposure
Scenario
Health K fleet.
Kndpoint and Study
POD (peak
hlood
concentration,
ing/l.)
Women
Childhearing
Age Kxposure.
Peak lilood
Concentration.
(		 (nig/I.)
moi:
Benchmark
MOI.
( Total I I )
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
2.014
217
30
High Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al. (2003);
Saillenfait et al. (2002)
437
15.13
29
30
Page 320 of 576
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One MOE calculated using a high-end estimate for acute exposure to consumers from the use of NMP -
containing paint removers is below the benchmark MOE (30); MOE High Intensity Use = 29.
Overall Confidence
The paint removers scenario is based on corresponding publicly available consumer product data,
specifically the weight fractions and the amount of product used and duration of use from consumer
survey data. EPA has a high confidence in these parameters for representing the paint removers
scenario.
EPA has a high confidence in the Multi-Chamber Concentration and Exposure Model (MCCEM), its
appropriate use for semi-volatile chemicals such as NMP in estimating air concentrations based on the
consumer use, activity patterns, and NMP physical and chemical properties. The emission rate used in
MCCEM for the paint removers scenario was based on emission data from a chamber study for a
product containing NMP. EPA has high confidence in the emission rate estimate based on peer-reviewed
study data.
The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by MCCEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a high confidence in the input parameters estimating the paint removers scenarios.
The studies that support the health concerns for adverse developmental effects following acute exposure
and adverse reproductive effects following chronic exposure are described above in Section 3.2. Overall,
EPA has high confidence in the health endpoint and POD selected for risk characterization of acute
exposure. Section 3.2.6 describes the justification for this confidence rating.
4.2.4.8 Risks to Bystanders
EPA evaluated bystander exposure to NMP for all COUs where risk estimates below the benchmark
were found for consumers, including use of NMP-containing paint removers, high weight fraction
adhesives and sealants, and engine cleaner/ degreasers. Bystander exposures and risks were not further
evaluated for scenarios that do not pose a risk to consumer users because bystander exposures are
expected to be lower than consumer user exposures. Risk estimates for adult bystanders are summarized
in Table 4-48. Risk estimates for child bystanders are summarized in Table 4-49. All MOEs calculated
using high-end estimates of acute exposure to bystanders are above the benchmark MOE (30).
Table 4-48. Risk Estimates for Acute Exposure to Adult Bystanders Following Consumer Use of
NMP
Kxposure Scenario
Health Kflect.
Kndpoint and Study
POD (peak
hlood
concentration,
mg/l.)
Women
(hildhearing
Age Kxposure.
Peak lilood
Concentration.
CnuxOllg/l.)
moi:
Benchmark
MOE
( Total I I )
Paint Removers
High Intensity Use
(In room of use) a
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
437
9.812
45
30
Page 321 of 576
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Kxposurc Sccnnrio
llcsihh KITccl.
Kndpoinl ;iihI Study
POD (posik
blood
coiKTiilmlion.
ing/l.)
W OIlH'll
(hildhciiring
Age Kxposuro.
Peak mood
Concent ml ion.
CnuxOllg/l.)
moi:
ISencli 111:1 rk
moi:
(Tolsil I I )

Saillenfait et al.
(2003); Saillenfait et
al (2.002)




Paint Removers
High Intensity Use
(In rest of house)
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
437
3.561
123
30
High Weight
Fraction Adhesives
and Sealants
High Intensity Use
(In room of use) a
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
al. (2002)
437
0.156
2,806
30
High Weight
Fraction Adhesives
and Sealants
High Intensity Use
(In rest of house)
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
al. (2.002)
437
0.000 b
N/A
30
Engine Cleaner/
Degreaser
High Intensity Use
(In room of use) a
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
al. (2002)
437
8.150
54
30
Engine Cleaner/
Degreaser
High Intensity Use
(In rest of house)
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
437
5.552
79
30
1 Bystander Cmax estimates in room of use assume exposure to the same NMP air concentrations as the user.
3 Cmax is assumed to be zero for bystanders in the rest of house, as outdoor use of the product is not expected to result in NMP
in indoor air.
N/A = not applicable
Page 322 of 576
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Table 4-49. Risk Est
timates for Acute Exposure to Child Bystanders via Consumer Use of NMP
Kxposure Scenario
Health Effect.
Endpoint and Study
POD (peak
hlood
concentration.
nig/I.)
Child (3-5yrs)
Exposure.
Peak lilood
Concentration.
('mux (lllg/l.)
moi:
Benchmark
MOE
(Total I I )
Paint Removers
High Intensity Use
(In room of use) a
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); MiMStet
al. (2002)
437
11.44
38
30
Paint Removers
High Intensity Use
(In rest of house)
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
437
3.609
121
30
High Weight
Fraction Adhesives
and Sealants
High Intensity Use
(In room of use) a
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
al. (2002)
437
0.200
2,187
30
High Weight
Fraction Adhesives
and Sealants
High Intensity Use
(In rest of house)
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
al. (2002)
437
0.000 b
N/A
30
Engine Cleaner/
Degreaser
High Intensity Use
(In room of use) a
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
al. (2002)
437
10.56
41
30
Engine Cleaner/
Degreaser
High Intensity Use
(In rest of house)
DEVELOPMENTAL
EFFECTS
Increased Post-
implantation Losses
Saillenfait et al.
(2003); Saillenfait et
437
6.512
67
30
bystander Cmax estimates in room of use assume exposure to the same NMP air concentrations as the user.
Page 323 of 576
-------
Kxposure Scenario
Health K fleet.
Kndpoint and Study
POD (peak
hlood
concentration.
nig/I.)
Child (3-5vrs)
Kxposure.
Peak lilood
Concent rat ion.
CnuxOllg/l.)
MOE
Benchmark
MOK
( Total I I )
Is assumed In he /cm fur In slanders in 1 lie resi nf house, as outdoor use nf I lie product is uol c\pecled In rcsull in \\1l'
in indoor air.
N/A = not applicable
Overall Confidence
The estimate of bystander exposures is based on the air concentration estimates developed in the
corresponding exposure scenarios: paint removers, high weight fraction adhesives and sealants, and
engine cleaner/degreaser. The overall confidence of these scenarios is found in Sections 4.2.4.1, 4.2.4.4,
and 4.2.4.7, respectively.
The studies that support the health concerns for adverse developmental effects following acute exposure
described above in Section 3.2. Overall, EPA has high confidence in the health endpoint and POD
selected for risk characterization of acute exposure. Section 3.2.6 describes the justification for this
confidence rating.
4.2.5 Risk Estimation for General Population Exposures to NMP
During problem formulation, EPA considered general population exposures to NMP through ambient
water, sediment, land-applied biosolids, and ambient air. Based on fate properties and screening level
analyses, EPA concluded that no further analysis of these pathways is required.
EPA has since updated the screening level analysis of risks from incidental exposure to NMP in surface
water based on more recent TRI release information from 2018. This updated exposure analysis is
described in Section 2.4.3 and updated release information is in Appendix E.
Table 4-50 and Table 4-51 show risk estimates for NMP exposure from incidental ingestion and dermal
contact with surface water. Calculated MOEs below the benchmark MOE of 30 would indicate a risk
concern. All MOEs calculated using high-end estimates of acute exposure to swimmers are above the
benchmark MOE (30).
Page 324 of 576
-------
Table 4-50. Risk Estimates for Acute Oral Exposure Through Incidental Ingestion of Water;
Benchmark MOE = 30
OES
I'sicililv/Data
Source"
Surface
Water
Concentration
(Hg/L)
Drinking
Water Acute
Dose. I'dnale
(mg/kg/da>) h
MOE
(Oral POD 418
mg/kg/dav)
Chemical Processing,
Excluding
Formulation
Spruance Plant
3.4E+00
1.3E-05
3.3E+07
Chemical Processing,
Excluding
Formulation
BASF Corp.,
Alabama
2.2E-01
8.2E-07
5.1E+08
Chemical Processing,
Excluding
Formulation
Fortran Industries
LLC
1.7E+00
6.5E-06
6.4E+07
Chemical Processing,
Excluding
Formulation
American Refining
Group, Inc.
1.1E-01
4.1E-07
1.0E+09
Chemical Processing,
Excluding
Formulation
BASF Corp,
Michigan
1.3E-04
4.7E-10
8.9E+11
Electronics
Manufacturing
GlobalFoundries,
Vermont
2.3E+00
8.6E-06
4.9E+07
Electronics
Manufacturing
GlobalFoundries,
New York
1.4E+00
5.2E-06
8.1E+07
Formulation
Essex Group Inc.
Chemical
Processing Plant
5.4E+00
2.0E-05
2.1E+07
Metal Finishing
Essex Group LLC
7.7E-01
2.9E-06
1.5E+08
a Site specific modeling to estimate surface water concentrations.
bDose is based on high-end incidental intake rate for adult females.
Table 4-51. Risk from Acute Dermal Exposure from Swimming; Benchmark MOE = 30
OES
I'sicililv/Data
Source"
Surface
Water
Concentration
(Hg/L)
Dermal Acute
Dose. Adult h
(mg/kg/dav)
MOE
(Dermal POD 418
mg/kg/dav)
Chemical Processing,
Excluding
Formulation
Spruance Plant
3.4E+00
1.3E+00
3.3E+02
Chemical Processing,
Excluding
Formulation
BASF Corp.,
Alabama
2.2E-01
8.3E-02
5.0E+03
Page 325 of 576
-------
oi:s
Source"
Surface
Water
Concentration
(MS/U
Derimil Acute
Dose. Adult h
(mg/kg/dav)
moi:
(Dermal POD 41S
mg/kg/dav)
Chemical Processing,
Excluding
Formulation
Fortran Industries
LLC
1.7E+00
6.6E-01
6.4E+02
Chemical Processing,
Excluding
Formulation
American
Refining Group,
Inc.
1.1E-01
4.2E-02
1.0E+04
Chemical Processing,
Excluding
Formulation
BASF Corp.,
Michigan
1.3E-04
4.8E-05
8.8E+06
Electronics
Manufacturing
GlobalFoundries,
Vermont
2.3E+00
8.7E-01
4.8E+02
Electronics
Manufacturing
GlobalFoundries,
New York
1.4E+00
5.2E-01
8.0E+02
Formulation
Essex Group Inc.
Chemical
Processing Plant
5.4E+00
2.0E+00
2.1E+02
Metal Finishing
Essex Group LLC
7.7E-01
2.9E-01
1.4E+03
a Site specific modeling to estimate surface water concentrations.
b Dose is based on high-end competitive swimmer (3 hrs/day).
Overall Confidence
Confidence ratings for general population ambient water exposure scenarios are informed by
uncertainties surrounding inputs and approaches used in modeling surface water concentrations and
estimating incidental oral and dermal doses. Estimated daily releases (kg/site-day) on a per occupational
exposure scenario (OES) basis reflect moderate confidence.
Other considerations that impact confidence in the ambient water exposure scenarios include the model
used (E-FAST 2014) and its associated default and user-selected values and related uncertainties. As
described, there are uncertainties related to the ability of E-FAST 2014 to incorporate downstream fate
and transport. Of note, as stated on EPA's E-FAST 2014 website, "modeled estimates of concentrations
and doses are designed to reasonably overestimate exposures, for use in an exposure assessment in the
absence of or with reliable monitoring data." Regarding the assumption that members of the general
population could reasonably be expected to swim at or near the point of release, there is relatively low
confidence.
There are no readily available NMP surface water monitoring data available that reflect ambient water
exposure levels in the United States thus, EPA relied on facility submitted data as reported in TRI.
Page 326 of 576
-------
Based on the above considerations, the general population ambient water exposure assessment scenarios
have an overall low to moderate confidence
The studies that support the health concerns for adverse developmental effects following acute exposure
described above in Section 3.2. Overall, EPA has high confidence in the health endpoint and POD
selected for risk characterization of acute exposure. Section 3.2.6 describes the justification for this
confidence rating.
4.3 Assumptions and Key Sources of Uncertainty
4.3.1 Assumptions and Uncertainties in Occupational Exposure Assessment
Assumptions and sources of uncertainty for occupational exposure estimates are described in greater
detail in Section 2.4.1.4. Sources of uncertainty and overall confidence in occupational exposure
estimates vary across occupational exposure scenarios. Overall confidence in exposure estimates for
specific conditions of use are described in Section 4.2.2.
A peer-reviewed PBPK model allows EPA to estimate aggregate exposures from simultaneous dermal
and inhalation and vapor-through-skin exposures with relatively high confidence. The body weight
parameter is related to all of these three routes. The assumed values for human body weight have
relatively lower uncertainties, and the median values used may underestimate exposures at the high-end
of PBPK exposure results.
Estimates of dermal exposure rely on a set of assumptions that introduce uncertainty because no data are
reasonably available for many parameters. The types of data and assumptions used to estimate exposure
for each exposure scenario is summarized in Table 4-53. Parameters that rely on such assumptions
include glove use and effectiveness, durations of contact with liquid, skin surface areas for contact with
liquids. For many OESs, the high-end surface area assumption of contact over the full area of two hands
likely overestimates exposures. EPA has more confidence in dermal exposure parameters that are
supported by data, such as NMP concentrations in formulas. There is also uncertainty around the impact
of vapors being trapped next to the skin during glove use. For most of the assumptions made for
exposure parameters and other sources of uncertainty, EPA does not have enough information to
determine whether most of these assumptions may overestimate or underestimate exposures. The NMP
concentrations in liquid used in dermal exposure predictions are likely to have a relatively low impact
(less than an order of magnitude, or factor of 10) on overestimation or underestimation of exposure.
Estimates of inhalation and vapor-through-skin exposures also rely on various assumptions that
introduce uncertainty. The specific types of data sources used estimated air concentrations that are based
on monitoring data where reasonably available and based on deterministic or probabilistic modeling for
exposure scenarios lacking monitoring data. Table 4-52 summarizes the types of data used to estimate
air concentrations for each occupational exposure scenario. The principal limitation of the air
concentration monitoring data is the uncertainty in the representativeness of the data. EPA identified a
limited number of exposure studies and data sets that provided data for facilities or job sites where NMP
was used. Some of these studies primarily focused on single sites. This small sample pool introduces
uncertainty as it is unclear how representative the data for a specific end use are for all sites and all
workers across the US. Limited monitoring datasets precluded EPA from describing actual parameter
distributions. In most scenarios where data were reasonably available, EPA did not find enough data to
determine complete statistical distributions to identify 50th and 95th percentile exposures. In the absence
of percentile data for monitoring, the means or midpoint of the range serve as substitutes for 50th
percentiles of the actual distributions and high ends of ranges serve as substitutes for 95th percentiles of
Page 327 of 576
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the actual distributions. The effects of limited air monitoring datasets of unknown representativeness on
the occupational exposure assessment are unknown. They may result in either over or underestimation
of exposures depending on the actual distribution.
Where air monitoring data were not reasonably available, exposure was estimated based on deterministic
or probabilistic modeling. Modeling approaches used to estimate air concentrations also have
uncertainties. Parameter values used in models did not all have distributions known to represent the
modeled scenario. It is also uncertain whether the model equations generate results that represent actual
workplace air concentrations. Some activity-based modeling does not account for exposures from other
activities. Additional model-specific uncertainties are included below. In general, the effects of model-
specific uncertainties on the exposure estimates are unknown, as the uncertainties may result in either
over or underestimation on exposures depending on the actual distributions of each of the model input
parameters. Dermal exposures to NMP vapor that may penetrate clothing fabrics and the potential for
associated direct skin contact with clothing saturated with NMP vapor are not included in quantifying
exposures, which could potentially result in underestimation of exposures.
Table 4-52. Summary of Occupational Air Concentration Estimate Approaches
Kxposure Scenario
Work Activity
Worker
Personal
lircathing
/one
Monitoring
Data
Modeling:
Deterministic
Worker 11
Modeling:
Probabilistic
Worker (X)
Near l-'ield/
OM lar
l-'ield (X ' )
Potential
OM -related
Data
1. Manufacturing
Loading NMP
into bulk
containers

X


Loading NMP
into drums


X

2. Repackaging
Unloading NMP
from bulk
containers

X


Unloading NMP
from drums


X

3. Chemical
Processing,
Excluding
Formulation
Unloading NMP
from drums


X

4. Incorporation into
Formulation,
Mixture, or
Reaction Product
Unloading liquid
NMP from drums


X

Maintenance,
bottling, shipping,
loading
X (23
samples)


A(area
monitoring) c
5. Metal finishing
Spray application
X (45
samples)


A(area
monitoring) c
Page 328 of 576
-------
Kxposnre Scenario
Work Activity
Worker
Person ;il
lirenthiii"
/one
Monitoring
Modeling:
Deterministic
Worker"
Modeling:
Probabilistic
Worker (\)
Nesir l-'ield/
OM Isir
l-'ield (\ ' )
Potent inl
OM -relsited

Dip application
X (103
samples)
Xb


Brush application

X b


6. Application of
Paints, Coatings,
Adhesives and
Sealants
Spray application
X (45
samples)


X(area
monitoring) c
Roll/ curtain
application

X


Dip application
X (103
samples)
X b


Roller/ brush and
syringe/ bead
application

X b


7. Recycling and
disposal
Unloading NMP
from bulk
containers

X


Unloading NMP
from drums


X

8. Removal of
Paints, Coatings,
Adhesives and
Sealants
Miscellaneous
paint, coating,
adhesive, and
sealant removal
X (unknown) d



Graffiti removal
X (25
samples)



9. Other Electronics
Manufacturing
Capacitor,
resistor, coil,
transformer, and
other inductor
manufacturing
X (4 samples)



10. Semiconductor
Manufacturing e
Container
handling, small
containers
X (19
samples)



Container
handling, drums
X (15
samples)



Fab worker
X (28
samples)


A(area
monitoring) c
Maintenance
X (45



Page 329 of 576
-------
Kxposnre Scenario
Work Activity
Worker
Person ;il
lirenthiii"
/one
Monitoring
Modeling:
Deterministic
Worker"
Modeling:
Probabilistic
Worker (\)
Nesir l-'ield/
OM Isir
l-'ield (\ ' )
Potent inl
OM -relsited


samples)



Virgin NMP
truck unloading
X (1 sample)



Waste truck
loading
X (1 sample)



11. Printing and
Writing
Printing
X (6 samples)



Writing
Inhalation not assessed
12. Soldering
Brush application

Xb


13. Commercial
Automotive
Servicing



X f

14. Laboratory Use
Laboratory use
X (1 sample)
Xb


15. Lithium Ion Cell
Manufacturing
Container
handling, small
containers
X (14
samples)



Container
handling, drums
X(10
samples)



Cathode coating
X (5 samples)



Cathode mixing
X (8 samples)



Research and
development
X (4 samples)



Miscellaneous
additional
activities
X (5 samples)



16. Cleaning
Dip cleaning /
degreasing
X (103
samples)
xb


Spray / wipe
cleaning
X (73
samples)
xb


17. Fertilizer
application
Spray application

xb


X = These data or modeling approaches were available and used to quantify air concentrations.
" The deterministic modeling approaches estimate worker exposures.
' These modeling estimates are from literature CRiviii, 2013). Other modeling estimates are from modeling performed bv
EPA.
Ac While area monitoring data were identified, EPA does not expect that these data are representative of ONU exposures for
these specific OESs because of the intended sample population and the selection of the specific monitoring location.
Page 330 of 576
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Kxposure Scenario
Work Activity
Worker
Personal
Breathing
/one
Monitoring
Data
Modeling:
Deterministic
Worker"
Modeling:
Probabilistic
Worker (\)
Near l-'ield/
OM lar
l-'ield (\ ' )
Potential
OM -related
Data
Therefore these data are not used.
d The number of samples is unknown. The data source only presented the range.
e The listed approaches for Semiconductor Manufacturing include EPA's approach and do not include industry-proposed
PBPK runs.
f This modeling includes Near Field modeling for worker exposures and Far Field modeling for ONU exposures. Far Field
modeling results are not included in the RE but are included in Risk Evaluation for n-Methylpyrrolidone (2-Pyrrolidinone,
1 Methvl-) (NMP), Supplemental Information on Occupational Exposure Assessment (U.S. EPA, 2020f).
Table 4-53. Summary of Worker Dermal Parameter Estimate Approaches
Kxposure
Scenario
Work Activity
YMP weight Traction in
the liquid product (data
source(s) used if
applicable)
Total skin
surface area of
hands in contact
with the liquid
product h
Duration of
dermal
contact with
the liquid
product'
1. Manufacturing
Loading NMP into
bulk containers
Data (2016 CDRa)
Default
Assumption
Default
Assumption
Loading NMP into
drums
2. Repackaging
Unloading NMP
from bulk
containers
Data (2016 CDRa)
Default
Assumption
Default
Assumption
Unloading NMP
from drums
3. Chemical
Processing,
Excluding
Formulation
Unloading NMP
from drums
Data (2016 CDRa, public
comments, and Use and
Market Profile for NMPa)
Default
Assumption
Default
Assumption
4. Incorporation
into
Formulation,
Mixture, or
Reaction
Product
Unloading liquid
NMP from drums
Data (2016 CDRa, public
comments, literature, and
Use and Market Profile for
NMPa)
Default
Assumption
Default
Assumption
Maintenance,
bottling, shipping,
loading
5. Metal finishing
Spray application
Data (2012 and 2016
CDRa)
Default
Assumption
Default
Assumption
Dip application
Brush application
6. Application of
Paints,
Coatings,
Spray application
Data (public comments,
literature, and Use and
Default
Assumption
Default
Assumption
Roll/ curtain
application
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r.xposill'c
Sconsirio
Work Activity
YMI* weight frsidion in
the liquid product (dsitn
sourcc(s) used if
;ipplic;ihlc)
1 ot:il skin
surfiicc jircsi of
lisinds in contsict
with the liquid
product h
Duration of
dcrmsil
contiict with
the liquid
product'
Adhesives and
Sealants
Dip application
Roller/ brush and
syringe/ bead
application
Market Profile for n-
Methy lpy rroli donea)


7. Recycling and
disposal
Unloading NMP
from bulk
containers
Unloading NMP
from drums
Data (SIAa) and Non-
default Assumption
Default
Assumption
Default
Assumption
8. Removal of
Paints,
Coatings,
Adhesives and
Sealants
Miscellaneous
paint, coating,
adhesive, and
sealant removal
Graffiti removal
Data (public comments,
literature, and Use and
Market Profile for n-
Methylpyrrolidonea)
Default
Assumption
Default
Assumption
9. Other
Electronics
Manufacturing
Capacitor, resistor,
coil, transformer,
and other inductor
manufacturing
Data (literature, public
comments, and the Use and
Market Profile for n-
Methylpyrrolidonea)
Default
Assumption
Default
Assumption
10. Semiconductor
Manufacturing
Container handling
(small containers);
Container
handling, drums
Fab worker
Maintenance
Virgin NMP truck
unloading
Waste truck
loading
Data (SIA, public
comments, literature, and
Use and Market Profile for
n-Methylpyrrolidonea)
Default
Assumption
Default
Assumption
11. Printing and
Writing
Printing
Data (public comments,
and Use and Market Profile
for n-Methylpyrrolidonea)
Default
Assumption
Default
Assumption
Writing
Data (Australian
Government
Department of
Health, 2016)
Non-default
Assumption
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r.xposill'c
Sconsirio
Work Activity
YMI* weight frsidion in
the liquid product (dsitn
sourcc(s) used if
;ipplic;ihlc)
1 ot:il skin
surfiicc jircsi of
lisinds in contsict
with the liquid
product h
Dursition of
dcrmsil
contiict with
the liquid
product'
12. Soldering
Soldering
Data (Use and Market
Profile for n-
Methylpyrrolidonea)
Default
Assumption
Default
Assumption
13. Commercial
Automotive
Servicing

Data (public comments and
the Use and Market Profile
for n-Methylpyrrolidonea)
Default
Assumption
Default
Assumption
14. Laboratory Use
Laboratory use
Non-default Assumption
Default
Assumption
Default
Assumption
15. Lithium Ion
Cell
Manufacturing
Container
handling, small
containers
Data (literature, public
comments, and the Use and
Market Profile for n-
Methylpyrrolidonea)
Default
Assumption
Default
Assumption
Container
handling, drums
Cathode coating
Cathode mixing
Research and
development
Miscellaneous
additional
activities
16. Cleaning
Dip cleaning /
degreasing
Data (public comments,
literature sources, and the
Use and Market Profile for
n-Methylpyrrolidonea)
Default
Assumption
Default
Assumption
Spray / wipe
cleaning
17. Fertilizer
application
Spray application
Data (literature, public
comments, and the Use and
Market Profile for n-
Methylpyrrolidonea)
Default
Assumption
Default
Assumption
a Sources for weiuht fractions: 2016 CDR (TJ.S. EPA, 2016a), Use and Market Profile for n-Methylpvrrolidone (
2017s). 2012 CDR (U.S. EPA, 2012b). SIA (2019c). as well as various Diiblic comments and literature sources.
b Default assumption for "Total skin surface area of hands in contact with the liquid product" is: (1) high-end value, which
represents two full hands in contact with a liquid: 890 cm2 (mean for females), 1070 cm2 (mean for males); (2) central
tendency value, which is half of two full hands (equivalent to one full hand) in contact with a liquid and represents only
the palm-side of both hands exposed to a liquid: 445 cm2 (females), 535 (males).
0 Default assumption for "Duration of dermal contact with the liquid product" is: (1) high-end value of a full-shift, usually 8
or 12 hours; central tendency value of value of half of a full-shift, usually 4 or 6 hours. For OES with available task
durations, EPA assessed "what-if' scenarios using the task duration as the duration of dermal contact with the liquid
product (in addition to the scenarios that use the default assumption).
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4.3.2 Data Uncertainties in Consumer Exposure Assessment
Systematic review was conducted to identify chemical- and product-specific monitoring and use data for
assessing consumer exposures. As no product-specific monitoring data were identified, exposure
scenarios were assessed using a modeling approach that requires the input of various chemical
parameters and exposure factors. When possible, default model input parameters were modified based
on chemical and product specific inputs reasonably available in literature and product databases.
Uncertainties related to these inputs are discussed below.
4.3.2.1	Product & Market Profile
The products and articles assessed in this risk evaluation are largely based on EPA's 2016-2017 Use and
Market Profile for n-Methylpyrrolidone, which provides information on commercial and consumer
products available in the US marketplace at that time (	). While it is possible that some
products may have changed since 2017, EPA believes that the timeframe is recent enough to still
represent the current market. Information on products from the Use and Market Profile was augmented
with other sources such as the NIH Household Product Survey and EPA's Chemical and Products
Database (CPDat), as well as reasonably available product labels and SDSs. However, it is still possible
that the entire universe of products may not have been identified, due to market changes or research
limitations.
4.3.2.2	Westat Survey
A number of product labels and/or technical fact sheets were identified for use in assessing consumer
exposure. The identified information often did not contain product-specific use data, and/or represented
only a small fraction of the product brands containing the chemical of interest. A comprehensive survey
of consumer use patterns in the United States, called the Household Solvent Product: A National Usage
Survey (	7), was used to parameterize critical consumer modeling inputs, based on
applicable product and use categories. This large survey of over 4,920 completed questionnaires,
obtained through a randomized sampling technique, is highly relevant because the primary purpose was
to provide statistics on the use of solvent-containing consumer products for the calculation of exposure
estimates. The survey focused on 32 different common household product categories, generally
associated with cleaning, painting, lubricating, and automotive care. Although there is uncertainty due to
the age of the use pattern data, as specific products in the household product categories have likely
changed over time, EPA assumes that the use pattern data presented in the Westat survey reflect
reasonable estimates for current use patterns of similar product type. The Westat study aimed to answer
the following key questions for each product category, some of which were used as key model inputs in
this consumer assessment:
room of product use (key input: environment of use);
how much time was spent using the product (key input: duration of product use per event);
how much of the product was used (key input: mass of product used per event);
how often the products were used;
when the product was last used;
product formulation;
brand names used; and
degree of ventilation or other protective measures undertaken during product use.
The strengths and weakness of the Westat survey are discussed in more detail below with an emphasis
on the key modeling inputs.
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Product Use Category
A crosswalk was completed to assign consumer products in the current risk evaluation to one of the
product or article scenarios in the CEM model, and then to an appropriate Westat survey category.
Although detailed product descriptions were not provided in the Westat survey, a list of product brands
and formulation type in each category was useful in pairing the Westat product categories to the
scenarios being assessed. In most cases, the product categories in the Westat survey aligned well with
the products being evaluated. For product scenarios without an obvious Westat scenario match,
professional judgment was used to make an assignment. For a limited number of scenarios, technical
fact sheets or labels with information on product use amounts were reasonably available, and this
information was used in the assessment as needed.
Another limitation of the Westat data is that while the overall respondent size of the survey was large,
the number of users in each product category varied, with some product categories having a much
smaller pool of respondents than others. Product categories such as spot removers, cleaning fluids, glues
and adhesives, lubricants, paints, wood stains, engine degreasers, and specialized electronic cleaners had
sample sizes ranging from roughly 500 to 2,000 users; whereas, categories such as shoe polish, adhesive
removers, rust removers, and brake cleaners had sample sizes of less than 500 users.
The survey was conducted for adults and adolescents ages 18 and older. Most consumer products are
targeted to this age category, and thus the respondent answers reflect the most representative age group.
However, adolescents may also be direct users of some consumer products. It is unknown how the usage
patterns compare between adult and adolescent users, but it is assumed that the product use patterns for
adults will be very similar to, or more conservative {i.e., longer use duration, higher frequency of use)
than use patterns for adolescents.
Room of Use
The CEM model requires specification of a room of use, which results in the following default model
assumptions (relevant for inhalation exposure only): ventilation rates, room volume, and the amount of
time per day that a person resides in the room of use. The Westat survey provided the location of
product use for the following room categories: basement, living room, other inside room, garage, and
outside. The room with the highest percentage was selected as the room to model in CEM. For some
specific product scenarios, however, professional judgement was used to assign the room of use; these
selections are documented above in Table 2-78 of Section 2.4.2.4. For many scenarios in which "other
inside room" was the highest percentage, the utility room was selected as the default room of use. The
utility room is a smaller room, and therefore may provide a more conservative assumption for peak
concentrations. In cases where outside was identified as the "room of use," but it was deemed reasonable
to assume the product could be used inside (such as for auto care products), the garage was typically
selected as the room of use.
Amount of Product Used and Duration of Product Use
The Westat survey reported the number of ounces per use, derived from the fluid ounces of product used
per year (based on can size and number of cans used), divided by the number of reported uses per year.
The duration of use (in minutes) reported in Westat was a direct survey question. An advantage to these
parameters is that the results are reported in percentile rankings and were used to develop profiles of
high intensity, moderate intensity, and low intensity users of the products (95th, 50th, and 10th percentile
values, respectively). In cases where a product was not crosswalked to a CEM scenario, the amount of
product used was tailored to those specific products instead of depending on Westat data.
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Ventilation and Protection
For most scenarios, the CEM model was ran using median air exchange rates from EPA's Exposure
Factors Handbook (2011). and interzone ventilation rates derived from the air exchange rates and the
default median building volume from EPA's Exposure Factors Handbook (2011). These inputs do not
incorporate any measures that would serve to increase air exchange. The Westat survey questions
indicated that most respondents did not have an exhaust fan on when using these products, most
respondents kept the door to the room open when using these products, and most people reported
reading the directions on the label. The modeling conducted by EPA did not account for specific product
instructions or warning labels. For example, some product labels might indicate that PPE (chemical
resistant gloves or respirator) should be worn, which would lower estimated exposures.
4.3.2.3 Other Parameters and Data Sources
Activity Patterns
EPA assumed that a consumer product would be used only once per day. This is a realistic assumption
for most scenarios, but a high-intensity user could use the same product multiple times in one day.
Additionally, CEM allows for selection of activity patterns based on a "stay-at-home" resident or a part-
time or full-time "out-of-the home" resident. The activity patterns were developed based on
Consolidated Human Activity Database (CHAD) data of activity patterns, which is an EPA database that
includes more than 54,000 individual study days of detailed human behavior. It was assumed that the
user followed a "stay-at-home" activity pattern that would place them in various rooms as well as
outside of the home and room of use for more time than a part-time or full-time "out-of-the home"
resident. Therefore, applying an "out-of-the home" resident activity pattern would reduce estimated
exposures.
Product Density
If reasonably available, product-specific densities were obtained from SDS information, and used to
convert the ounces of the product used from Westat, to grams of product used. If product-specific
densities were not reasonably available, default product densities from the CEM User Guide were used.
Outdoor Scenario
The CEM model does not currently accommodate outdoor scenarios. For products that are solely
intended to be used outdoors, modifications to the CEM inputs were made to simulate an outdoor
scenario by adjusting Zone 1 parameters (which represents the room of use, or outside). The garage was
selected as the room of use, but the room volume was changed to 16 m3 to represent a half dome
chemical cloud around the person using the product. Additionally, the air exchange rate for Zone 1 was
set to 100 to reflect the high rate between the cloud and the rest of outside. The interzone ventilation rate
was set to 0, which effectively blocks the exchange of air between Zone 1 and the rest of the house.
Thus, the concentrations users are exposed to inside the home after product use is zero. In the outside
scenario, non-users are assumed to have zero exposures. These assumptions may be either an
underestimation of exposures given outdoor conditions such as high temperatures in summer which
could increase volatilization of NMP in the product but could also be an overestimation of exposures if
outdoor conditions could include wind that effectively disperses the NMP in air.
4.3.3 Approach and Methodology for Uncertainties in Consumer Exposure
Assessment
EPA's approach recognizes the need to include an uncertainty analysis. An important distinction for
such an analysis concerns variability versus uncertainty - both aspects need to be addressed. Variability
refers to the inherent heterogeneity or diversity of data in an assessment. It is "a quantitative description
of the range or spread of a set of values" and is often expressed through statistical metrics, such as
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variance or standard deviation, that reflect the underlying variability of the data. Uncertainty refers to a
lack of data or an incomplete understanding of the context of the risk assessment decision.
Variability cannot be reduced, but it can be better characterized. Uncertainty can be reduced by
collecting more or better data. Quantitative methods to address uncertainty include non-probabilistic
approaches such as sensitivity analysis and probabilistic methods such as Monte Carlo analysis.
Uncertainty can also be addressed qualitatively, by including a discussion of factors such as data gaps
and subjective decisions or instances where professional judgment was used.
4.3.3.1	Deterministic vs. Stochastic Approaches
With deterministic approaches, the output of the model is fully determined by the choices of parameter
values and initial conditions. Stochastic approaches feature inherent randomness, such that a given set of
parameter values and initial conditions can lead to an ensemble of different model outputs. Because
EPA's largely deterministic approach involves choices regarding low, medium, and high values for
highly influential factors such as chemical mass and frequency/duration of product use, it likely captures
the range of potential exposure levels although it does not necessarily enable characterization of the full
probabilistic distribution of all possible outcomes.
4.3.3.2	Sensitive Inputs
Certain inputs to which model outputs are sensitive, such as zone volumes and airflow rates, were not
varied across product-use scenarios. As a result, model outcomes for extreme circumstances such as a
relatively large chemical mass in a relatively low-volume environment likely are not represented among
the model outcomes. Such extreme outcomes are believed to lie near the upper end (e.g., at or above the
90th percentile) of the exposure distribution.
4.3.4 Environmental Hazard and Exposure Assumptions Uncertainties
In the NMP ProMem I oinuilalion (	;) and this risk evaluation, EPA completed a
screening level evaluation of environmental risk using inherently conservative assumptions. The
analysis was completed using estimated concentrations of NMP in the aquatic environment as described
in Section 2.3.2 and compared those acute and chronic exposure estimates to conservative measures of
acute and chronic hazard (COCs) as described in Section 3.1.2. There is some uncertainty associated
with the acute and chronic COCs calculated for aquatic receptors. First, more acute duration data were
reasonably available in the literature than chronic duration data. Therefore, EPA is less certain of
chronic hazard values compared to the acute hazard values. For the chronic fish endpoint, an ACR
approach was used to extrapolate a chronic toxicity value for NMP based on the reported acute values.
Utilizing a single value of 10 to extrapolate from acute to chronic hazard for species in the aquatic
environment is consistent with existing EPA methodology for the screening and analysis of industrial
chemicals (U.S. EPA, 2012e). While this value is routinely utilized by EPA to assess the hazard of new
industrial chemicals, there is uncertainty regarding using a single ACR value to estimate chronic hazards
across species and chemicals. Second, AFs were also used to calculate the acute and chronic COCs for
NMP. AFs account for differences in inter- and intra-species variability, as well as laboratory-to-field
variability and are routinely used within TSCA for assessing the hazard of new industrial chemicals
(with very limited environmental test data). There is some uncertainty associated with the use of
standardized AFs used the hazard assessment. EPA in the NMP Problem Formulation (U.S. EPA.
2018c) did not conduct any further analyses on pathways of exposure for terrestrial receptors as
described in Section 2.5.3.1 of the NMP Problem Formulation and further described in Section 2.2 and
2.3 of this risk evaluation.
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4.3.5 Human Health Hazard Assumptions and Uncertainties
There is a robust dataset for the critical reproductive and developmental effects that serve as the basis
for the points of departure used in this risk characterization. High quality studies have consistently
documented the developmental effects of NMP exposure across species and following dermal, oral, and
inhalation exposures. The high quality of studies, consistency of effects, relevance of effects for human
health, coherence of the spectrum of reproductive and developmental effects observed and biological
plausibility of the observed effects of NMP contribute to the overall confidence in the PODs identified
based on reproductive and developmental endpoints.
Data on the reproductive and developmental toxicity of NMP in humans are not reasonably available.
Therefore, this risk evaluation relies on the assumption that reproductive and developmental toxicity
observed in animal models is relevant to human health. It is unknown whether this assumption
contributes to an overestimation or underestimation of risk.
The rat PBPK model used to derive PODs based on internal doses facilitates integration of dose-
response information from multiple high-quality studies that assessed the effects of NMP exposure
across multiple routes. This model incorporates toxicokinetic information, reducing a key source of
uncertainty in animal-to-human extrapolation. Furthermore, the availability of this model in combination
with studies directly evaluating developmental toxicity across multiple exposure routes eliminates the
need for route-to-route extrapolation thereby eliminating another source of uncertainty.
There are several remaining sources of uncertainty around the identification of PODs. As discussed in
Section 3.2.1, there is uncertainty associated with the reproductive endpoints selected as the basis for the
POD used to evaluate risks from chronic NMP exposure. Because NMP exposures occurred throughout
development and into adulthood in the key study, it is not known which period(s) of exposure
contributed to the reduced fertility seen in adult rats. It is also unclear which life stages may be most
sensitive to the adverse reproductive effects of NMP exposure in humans. Although effects on male
fertility and female fecundity were not consistently observed across studies, the POD derived from the
key study (183 hr mg/L), is within close range of other PODs (223 and 414 hr mg/L), derived from
effects on fetal body weight that are consistently observed across studies, species, and routes of
exposure. It is unknown whether the limited set of 2-generation studies contributed to an overestimation
or underestimation of risk. The concordance of PODs across reproductive and developmental endpoints
and consistency of developmental effects across species and exposure routes contributes to the overall
confidence in the POD.
In developmental toxicity studies, there is inherent uncertainty around the potential contribution of
maternal toxicity to observed developmental effects. The maternal effect reported in the Saillenfait et al.
(2003) inhalation study (transient decrease in body weight gain and food consumption) has been cited as
a confounding factor by some study authors. EPA does not concur with this assertion, specifically as it
relates to the observed decrease in maternal body weight gain on GD 6-21 (minus gravid uterine
weight). Although a decrease in maternal body weight gain was observed, it is not statistically
significant. Dams weighed roughly 235 g at GD 0, and whereas the controls gained approximately 32
grams, the high dose dams gained slightly less, roughly 26 grams. Given the lack of significant change
in maternal body weight gain, it is unlikely that the observed decreases in fetal and pup body weights
reflect a secondary effect of maternal toxicity. In other key and supporting studies, including an
inhalation study (Solomon	>; E. I. Dupont De Nemours & Co. 1990). and an oral gavage study
(Saillenfait et al.. 2002). similar decreases in pup body weight were observed at similar exposure levels,
in the absence of any effects on maternal body weight. These findings support EPA's conclusion that
this developmental effect is a direct consequence of NMP exposure.
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In whole body inhalation studies, there is uncertainty around the techniques used to generate NMP air
concentration. Experimental conditions may have inadvertently resulted in the inclusion of aerosolized
particles in the exposure chamber in some inhalation exposure studies. In addition, because the partial
pressure of NMP depends on the temperature and relative humidity of the test system, variations in test
protocol can introduce uncertainty regarding the actual exposure concentrations achieved in some of the
inhalation studies used for hazard characterization. Aerosol formation would result in increased dermal
and/or oral exposures (from grooming behavior) in addition to the intended inhalation exposure. The
PODs that were ultimately selected as the basis for risk calculations did not rely on studies with this
source of uncertainty, making it unlikely that this uncertainty contributes to an overall over or under-
estimate of risk.
Another important source of uncertainty around POD selection is the lack of complete information on
potentially sensitive endpoints, including endocrine effects, sensitization, immunotoxicity,
cardiometabolic effects, and developmental neurotoxicity. Though the database for developmental
toxicity is robust, some endpoints have not been fully characterized. For example, as described in
Section 3.2.3.1, there is evidence of neurodevelopmental effects following gestational exposure to a
relatively high dose of NMP, but a NOAEL for neurodevelopmental endpoints has not been identified.
Incomplete information on potentially sensitive endpoints could lead to an underestimation of risk.
Overall, EPA has high confidence in the acute and chronic PODs identified for evaluating risk from
NMP. The PODs are derived from endpoints that fall along a continuum of reproductive and
developmental effects that are consistently observed in response to NMP across oral, dermal and
inhalation exposure routes. Application of the PBPK model reduces uncertainties associated with
extrapolation across species and exposure routes, further contributing to overall confidence in the PODs.
4.3.6 PBPK Model Assumptions and Uncertainties
There are several assumptions and sources of uncertainty associated with the PBPK model used to
convert exposure estimates and hazard PODs to internal dose metrics.
While parameters for the rates of dermal and oral uptake, metabolism, and urinary elimination have been
fit to the PK data it should be recognized that the physiological parameters that define the tissue
volumes, blood flow rates, and respiration rate, as well as the chemical-specific parameter that define
tissue-blood and tissue-air partitioning, but are measured independently {in vitro) have not been adjusted
to fit the data. Hence there has not been any compromise in the model's biological realism or
"correctness." Further, the partition coefficient values are obtained in a manner that is unambiguous and
does not confound them with other parameters. Given this solid physiological and biochemical
underpinning, the fitting of the remaining chemical-specific parameters to the available data allows for
interpolation of internal doses between the specific levels used in those experiments, some extrapolation
beyond them, and for an analysis of the internal doses when exposure via both inhalation and dermal
absorption occurs.
More specifically, the fact that several data sets are available for rats provides reasonable confidence in
the model's ability to predict dosimetry in the test animals. The carefully controlled human PK data
provide data of a quality that is rarely available for humans, providing fairly good confidence in the
ability to predict inhalation dosimetry in humans, although the modest number of subjects (8) gives
some uncertainty as to how well it represents the population as a whole. When compared to worker and
observer data from Xiaofei et al. (2000). the model did under-predict the measured blood concentrations
by a factor of 1.5 to 6, depending on the particular comparison. Some of this discrepancy could be due to
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underestimation of exposure, but the result suggests that blood concentrations may be underestimated
for some groups. There is also uncertainty with respect to how dermal absorption might vary with
dilution and matrix, but the fact that data are available for neat vs. 50% dilution provides a measure of
the impact of dilution.
Importantly, the PBPK model is being used to estimate the dosimetry in an average adult human, and the
question being addressed here is the degree of uncertainty in the estimation of that average, rather than
an estimation of variability across the population. Hence the modeling does not evaluate the effect of
variation in physiological and metabolic parameters. Instead the use of a MOE of 30 is intended to
include a factor of 10 for inter-individual variability in both pharmacokinetics and in pharmacodynamic
sensitivity. It also includes a factor of 3 for possible greater pharmacodynamic sensitivity of humans to
an NMP exposure compared to the rats used in the bioassays.
One source of uncertainty is around the dose metric: it is assumed that the parent NMP is the primary
toxicant, that average concentration (or AUC) is a measure of risk for BW effects, and peak
concentration for skeletal abnormalities. However, one must recognize that under any exposure scenario,
AUC and peak concentration are closely related: as peak concentration increases, so does AUC and
vice-versa. For example, limiting exposure to limit the peak concentration to avoid skeletal
abnormalities also limits the AUC. Because both metrics have been used to estimate toxicological limits,
possible exposures will be limited in both dimensions: the peak concentration is limited, even if it is
associated with a relatively low AUC, and AUC is limited even if it is from more continuous low-level
exposure where the peak is less high. This limits the possible impact of this uncertainty on total risk.
Another uncertainty is uncertainty around the potential contribution of NMP metabolites to toxicity.
Risk would be inversely correlated with metabolic rate if the parent compound is responsible, while it
will be positively correlated with metabolic rate if risk is due to a metabolite. Here, the fact that human
PK data are available to evaluate the metabolic rate strongly mitigates the uncertainty; within the bounds
of the remaining modest uncertainty, limiting AUC also limits the total amount of metabolism occurring.
Because metabolism is the primary route of elimination, the total amount of metabolism is not highly
sensitive to the metabolic rate: if metabolism is 25% less than predicted, it takes longer to eliminate the
NMP, allowing more to be eliminated by other routes, but the total metabolism might only be reduced
20%. AUC of parent NMP and the total amount metabolized will remain closely correlated despite
uncertainty in the metabolic rate. The risk from continuous (24 h/d, 7 d/w) exposure is not being
evaluated for the NMP uses under consideration, hence there is not a concern for that type of scenario
leading to a cumulative effect not captured by this analysis.
The specific elements listed above are those aspects of the model for which uncertainty is the greatest.
But for the reasons given, none of them is believed to create a high level of uncertainty. Toxicity was
evaluated for exposure by oral gavage, feed, dermal exposure, and inhalation. The reduction in pup
bodyweight response appears to be more sensitive to inhalation exposure than dermal exposure: all
internal doses are lower for the inhalation LOAEL than the dermal LOAEL. But this means that a
human MOE based on the inhalation response will be protective compared to the response after dermal
exposure. For skeletal abnormalities the dose-response relationship was comparable for each route,
which gives more confidence that the model is providing meaningful predictions and allows the data
from both routes to be combined in the dose-response analysis, increasing the statistical power of the
analysis. This benefit is obtained because the PBPK model is available for use. Hence, there is little
uncertainty in applying the PBPK model to estimate risk for either or both dermal and inhalation
exposure , thanks to the bioassay results for multiple routes of exposure.
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4.3.7 Risk Characterization Assumptions and Uncertainties
This risk characterization uses peer-reviewed human and rat PBPK models for NMP to make a direct
comparison of internal doses (blood concentrations) predicted in humans in specific exposure scenarios
to internal concentrations that occurred in rats in toxicology studies. The human PBPK models allows
EPA to estimate total human exposures from combined inhalation and dermal exposures associated with
specific exposure scenarios. The rat PBPK model facilitates integration of data from studies using
different routes of exposure. Both models incorporate information on toxicokinetics, providing more
robust exposure estimates and reducing uncertainties about species differences. As described above in
Section 4.3.6, there are several assumptions and sources of uncertainty associated with the PBPK
models, but these uncertainties are expected to have limited impact overall risk estimates.
The peer-reviewed human PBPK models for NMP allow EPA to estimate total human exposures from
combined inhalation and dermal exposures associated with specific exposure scenarios. While the PBPK
models allowed EPA to consider aggregate exposure across exposure routes, EPA did not have
sufficient information to consider aggregate exposure across conditions of use. This is a source of
uncertainty that may underestimate risk.
The relative exposures from dermal, inhalation and vapor through skin can be deduced by comparing the
internal exposure to workers due to inhalation, vapor through skin and dermal liquid contact with
internal exposure to ONUs due to inhalation and vapor through skin exposure (a subtraction technique).
The chronic exposures to workers assuming no protective glove use and ONUs and calculated percent
exposure due to dermal contact with liquid are shown in Table 4-54.
Table 4-54. Comparison of NMP Exposures by Route Showing Percent Exposure Due to Dermal
Contact with Liquid from Chronic NMP Exposures			


Chronic

Percent
Kxposure Due
to l)crm;il
C'ontiict with
Occnp:itioiilo\cs
Chronic
Kxposure
OM '. AI (
(lir m»/L)


Liquid '

Central Tendency
470
0.064
100%

High-End
4500
0.41
100%
Manufacturing of NMP
What-if (Central
Tendency)
40
0.016
100%

What-if (High-
End)
510
0.33
100%

Central Tendency
470
0.064
100%

High-End
4500
0.41
100%
Repackaging
What-if (Central
Tendency)
40
0.016
100%

What-if (High-
End)
510
0.33
100%
Chemical Processing, Excluding
Central Tendency
470
0.069
100%
Formulation
High-End
4500
0.16
100%
Page 341 of 576
-------


Chronic

Percent
Kxposure Due
to l)crm;il
C'ontiict with
Liquid '
()ccup;ition;il Kxposure
Scenario ''
Kxposiliv I.C\el
Kxposure
Worker'. AI (
(lir m»/l.)
Chronic
Kxposure
OM '. AI (


No protect i\c
<>lo\cs
(lir m»/L)

What-if (Central
Tendency)
28
0.020
100%

What-if (High-
End)
60
0.058
100%

Central Tendency
470
0.069
100%
Incorporation into Formulation,
High-End
4500
0.16
100%
Mixture, or Reaction Product -
Drum unloading
What-if (Central
Tendency)
28
0.020
100%

What-if (High-
End)
60
0.058
100%
Incorporation into Formulation,
Mixture, or Reaction Product -
Maintenance, analytical, loading
Central Tendency
22
0.074
100%
High-End
4300
1.4
100%
Metal Finishing - Spray
Central Tendency
76
0.066
100%
application
High-End
2700
1.0
100%
Metal Finishing - Dip
Central Tendency
77
0.21
100%
application
High-End
2700
0.64
100%
Metal Finishing - Brush
Central Tendency
77
0.85
99%
application
High-End
2700
0.92
100%
Application of Paints, Coatings,
Adhesives, and Sealants - Spray
application
Central Tendency
1.4
0.054
96%
High-End
230
0.93
100%
Application of Paints, Coatings,
Adhesives, and Sealants -
Roll/curtain application
Central Tendency
1.4
0.0063
100%
High-End
230
0.055
100%
Application of Paints, Coatings,
Adhesives, and Sealants - Dip
application
Central Tendency
1.6
0.20
88%
High-End
230
0.57
100%
Application of Paints, Coatings,
Adhesives, and Sealants - Brush
application
Central Tendency
2.2
0.84
62%
High-End
230
0.85
100%

Central Tendency
350
0.053
100%

High-End
4500
0.20
100%
Recycling and Disposal
What-if (Central
Tendency)
32
0.015
100%

What-if (High-
End)
110
0.097
100%
Page 342 of 576
-------


Chronic

Percent
Kxposure Due
to Dernuil
C'ontiict with
Liquid '
()ccup;ition;il Kxposure
Scenario ''
Kxposiliv I.C\el
Kxposure
Worker'. AI (
(lir m»/l.)
Chronic
Kxposure
OM '. AI (


No protect i\c
<>lo\cs
(lir m»/L)

Central Tendency
29
6.7
77%
Paint and Coating Removal -
Misc. removal
High-End
810
13
98%
What-if (Central
Tendency)
5.6
0.34
94%

What-if (High-
End)
70
7.2
90%
Paint and coating removal -
Central Tendency
36
0.21
99%
Graffiti removal
High-End
440
0.94
100%
Other Electronics Manufacturing
- Capacitor, resistor, coil,
transformer, and other inductor
mfg.
Central Tendency
77
0.61
99%
High-End
4500
9.2
100%

Central Tendency
120
0.096
100%

High-End
2100
0.26
100%
Semiconductor Manufacturing -
Container handling, small
containers
What-if (Central
Tendency)
1.4
0.0013
100%
What-if (High-
End)
78
0.022
100%
Industry-proposed
(Central
Tendency)
0.017 f
0.0053
69%

Industry-proposed
(High-End)
0.27 f
0.022
92%

Central Tendency
55
0.011
100%

High-End
2100
0.54
100%

What-if (Central
Tendency)
0.28
0.000063
100%
Semiconductor Manufacturing -
Container handling, drums
What-if (High-
End)
24
0.015
100%

Industry-proposed
(Central
Tendency)
0.0064 f
0.00063
90%

Industry-proposed
(High-End)
0.29 f
0.046
84%

Central Tendency
2.6
0.021
99%
Semiconductor Manufacturing -
Fab worker
High-End
21
0.12
99%
What-if (Central
Tendency)
4.5
0.038
99%

What-if (High-
End)
18
0.11
99%
Page 343 of 576
-------


Chronic

Percent
Kxposure Due
to Dernuil
C'ontiict with
Liquid '
()ccup;ition;il Kxposure
Scenario ''
Kxposiliv I.C\el
Kxposure
Worker'. AI (
(lir m»/l.)
Chronic
Kxposure
OM '. AI (


No protect i\c
<>lo\cs
(lir m»/L)
Semiconductor Manufacturing -
Fab worker with container
Industry-proposed
(Central
Tendency)
0.0014 f
0.001 lf
21%
changeout
Industry-proposed
(High-End)
0.016 f
0.010f
38%

Central Tendency
55
0.013
100%

High-End
9200
0.37
100%

What-if (Central
Tendency)
0.98
0.00024
100%
Semiconductor Manufacturing -
Maintenance
What-if (High-
End)
7900
0.34
100%

Industry-proposed
(Central
Tendency)
0.070 f
0.00069
99%

Industry-proposed
(High-End)
2.6 f
0.031
99%

Central Tendency
470
1.0
100%

High-End
4500
1.1
100%

What-if (Central
Tendency)
200
1.0
100%
Semiconductor Manufacturing -
Virgin NMP truck unloading f
What-if (High-
End)
500
1.0
100%

Industry-proposed
(Central
Tendency)
0.22 f
0.045
80%

Industry-proposed
(High-End)
1.9 f
0.14
93%

Central Tendency
350
0.12
100%

High-End
3000
0.23
100%

What-if (Central
Tendency)
150
0.058
100%
Semiconductor Manufacturing -
Waste truck unloading
What-if (High-
End)
370
0.058
100%

Industry-proposed
(Central
Tendency)
0.15 f
0.010
93%

Industry-proposed
(High-End)
1.5 f
0.029
98%
Printing
Central Tendency
3.4
0.023
99%
High-End
20
0.024
100%
Page 344 of 576
-------


Chronic

Percent
Kxposure Due
to Dernuil
C'ontiict with
Liquid '
()ccup;ition;il Kxposure
Scenario ''
Kxposiliv I.C\el
Kxposure
Worker'. AI (
(lir m»/l.)
Chronic
Kxposure
OM '. AI (


No protect i\c
<>lo\cs
(lir m»/L)

What-if (Central
Tendency)
0.73
0.023
97%

What-if (High-
End)
2.0
0.023
99%
Writing
Central Tendency
0.0016
0.00016
90%
High-End
0.0016
0.00032
80%
Soldering
Central Tendency
1.5
0.84
44%
High-End
7.7
0.84
89%

Central Tendency
3.0
1.3
57%
Commercial Automotive
Servicing
High-End
110
8.9
92%
What-if (Central
Tendency)
0.92
0.51
45%

What-if (High-
End)
15
3.3
78%

Central Tendency
470
0.064
100%

High-End
4500
0.95
100%
Laboratory Use
What-if (Central
Tendency)
190
0.037
100%

What-if (High-
End)
490
0.037
100%

Central Tendency
790
0.16
100%
Lithium Ion Cell Manufacturing
High-End
9200
0.35
100%
- Container handling, small
containers
What-if (Central
Tendency)
39
0.013
100%

What-if (High-
End)
200
0.029
100%

Central Tendency
120
0.021
100%
Lithium Ion Cell Manufacturing
- Container handling, drums
High-End
9200
0.63
100%
What-if (Central
Tendency)
8.6
0.0017
100%

What-if (High-
End)
200
0.053
100%

Central Tendency
78
1.0
99%
Lithium Ion Cell Manufacturing
- Cathode coating
High-End
410
8.2
98%
What-if (Central
Tendency)
37
0.99
97%
Page 345 of 576
-------


Chronic

Percent
Kxposure Due
to l)crm;il
C'ontiict with
Liquid '
()ccup;ition;il Kxposure
Scenario ''
Kxposiliv I.C\el
Kxposure
Worker'. AI (
(lir m»/l.)
Chronic
Kxposure
OM '. AI (


No protect i\c
<>lo\cs
(lir m»/L)

What-if (High-
End)
290
8.2
97%

Central Tendency
77
0.46
99%
Lithium Ion Cell Manufacturing
- Cathode slurry mixing
High-End
400
2.0
100%
What-if (Central
Tendency)
9.0
0.45
95%

What-if (High-
End)
20
2.0
90%

Central Tendency
77
0.088
100%
Lithium Ion Cell Manufacturing
- Research and development
High-End
4500
0.93
100%
What-if (Central
Tendency)
46
0.083
100%

What-if (High-
End)
670
0.86
100%

Central Tendency
78
1.2
98%
Lithium Ion Cell Manufacturing
High-End
4500
1.6
100%
- Miscellaneous additional
activities
What-if (Central
Tendency)
19
1.2
94%

What-if (High-
End)
1300
1.5
100%
Cleaning - Dip
Central Tendency
260
0.15
100%
High-End
4400
0.65
100%
Cleaning - Spray / Wipe
Central Tendency
22
0.10
100%
High-End
4200
0.65
100%
Fertilizer Application
Central Tendency
0.66
0.60
9%
High-End
21
1.1
95%
11 Use of PPE is not assumed for ONUs. Percent due to dermal liquid exposure is the worker exposure (inhalation, vapor
through skin and dermal liquid contact) minus ONU exposure (inhalation and vapor through skin exposure) divided by
worker exposure.
b Central tendency means: typical air concentration for most scenarios. High-end means worst-case air concentration for
most scenarios. ONUs are not expected to have direct contact with NMP-containing liquids (see Section 2.4.1.1). These
exposure scenarios do not assume glove use.
0 See tables of exposure estimates in Section 4.2.2.
d See tables of exposure estimates in Section 4.2.3.
e Due to rounding 100% is shown when the inhalation and vapor through skin exposures are small relative to dermal liquid
contact however inhalation and vapor through skin exposures are not zero, see the exposure estimates and MOEs
calculation in Section 4.2.3.
f The SIA industry proposed PBPK runs assume all workers and fab ONUs always wear gloves with PF = 20.
Page 346 of 576
-------
Uncertainty factors used to generate benchmark MOEs used in the risk characterization account for
various sources of uncertainty for each non-cancer POD. In this evaluation, benchmark MOEs for all
scenarios are consistently low, reflecting the relatively low degree of overall uncertainty. As described
in detail in Section 3.2.5.6, there are two uncertainty factors used in this risk characterization across both
acute and chronic exposure scenarios:
•	An interspecies uncertainty/variability factor of 3 (UFa) was applied for animal-to-human
extrapolation to account for toxicodynamic differences between species. Toxicokinetic
differences are incorporated into PBPK models.
•	A default intraspecies uncertainty/variability factor (UFh) of 10 was applied to account for
variation in sensitivity within human populations, including variation across gender, age, health
status, or genetic makeup.
The human populations considered in this final risk evaluation include pregnant women and men and
women of reproductive age in occupational and consumer settings. Although exposures to younger non-
users may be possible, there is insufficient data regarding specific genetic and/or life stage differences
that could impact NMP metabolism and toxicity for further refinement of quantitative risk estimates.
EPA does not have sufficient information to determine whether these uncertainty factors may lead to an
overestimation or underestimation of risk.
4.4 Potentially Exposed or Susceptible Subpopulations
TSCA Section 6(b)(4) requires that EPA conduct a risk evaluation to "determine whether a chemical
substance presents an unreasonable risk of injury to health or the environment, without consideration of
cost or other non-risk factors, including an unreasonable risk to a potentially exposed or susceptible
subpopulation identified as relevant to the risk evaluation by the Administrator, under the conditions of
use." TSCA Section 3(12) states that "the term 'potentially exposed or susceptible subpopulation' means
a group of individuals within the general population identified by the Administrator who, due to either
greater susceptibility or greater exposure, may be at greater risk than the general population of adverse
health effects from exposure to a chemical substance or mixture, such as infants, children, pregnant
women, workers, or the elderly."
As described in Section 3.2.5.3, certain biological characteristics may increase susceptibility to NMP
exposure. The developmental effects identified as a critical human health endpoint for acute exposures
in this risk evaluation are a major concern for pregnant women, the developing fetus, and women who
may become pregnant. The reproductive effects identified as a critical human health endpoint for
chronic exposures may be of concern for all males and females of reproductive age as well as for
infants, children and adolescents whose reproductive systems are still developing. Other populations that
may be more sensitive to the hazards of NMP exposure include people with pre-existing conditions, and
people with lower metabolic capacity due to life stage, genetic variation, or impaired liver function. The
magnitude of the effect of each of these factors alone or in combination on overall risk is unknown.
The acute and chronic PODs used in this risk characterization are based on studies that evaluated effects
of exposure during sensitive life stages in rats. Toxicology data (Exxon. IC)()Q demonstrate early
postnatal body weight decreases and early postnatal death increases at doses that are greater than the
POD derived for decreased fertility from the same study. It is considered likely that these postnatal
outcomes are the result of repeated exposures to NMP. These findings could be considered a surrogate
for analysis of risks to newborns and young infants. Nonetheless , there is uncertainty around the impact
of metabolic differences in newborns and young infants on susceptibility. There is also uncertainty
around susceptibility of infants and young children to potential neurodevelopmental effects of NMP
Page 347 of 576
-------
which have been observed in animals exposed at a high dose, but have not been characterized at lower
doses.
There is insufficient information to support a quantitative analysis of interindividual variability in other
potentially susceptible populations. An uncertainty factor of 10 was applied to account for
interindividual variability across gender, age, health status, genetic makeup, or other factors, but the
actual effect of various factors contributing to biological susceptibility on overall risk is unknown.
As described in Section 2.5.1, EPA identified workers, occupational non-users, consumers of NMP-
containing products and bystanders, including children, as potentially exposed populations. The
exposure factors and hazard endpoints used in this risk evaluation are representative of the most
sensitive subpopulations (i.e., pregnant women or women who might become pregnant, male workers,
and the fetus). The associated risk findings are expected to be protective of children and adolescents. In
developing the risk evaluation, EPA analyzed the reasonably available information to ascertain whether
some human receptor groups may have greater exposure than the general population to the hazard posed
by a chemical. For example, EPA estimated acute exposures for children who may be located near the
consumer user at the time of use and determined that these exposures were below levels that may pose a
risk.
4.5 Aggregate and Sentinel Exposures
Section 2605(b)(4)(F)(ii) of TSCA requires EPA, as a part of the risk evaluation, to describe whether
aggregate or sentinel exposures under the conditions of use were considered and the basis for their
consideration. EPA has defined aggregate exposure as "the combined exposures to an individual from a
single chemical substance across multiple routes and across multiple pathways (40 CFR Section
702.33)."
In many exposure scenarios, NMP exposure occurs through multiple routes. Considering risk from a
single exposure route at a time instead of evaluating total exposures could underestimate risk. This risk
characterization therefore uses PBPK modeling to derive exposure estimates that account for multiple
simultaneous routes of exposure to NMP. Exposure for each condition of use was evaluated by
determining both the exposure to NMP vapor and dermal contact with the liquid. Time profiles of each
type of exposure were estimated for a variety of job categories and household consumer uses, behaviors,
and activity profiles. Vapor exposure is specified by the air concentration encountered as a function of
time during the work day or for 24 h from the start of a household application. Dermal contact is
characterized by the weight fraction (WF) of NMP in the product being used, the surface area of skin
(hands) exposed, and the duration of the dermal exposure. For workplace exposures vapor and dermal
exposures are assumed to be only simultaneous (both end at the end of the task, shift, or work day). For
household exposures vapor exposure typically continues for some time after the application is complete
due to slower air exchange but is lower for the rest of house than the location where the project is done,
with movement of the individual between these zones included. Dermal exposure for consumers is also
limited to the user's direct contact with the product as defined by the duration of use.
The availability of validated rat and human PBPK models that include a dermal compartment PBPK
allowed EPA to integrate absorption from both vapor and liquid contact via three pathways: inhalation
of vapors, absorption of liquid in contact with the skin, and absorption of vapor by exposed skin.
Exhalation and desorption of vapor from skin are also post-exposure elimination pathways. Vapor
absorption through the skin is a minor component of total exposure in most scenarios but is included for
completeness and uses the same dermal resistance as liquid absorption to account for absorption from
un-occluded areas of the face, neck, arms and hands. Use of a face mask is assumed to reduce
Page 348 of 576
-------
concentration inside the mask by a factor of 10 {i.e., the mask has a protection factor, PF = 10) while use
of gloves is assumed to reduce the surface area of the skin exposed to liquid NMP, where the PF was
varied for different quality gloves.
While this assessment evaluates specific COUs based on exposure estimates that incorporate multiple
routes of exposure, it does not consider the potential for aggregate exposures from multiple conditions of
use. For example, it does not evaluate the aggregate risk to individuals exposed via occupational and
consumer uses. This could result in an underestimation of risk.
EPA defines sentinel exposure as "the exposure to a single chemical substance that represents the
plausible upper bound of exposure relative to all other exposures within a broad category of similar or
related exposures (40 CFR Section 702.33)." In this risk evaluation, EPA considered sentinel exposure
in the form of high-end estimates for consumer and occupational exposure scenarios which incorporate
dermal and inhalation exposure, as these routes are expected to present the highest exposure potential
based on details provided for the manufacturing, processing and use scenarios discussed in Section 2.4.
The exposure calculation used to estimate dermal exposure to liquid is conservative for high-end
occupational and consumer scenarios where it assumes full contact of both hands and no protective
glove use.
4.6 Risk Conclusions
4.6.1 Environmental Risk Conclusions
EPA did not identify risks to fish, aquatic invertebrates or algae from NMP releases to ambient water.
EPA used environmental release data from EPA's TRI and a "first-tier" exposure assessment to derive
conservative estimates of NMP surface water concentrations near facilities reporting the highest NMP
water releases. Using the 2015 and 2018 TRI data and EPA's Exposure and Fate Assessment Screening
Tool (EFAST, Version 2014) EPA predicted NMP surface water concentrations for the acute and
chronic scenarios, respectively. Table 4-2 and Table 4-3 summarize the RQs and days of exceedance
used to characterize risk to aquatic organisms from acute and chronic exposures to NMP. Based on these
values (acute RQs all < 1, and chronic RQs < 1 or RQ > 1 but < 20 days of exceedance) risk to aquatic
organisms from acute or chronic exposure to NMP in surface water was not indicated.
During problem formulation, EPA also considered fate properties of NMP and performed first tier
analysis of environmental risks from NMP exposure through sediment, land-applied biosolids, and
ambient air. EPA did not identify environmental risks from these pathways. As described in problem
formulation, NMP is not expected to adsorb to sediment due to its water solubility (>1000 g/L) and low
partitioning to organic matter (Log Koc = 0.9). No ecotoxicity studies were identified for sediment
dwelling organisms; however, the reasonably available hazard data indicate a low concern for NMP
toxicity to aquatic organisms and plants. Because NMP toxicity to sediment-dwelling invertebrates is
expected to be comparable to that of aquatic invertebrates and NMP is unlikely to accumulate in
sediment, a low risk concern is expected for this environmental compartment.
During problem formulation, EPA did not identify risks from land releases of NMP, including those that
may result from land application of biosolids. NMP exhibits high water solubility and limited potential
for adsorption to organic matter; therefore, land releases will ultimately partition to the aqueous phase
{i.e., biosolids associated wastewater and soil pore water) upon release into the environment. Because
NMP readily biodegrades in environments with active microbial populations, NMP residues that remain
following wastewater treatment are not expected to persist. NMP concentrations in biosolids-associated
water are expected to decrease, primarily via aerobic degradation, during transport, processing
Page 349 of 576
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(including dewatering), handling, and land application of biosolids (which may include spraying).
Migration of NMP between ground water and surface water has not been documented but may be
mitigated by abiotic and biotic degradation in the water column.
In addition, the bioaccumulation potential for NMP are expected to be low (BCF = 3.16, BAF= 0.9; see
Table 2-1). Negligible volatilization of NMP is expected from moist soil and wastewater. Because NMP
exhibits low volatility and readily biodegrades under aerobic conditions, the concentration in ambient air
is unlikely to reach levels that would present a risk concern for terrestrial organisms. In a quantitative
analyses completed by EPA in support of the derivation of Ecological Screening Levels (Eco-SSLs) for
soils exposures and risks associated with inhalation of chemical contamination in soils for terrestrial
wildlife are negligible compared to oral exposures (incidental ingestion and dietary) (ranged from
0.0001% to 0.1022% of the oral risks, and averaged 0.0172% of oral risks) (U.S. EPA. 2005).
4.6.2 Human Health Risk Conclusions
4.6.1.1 Summary of Risk Estimates for Workers and ONUs
Table 4-55 summarizes the acute and chronic risks of combined inhalation, dermal and vapor-through-
skin exposures for all occupational exposure scenarios. Exposure and risk estimates for each
occupational exposure scenario are described in more detail in Section 2.4.1.2 and Section 4.2.2,
respectively. Risk estimates for each condition of use are shown for use without gloves or respirators,
with gloves or respirators alone, or with both gloves and respirators. For PPE use, risk estimates are
primarily shown for glove PFs of 5 and respirator APFs of 10, unless otherwise indicated in footnotes.
Risk estimates that indicate risk relative to the benchmark MOE {i.e., non-cancer MOEs that are below
the benchmark MOE) are highlighted by shading the cell.
In general, the conditions of use that present the lowest concern for human health risks include those that
incorporate a high level of containment or small-scale use of NMP. The conditions of use which involve
a lower level of containment, elevated temperatures or high intensity use show greater risk even when
PPE is considered. For example, high-end occupational exposure estimates for NMP use in cleaning,
metal finishing, electronic parts manufacturing, automotive servicing, and use in (or removal of) paints,
coatings, adhesives and sealants show risks that are not mitigated via glove use.
Risk estimates for ONUs indicate risk relative to the benchmark MOEs for several conditions of use,
including paint and coating removal, commercial automotive servicing, and some electronics parts
manufacturing. ONUs are assumed not to wear respirators.
EPA has high confidence in the POD used to evaluate risks associated with acute exposure and medium
confidence in the POD used to evaluate chronic NMP exposure. As discussed in Section 3.2.6, post-
implantation loss (resorptions and fetal mortality) and reduced fertility were considered relevant hazards
for evaluating risks following acute and chronic NMP exposure, respectively. While there is some
uncertainty regarding temporal windows of vulnerability for developmental toxicity and whether the
timing of a single exposure can produce a permanent adverse effect on human development, EPA
considers the post-implantation loss endpoint associated with NMP exposure to be applicable to acute
exposures. The reasonably available literature suggests that a single developmental exposure may have
sustained effects on the conceptus. Fetal mortality represents the most severe endpoint associated with
the developmental hazard profile for NMP. Reduced fertility in males is the most sensitive effect
associated with chronic exposures. The chronic POD based on effects on reduced male fertility is
supported by effects on female fecundity and developmental toxicity in a similar dose range.
Page 350 of 576
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Table 4-55. Summary of Risk Estimates for Aggregate Exposures to Workers by Condition of Use
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Section 2.4.1.2.1 -
Manufacturing
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
32
32
2.8
2.8
High-
End
5
10
10
0.6
0.6
Central
Tendency
10
65
65
6.0
6.0
High-
End
10
23
23
1.3
1.3
ONU
Central
Tendency
1
-
-
2,870
NA
High-
End
1
-
-
443
NA
Manufacture/
Import
Import
Section 2.4.1.2.2 -
Repackaging
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
32
32
2.8
2.8
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,870
NA
High-
End
1
-
-
443
NA
Page 351 of 576
-------
l.ili- Cjolc
SI iik/
(
Sul>c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sci'iiiirio
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;il»r
(API 10) '¦
Cliroiii
lii-nclintiirl
No
Ui's|)ir;iior
l* Mor.s
W illi
Ui'spiniior
(AIM 10) '¦
Processing/
Processing as a
reactant or
intermediate
Intermediate in Plastic
Material and Resin
Manufacturing
Section 2.4.1.2.3 -
Chemical Processing,
Excluding
Formulation
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Other Non-Incorporative
Processing
Central
Tendency
5
32
32
2.8
2.8
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,642
NA
High-
End
1
-
-
1,130
NA
Processing/
Incorporated
into
formulation,
mixture or
reaction
product
Adhesives and sealant
chemicals in Adhesive
Manufacturing
Section 2.4.1.2.4 -
Incorporation into
Formulation, Mixture,
or Reaction Product
(unloading drums)
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
Anti-adhesive agents in
Printing and Related
Support Activities
High-
End
1
1.1
1.1
0.04
0.04
Paint additives and coating
additives not described by
other codes in Paint and
Coating Manufacturing;
and Print Ink
Manufacturing
Central
Tendency
5
32
32
2.8
2.8
Processing aids not
otherwise listed in Plastic
Material and Resin
Manufacturing
High-
End
5
10
10
0.6
0.6
Page 352 of 576
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l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sci'iiiirio

l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Cliroiii
licnchnuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Solvents (for cleaning or
degreasing) in Non-
Metallic Mineral Product
Manufacturing; Machinery
Manufacturing; Plastic
Material and Resin;
Manufacturing; Primary
Metal Manufacturing;
Soap, Cleaning Compound
and Toilet Preparation
Manufacturing;
Transportation Equipment
Manufacturing; All Other
Chemical Preparation
Manufacturing; Printing
and Related Support
Activities; Services;
Wholesale and Retail
Trade
ONU
Central
Tendency
1
-
-
2,642
NA
Surface active agents in
Soap, Cleaning Compound
and Toilet Preparation
Manufacturing
High-
End
1
-
-
1,130
NA
Plating agents and surface
treating agents in
Fabricated Metal Product
Manufacturing
Section 2.4.1.2.4 -
Incorporation into
Formulation, Mixture,
or Reaction Product
(miscellaneous)
Worker
Central
Tendency
1
91
91
8.4
8.4
Solvents (which become
part of product formulation
or mixture) in Electrical
Equipment, Appliance and
Component
Manufacturing; Other
Manufacturing; Paint and
Coating Manufacturing;
Print Ink Manufacturing;
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
459
465
43
43
High-
End
5
10
10
0.6
0.6
Page 353 of 576
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l.ili- Cjolc
SI iik/
Sul>c:iU-<>»n
Soap, Cleaning Compound
and Toilet Preparation
Manufacturing;
Transportation Equipment
Manufacturing; All Other
Chemical Product and
Preparation Manufacturing;
Printing and Related
Support Activities;
Wholesale and Retail
Trade
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sci'iiiirio
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;il»r
(API III) '¦
Cliroiii
lii-nclintiirl
No
Ui's|)ir;iior
l* Mor.s
W illi
Ui'spiniior
(AIM 10) '¦






Other uses in Oil and Gas
Drilling, Extraction and
Support Activities; Plastic
Material and Resin
Manufacturing; Services
ONU
Central
Tendency
1
-
-
2,487
NA
High-
End
1
-
-
133
NA
Processing/
Incorporated
into article
Lubricants and lubricant
additives in Machinery
Manufacturing
Section 2.4.1.2.5 -
Metal Finishing
(Spray Application)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.7
1.7
0.1
0.1
Central
Tendency
5
143
144
13
13
High-
End
5
14
14
0.8
0.8
ONU
Central
Tendency
1
-
-
2,763
NA
High-
End
1
-
-
184
NA
Section 2.4.1.2.5 -
Metal Finishing
Pip)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.7
1.7
0.1
0.1
Page 354 of 576
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l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sci'iiiirio
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;il»r
(API III) '¦
Clironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Central
Tendency
5
142
143
13
13
High-
End
5
14
14
0.8
0.8
ONU
Central
Tendency
1
-
-
859
NA
High-
End
1
-
-
286
NA
Section 2.4.1.2.5 -
Metal Finishing
(Brush)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.7
1.7
0.1
0.1
Central
Tendency
5
135
141
12
13
High-
End
5
14
14
0.8
0.8
ONU
Central
Tendency
1
-
-
215
NA
High-
End
1
-
-
199
NA
Paint additives and coating
additives not described by
other codes in
Transportation Equipment
Manufacturing
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Spray
Application)
Worker
Central
Tendency
1
1,395
1,436
130
134
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
6,070
6,929
567
645
High-
End
5
81
82
4.8
4.9
ONU
Central
Tendency
1
-
-
3,394
NA
Page 355 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
(lironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
1
-
-
197
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants
(Roll/Curtain)
Worker
Central
Tendency
1
1,445
1,450
134
135
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
7,110
7,229
661
672
High-
End
5
83
83
4.9
4.9
ONU
Central
Tendency
1
-
-
28,925
NA
High-
End
1
-
-
3,329
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Dip)
Worker
Central
Tendency
1
1,261
1,396
118
130
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
4,182
6,142
394
576
High-
End
5
81
83
4.8
4.9
ONU
Central
Tendency
1
-
-
911
NA
High-
End
1
-
-
319
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Brush)
Worker
Central
Tendency
1
890
1,244
84
117
High-
End
1
14
14
0.8
0.8
Page 356 of 576
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l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sci'iiiirio
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API 10) '¦
Clironi
licnchnuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Central
Tendency
5
1,780
4,118
169
393
High-
End
5
81
82
4.8
4.9
ONU
Central
Tendency
1
-
-
218
NA
High-
End
1
-
-
214
NA
Solvents (which become
part of product formulation
or mixture), including in
Textiles, Apparel and
Leather Manufacturing
Section 2.4.1.2.4 -
Incorporation into
Formulation, Mixture,
or Reaction Product
(unloading drums)
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
Worker
High-
End
1
1.1
1.1
0.04
0.04
Worker
Central
Tendency
5
32
32
2.8
2.8
Worker
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,642
NA
ONU
High-
End
1
-
-
1,130
NA
Section 2.4.1.2.4 -
Incorporation into
Formulation, Mixture,
or Reaction Product
(miscellaneous)
Worker
Central
Tendency
1
91
91
8.4
8.4
Worker
High-
End
1
1.1
1.1
0.04
0.04
Worker
Central
Tendency
5
459
465
43
43
Worker
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,487
NA
Page 357 of 576
-------
l.ili- Cjolc
SI iik/
Sul>c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io

l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;ii»r
(API 10) '¦
(lironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
ONU
High-
End
1
-
-
133
NA
Processing/
Incorporated
into article
Other, including in Plastic
Product Manufacturing
Section 2.4.1.2.3 -
Chemical Processing,
Excluding
Formulation
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
32
32
2.8
2.8
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,642
NA
High-
End
1
-
-
1,130
NA
Processing/
Recycling
Recycling
Section 2.4.1.2.7 -
Recycling and
Disposal
Worker
Central
Tendency
1
6.8
6.8
0.5
0.5
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
40
40
3.6
3.6
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
3,432
NA
High-End
1
-
-
926
NA
Processing/
Repackaging
Wholesale and Retail
Trade
Section 2.4.1.2.2 -
Repackaging
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Page 358 of 576
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l.ili- Cjolc
SI iik/
Sul>c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Cliroiii
licnchnuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Central
Tendency
5
32
32
2.8
2.8
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,870
NA
High-
End
1
-
-
443
NA
Distribution in
Commerce/
Distribution
Distribution in commerce
Distribution in
commerce
Worker
Central
Tendency
N/A - Not Separately addressed; exposures/releases from distribution are
considered within each condition of use
Industrial, and
commercial
use/ Paint and
coatings
Paint and coating removers
Section 2.4.1.2.8 -
Removal of Paints,
Coatings, Adhesives,
and Sealants (Misc.
Removal)
Worker
Central
Tendency
1
70
85
6.4
7.9
Adhesives removers
High-
End
1
4.4
4.6
0.2
0.2
Central
Tendency
5
182
339
17
32
High-
End
5
27
31
1.6
1.8
ONU
Central
Tendency
1
-
-
27
NA
High-
End
1
-
-
14
NA
Section 2.4.1.2.8 -
Removal of Paints,
Coatings, Adhesives,
and Sealants (Graffiti
Removal)
Worker
Central
Tendency
1
55
56
5.0
5.1
High-
End
1
7.7
7.7
0.4
0.4
Central
Tendency
5
280
286
26
26
High-
5
49
49
2.9
2.9
Page 359 of 576
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l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;il»r
(API III) '¦
Clironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
End





ONU
Central
Tendency
1
-
-
868
NA
High-
End
1
-
-
194
NA
Lacquers, stains, varnishes,
primers and floor finishes
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Spray
Application)
Worker
Central
Tendency
1
1,395
1,436
130
134
Powder coatings (surface
preparation)
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
6,070
6,929
567
645
High-
End
5
81
82
4.8
4.9
ONU
Central
Tendency
1
-
-
3,394
NA
High-
End
1
-
-
197
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants
(Roll/Curtain)
Worker
Central
Tendency
1
1,445
1,450
134
135
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
7,110
7,229
661
672
High-
End
5
83
83
4.9
4.9
ONU
Central
Tendency
1
-
-
28,925
NA
High-
End
1
-
-
3,329
NA
Page 360 of 576
-------
l.ili- Cjolc
SI iik/
(
Sul>c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Cliroiii
licnchnuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Dip)
Worker
Central
Tendency
1
1,261
1,396
118
130
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
4,182
6,142
394
576
High-
End
5
81
83
4.8
4.9
ONU
Central
Tendency
1
-
-
911
NA
High-
End
1
-
-
319
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Brush)
Worker
Central
Tendency
1
890
1,244
84
117
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
1,780
4,118
169
393
High-
End
5
81
82
4.8
4.9
ONU
Central
Tendency
1
-
-
218
NA
High-
End
1
-
-
214
NA
Industrial, and
commercial
use/ Paint
additives and
coating
additives not
Use in Computer and
Electronic Product
Manufacturing in
Electronic Parts
Manufacturing a
Section 2.4.1.2.9 -
Other Electronics
Manufacturing
(Capacitor, Resistor,
Coil, Transformer,
and Other Inductor
Manufacturing)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
137
142
13
13
Page 361 of 576
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l.ili- Cjolc
SI iik/
described by
other codes
Sul>c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Clironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
5
9.6
9.9
0.5
0.6
Central
Tendency
10
266
284
25
26
High-
End
10
21
22
1.2
1.3
ONU
Central
Tendency
1
-
-
299
NA
High-
End
1
-
-
20
NA
Use in Computer and
Electronic Product
Manufacturing in
Semiconductor
Manufacturing a
Section 2.4.1.2.10 -
Semiconductor
Manufacturing
(Container Handling,
Small Containers)
Worker
Central
Tendency
1
23
23
1.5
1.5
High-
End
1
2.3
2.3
0.1
0.1
Central
Tendency
5
125
125
8.7
8.8
High-
End
5
21
21
0.9
0.9
Central
Tendency
10
252
253
18
18
High-
End
10
47
47
2.1
2.1
Central
Tendency
20
504
510
35
36
High-
End
20
98
98
4.3
4.3
ONU
Central
Tendency
1
-
-
1,909
NA
High-
End
1
-
-
704
NA
Page 362 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
(lironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Section 2.4.1.2.10 -
Semiconductor
Manufacturing
(Container Handling,
Drums)
Worker
Central
Tendency
1
48
48
3.3
3.3
High-
End
1
2.3
2.3
0.1
0.1
Central
Tendency
5
253
253
18
18
High-
End
5
21
21
0.9
0.9
Central
Tendency
10
508
509
36
36
High-
End
10
46
47
2.0
2.1
Central
Tendency
20
1,020
1,021
72
72
High-
End
20
97
98
4.3
4.3
ONU
Central
Tendency
1
-
-
15,989
NA
High-
End
1
-
-
336
NA
Section 2.4.1.2.10 -
Semiconductor
Manufacturing (Fab
Worker, 75% Body
Coverage)
Worker
Central
Tendency
1
1,013
1,019
71
72
High-
End
1
198
199
8.7
8.8
Central
Tendency
5
4,916
5,067
346
356
High-
End
5
988
1,011
44
44
Central
Tendency
10
9,461
10,037
667
707
Page 363 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
r.\i)»suiv
I.IM-I
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Clironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
10
1,925
2,012
85
89
Central
Tendency
20
17,586
19,683
1,242
1,387
High-
End
20
3,646
3,971
161
175
ONU
Central
Tendency
1
-
-
8,540
NA
High-
End
1
-
-
1,465
NA
Section 2.4.1.2.10 -
Semiconductor
Manufacturing
(Maintenance)
Worker
Central
Tendency
1
48
48
3.3
3.3
High-
End
1
0.6
0.6
0.02
0.02
Central
Tendency
5
252
253
18
18
High-
End
5
7.9
8.0
0.3
0.3
Central
Tendency
10
508
509
36
36
High-
End
10
19
19
0.8
0.8
Central
Tendency
20
1,020
1,021
72
72
High-
End
20
43
43
1.9
1.9
ONU
Central
T endency
1
-
-
14,630
NA
High-
End
1
-
-
492
NA
Page 364 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sci'iiiirio
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Clironi
lii-nclintiirl
No
Ui's|)ir;iior
l* Mor.s
W illi
Ui'spiniior
(AIM 10) '¦
Section 2.4.1.2.10 -
Semiconductor
Manufacturing
(Waste Truck
Loading)
Worker
Central
Tendency
1
6.8
6.8
0.5
0.5
High-
End
1
1.5
1.5
0.1
0.1
Central
Tendency
5
40
40
3.6
3.6
High-
End
5
13
13
0.7
0.7
Central
Tendency
10
81
82
7.4
7.5
High-
End
10
29
29
1.7
1.7
Central
Tendency
20
165
165
15
15
High-
End
20
61
62
3.6
3.6
ONU
Central
Tendency
1
-
-
1,584
NA
High-
End
1
-
-
792
NA
Use in Construction,
Fabricated Metal Product
Manufacturing, Machinery
Manufacturing, Other
Manufacturing, Paint and
Coating Manufacturing,
Primary Metal
Manufacturing,
Transportation Equipment
Manufacturing, Wholesale
and Retail Trade
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Spray
Application)
Worker
Central
Tendency
1
1,395
1,436
130
134
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
6,070
6,929
567
645
High-
End
5
81
82
4.8
4.9
ONU
Central
Tendency
1
-
-
3,394
NA
Page 365 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
(lironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
1
-
-
197
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants
(Roll/Curtain)
Worker
Central
Tendency
1
1,445
1,450
134
135
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
7,110
7,229
661
672
High-
End
5
83
83
4.9
4.9
ONU
Central
Tendency
1
-
-
28,925
NA
High-
End
1
-
-
3,329
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Dip)
Worker
Central
Tendency
1
1,261
1,396
118
130
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
4,182
6,142
394
576
High-
End
5
81
83
4.8
4.9
ONU
Central
Tendency
1
-
-
911
NA
High-
End
1
-
-
319
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Brush)
Worker
Central
Tendency
1
890
1,244
84
117
High-
End
1
14
14
0.8
0.8
Page 366 of 576
-------
l.ili- Cjolc
SI iik/
(
Sul>c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Cliroiii
licnchnuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Central
Tendency
5
1,780
4,118
169
393
High-
End
5
81
82
4.8
4.9
ONU
Central
Tendency
1
-
-
218
NA
High-
End
1
-
-
214
NA
Industrial, and
commercial
use/ Solvents
(for cleaning or
de greasing)
Use in Electrical
Equipment Appliance and
Component
Manufacturing a
Section 2.4.1.2.9 -
Other Electronics
Manufacturing
(Capacitor, Resistor,
Coil, Transformer,
and Other Inductor
Manufacturing)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
137
142
13
13
High-
End
5
9.6
9.9
0.5
0.6
Central
Tendency
10
266
284
25
26
High-
End
10
21
22
1.2
1.3
ONU
Central
Tendency
1
-
-
299
NA
High-
End
1
-
-
20
NA
Use in Electrical
Equipment Appliance and
Component Manufacturing
in Semiconductor
Manufacturing a
Section 2.4.1.2.10 -
Semiconductor
Manufacturing
(Container Handling,
Small Containers)
Worker
Central
Tendency
1
23
23
1.5
1.5
High
-End
1
2.3
2.3
0.1
0.1
Central
Tendency
5
125
125
8.7
8.8
Page 367 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
(lironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
5
21
21
0.9
0.9
Central
Tendency
10
252
253
18
18
High-
End
10
47
47
2.1
2.1
Central
Tendency
20
504
510
35
36
High-
End
20
98
98
4.3
4.3
ONU
Central
Tendency
1
-
-
1,909
NA
High-
End
1
-
-
704
NA
Section 2.4.1.2.10 -
Semiconductor
Manufacturing
(Container Handling,
Drums)
Worker
Central
Tendency
1
48
48
3.3
3.3
High-
End
1
2.3
2.3
0.1
0.1
Central
Tendency
5
253
253
18
18
High-
End
5
21
21
0.9
0.9
Central
Tendency
10
508
509
36
36
High-
End
10
46
47
2.0
2.1
Central
Tendency
20
1,020
1,021
72
72
High-
End
20
97
98
4.3
4.3
Page 368 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io

l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
(lironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
ONU
Central
Tendency
1
-
-
15,989
NA
High-
End
1
-
-
336
NA
Section 2.4.1.2.10 -
Semiconductor
Manufacturing (Fab
Worker, 75% Body
Coverage)
Worker
Central
Tendency
1
1,013
1,019
71
72
High-
End
1
198
199
8.7
8.8
Central
Tendency
5
4,916
5,067
346
356
High-
End
5
988
1,011
44
44
Central
Tendency
10
9,461
10,037
667
707
High-
End
10
1,925
2,012
85
89
Central
Tendency
20
17,586
19,683
1,242
1,387
High-
End
20
3,646
3,971
161
175
ONU
Central
Tendency
1
-
-
8,540
NA
High-
End
1
-
-
1,465
NA
Section 2.4.1.2.10 -
Semiconductor
Manufacturing
(Maintenance)
Worker
Central
Tendency
1
48
48
3.3
3.3
High-
End
1
0.6
0.6
0.02
0.02
Central
Tendency
5
252
253
18
18
Page 369 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
(lironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
5
7.9
8.0
0.3
0.3
Central
Tendency
10
508
509
36
36
High-
End
10
19
19
0.8
0.8
Central
Tendency
20
1,020
1,021
72
72
High-
End
20
43
43
1.9
1.9
ONU
Central
Tendency
1
-
-
14,630
NA
High-
End
1
-
-
492
NA
Section 2.4.1.2.10 -
Semiconductor
Manufacturing
(Virgin NMP Truck
Unloading)
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
31
31
2.8
2.8
High-
End
5
10
10
0.6
0.6
Central
Tendency
10
63
65
5.8
5.9
High-
End
10
23
23
1.3
1.3
Central
Tendency
20
125
131
11
12
High-
End
20
48
49
2.8
2.9
Page 370 of 576
-------
l.ili- Cjolc
SI iik/
(
Sul>c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io

l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
(lironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
ONU
Central
Tendency
1
-
-
179
NA
High-
End
1
-
-
170
NA
Section 2.4.1.2.10 -
Semiconductor
Manufacturing
(Waste Truck
Loading)
Worker
Central
Tendency
1
6.8
6.8
0.5
0.5
High-
End
1
1.5
1.5
0.1
0.1
Central
Tendency
5
40
40
3.6
3.6
High-
End
5
13
13
0.7
0.7
Central
Tendency
10
81
82
7.4
7.5
High-
End
10
29
29
1.7
1.7
Central
Tendency
20
165
165
15
15
High-
End
20
61
62
3.6
3.6
ONU
Central
Tendency
1
-
-
1,584
NA
High-
End
1
-
-
792
NA
Industrial, and
commercial
use/ Ink, toner,
and colorant
products
Printer Ink
Section 2.4.1.2.11 -
Printing and Writing:
Printing
Worker
Central
Tendency
1
575
578
53
54
High-
End
1
158
158
9.4
9.4
Central
Tendency
5
2,812
2,882
261
268
Page 371 of 576
-------
l.ili- Cjolc
SI iik/
(
Sul>c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Clironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
5
802
805
48
48
ONU
Central
Tendency
1
-
-
7,888
NA
High-
End
1
-
-
7,520
NA
Inks in writing equipment
Section 2.4.1.2.11 -
Printing and Writing:
Writing
Worker
Central
Tendency
1
470,210
470,210
116,016
116,016
High-
End
1
470,210
470,210
116,016
116,016
Central
Tendency
5
2,357,126
2,357,126
578,404
578,404
High-
End
5
2,357,126
2,357,126
578,404
578,404
ONU
Central
Tendency
1
-
-
1,159,299
NA
High-
End
1
-
-
580,042
NA
Industrial, and
commercial
use/ Processing
aids, specific to
petroleum
production
Petrochemical
Manufacturing
Section 2.4.1.2.3 -
Chemical Processing,
Excluding
Formulation
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
32
32
2.8
2.8
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,642
NA
High-
End
1
-
-
1,130
NA
Page 372 of 576
-------
l.ili- Cjolc
SI iik/
(
Sul>c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sci'iiiirio
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;il»r
(API 10) '¦
Cliroiii
lii-nclintiirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Industrial, and
commercial
use/ Other Uses
Other uses in Oil and Gas
Drilling, Extraction and
Support Activities
Section 2.4.1.2.3 -
Chemical Processing,
Excluding
Formulation
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
32
32
2.8
2.8
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,642
NA
High-
End
1
-
-
1,130
NA
Functional Fluids (closed
systems)
Section 2.4.1.2.3 -
Chemical Processing,
Excluding
Formulation
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
32
32
2.8
2.8
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,642
NA
High-
End
1
-
-
1,130
NA
Industrial, and
commercial
use/ Adhesives
and sealants
Adhesives and sealant
chemicals including
binding agents
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Spray
Application)
Worker
Central
Tendency
1
1,395
1,436
130
134

High-
End
1
14
14
0.8
0.8
Page 373 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Single component glues
and adhesives, including
lubricant adhesives
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Clironi
licnchnuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Central
Tendency
5
6,070
6,929
567
645
Two-component glues and
adhesives, including some
resins
High-
End
5
81
82
4.8
4.9
ONU
Central
Tendency
1
-
-
3,394
NA
High-
End
1
-
-
197
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants
(Roll/Curtain)
Worker
Central
Tendency
1
1,445
1,450
134
135
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
7,110
7,229
661
672
High-
End
5
83
83
4.9
4.9
ONU
Central
Tendency
1
-
-
28,925
NA
High-
End
1
-
-
3,329
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Dip)
Worker
Central
Tendency
1
1,261
1,396
118
130
High-End
1
14
14
0.8
0.8
Central
Tendency
5
4,182
6,142
394
576
High-
End
5
81
83
4.8
4.9
ONU
Central
Tendency
1
-
-
911
NA
Page 374 of 576
-------
l.ili- Cjolc
SI iik/
(
Sul>c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
(lironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
1
-
-
319
NA
Section 2.4.1.2.6 -
Application of Paints,
Coatings, Adhesives,
and Sealants (Brush)
Worker
Central
Tendency
1
890
1,244
84
117
High-
End
1
14
14
0.8
0.8
Central
Tendency
5
1,780
4,118
169
393
High-
End
5
81
82
4.8
4.9
ONU
Central
Tendency
1
-
-
218
NA
High-
End
1
-
-
214
NA
Industrial, and
commercial
use/ Other uses
Soldering materials
Section 2.4.1.2.12 -
Soldering
Worker
Central
Tendency
1
1,285
2,180
122
207
High-
End
1
400
436
24
26
Central
Tendency
5
2,030
5,747
194
555
High-
End
5
1,398
1,964
84
118
ONU
Central
Tendency
1
-
-
218
NA
High-
End
1
-
-
218
NA
Anti-freeze and de-icing
products
Section 2.4.1.2.13 -
Commercial
Automotive Servicing
Worker
Central
Tendency
1
651
962
62
91
Automotive care products
High-
End
1
28
29.8
1.6
1.8
Page 375 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;il»r
(API III) '¦
Clironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Lubricants and greases
Central
Tendency
5
1,207
2,986
115
286
High
-End
5
111
149
6.7
8.9
ONU
Central
Tendency
1
-
-
141
NA
High-
End
1
-
-
21
NA
Metal products not covered
elsewhere
Section 2.4.1.2.5 -
Metal Finishing
(Spray Application)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.7
1.7
0.1
0.1
Central
Tendency
5
143
144
13
13
High-
End
5
14
14
0.8
0.8
ONU
Central
Tendency
1
-
-
2,763
NA
High-
End
1
-
-
184
NA
Section 2.4.1.2.5 -
Metal Finishing (Dip)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.7
1.7
0.1
0.1
Central
Tendency
5
142
143
13
13
High-
End
5
14
14
0.8
0.8
ONU
Central
Tendency
1
-
-
859
NA
Page 376 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;il»r
(API III)
(lironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
1
-
-
286
NA
Section 2.4.1.2.5 -
Metal Finishing
(Brush)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.7
1.7
0.1
0.1
Central
Tendency
5
135
141
12
13
High-
End
5
14
14
0.8
0.8
ONU
Central
Tendency
1
-
-
215
NA
High-
End
1
-
-
199
NA
Lubricant and lubricant
additives, including
hydrophilic coatings
Section 2.4.1.2.5 -
Metal Finishing
(Spray Application)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.7
1.7
0.1
0.1
Central
Tendency
5
143
144
13
13
High-
End
5
14
14
0.8
0.8
ONU
Central
Tendency
1
-
-
2,763
NA
High-
End
1
-
-
184
NA
Section 2.4.1.2.5 -
Metal Finishing (Dip)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.7
1.7
0.1
0.1
Page 377 of 576
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l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;il»r
(API III) '¦
Clironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Central
Tendency
5
142
143
13
13
High-
End
5
14
14
0.8
0.8
ONU
Central
Tendency
1
-
-
859
NA
High-
End
1
-
-
286
NA
Section 2.4.1.2.5 -
Metal Finishing
(Brush)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.7
1.7
0.1
0.1
Central
Tendency
5
135
141
12
13
High-
End
5
14
14
0.8
0.8
ONU
Central
Tendency
1
-
-
215
NA
High-
End
1
-
-
199
NA
Laboratory chemicals
Section 2.4.1.2.14 -
Laboratory Use
Worker
Central
Tendency
1
5.3
5.3
0.4
0.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
32
32
2.8
2.8
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
2,847
NA
Page 378 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API 10) '¦
(lironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
1
-
-
193
NA
Lithium Ion Battery
Manufacturing a
Section 2.4.1.2.15 -
Lithium Ion Cell
Manufacturing (Small
Container Handling)
Worker
Central
Tendency
1
4.1
4.1
0.2
0.2
High-
End
1
0.6
0.6
0.02
0.02
Central
Tendency
5
27
27
1.9
1.9
High-
End
5
8.0
8.0
0.3
0.3
Central
Tendency
10
58
58
4.0
4.0
High-
End
10
19
19
0.8
0.8
Central
Tendency
20
119
119
8.3
8.3
High-
End
20
43
43
1.9
1.9
ONU
Central
Tendency
1
-
-
1,172
NA
High-
End
1
-
-
527
NA
Section 2.4.1.2.15 -
Lithium Ion Cell
Manufacturing (Drum
Handling)
Worker
Central
Tendency
1
23
23
1.5
1.5
High-
End
1
0.6
0.6
0.02
0.02
Central
Tendency
5
125
125
8.8
8.8
High-
End
5
7.9
8.0
0.3
0.3
Page 379 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Clironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Central
Tendency
10
254
254
18
18
High-
End
10
19
19
0.8
0.8
Central
Tendency
20
511
511
36
36
High-
End
20
43
43
1.9
1.9
ONU
Central
Tendency
1
-
-
8,792
NA
High-
End
1
-
-
290
NA
Section 2.4.1.2.15 -
Lithium Ion Cell
Manufacturing
(Cathode Coating)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
8.1
8.3
0.4
0.5
Central
Tendency
5
134
141
12
13
High-
End
5
46
51
2.7
3.0
Central
Tendency
10
253
280
23
26
High-
End
10
84
102
5.0
6.1
Central
Tendency
20
450
543
42
51
High-
End
20
139
195
8.4
12
ONU
Central
Tendency
1
-
-
183
NA
Page 380 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
(lironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
1
-
-
22
NA
Section 2.4.1.2.15 -
Lithium Ion Cell
Manufacturing
(Cathode Slurry
Mixing)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
8.3
8.4
0.5
0.5
Central
Tendency
5
139
143
13
13
High-
End
5
51
53
3.0
3.1
Central
Tendency
10
272
285
25
26
High-
End
10
102
108
6.1
6.4
Central
Tendency
20
514
564
48
52
High-
End
20
195
216
12
13
ONU
Central
Tendency
1
-
-
401
NA
High-
End
1
-
-
93
NA
Section 2.4.1.2.15 -
Lithium Ion Cell
Manufacturing
(Research and
Development)
Worker
Central
Tendency
1
27
27
2.4
2.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
143
143
13
13
High-
End
5
10
10
0.6
0.6
Page 381 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi-cu|>:ilioiiiil
I'.\|)omiiv Sciiiiii'io
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Clironi
Itcmhnuirl
No
Ui's|)ir;iior
l* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Central
Tendency
10
287
289
27
27
High-
End
10
23
23
1.3
1.3
Central
Tendency
20
570
579
53
54
High-
End
20
48
49
2.9
2.9
ONU
Central
Tendency
1
-
-
2,077
NA
High-
End
1
-
-
197
NA
Section 2.4.1.2.15 -
Lithium Ion Cell
Manufacturing
(Miscellaneous)
Worker
Central
Tendency
1
26
27
2.3
2.4
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
131
140
12
13
High-
End
5
10
10
0.6
0.6
Central
Tendency
10
245
277
23
26
High-
End
10
22
23
1.3
1.3
Central
Tendency
20
426
534
40
50
High-
End
20
48
49
2.8
2.9
ONU
Central
T endency
1
-
-
147
NA
Page 382 of 576
-------
l.ili- Cjolc
SI iik/
Sul)c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sci'iiiirio
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|)ir;il»r
(API 10) '¦
(lironi
licnclinuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
High-
End
1
-
-
115
NA
Cleaning and furniture care
products, including wood
cleaners, gasket removers
Section 2.4.1.2.16 -
Cleaning (Dip
Cleaning)
Worker
Central
Tendency
1
8.8
8.8
0.7
0.7
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
50
50
4.5
4.5
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
1,217
NA
High-
End
1
-
-
281
NA
Section 2.4.1.2.16 -
2.4.1.2.16
(Spray/Wipe
Cleaning)
Worker
Central
Tendency
1
90
90
8.3
8.3
High-
End
1
1.1
1.1
0.04
0.04
Central
Tendency
5
451
459
42
43
High-
End
5
10
10
0.6
0.6
ONU
Central
Tendency
1
-
-
1,774
NA
High-
End
1
-
-
280
NA
Fertilizer and other
agricultural chemical
manufacturing-processing
aids and solvents
Section 2.4.1.2.17 -
Fertilizer Application
Worker
Central
Tendency
1
2,892
8,571
279
849
High-
End
1
149
156
8.9
9.3
Page 383 of 576
-------
l.ili- Cjolc
SI iik/
Sul>c:iU-<>»n
Oi'cu|>:ilioiiiil
I'.\|)omiiv Sci'iiiirio
l*o|>nLil ictn
l.\|>OMIIV
l.lMl
n
11 = iki
.Willi-
liciulinuirk
No
Ui's|)ir;iior
Mor.s
M(ti: = jo
\\ illi
Ui's|>ir;ilor
(API III) '¦
Clironi
licnchnuirl
No
Ui's|)ir;iior
i* Mor.s
\\ illi
Ui'spiniior
(AIM 10) '¦
Central
T endency
5
3,210
12,118
307
1,196
High-
End
5
628
754
38
45
ONU
Central
Tendency
1
-
-
304
NA
High-
End
1
-
-
171
NA
Disposal
Industrial pre-treatment
Section 2.4.1.2.7 -
Recycling and
Disposal
Worker
Central
Tendency
1
6.8
6.8
0.5
0.5
Industrial wastewater
treatment
High-
End
1
1.1
1.1
0.04
0.04
Publicly owned treatment
works (POTW)
Central
Tendency
5
40
40
3.6
3.6
Underground injection
High-
End
5
10
10
0.6
0.6
Landfill (municipal,
hazardous or other land
disposal)
ONU
Central
Tendency
1
-
-
3,432
NA
Incinerators (municipal and
hazardous waste)
High-
End
1
-
-
926
NA
Emissions to air
NA = not assessed because ONUs are not assumed to be wearing PPE; " = ONU risk from acute exposures are not expected to be below the MOE; see further
explanation in Section 4.2.3
a Risks for glove PFs 10 and 20 are included for some COUs where appropriate based on glove use information described in Sections 2.4.1 and 2.4.1.2.
b To achieve an APF of 10, EPA assumes use of a half mask air-purifying respirator with organic vapor cartridges.
Page 384 of 576
-------
4.6.1.2 Summary of Risk Estimates for Consumers and Bystanders
Table 4-56 summarizes the acute risks of combined inhalation, dermal and vapor-through-skin
exposures for all consumer exposure scenarios. For consumers, risk concerns are indicated for acute
exposures associated with high intensity use of paint removers, high weight fraction adhesives and
engine cleaners/degreasers. The main factors that impact consumer exposures during use of NMP -
containing products include the NMP weight fraction, duration of product use and the actual amount of
product used (see Table 2-85 and Table 2-91). In addition, specific factors related to the room of use
(e.g., room size, air exchange rate) may affect the estimated NMP air concentrations to which consumers
may be exposed. For example, air concentrations can vary depending on whether windows or garage
doors are open or closed during product use. Variations in individual activity patterns can also impact
exposure potential (e.g., risks associated with the engine degreasing activity may be underestimated if
the product is used continuously).
EPA evaluated risks to child and adult bystanders for all COUs where risk was found for consumer
users, including use of NMP-containing paint removers, high weight fraction adhesives and sealants, and
engine cleaner/degreasers. (Section 4.2.4.8). These exposure scenarios did not present a risk concern to
bystanders. Bystander risks were not further evaluated for scenarios that do not pose a risk to consumer
users because bystander exposures are expected to be lower than consumer user exposures.
EPA has high confidence in the POD used to evaluate risks associated with acute exposure and medium
confidence in the POD used to evaluate chronic NMP exposure. As discussed in Section 3.2.6, post-
implantation loss (resorptions and fetal mortality) and reduced fertility were considered relevant hazards
for evaluating risks following acute and chronic NMP exposure, respectively. While there is some
uncertainty regarding temporal windows of vulnerability for developmental toxicity and whether the
timing of a single exposure can produce a permanent adverse effect on human development, EPA
considers the post-implantation loss endpoints associated with NMP exposure to be applicable to acute
exposures. The reasonably available literature suggests that a single developmental exposure may have
sustained effects on the conceptus. Fetal mortality represents the most severe endpoint associated with
the developmental hazard profile for NMP. Reduced fertility in males is the most sensitive effect
associated with chronic exposures. The chronic POD based on effects on reduced male fertility is
supported by effects on female fecundity and developmental toxicity in a similar dose range.
Page 385 of 576
-------
Table 4-56. Summary of Risk Estimates from Acute Exposures to Consumers by Conditions of Use
Life Cycle Slji»e/
C:ilcj>or\
Suhciile«»orv
Consumer Condition of
I se/K\posure Scenario
Population
Lxposure Le\el
Risk Lsliniiile
Acute Non-C:incer
(lien chin iirk MOL = 30)
Consumer use/
Paints and
coatings
Paint and coating removers
Section 2.4.2.5,
Paint Removers
Consumer
Medium-Intensity User
217
High-Intensity User
29
Bystander3
(In room of use)
Medium-Intensity User
N/A
High-Intensity User
45
Bystander
(In rest of house)
Medium-Intensity User
N/A
High-Intensity User
123
Adhesive removers
Section 2.4.2.5,
Adhesive Removers
Consumer
Medium-Intensity User
338
High-Intensity User
73
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Lacquer, stains, varnishes,
primers and floor finishes
Section 2.4.2.5,
Stains, Varnishes
Consumer
Medium-Intensity User
1,283
High-Intensity User
224
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Consumer use/
Paint additives and
coatings additives
not described by
other codes
Paints and Arts and Crafts
Paints
Section 2.4.2.5,
Paint
Consumer
Medium-Intensity User
1,169
High-Intensity User
307
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Section 2.4.2.5,
Arts and Crafts
Consumer
Medium-Intensity User
6,139
High-Intensity User
1,970
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Page 386 of 576
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Life C ycle Slji«e/
Category
Subcategory
Consumer C ondition of
I se/Kxposure Scenario
Population
KxpOSIII'C I.C\cl
Risk Kslimale
Acute Non-Cancer
(Benchmark MOK = 30)
Consumer use/
adhesives and
sealants
Glues and adhesives, including
lubricant adhesives
Section 2.4.2.5,
High Weight Fraction
Adhesives and Sealants
Consumer
Medium-Intensity User
107
High-Intensity User
23
Bystander3
(In room of use)
Medium-Intensity User
N/A
High-Intensity User
2,806
Bystander
(In rest of house)
Medium-Intensity User
N/A
High-Intensity User
N/Ab
Section 2.4.2.5,
Low Weight Fraction
Adhesives and Sealants
Consumer
Medium-Intensity User
38,758
High-Intensity User
6,248
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Consumer use/
Other uses
Automotive care products
Section 2.4.2.5,
Auto Interior Cleaner
Consumer
Medium-Intensity User
1,710
High-Intensity User
100
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Section 2.4.2.5,
Auto Interior Spray
Cleaner
Consumer
Medium-Intensity User
4,676
High-Intensity User
2,381
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Cleaning and furniture care
products, including wood
cleaners, gasket removers
Section 2.4.2.5,
Cleaners/Degreaser
Consumer
Medium-Intensity User
423
High-Intensity User
33
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Section 2.4.2.5,
Consumer
Medium-Intensity User
260
Page 387 of 576
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Life C ycle Slji«e/
Category
Subcategory
Consumer C ondition of
I se/Kxposure Scenario
Engine Cleaner/
Degreaser
Population
KxpOSIII'C I.C\cl
Risk Kslimale
Acute Non-Cancer
(Benchmark MOK = 30)
High-Intensity User
27
Bystandera
(In room of use)
Medium-Intensity User
N/A
High-Intensity User
54
Bystander
(In rest of house)
Medium-Intensity User
N/A
High-Intensity User
79
Consumer use/
Other uses
Lubricant and lubricant
additives, including
hydrophilic coatings
Section 2.4.2.5,
Spray Lubricant
Consumer
Medium-Intensity User
1,316
High-Intensity User
153
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
a Bystander risk (MOEs) estimates for bystanders in the room of use assume exposure to the same NMP air concentrations as the user.
b Cmax is assumed to be zero for bystanders in the rest of house, as outdoor use of the product is not expected to result in NMP in indoor air. No MOE was calculated.
N/A = not assessed
Page 388 of 576
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4.6.1.3 Summary of Risk for the General Population
EPA considered reasonably available information to characterize general population exposure and risk.
During problem formulation, EPA evaluated potentials exposures and risks to the general population
through ambient water, land-applied biosolids, and ambient air. Based on environmental fate properties
of NMP and first-tier screening level analyses, EPA did not identify risk to the general population from
these pathways.
Surface water pathway
EPA did not identify risks from exposure to NMP through surface water pathways. Based on 2015 TRI
reporting, an estimate 14,092 pounds of NMP was released to surface water from industrial and
commercial sources. Although NMP exhibits high water solubility, it is not expected to persist in surface
waters because it readily biodegrades under aerobic conditions. In this risk evaluation, EPA updated the
screening level analysis of ambient water pathways using recent TRI reporting data from 2018
(Appendix E). A first-tier analysis used to estimate NMP surface water concentrations based on the
highest water releases reported in 2018 did not identify risks from incidental ingestion of surface water
or from dermal contact during swimming (Section 2.4.3 and 4.2.5).
Land-applied biosolids pathway
EPA did not identify risks from land releases of NMP, including those that may result from land
application of biosolids. NMP exhibits high water solubility and limited potential for adsorption to
organic matter; therefore, land releases will ultimately partition to the aqueous phase {i.e., biosolids
associated wastewater and soil pore water) upon release into the environment. Because NMP readily
biodegrades in environments with active microbial populations, NMP residues that remain following
waste water treatment are not expected to persist. NMP concentrations in biosolids-associated water are
expected to decrease, primarily via aerobic degradation, during transport, processing (including
dewatering), handling, and land application of biosolids (which may include spraying).
Migration of NMP between ground water and surface has not been documented, but may be mitigated
by abiotic and biotic degradation in the water column. Overall, the NMP concentrations in surface water
resulting from land application of biosolids are expected to be much less than those associated with
direct release of waste water treatment plant effluents to surface water. During problem formulation,
EPA's conservative assessment of this exposure scenario predicted NMP surface water concentrations
that are well below the hazard benchmarks identified for humans and aquatic organisms; therefore, this
exposure pathway is not expected to present a risk concern.
Ambient air pathway
EPA did not identify risks from human exposures that may result from inhalation of outdoor air
containing NMP released from industrial and commercial facilities. During problem formulation, EPA
performed a first-tier screening analysis to estimate the potential (near field) exposure to populations
located downwind of facilities reporting the highest NMP air releases based on 2015 TRI data. Using
EPA's SCREEN3 Model and the highest reported stack emissions, the estimated NMP concentration in
ambient air was approximately 0.41 mg/m3. EPA assessed the risks associated with chronic NMP
exposure by comparing the estimated concentration of NMP in ambient air to hazard benchmarks. This
resulted in a MOE that exceeded the benchmark.
Page 389 of 576
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5 UNREASONABLE RISK DETERMINATION
5.1 Overview
In each risk evaluation under TSCA Section 6(b), EPA determines whether a chemical substance
presents an unreasonable risk of injury to health or the environment, under the conditions of use. These
determinations do not consider costs or other non-risk factors. In making these determinations, EPA
considers relevant risk-related factors, including, but not limited to: the effects of the chemical substance
on health and human exposure to such substance under the conditions of use (including cancer and non-
cancer risks); the effects of the chemical substance on the environment and environmental exposure
under the conditions of use; the population exposed (including any PESS); the severity of hazard
(including the nature of the hazard, the irreversibility of the hazard); and the uncertainties. EPA also
takes into consideration the Agency's confidence in the data used in the risk estimates. This includes an
evaluation of the strengths, limitations and uncertainties associated with the information used to inform
the risk estimates and the risk characterization. This approach is in keeping with the Agency's final rule,
Procedures for Chemical Risk Evaluation Under the Amended Toxic Substances Control Act (82 FR
33726).8
This section describes the final unreasonable risk determinations for the conditions of use in the scope of
the risk evaluation. The final unreasonable risk determinations are based on the risk estimates and
consideration of other risk-related factors in the final risk evaluation, which may differ from the draft
risk evaluation due to peer review and public comments. The relevant risk-related factors for NMP are
further explained in Section 5.1.1 below and in Section 4.3 and Section 4.4 of the risk characterization.
In Section 5.1.1, the relevant risk-related factors are identified for each condition of use, such as the
health effects considered, the use of high-end risk estimates to address PESS, and other uncertainties
relevant to each condition of use. Therefore, the final unreasonable risk determinations of some
conditions of use may differ from those in the draft risk evaluation.
5.1.1 Human Health
EPA's risk evaluation identified non-cancer adverse effects from acute (developmental) and chronic
(reproductive) inhalation and dermal exposures to NMP. The health risk estimates for all conditions of use
are in Section 4.6 (Table 4-55 and Table 4-56).
For the NMP risk evaluation, EPA identified as Potentially Exposed or Susceptible Subpopulations:
workers and ONUs, consumers and bystanders, males and females of reproductive age, pregnant women
and the developing fetus, infants, children and adolescents, people with pre-existing conditions and people
with lower metabolic capacity due to life stage, genetic variation, or impaired liver function.
EPA evaluated exposures to workers, ONUs, consumer users, and bystanders using reasonably available
monitoring and modeling data for inhalation and dermal exposures, as applicable. For example, EPA
assumed that ONUs and bystanders do not have direct contact with NMP; therefore, non-cancer effects
from dermal exposures to NMP are not expected and were not evaluated. Additionally, EPA did not
evaluate chronic exposures for consumer users and bystanders because daily use intervals are not
reasonably expected to occur for all consumer uses. The description of the data used for human health
8 This risk determination is being issued under TSCA Section 6(b) and the terms used, such as unreasonable risk, and the
considerations discussed are specific to TSCA. Other statutes have different authorities and mandates and may involve risk
considerations other than those discussed here.
Page 390 of 576
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exposure is in Section 2.4. Uncertainties in the analysis are discussed in Section 4.3 and considered in the
unreasonable risk determination for each condition of use presented below in Section 5.2.
EPA considered potential exposure pathways for the general population via ambient water, ambient air
and land-applied biosolids. EPA evaluated environmental fate properties, reasonably available information
and first-tier screening level analyses to characterize general population exposure from these pathways.
EPA determined there is no general population risk for these pathways. The exposures to the general
population via drinking water and disposal pathways fall under the jurisdiction of other environmental
statutes administered by EPA, i.e., CAA, SDWA, CWA, and CERCLA. EPA did not evaluate risks to the
general population from drinking water or disposal pathways. Additional details regarding general
population are found in Sections 1.4.2 and 4.6.1.3.
5.1.1.1	Non-Cancer Risk Estimates
The risk estimates of non-cancer effects (MOEs) refer to adverse health effects associated with health
endpoints other than cancer, including to the body's organ systems, such as reproductive/developmental
effects, cardiac and lung effects, and kidney and liver effects. The MOE is the POD (an approximation of
the no-observed adverse effect level (NOAEL) or benchmark dose level (BMDL)) for a specific health
endpoint divided by the exposure concentration for the specific scenario of concern. Section 3.2.5 presents
the PODs for non-cancer effects for NMP and Section 4.2 presents the MOEs for non-cancer effects.
The MOEs are compared to a benchmark MOE. The benchmark MOE accounts for the total uncertainty in
a POD, including, as appropriate: (1) the variation in sensitivity among the members of the human
population (i.e., intrahuman/intraspecies variability); (2) the uncertainty in extrapolating animal data to
humans (i.e., interspecies variability); (3) the uncertainty in extrapolating from data obtained in a study
with less-than-lifetime exposure to lifetime exposure (i.e., extrapolating from subchronic to chronic
exposure); and (4) the uncertainty in extrapolating from a LOAEL rather than from a NOAEL. A lower
benchmark MOE (e.g., 30) indicates greater certainty in the data (because fewer of the default UFs
relevant to a given POD as described above were applied). A higher benchmark MOE (e.g., 1000) would
indicate more uncertainty for specific endpoints and scenarios. However, these are often not the only
uncertainties in a risk evaluation. The benchmark MOE for acute and chronic non-cancer risks for NMP is
30 (accounting for interspecies and intraspecies variability). Additional information regarding the
benchmark MOE is in Section 4.2.1.
5.1.1.2	Cancer Risk Estimates
Cancer risk estimates represent the incremental increase in probability of an individual in an exposed
population developing cancer over a lifetime (excess lifetime cancer risk) following exposure to the
chemical. Standard cancer benchmarks used by EPA and other regulatory agencies are an increased
cancer risk above benchmarks ranging from 1 in 1,000,000 to 1 in 10,000 (i.e., lxlO"6 to lxlO"4)
depending on the subpopulation exposed.9
9 As an example, whenEPA's Office of Water in 2017 updated the Human Health Benchmarks for Pesticides, the benchmark
for a "theoretical upper-bound excess lifetime cancer risk" from pesticides in drinking water was identified as 1 in
1,000,000 to 1 in 10,000 over a lifetime of exposure (EPA. Human Health Benchmarks for Pesticides: Updated 2017
Technical Document (pp.5). (EPA 822-R -17 -001). Washington, DC: U.S. Environmental Protection Agency, Office of
Water. January 2017. https://www.epa.gov/sites/production/files/2015-10/documents/hh-benchmarks-techdoc.pdf).
Similarly, EPA's approach under the CAA to evaluate residual risk and to develop standards is a two-step approach that
"includes a presumptive limit on maximum individual lifetime [cancer] risk (MIR) of approximately 1 in 10 thousand" and
consideration of whether emissions standards provide an ample margin of safety to protect public health "in consideration
of all health information, including the number of persons at risk levels higher than approximately 1 in 1 million, as well as
other relevant factors" (54 FR 38044, 38045, September 14, 1989).
Page 391 of 576
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With respect to cancer risks, as discussed in Section 2.4.2.2 of the Problem Formulation of the Risk
Evaluation for NMP, NMP is not mutagenic and is not considered carcinogenic so EPA did not conduct
analysis of genotoxicity and cancer hazards during risk evaluation.
5.1.1.3 Determining Unreasonable Risk of Injury to Health
Calculated risk estimates (MOEs) can provide a risk profile by presenting a range of estimates for
different health effects for different conditions of use. A calculated MOE that is less than the benchmark
MOE supports a determination of unreasonable risk of injury to health, based on non-cancer effects.
Similarly, a calculated cancer risk estimate that is greater than the cancer benchmark supports a
determination of unreasonable risk of injury to health from cancer. Whether EPA makes a determination
of unreasonable risk depends upon other risk-related factors, such as the endpoint under consideration, the
reversibility of effect, exposure-related considerations (e.g., duration, magnitude, or frequency of
exposure, or population exposed), and the confidence in the information used to inform the hazard and
exposure values. A calculated MOE greater than the benchmark MOE or a calculated cancer risk estimate
less than the cancer benchmark alone do not support a determination of no unreasonable risk, since EPA
may consider other risk-based factors when making an unreasonable risk determination.
When making an unreasonable risk determination based on injury to health of workers (who are one
example of PESS), EPA also makes assumptions regarding workplace practices and the implementation of
the required hierarchy of controls from OSHA. EPA assumes that feasible exposure controls, including
engineering controls, or use of PPE are implemented in the workplace. EPA's decisions for unreasonable
risk to workers are based on high-end exposure estimates, in order to capture not only exposures for PESS
but also to account for the uncertainties related to whether or not workers are using PPE. However, EPA
does not assume that ONUs use PPE. For each condition of use of NMP, depending on the information
available and professional judgement, EPA assumes the use of appropriate respirators with APF 10. Based
on peer review and public comments, EPA adjusted glove PF assumptions. Once EPA has applied the
appropriate PPE assumption for a particular condition of use in each unreasonable risk determination, in
those instances when EPA assumes PPE is used, EPA also assumes that the PPE is used in a manner that
achieves the stated APF or PF.
In the NMP risk characterization, the best representative endpoints for non-cancer effects were from acute
(reproductive toxicity) and chronic (developmental toxicity) inhalation and dermal exposures for all
conditions of use. Additional risks associated with other adverse effects (e.g., liver toxicity, kidney
toxicity, immunotoxicity, neurotoxicity, irritation and sensitization) were identified for acute and chronic
inhalation and dermal exposures.
The previous EPA assessment (U.S. EPA. 2015 c). did not characterize dose-response for these fertility
endpoints because the effect observed in one study (reduced fertility) was not replicated in more recent
studies. However, together, the acute and chronic effects indicate a continuum of reproductive and
developmental effects associated with NMP exposure. The complete basis for selection of endpoints is
described in detail in Section 3.2.5.1 (Selection of Endpoints for Dose-Response Assessment) and Section
3.2.5.6 (Points of Departure for Human Health Hazard Endpoints).
When making a determination of unreasonable risk, the Agency has a higher degree of confidence where
uncertainty is low. Similarly, EPA has high confidence in the hazard and exposure characterizations when,
for example, the basis for characterizations is measured or monitoring data or a robust model and the
hazards identified for risk estimation are relevant for conditions of use. Where EPA has made assumptions
Page 392 of 576
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in the scientific evaluation, whether or not those assumptions are protective is also a consideration.
Additionally, EPA considers the central tendency and high-end exposure levels when determining the
unreasonable risk. High-end risk estimates (e.g., 95th percentile) are generally intended to cover
individuals or sub-populations with greater exposure (PESS) as well as to capture individuals with sentinel
exposure, and central tendency risk estimates are generally estimates of average or typical exposure.
EPA may make a determination of no unreasonable risk for conditions of use where the substance's
hazard and exposure potential, or where the risk-related factors described previously, lead the Agency to
determine that the risks are not unreasonable.
5.1.2 Environment
EPA calculated a RQ to compare environmental concentrations against an effect level. The environmental
concentration is determined based on the levels of the chemical released to the environment (e.g., surface
water, sediment, soil, biota) under the conditions of use, based on the fate properties, release potential, and
reasonably available environmental monitoring data. The effect level is calculated using COCs that
represent hazard data for aquatic, sediment-dwelling, and terrestrial organisms. Section 4.1 provides more
detail regarding the RQ for NMP.
5.1.2.1 Determining Unreasonable Risk of Injury to the Environment
An RQ equal to 1 indicates that the exposures are the same as the concentration that causes effects. An RQ
less than 1, when the exposure is less than the effect concentration, supports a determination that there is
no unreasonable risk of injury to the environment. An RQ greater than 1, when the exposure is greater
than the effect concentration, supports a determination that there is unreasonable risk of injury to the
environment. Consistent with EPA's human health evaluations, other risk-based factors may be
considered (e.g., confidence in the hazard and exposure characterization, duration, magnitude, uncertainty)
for purposes of making an unreasonable risk determination.
EPA considered the effects on aquatic, sediment-dwelling, and terrestrial organisms. EPA provides
estimates for environmental risk in Section 4.1, while the details for determining whether there is
unreasonable risk to the environment are discussed in Section 5.2.2.
5.2 Detailed Unreasonable Risk Determinations by Conditions of Use
Table 5-1. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life ( \clc S(;i»c

Siibciik'jion '¦
I niviisoiiiihlc
Risk
Di'liiilcri Risk
Ik-liTiiiiiiiilinn
Manufacturing
Domestic manufacture
Domestic manufacture
Yes
Section 5.2.1.1, Section
5.2.1.38 and Section 5.2.2
Import
Import
Yes
Section 5.2.1.2, Section
5.2.1.38 and Section 5.2.2
Processing
Processing as a reactant or
intermediate
Intermediate in Plastic
Material and Resin
Manufacturing
Yes
Section 5.2.1.3, Section
5.2.1.38 and Section 5.2.2
Other Non-Incorporative
Processing
Page 393 of 576
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I.il'c (vclc Slii»o
C.ik'Sion ¦'
SiibciiK'iion
I mv;isnn;il>k*
Risk
l)ol;iik'(l Risk
Ik-li'i'iiiiiiiilinn
Incorporation into
formulation, mixture or
reaction products
Adhesives and sealant
chemicals in Adhesive
Manufacturing
Anti-adhesive agents in
Printing and Related
Support Activities
Paint additives and coating
additives not described by
other codes in Paint and
Coating Manufacturing; and
Print Ink Manufacturing
Processing aids not
otherwise listed in Plastic
Material and Resin
Manufacturing
Solvents (for cleaning or
degreasing) in Non-Metallic
Mineral Product
Manufacturing; Machinery
Manufacturing; Plastic
Material and Resin
Manufacturing; Primary
Metal Manufacturing; Soap,
Cleaning Compound and
Toilet Preparation
Manufacturing;
Transportation Equipment
Manufacturing; All Other
Chemical Product and
Preparation Manufacturing;
Printing and Related
Support Activities; Services;
Wholesale and Retail Trade
Surface active agents in
Soap, Cleaning Compound
and Toilet Preparation
Manufacturing
Plating agents and surface
treating agents in Fabricated
Metal Product
Manufacturing
Solvents (which become
part of product formulation
or mixture) in Electrical
Equipment, Appliance and
Component Manufacturing;
Other Manufacturing; Paint
and Coating Manufacturing;
Print Ink Manufacturing;
Soap, Cleaning Compound
and Toilet Preparation
Yes
Section 5.2.1.4, Section
5.2.1.38 and Section 5.2.2
Page 394 of 576
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Life (vclc Slii»c
C.ik'Sion ¦'
SiibciiK'iion
I mv;isnii;il>k-
Risk
IH'liiik'ri Risk
Ik-li'i'iiiiiiiilinn


Manufacturing;
Transportation Equipment
Manufacturing; All Other
Chemical Product and
Preparation Manufacturing;
Printing and Related
Support Activities;
Wholesale and Retail Trade




Other uses in Oil and Gas
Drilling, Extraction and
Support Activities; Plastic
Material and Resin
Manufacturing; Services


Processing
Incorporation into articles
Lubricants and lubricant
additives in Machinery
Manufacturing
Yes
Section 5.2.1.5, Section
5.2.1.38 and Section 5.2.2


Paint additives and coating
additives not described by
other codes in
Transportation Equipment
Manufacturing
Yes
Section 5.2.1.6, Section
5.2.1.38 and Section 5.2.2


Solvents (which become
part of product formulation
or mixture), including in
Textiles, Apparel and
Leather Manufacturing
Yes
Section 5.2.1.7, Section
5.2.1.38 and Section 5.2.2


Other, including in Plastic
Product Manufacturing
Yes
Section 5.2.1.8, Section
5.2.1.38 and Section 5.2.2
Processing
Repackaging
Wholesale and Retail Trade
Yes
Section 5.2.1.9, Section
5.2.1.38 and Section 5.2.2
Processing
Recycling
Recycling
Yes
Section 5.2.1.10, Section
5.2.1.38 and Section 5.2.2
Distribution in
commerce
Distribution
Distribution in commerce
No
Section 5.2.1.11, Section
5.2.1.38 and Section 5.2.2
Page 395 of 576
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Life (vclc Slii»c
C.ik'Sion ¦'
SiibciiK'iion
I mv;isnii;il>k-
Risk
IH'liiik'ri Risk
Ik-li'i'iiiiiiiilinn
Industrial and
Commercial use
Paints and coatings
Paint and coating removers
Yes
Section 5.2.1.12, Section
5.2.1.38 and Section 5.2.2
Adhesive removers
Lacquers, stains, varnishes,
primers and floor finishes
Yes
Section 5.2.1.13, Section
5.2.1.38 and Section 5.2.2
Powder coatings (surface
preparation)
Paint additives and coating
additives not described by
other codes
Use in Computer and
Electronic Product
Manufacturing in Electronic
Parts Manufacturing
Yes
Section 5.2.1.14, Section
5.2.1.38 and Section 5.2.2
Use in Computer and
Electronic Product
Manufacturing in
Semiconductor
Manufacturing
Yes
Section 5.2.1.15, Section
5.2.1.38 and Section 5.2.2
Use in Construction,
Fabricated Metal Product
Manufacturing, Machinery
Manufacturing, Other
Manufacturing, Paint and
Coating Manufacturing,
Primary Metal
Manufacturing,
Transportation Equipment
Manufacturing, Wholesale
and Retail Trade
Yes
Section 5.2.1.16, Section
5.2.1.38 and Section 5.2.2
Solvent (for cleaning or
degreasing)
Use in Electrical Equipment,
Appliance and Component
Manufacturing
Yes
Section 5.2.1.17, Section
5.2.1.38 and Section 5.2.2
Use in Electrical Equipment
Appliance and Component
Manufacturing in
Semiconductor
Manufacturing
Yes
Section 5.2.1.18, Section
5.2.1.38 and Section 5.2.2
Ink, toner, and colorant
products
Printer Ink
No
Section 5.2.1.19, Section
5.2.1.38 and Section 5.2.2
Inks in writing equipment
Processing aids, specific to
petroleum production
Petrochemical
Manufacturing
Yes
Section 5.2.1.20, Section
5.2.1.38 and Section 5.2.2
Other uses
Other uses in Oil and Gas
Drilling, Extraction and
Support Activities
Functional fluids (closed
systems)
Adhesives and sealants
Adhesives and sealant
chemicals including binding
agents
Yes
Section 5.2.1.21, Section
5.2.1.38 and Section 5.2.2
Page 396 of 576
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Life (vclc Slii»c
C.ik'Sion ¦'
SiibciiK'iion
I mv;isnii;il>k-
Risk
IH'liiik'ri Risk
Ik-li'i'iiiiiiiilinn


Single component glues and
adhesives, including
lubricant adhesives




Two-component glues and
adhesives, including some
resins



Other uses
Soldering materials
No
Section 5.2.1.22, Section
5.2.1.38 and Section 5.2.2


Anti-freeze and de-icing
Yes
Section 5.2.1.23, Section


Automotive care products

5.2.1.38 and Section 5.2.2


Lubricants and greases




Metal products not covered
elsewhere
Yes
Section 5.2.1.24, Section
5.2.1.38 and Section 5.2.2


Lubricant and lubricant
additives, including
hydrophilic coatings




Laboratory chemicals
Yes
Section 5.2.1.25, Section
5.2.1.38 and Section 5.2.2


Lithium Ion battery
manufacturing
Yes
Section 5.2.1.26, Section
5.2.1.38 and Section 5.2.2


Cleaning and furniture care
products, including wood
cleaners, gasket removers
Yes
Section 5.2.1.27, Section
5.2.1.38 and Section 5.2.2


Fertilizer and other
agricultural chemical
manufacturing - processing
aids and solvents
No
Section 5.2.1.28, Section
5.2.1.38 and Section 5.2.2
Consumer Uses
Paints and coatings
Paint and coating removers
No
Section 5.2.1.29, Section
5.2.1.38 and Section 5.2.2


Adhesive removers
No
Section 5.2.1.30, Section
5.2.1.38 and Section 5.2.2


Lacquers, stains, varnishes,
primers and floor finishes
No
Section 5.2.1.31, Section
5.2.1.38 and Section 5.2.2
Consumer Uses
Paint additives and coating
additives not described by
other codes
Paints and Arts and Crafts
Paints
No
Section 5.2.1.32, Section
5.2.1.38 and Section 5.2.2
Consumer Uses
Adhesives and sealants
Glues and adhesives,
including lubricant
adhesives
Yes
Section 5.2.1.33, Section
5.2.1.38 and Section 5.2.2
Consumer Uses
Other uses
Automotive care products
No
Section 5.2.1.34, Section
5.2.1.38 and Section 5.2.2


Cleaning and furniture care
products, including wood
cleaners, gasket removers
No
Section 5.2.1.35, Section
5.2.1.38 and Section 5.2.2
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Life (vclc Slii»c
C.ik'Sion ¦'
SiibciiK'iion
I mv;isnii;il>k-
Risk
IH'liiik'ri Risk
Ik-li'i'iiiiiiiilinn


Lubricant and lubricant
additives, including
hydrophilic coatings
No
Section 5.2.1.36, Section
5.2.1.38 and Section 5.2.2
Disposal
Disposal
Industrial pre-treatment
Industrial wastewater
treatment
Publicly owned treatment
works (POTW)
Underground injection
Landfill (municipal,
hazardous or other land
disposal)
Incinerators (municipal and
hazardous waste)
Emissions to air
Yes
Section 5.2.1.37, Section
5.2.1.38 and Section 5.2.2
a These categories of conditions of use appear in the Life Cycle Diagram, reflect CDR codes, and broadly represent conditions
of use of NMP in industrial and/or commercial settings.
b These subcategories reflect more specific information regarding the conditions of use of NMP.
5,2.1 Human Health
5.2.1.1 Manufacture - Domestic manufacture (Domestic manufacture)
Section 6(b)(4)(A) unreasonable risk determination for domestic manufacture of NMP: Presents an
unreasonable risk of injury to health (workers); does not present an unreasonable risk of injury to
health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that domestic manufacture of NMP presents an unreasonable risk is based on the
comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other
considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
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exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and-vapor-through-
skin exposures when determining ONUs' unreasonable risk.
• Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of loading of bulk storage containers
and drums, which EPA expects presents the largest range of potential exposures, though EPA
does expect that workers may perform additional activities during this scenario, such as sampling
or maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from domestic manufacturing of NMP.
5.2.1.2 Manufacture - Import (Import)
Section 6(b)(4)(A) unreasonable risk determination for import of NMP: Presents an unreasonable risk
of injury to health (workers); does not present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that import of NMP presents an unreasonable risk is based on the comparison of
the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other considerations. As
explained in Section 5.1, EPA also considered the health effects of NMP, the exposures from the
condition of use, and the uncertainties in the analysis (Section 4.3), including uncertainties related to the
exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of unloading of various containers,
which EPA expects presents the largest range of potential exposures, though EPA does expect
that workers may perform additional activities during this scenario, such as sampling or
maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from import of NMP.
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5.2.1.3 Processing - Processing as a reactant or intermediate - Intermediate in
Plastic Material and Resin Manufacturing; Other Non-Incorporative
Processing (Processing as a reactant or intermediate)
Section 6(b)(4)(A) unreasonable risk determination for the processing of NMP as a reactant or
intermediate in plastic material and resin manufacturing and other non-incorporative processing:
Presents an unreasonable risk of injury to health (workers); does not present an unreasonable risk of
injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the processing of NMP as a reactant or intermediate in plastic material and
resin manufacturing and other non-incorporative processing presents an unreasonable risk is based on
the comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other
considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of the unloading of various
containers, which EPA expects presents the largest range of potential exposures, though EPA
does expect that workers may perform additional activities during this scenario, such as sampling
or maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the processing of NMP as a reactant or intermediate in plastic material and resin manufacturing
and other non-incorporative processing.
5.2.1.4 Processing - Incorporation into formulation, mixture or reaction product
- in multiple industrial sectors (listed in Table 5-1) (Processing into a
formulation, mixture, or reaction product)
Section 6(b)(4)(A) unreasonable risk determination for processing of NMP for incorporation into a
formulation, mixture or reaction product in multiple industrial sectors: Presents an unreasonable risk
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of injury to health (workers); does not present an unreasonable risk of injury to health (ONUs) at the
central tendency.
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the processing of NMP for incorporation into a formulation, mixture or
reaction product in multiple industrial sectors presents an unreasonable risk is based on the comparison
of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other considerations. As
explained in Section 5.1, EPA also considered the health effects of NMP, the exposures from the
condition of use, and the uncertainties in the analysis (Section 4.3), including uncertainties related to the
exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of unloading of various containers,
and from maintenance, bottling, shipping, and loading of NMP in formulation, which EPA
expects present the largest range of potential exposures, though EPA does expect that workers
may perform additional activities during this scenario, such as sampling or maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from processing of NMP for incorporation into a formulation, mixture or reaction product in multiple
industrial sectors.
5.2.1.5 Processing - Incorporation into articles - Lubricants and lubricant
additives in Machinery Manufacturing (processing into articles in
lubricant and lubricant additives)
Section 6(b)(4)(A) unreasonable risk determination for the processing of NMP for incorporation into
articles in lubricants and lubricant additives in machinery manufacturing: Presents an unreasonable
risk of injury to health (workers); does not present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
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from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the processing of NMP for incorporation into articles in lubricants and
lubricant additives in machinery manufacturing presents an unreasonable risk is based on the
comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other
considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of metal finishing products
containing NMP, including brush, spray, and dip applications, which EPA expects present the
largest range of potential exposures, though EPA does expect that workers may perform
additional activities during this scenario, such as sampling or maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from processing of NMP for incorporation into articles in lubricants and lubricant additives in
machinery manufacturing.
5.2.1.6 Processing - Incorporation into articles - Paint additives and coating
additives not described by other codes in Transportation Equipment
Manufacturing (Processing into articles in paint and coating additives)
Section 6(b)(4)(A) unreasonable risk determination for the processing of NMP for incorporation into
articles in paint additives and coating additives not described by other codes in transportation equipment
manufacturing: Presents an unreasonable risk of injury to health (workers); does not present an
unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from chronic
(reproductive) inhalation and dermal exposures at the high-end, even when assuming use of PPE.
For ONUs, EPA found that there was no unreasonable risk of non-cancer effects from acute
(developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at the central
tendency.
EPA's determination that the processing of NMP for incorporation_into articles in paint additives and
coating additives not described by other codes in transportation equipment manufacturing presents an
unreasonable risk is based on the comparison of the risk estimates for non-cancer effects (reproductive)
to the benchmarks (Table 4-55) and other considerations. As explained in Section 5.1, EPA also
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considered the health effects of NMP, the exposures from the condition of use, and the uncertainties in
the analysis (Section 4.3), including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the high-
end support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end
do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of spray, roll/curtain, dip, and brush
application exposures to paints, coatings, adhesives, and sealants containing NMP. While EPA
does expect that workers may perform additional activities during this scenario, such as
unloading or sampling, EPA expects that application activities present the largest range of
potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from processing of NMP for incorporation into articles in paint additives and coating additives not
described by other codes in transportation equipment manufacturing.
5.2.1.7 Processing - Incorporation into articles - Solvents (which become part of
product formulation or mixture), including in Textiles, Apparel and
Leather Manufacturing (Processing as an article in solvents (which
become part of product formulation or mixture))
Section 6(b)(4)(A) unreasonable risk determination for the processing of NMP for incorporation into
articles as a solvent (which become part of product formulation or mixture) including in textiles, apparel
and leather manufacturing: Presents an unreasonable risk of injury to health (workers); does not
present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the processing of NMP for incorporation_into articles as a solvent (which
become part of product formulation or mixture) including in textiles, apparel and leather manufacturing
presents an unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to
the benchmarks (Table 4-55) and other considerations. As explained in Section 5.1, EPA also considered
the health effects of NMP, the exposures from the condition of use, and the uncertainties in the analysis
(Section 4.3), including uncertainties related to the exposures for ONUs:
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•	For workers, when assuming the use of respirators with APF 10 and gloves with PF of 5, the risk
estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end, and
from chronic inhalation and dermal exposures at the central tendency and high-end support an
unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of unloading of various containers,
and from maintenance, bottling, shipping, and loading of NMP in formulation, which EPA
expects present the largest range of potential exposures, though EPA does expect that workers
may perform additional activities during this scenario, such as sampling or maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from processing of NMP for incorporation into articles as a solvent (which become part of product
formulation or mixture) including in textiles, apparel and leather manufacturing.
5.2.1.8 Processing - Incorporation into articles - Other, including in Plastic
Product Manufacturing (Processing into articles in plastic product
manufacturing)
Section 6(b)(4)(A) unreasonable risk determination for processing of NMP for incorporation into articles
in other sectors, including in plastic product manufacturing: Presents an unreasonable risk of injury
to health (workers); does not present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the processing of NMP for incorporation_into articles in other sectors,
including in plastic product manufacturing presents an unreasonable risk is based on the comparison of
the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other considerations. As
explained in Section 5.1, EPA also considered the health effects of NMP, the exposures from the
condition of use, and the uncertainties in the analysis (Section 4.3), including uncertainties related to the
exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
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EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
• Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of the unloading of various
containers, which EPA expects presents the largest range of potential exposures, though EPA
does expect that workers may perform additional activities during this scenario, such as sampling
or maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from processing of NMP for incorporation into articles in other sectors, including plastic product
manufacturing.
5.2.1.9 Processing - Repackaging - Wholesale and Retail Trade (Processing for
repackaging)
Section 6(b)(4)(A) unreasonable risk determination for processing of NMP for repackaging in wholesale
and retail trade: Presents an unreasonable risk of injury to health (workers); does not present an
unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the processing of NMP for repackaging in wholesale and retail trade_presents
an unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-55) and other considerations. As explained in Section 5.1, EPA also considered the
health effects of NMP, the exposures from the condition of use, and the uncertainties in the analysis
(Section 4.3), including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of unloading of various containers,
which EPA expects presents the largest range of potential exposures, though EPA does expect
that workers may perform additional activities during this scenario, such as sampling or
maintenance work.
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In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the processing of NMP for repackaging in wholesale and retail trade.
5.2.1.10 Processing - Recycling - Recycling (processing as recycling)
Section 6(b)(4)(A) unreasonable risk determination for recycling of NMP: Presents an unreasonable
risk of injury to health (workers); does not present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the recycling of NMP presents an unreasonable risk is based on the
comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other
considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of unloading of various containers
containing waste NMP, which EPA expects presents the largest range of potential exposures,
though EPA does expect that workers may perform additional activities during this scenario,
such as sampling or maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the recycling of NMP.
5.2.1.11 Distribution in Commerce
Section 6(b)(4)(A) unreasonable risk determination for distribution in commerce of NMP: Does not
present an unreasonable risk of injury to health (workers and ONUs).
For the purposes of the unreasonable risk determination, distribution in commerce of NMP is the
transportation associated with the moving of NMP in commerce. EPA is assuming that workers and
ONUs will not be handling NMP because the loading and unloading activities are associated with other
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conditions of use and EPA assumes transportation of NMP is in compliance with existing regulations for
the transportation of hazardous materials (49 CFR 172). Emissions are therefore minimal during
transportation, so there is limited exposure (with the exception of spills and leaks, which are outside the
scope of the risk evaluation). Based on the limited emissions and exposures from the transportation of
chemicals, EPA determined there is no unreasonable risk of injury to health (workers and ONUs) from
the distribution in commerce of NMP.
5.2.1.12 Industrial and Commercial Use - Paints and coatings - Paint and Coating
Removers; Adhesive Removers (paint, coating, and adhesive removers)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
paints, coatings, and adhesive removers: Presents an unreasonable risk of injury to health (workers).
For workers, EPA found that there was unreasonable risk of non-cancer effects from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
(reproductive) from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin
exposures at the central tendency.
EPA's determination that the industrial and commercial use of NMP in paint, coating, and adhesive
removers presents an unreasonable risk is based on the comparison of the risk estimates for non-cancer
effects to the benchmarks (Table 4-55) and other considerations. As explained in Section 5.1, EPA also
considered the health effects of NMP, the exposures from the condition of use, and the uncertainties in
the analysis (Section 4.3), including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the central
tendency and high-end support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end
do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of application exposures to paints,
coatings, adhesives, and sealant removal products containing NMP in miscellaneous paint and
coating removal and graffiti removal. While EPA does expect that workers may perform
additional activities during this scenario, such as unloading or sampling, EPA expects that
removal activities present the largest range of potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in paints, coatings, and adhesive removers.
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5.2.1.13 Industrial and Commercial Use - Paints and coatings - Lacquers, stains,
varnishes, primers and floor finishes; Powder coatings (surface
preparation) (paints and coatings)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
paints and coatings in lacquers, stains, varnishes, primers and floor finishes, and powder coatings in
surface preparation: Presents an unreasonable risk of injury to health (workers); does not present an
unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from chronic
(reproductive) inhalation and dermal exposures at the high-end, even when assuming use of PPE.
For ONUs, EPA found that there was no unreasonable risk of non-cancer effects from acute
(developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at the central
tendency.
EPA's determination that the industrial and commercial use of NMP in paints and coatings in lacquers,
stains, varnishes, primers and floor finishes, and powder coatings in surface preparation presents an
unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-55) and other considerations. As explained in Section 5.1, EPA also considered the
health effects of NMP, the exposures from the condition of use, and the uncertainties in the analysis
(Section 4.3), including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the high-
end support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end
do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of spray, roll/curtain, dip, and brush
application exposures to paints, coatings, adhesives, and sealants containing NMP. While EPA
does expect that workers may perform additional activities during this scenario, such as
unloading or sampling, EPA expects that application activities present the largest range of
potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in paints and coatings in lacquers, stains, varnishes,
primers and floor finishes, and powder coatings in surface preparation.
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5.2.1.14 Industrial and Commercial Use - Paint additives and coating additives not
described by other codes - Use in Computer and Electronic Product
Manufacturing in Electronic Parts Manufacturing (Electronic Parts
Manufacturing)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
paint additives and coating additives not described by other codes in computer and electronic product
manufacturing in electronic parts manufacturing: Presents an unreasonable risk of injury to health
(workers); does not present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the industrial and commercial use of NMP in paint additives and coating
additives not described by other codes in computer and electronic product manufacturing in electronic
parts manufacturing presents an unreasonable risk is based on the comparison of the risk estimates for
non-cancer effects to the benchmarks (Table 4-55) and other considerations. As explained in Section
5.1, EPA also considered the health effects of NMP, the exposures from the condition of use, and the
uncertainties in the analysis (Section 4.3), including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of capacitor, resistor, coil,
transformer, and other inductor manufacturing, which EPA expects present the largest range of
potential exposures, though EPA does expect that workers may perform additional activities
during this scenario, such as sampling or maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in paint additives and coating additives not described by
other codes in computer and electronic product manufacturing in electronic parts manufacturing.
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5.2.1.15 Industrial and Commercial Use - Paint additives and coating additives not
described by other codes - Use in Computer and Electronic Product
Manufacturing in Semiconductor Manufacturing (Semiconductor
Manufacturing)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
paint additives and coating additives not described by other codes in computer and electronic product
manufacturing for use in semiconductor manufacturing: Presents an unreasonable risk of injury to
health (workers); does not present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the industrial and commercial use of NMP in paint additives and coating
additives not described by other codes in computer and electronic product manufacturing for use in
semiconductor manufacturing presents an unreasonable risk is based on the comparison of the risk
estimates for non-cancer effects to the benchmarks (Table 4-55) and other considerations. As explained
in Section 5.1, EPA also considered the health effects of NMP, the exposures from the condition of use,
and the uncertainties in the analysis (Section 4.3), including uncertainties related to the exposures for
ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the central
tendency and high-end in container handling small container activities and waste truck loading
support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the high-
end in container handling drum activities support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute and chronic inhalation and dermal exposures at
the high-end in maintenance activities support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high end
in container handling small container, container handling drums, and waste truck loading
activities do not support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute and chronic inhalation and dermal exposures at
the high end in fab worker activities do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
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• Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of activities in semiconductor
manufacturing, including exposures from container handling small containers, container
handling drums, fab workers, maintenance, and waste truck loading activities, which EPA
expects present the largest range of potential exposures, though EPA does expect that workers
may perform additional activities during this scenario, such as sampling work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in paint additives and coating additives not described by
other codes in computer and electronic product manufacturing for use in semiconductor manufacturing.
5.2.1.16 Industrial and Commercial Use -Paint additives and coating additives not
described by other codes - Use in Construction, Fabricated Metal Product
Manufacturing, Machinery Manufacturing, Other Manufacturing, Paint
and Coating Manufacturing, Primary Metal Manufacturing,
Transportation Equipment Manufacturing, Wholesale and Retail Trade
(paint additives and coating additives not described by other codes, other
manufacturing and trade)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
paint additives and coating additives not described by other codes in multiple manufacturing sectors:
Presents an unreasonable risk of injury to health (workers); does not present an unreasonable risk of
injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from chronic
(reproductive) inhalation and dermal exposures at the high-end, even when assuming use of PPE.
For ONUs, EPA found that there was no unreasonable risk of non-cancer effects from acute
(developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at the central
tendency.
EPA's determination that the industrial and commercial use of NMP in paint additives and coating
additives not described by other codes in multiple manufacturing sectors presents an unreasonable risk is
based on the comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and
other considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the high-
end support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end
do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation and
vapor-through-skin exposures for workers directly handling the chemical substance. To account
for this uncertainty, EPA considered the workers' central tendency risk estimates from inhalation
exposures when determining ONUs' unreasonable risk.
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• Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of spray, roll/curtain, dip, and brush
application exposures to paint additives and coating additives containing NMP. While EPA does
expect that workers may perform additional activities during this scenario, such as unloading or
sampling, EPA expects that application activities present the largest range of potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP paint additives and coating additives not described by
other codes in multiple manufacturing sectors.
5.2.1.17 Industrial and Commercial Use - Solvents (for cleaning or degreasing) -
Use in Electrical Equipment, Appliance and Component Manufacturing
(Solvents for electrical equipment, appliance and component
manufacturing)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP as a
solvent (for cleaning or degreasing) in electrical equipment appliance and component manufacturing:
Presents an unreasonable risk of injury to health (workers); does not present an unreasonable risk of
injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the industrial and commercial use of NMP as a solvent (for cleaning or
degreasing) in electrical equipment, appliance and component manufacturing presents an unreasonable
risk is based on the comparison of the risk estimates for non-cancer effects to the benchmarks (Table
4-55) and other considerations. As explained in Section 5.1, EPA also considered the health effects of
NMP, the exposures from the condition of use, and the uncertainties in the analysis (Section 4.3),
including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of capacitor, resistor, coil,
transformer, and other inductor manufacturing, which EPA expects presents the largest range of
potential exposures, though EPA does expect that workers may perform additional activities
during this scenario, such as sampling or maintenance work.
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In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP as a solvent (for cleaning or degreasing) in electrical
equipment, appliance and component manufacturing.
5.2.1.18 Industrial and Commercial Use - Solvents (for cleaning or degreasing) -
Use in Electrical Equipment, Appliance and Component Manufacturing
in Semiconductor Manufacturing (Solvents for electrical equipment,
appliance and component manufacturing in semiconductor
manufacturing)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP as a
solvent (for cleaning or degreasing) in electrical equipment appliance and component manufacturing for
use in semiconductor manufacturing: Presents an unreasonable risk of injury to health (workers);
does not present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the industrial and commercial use of NMP as a solvent (for cleaning or
degreasing) in electrical equipment, appliance and component manufacturing for use in semiconductor
manufacturing presents an unreasonable risk is based on the comparison of the risk estimates for non-
cancer effects to the benchmarks (Table 4-55) and other considerations. As explained in Section 5.1,
EPA also considered the health effects of NMP, the exposures from the condition of use, and the
uncertainties in the analysis (Section 4.3), including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the central
tendency and high-end in container handling small container and waste truck loading activities
support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the high-
end in container handling drum activities support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute and chronic inhalation and dermal exposures at
the high-end in maintenance activities support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end in virgin
NMP truck unloading activities support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end
in container handling small container, container handling drums, and waste truck loading
activities do not support an unreasonable risk determination.
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•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute and chronic inhalation and dermal exposures at
the high-end in fab worker activities do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of activities in semiconductor
manufacturing, including exposures from container handling small containers, container
handling drums, fab workers, maintenance, virgin NMP truck unloading, and waste truck loading
activities, which EPA expects presents the largest range of potential exposures, though EPA does
expect that workers may perform additional activities during this scenario, such as sampling
work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP as a solvent (for cleaning or degreasing) in electrical
equipment, appliance and component manufacturing for use in semiconductor manufacturing.
5.2.1.19 Industrial and Commercial Use - Ink, toner, and colorant products -
Printer ink; Inks in writing equipment (Ink, toner, and colorant products)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
ink, toner, and colorant products in printer ink and inks in writing equipment: Does not present an
unreasonable risk of injury to health (workers and ONUs).
For workers, EPA did not identify an unreasonable risk of non-cancer effects from acute
(developmental) and chronic (reproductive) inhalation and dermal exposures at the central tendency and
high-end when considering use of PPE. For ONUs, EPA did not identify an unreasonable risk of non-
cancer effects from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin
exposures at the central tendency.
EPA's determination that the industrial and commercial use of NMP in ink, toner, and colorant products
in printer ink and inks in writing equipment does not present an unreasonable risk is based on the
comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other
considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute and chronic inhalation and dermal exposures at
the central tendency and high-end do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
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EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
• Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of inhalation, vapor-through-skin,
and dermal exposures to inks containing NMP during printing activities and dermal exposures to
inks containing NMP during writing activities. While EPA does expect that workers may
perform additional activities during this scenario, such as unloading or maintenance activities,
EPA expects that printing and writing activities present the largest range of potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from the industrial and commercial use of NMP in ink, toner, and colorant products in
printer ink and inks in writing equipment.
5.2.1.20 Industrial and Commercial Use - Processing aids, specific to petroleum
production - Petrochemical Manufacturing; - Other uses - Other uses in
Oil and Gas Drilling, Extraction and Support Activities; Functional fluids
(closed systems) (petrochemical manufacturing and other uses in oil and
gas drilling and as functional fluids (closed systems))
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
processing aids, specific to petroleum production in petrochemical manufacturing, in other uses in oil
and gas drilling, extraction and support activities, and in functional fluids (closed systems): Presents an
unreasonable risk of injury to health (workers); does not present an unreasonable risk of injury to
health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the industrial and commercial use of NMP in processing aids, specific to
petroleum production in petrochemical manufacturing, other uses in oil and gas drilling, extraction and
support activities, and in functional fluids (closed systems) presents an unreasonable risk is based on the
comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other
considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
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EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
• Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of the unloading of various
containers, which EPA expects presents the largest range of potential exposures, though EPA
does expect that workers may perform additional activities during this scenario, such as sampling
or maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in processing aids, specific to petroleum production in
petrochemical manufacturing, other uses in oil and gas drilling,_extraction and support activities, and in
functional fluids (closed systems).
5.2.1.21 Industrial and Commercial Use - Adhesives and Sealants - Adhesives and
sealant chemicals including binding agents; Single component glues and
adhesives, including lubricant adhesives; Two-component glues and
adhesives, including some resins (Adhesives and Sealants)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
adhesives and sealants including binding agents, single component glues and adhesives. including
lubricant adhesives. and two-component glues and adhesives including some resins: Presents an
unreasonable risk of injury to health (workers); does not present an unreasonable risk of injury to
health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from chronic
(reproductive) inhalation and dermal exposures at the high-end, even when assuming use of PPE.
For ONUs, EPA found that there was no unreasonable risk of non-cancer effects from acute
(developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at the central
tendency.
EPA's determination that the industrial and commercial use of NMP in adhesives and sealants including
binding agents, single component glues and adhesives, including lubricant adhesives, and two-
component glues and adhesives including some resins presents an unreasonable risk is based on the
comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other
considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the high-
end support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end
do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
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EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
• Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of spray, roll/curtain, dip, and brush
application exposures to paints, coatings, adhesives, and sealants containing NMP. While EPA
does expect that workers may perform additional activities during this scenario, such as
unloading or sampling, EPA expects that application activities present the largest range of
potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in adhesives and sealants including binding agents,
single component glues and adhesives, including lubricant adhesives, and two-component glues and
adhesives including some resins.
5.2.1.22 Industrial and Commercial Use - Other Uses - Soldering materials
(soldering materials)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
other uses in soldering materials: Does not present an unreasonable risk of injury to health (workers and
ONUs).
For workers, EPA did not identify an unreasonable risk of non-cancer effects from acute
(developmental) and chronic (reproductive) inhalation and dermal exposures at the central tendency and
high-end when considering use of PPE. For ONUs, EPA did not identify an unreasonable risk of non-
cancer effects from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin
exposures at the central tendency.
EPA's determination that the industrial and commercial use of NMP in other uses in soldering materials
does not present an unreasonable risk is based on the comparison of the risk estimates for non-cancer
effects to the benchmarks (Table 4-55) and other considerations. As explained in Section 5.1, EPA also
considered the health effects of NMP, the exposures from the condition of use, and the uncertainties in
the analysis (Section 4.3), including uncertainties related to the exposures for occupational non-users:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute and chronic inhalation and dermal exposures at
the high-end do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of inhalation, vapor-through-skin,
and dermal exposures to NMP during soldering activities. While EPA does expect that workers
may perform additional activities during this scenario, such as unloading or maintenance
activities, EPA expects that soldering activities present the largest range of potential exposures.
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In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from the industrial and commercial use of NMP in other uses in soldering materials.
5.2.1.23 Industrial and Commercial Use - Other Uses - Anti-freeze and de-icing
products; Automotive care products; Lubricants and greases (automotive
products)
Section 6(b)(4)(A) unreasonable risk determination for industrial and commercial use of NMP in other
uses in anti-freeze and de-icing products, automotive care products, and lubricants and greases: Presents
an unreasonable risk of injury to health (workers); does not present an unreasonable risk of injury to
health (ONUs).
For workers, EPA identified an unreasonable risk of non-cancer effects (reproductive) from
chronic inhalation and dermal exposures at the high-end, even when considering use of PPE. For
ONUs, EPA did not identify an unreasonable risk of non-cancer effects from acute (developmental) and
chronic (reproductive) inhalation and vapor-through-skin exposures at the central tendency.
EPA's determination that the industrial and commercial use of NMP in other uses in anti-freeze and de-
icing products, automotive care products, and lubricants and greases presents an unreasonable risk is
based on the comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and
other considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the high-
end support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end
do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of automotive servicing with
products containing NMP. For this commercial exposure scenario, EPA assessed inhalation,
vapor-through-skin, and dermal exposures to products containing NMP during aerosol
degreasing of automotive brakes. While EPA does expect that workers may perform additional
activities during this scenario, such as unloading or sampling, EPA expects that aerosol
degreasing activities present the largest range of potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in other uses in anti-freeze and de-icing products,
automotive care products, and lubricants and greases.
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5.2.1.24 Industrial and Commercial Use - Other Uses - Metal products not
covered elsewhere; Lubricant and lubricant additives, including
hydrophilic coatings (metal products and lubricant and lubricant
additives)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
other uses in metal products not covered elsewhere, and lubricants and lubricant additives including
hydrophilic coatings: Presents an unreasonable risk of injury to health (workers); does not present
an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the industrial and commercial use of NMP in other uses in metal products not
covered elsewhere, and lubricants and lubricant additives including hydrophilic coatings presents an
unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-55) and other considerations. As explained in Section 5.1, EPA also considered the
health effects of NMP, the exposures from the condition of use, and the uncertainties in the analysis
(Section 4.3), including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of metal finishing products
containing NMP, including brush, spray, and dip applications.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in other uses in metal products not covered elsewhere,
and lubricants and lubricant additives including hydrophilic coatings.
5.2.1.25 Industrial and Commercial Use - Other Uses - Laboratory chemicals
(laboratory chemicals)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
other uses in laboratory chemicals: Presents an unreasonable risk of injury to health (workers); does
not present an unreasonable risk of injury to health (ONUs).
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For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the industrial and commercial use of NMP in other uses in laboratory
chemicals presents an unreasonable risk is based on the comparison of the risk estimates for non-cancer
effects to the benchmarks (Table 4-55) and other considerations. As explained in Section 5.1, EPA also
considered the health effects of NMP, the exposures from the condition of use, and the uncertainties in
the analysis (Section 4.3), including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of exposure to 100% NMP during
laboratory activities. While EPA does expect that workers may perform additional activities
during this scenario, such as unloading, EPA expects that laboratory use activities present the
largest range of potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in other uses in laboratory chemicals.
5.2.1.26 Industrial and Commercial Use - Other Uses - Lithium Ion battery
manufacturing (Lithium Ion battery manufacturing)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
other uses in lithium ion battery manufacturing: Presents an unreasonable risk of injury to health
(workers); does not present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that the industrial and commercial use of NMP in other uses in lithium ion battery
manufacturing presents an unreasonable risk is based on the comparison of the risk estimates for non-
cancer effects to the benchmarks (Table 4-55) and other considerations. As explained in Section 5.1,
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EPA also considered the health effects of NMP, the exposures from the condition of use, and the
uncertainties in the analysis (Section 4.3), including uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end in small
container handling, drum handling, research and development, and miscellaneous activities
support an unreasonable risk determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from chronic inhalation and dermal exposures at the high-
end in cathode coating and cathode slurry mixing activities support an unreasonable risk
determination.
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 10, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high end
in cathode coating and cathode slurry mixing activities do not support an unreasonable risk
determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of activities in other uses in lithium
ion battery manufacturing, including exposures from small container handling, drum handling,
cathode coating, cathode slurry mixing, research and development, and miscellaneous activities,
which EPA expects present the largest range of potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in other uses in lithium ion battery manufacturing.
5.2.1.27 Industrial and Commercial Use - Other Uses - Cleaning and furniture
care products, including wood cleaners, gasket removers (cleaning and
furniture care products)
Section 6(b)(4)(A) unreasonable risk determination for industrial and commercial use of NMP in other
uses in cleaning and furniture care products, including wood cleaners and gasket removers: Presents an
unreasonable risk of injury to health (workers); does not present an unreasonable risk of injury to
health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
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EPA's determination that the industrial and commercial use of NMP in other uses in cleaning and
furniture care products, including wood cleaners and gasket removers presents an unreasonable risk is
based on the comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and
other considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and chronic inhalation and dermal exposures at the central tendency and high-end support an
unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of exposure to cleaning products
containing NMP from the following dip cleaning and degreasing, and spray and wipe cleaning.
While EPA does expect that workers may perform additional activities during this scenario, such
as unloading or sampling, EPA expects that cleaning activities present the largest range of
potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from the industrial and commercial use of NMP in other uses in cleaning and furniture care products,
including wood cleaners and gasket removers.
5.2.1.28 Industrial and Commercial Use - Other Uses - Fertilizer and other
agricultural chemical manufacturing - processing aids and solvents
(fertilizer manufacturing)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of NMP in
other uses in fertilizer and other agricultural chemical manufacturing, processing aids and solvents: Does
not present an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA did not identify an unreasonable risk of non-cancer effects from acute
(developmental) and chronic (reproductive) inhalation and dermal exposures at the central tendency and
high-end when considering use of PPE. For ONUs, EPA did not identify an unreasonable risk of non-
cancer effects from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin
exposures at the central tendency.
EPA's determination that the industrial and commercial use of NMP in other uses in fertilizer and other
agricultural chemical manufacturing, processing aids and solvents does not present an unreasonable risk
is based on the comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-55)
and other considerations. As explained in Section 5.1, EPA also considered the health effects of NMP,
the exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for occupational non-users:
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•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute and chronic inhalation and dermal exposures at
the high-end do not support an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of exposures during application of
fertilizers. While EPA does expect that workers may perform additional activities during this
scenario, such as unloading or maintenance activities, EPA expects that fertilizer application
presents the largest range of potential exposures.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from the industrial and commercial use of NMP in other uses in fertilizer and other
agricultural chemical manufacturing, processing aids and solvents.
5.2.1.29 Consumer Use - Paints and coatings - Paint and coating removers (paint
and coating removers)
Section 6(b)(4)(A) unreasonable risk determination for consumer use of NMP in paint and coating
removers: Does not present an unreasonable risk of injury to health (consumers and bystanders).
For consumers, EPA found that there was no unreasonable risk of non-cancer effects (developmental)
from acute inhalation, dermal, and vapor-through-skin exposures at the moderate and high intensity use.
For bystanders, EPA found there was no unreasonable risk of non-cancer effects (developmental) from
acute inhalation and vapor-through-skin exposures at the high intensity use.
EPA's determination that the consumer use of NMP in paint and coating removers presents no
unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-56) and other considerations. As explained in Section 5.1, EPA also considered the
health effects of NMP, the exposures from the condition of use, and the uncertainties in the analysis
(Section 4.3):
•	For consumers, the risk estimates of non-cancer effects from acute inhalation, dermal, and vapor-
through-skin exposures do not support an unreasonable risk determination.
•	Risk estimates for the consumer use of NMP in paint and coating removers were based on
modeled risk estimates from 35 products.
•	Consumer exposure resulting from inhalation, dermal and vapor through skin results were
assessed using modeled data as inputs to the PBPK model.
•	The PBPK model was used to derive internal exposure estimates for consumer and bystander
acute exposures. The PBPK model required a set of input parameters related to exposure by the
dermal and inhalations routes; NMP weight fraction in the liquid product, total skin surface area
of hands in contact with the liquid product; duration of dermal contact with the liquid product;
air concentration for inhalation and vapor-through-skin exposure; and body weight of the
exposed consumer/user.
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In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health
(consumers and bystanders) from the consumer use of NMP in paint and coating removers.
5.2.1.30 Consumer Use - Paints and coatings - Adhesive removers (adhesive
removers)
Section 6(b)(4)(A) unreasonable risk determination for consumer use of NMP in adhesive removers:
Does not present an unreasonable risk of injury to health (consumers and bystanders).
For consumers, EPA found that there was no unreasonable risk of non-cancer effects (developmental)
from acute inhalation, dermal, and vapor-through-skin exposures at the moderate and high intensity use.
For bystanders, EPA found there was no unreasonable risk of non-cancer effects (developmental) from
acute inhalation and vapor-through-skin exposures.
EPA's determination that the consumer use of NMP in adhesive removers does not present an
unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-56) and other considerations. As explained in Section 5.1, EPA also considered the
health effects of NMP, the exposures from the condition of use, and the uncertainties in the analysis
(Section 4.3):
•	Risk estimates for the consumer use of NMP in adhesive removers were based on modeled risk
estimates from five products.
•	Consumer exposure resulting from inhalation, dermal and vapor through skin results were
assessed using modeled data as inputs to the PBPK model.
•	The PBPK model was used to derive internal exposure estimates for consumer acute exposures.
The PBPK model required a set of input parameters related to exposure by the dermal and
inhalations routes; NMP weight fraction in the liquid product, total skin surface area of hands in
contact with the liquid product; duration of dermal contact with the liquid product; air
concentration for inhalation and vapor-through-skin exposure; and body weight of the exposed
consumer/user.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health
(consumers and bystanders) from the consumer use of NMP in adhesive removers.
5.2.1.31 Consumer Use - Paints and coatings - Lacquers, stains, varnishes,
primers and floor finishes (lacquers, stains, varnishes, primers and floor
finishes)
Section 6(b)(4)(A) unreasonable risk determination for consumer use of NMP in paints and coatings in
lacquers, stains, varnishes, primers and floor finishes: Does not present an unreasonable risk of injury to
health (consumers and bystanders).
For consumers, EPA found that there was no unreasonable risk of non-cancer effects (developmental)
from acute inhalation, dermal, and vapor-through-skin exposures at the moderate and high intensity use.
For bystanders, EPA found there was no unreasonable risk of non-cancer effects (developmental) from
acute inhalation and vapor-through-skin exposures.
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EPA's determination that the consumer use of NMP in paints and coatings in lacquers, stains, varnishes,
primers and floor finishes does not present an unreasonable risk is based on the comparison of the risk
estimates for non-cancer effects to the benchmarks (Table 4-56) and other considerations. As explained
in Section 5.1, EPA also considered the health effects of NMP, the exposures from the condition of use,
and the uncertainties in the analysis (Section 4.3):
•	Risk estimates for the consumer use of NMP in lacquers, stains, varnishes, primers and floor
finishes were based on modeled risk estimates from nine products.
•	Consumer exposure resulting from inhalation, dermal and vapor through skin results were
assessed using modeled data as inputs to the PBPK model.
•	The PBPK model was used to derive internal exposure estimates for consumer acute exposures.
The PBPK model required a set of input parameters related to exposure by the dermal and
inhalations routes; NMP weight fraction in the liquid product, total skin surface area of hands in
contact with the liquid product; duration of dermal contact with the liquid product; air
concentration for inhalation and vapor-through-skin exposure; and body weight of the exposed
consumer/user.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health
(consumers and bystanders) from the consumer use of NMP in paints and coatings in lacquers, stains,
varnishes, primers and floor finishes.
5.2.1.32 Consumer Use - Paint additives and coating additives not described by
other codes - Paints and Arts and Crafts Paints (paint additives and
coating additives not described by other codes)
Section 6(b)(4)(A) unreasonable risk determination for consumer use of NMP in paint additives and
coating additives not described by other codes in paints and arts and crafts paints: Does not present an
unreasonable risk of injury to health (consumers and bystanders).
For consumers, EPA found that there was no unreasonable risk of non-cancer effects (developmental)
from acute inhalation, dermal, and vapor-through-skin exposures at the moderate and high intensity use.
For bystanders, EPA found there was no unreasonable risk of non-cancer effects (developmental) from
acute inhalation and vapor-through-skin exposures.
EPA's determination that the consumer use of NMP in paint additives and coating additives not
described by other codes in paints and arts and crafts paints does not present an unreasonable risk is
based on the comparison of the risk estimates for non-cancer effects to the benchmarks (Table 4-56) and
other considerations. As explained in Section 5.1, EPA also considered the health effects of NMP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3):
•	Risk estimates for the consumer use of NMP in paint additives and coating additives not
described by other codes were based on modeled risk estimates from four products, and two
consumer exposure scenarios, paint and arts and crafts.
•	Consumer exposure resulting from inhalation, dermal and vapor through skin results were
assessed using modeled data as inputs to the PBPK model.
•	The PBPK model was used to derive internal exposure estimates for consumer acute exposures.
The PBPK model required a set of input parameters related to exposure by the dermal and
inhalations routes; NMP weight fraction in the liquid product, total skin surface area of hands in
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contact with the liquid product; duration of dermal contact with the liquid product; air
concentration for inhalation and vapor-through-skin exposure; and body weight of the exposed
consumer/user.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health
(consumers and bystanders) from the consumer use of NMP in paint additives and coating additives not
described by other codes in paints and arts and crafts paints.
5.2.1.33 Consumer Use - Adhesives and sealants - Glues and adhesives, including
lubricant adhesives (adhesives and sealants)
Section 6(b)(4)(A) unreasonable risk determination for consumer use of NMP in adhesives and sealants
in glues and adhesives, including lubricant adhesives and sealants: Presents an unreasonable risk of
injury to health (consumers); does not present an unreasonable risk of injury to health (bystanders).
For consumers, EPA found there was unreasonable risk of non-cancer effects (development) from
acute inhalation, dermal, and vapor-through-skin exposures at the high intensity use. For
bystanders, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute inhalation and vapor-through-skin exposures at the high intensity use.
EPA's determination that the consumer use of NMP in adhesives and sealants in glues and adhesives,
including lubricant adhesives and sealants presents an unreasonable risk is based on the comparison of
the risk estimates for non-cancer effects to the benchmarks (Table 4-56) and other considerations. As
explained in Section 5.1, EPA also considered the health effects of NMP, the exposures from the
condition of use, and the uncertainties in the analysis (Section 4.3):
•	Risk estimates for the consumer use of NMP in adhesives and sealants were based on modeled
risk estimates from four products and two consumer exposure scenarios, high weight fraction
adhesives and sealants and low weight fraction adhesives and sealants.
•	Consumer exposure resulting from inhalation, dermal and vapor through skin results were
assessed using modeled data as inputs to the PBPK model.
•	The PBPK model was used to derive internal exposure estimates for consumer and bystander
acute exposures. The PBPK model required a set of input parameters related to exposure by the
dermal and inhalations routes; NMP weight fraction in the liquid product, total skin surface area
of hands in contact with the liquid product; duration of dermal contact with the liquid product;
air concentration for inhalation and vapor-through-skin exposure; and body weight of the
exposed consumer/user.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (consumers)
from the consumer use of NMP in adhesives and sealants in glues and adhesives, including lubricant
adhesives and sealants.
5.2.1.34 Consumer Use - Other uses - Automotive care products (automotive care
products)
Section 6(b)(4)(A) unreasonable risk determination for consumer use of NMP in other uses in
automotive care products: Does not present an unreasonable risk of injury to health (consumers and
bystanders).
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For consumers, EPA found that there was no unreasonable risk of non-cancer effects (developmental)
from acute inhalation, dermal and vapor-through-skin exposures at the moderate and high intensity use.
For bystanders, EPA found there was no unreasonable risk of non-cancer effects (developmental) from
acute inhalation and vapor-through-skin exposures.
EPA's determination that the consumer use of NMP in other uses in automotive care products does not
present an unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to
the benchmarks (Table 4-56) and other considerations. As explained in Section 5.1, EPA also considered
the health effects of NMP, the exposures from the condition of use, and the uncertainties in the analysis
(Section 4.3):
•	Risk estimates for the consumer use of NMP in automotive care products were based on modeled
risk estimates from two products and two consumer exposure scenarios, auto interior cleaner and
auto interior spray cleaner.
•	Consumer exposure resulting from inhalation, dermal and vapor through skin results were
assessed using modeled data as inputs to the PBPK model.
•	The PBPK model was used to derive internal exposure estimates for consumer acute exposures.
The PBPK model required a set of input parameters related to exposure by the dermal and
inhalations routes; NMP weight fraction in the liquid product, total skin surface area of hands in
contact with the liquid product; duration of dermal contact with the liquid product; air
concentration for inhalation and vapor-through-skin exposure; and body weight of the exposed
consumer/user.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health
(consumers and bystanders) for the consumer use of NMP in other uses in automotive care products.
5.2.1.35 Consumer Use - Other Uses - Cleaning and furniture care products,
including wood cleaners, gasket removers (cleaning and furniture care
products)
Section 6(b)(4)(A) unreasonable risk determination for consumer use of NMP in other uses in cleaning
and furniture care products, including wood cleaners and gasket removers: Does not present an
unreasonable risk of injury to health (consumers and bystanders).
For consumers, EPA found there was no unreasonable risk of non-cancer effects (developmental) from acute
inhalation, dermal and vapor-through-skin exposures at the moderate and high intensity use. For bystanders,
EPA found there was no unreasonable risk of non-cancer effects (developmental) from acute inhalation and
vapor-through skin exposures at the high intensity use.
EPA's determination that the consumer use of NMP in other uses in cleaning and furniture care products,
including wood cleaners and gasket removers does not present an unreasonable risk is based on the comparison
of the risk estimates for non-cancer effects to the benchmarks (Table 4-56) and other considerations. As
explained in Section 5.1, EPA also considered the health effects of NMP, the exposures from the condition of
use, and the uncertainties in the analysis (Section 4.3):
• For consumers, the risk estimates of non-cancer effects from acute inhalation, dermal and vapor-
through skin exposures do not support an unreasonable risk determination.
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•	Risk estimates for the consumer use of NMP in cleaning and furniture care products were based
on modeled risk estimates from 10 products and two consumer exposure scenarios,
cleaners/degreasers and engine cleaner/degreaser.
•	Consumer exposure resulting from inhalation, dermal and vapor through skin results were
assessed using modeled data as inputs to the PBPK model.
•	The PBPK model was used to derive internal exposure estimates for consumer and bystander
acute exposures. The PBPK model required a set of input parameters related to exposure by the
dermal and inhalations routes; NMP weight fraction in the liquid product, total skin surface area
of hands in contact with the liquid product; duration of dermal contact with the liquid product;
air concentration for inhalation and vapor-through-skin exposure; and body weight of the
exposed consumer/user.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health
(consumers and bystanders) for the consumer use of NMP in other uses in cleaning and furniture care
products, including wood cleaners and gasket removers.
5.2.1.36 Consumer Use - Other Uses - Lubricant and lubricant additives;
including hydrophilic coatings (lubricant and lubricant additives,
including hydrophilic coatings)
Section 6(b)(4)(A) unreasonable risk determination for consumer use of NMP in other uses in lubricant
and lubricant additives, including hydrophilic coatings: Does not present an unreasonable risk of injury
to health (consumers and bystanders).
For consumers, EPA found that there was no unreasonable risk of non-cancer effects (developmental)
from acute inhalation, dermal and vapor-through-skin exposures at the moderate and high intensity use.
For bystanders, EPA found there was no unreasonable risk of non-cancer effects (developmental) from
acute inhalation and vapor-through-skin exposures.
EPA's determination that the consumer use of NMP in other uses in lubricant and lubricant additives,
including hydrophilic coatings does not present an unreasonable risk is based on the comparison of the
risk estimates for non-cancer effects to the benchmarks (Table 4-56) and other considerations. As
explained in Section 5.1, EPA also considered the health effects of NMP, the exposures from the
condition of use, and the uncertainties in the analysis (Section 4.3):
•	Risk estimates for the consumer use of NMP in lubricant and lubricant additives, including
hydrophilic coatings were based on modeled risk estimates from one spray product.
•	Consumer exposure resulting from inhalation, dermal and vapor through skin results were
assessed using modeled data as inputs to the PBPK model.
•	The PBPK model was used to derive internal exposure estimates for consumer acute exposures.
The PBPK model required a set of input parameters related to exposure by the dermal and
inhalations routes; NMP weight fraction in the liquid product, total skin surface area of hands in
contact with the liquid product; duration of dermal contact with the liquid product; air
concentration for inhalation and vapor-through-skin exposure; and body weight of the exposed
consumer/user.
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In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health
(consumers and bystanders) for the consumer use of NMP in other uses in lubricant and lubricant
additives, including hydrophilic coatings.
5.2.1.37 Disposal - Disposal - Industrial pre-treatment; industrial wastewater
treatment; publicly owned treatment works (POTW); underground
injection; landfill (municipal, hazardous or other land disposal); emissions
to air; incinerators (municipal and hazardous waste) (disposal)
Section 6(b)(4)(A) unreasonable risk determination for disposal of NMP: Presents an unreasonable
risk of injury to health (workers); does not present an unreasonable risk of injury to health (ONUs).
For workers, EPA found that there was unreasonable risk of non-cancer effects from acute
(developmental) inhalation and dermal exposures at the high-end, and from chronic
(reproductive) inhalation and dermal exposures at the central tendency and high-end, even when
assuming use of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects
from acute (developmental) and chronic (reproductive) inhalation and vapor-through-skin exposures at
the central tendency.
EPA's determination that disposal of NMP presents an unreasonable risk is based on the comparison of
the risk estimates for non-cancer effects to the benchmarks (Table 4-55) and other considerations. As
explained in Section 5.1, EPA also considered the health effects of NMP, the exposures from the
condition of use, and the uncertainties in the analysis (Section 4.3), including uncertainties related to the
exposures for ONUs:
•	For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute inhalation and dermal exposures at the high-end,
and from chronic inhalation and dermal exposures at the central tendency and high-end support
an unreasonable risk determination.
•	Based on EPA's analysis, the data for worker and ONU inhalation exposures could not be
distinguished; however, ONU inhalation exposures are assumed to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for this uncertainty,
EPA considered the workers' central tendency risk estimates from inhalation and vapor-through-
skin exposures when determining ONUs' unreasonable risk.
•	Inhalation, vapor-through-skin, and dermal exposures were assessed by inputting exposure
parameters into a PBPK model. The model is representative of waste NMP unloading activities,
which EPA expects presents the largest range of potential exposures, though EPA does expect
that workers may perform additional activities during this scenario, such as sampling or
maintenance work.
In summary, the risk estimates, the health effects of NMP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers)
from disposal of NMP.
5.2.1.38 General Population
Section 6(b)(4)(A) unreasonable risk determination for all conditions of use of NMP: Does not present
an unreasonable risk of injury to health (general population). For all conditions of use, EPA determined
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that exposures to ambient water, ambient air, and land-applied biosolids do not support an unreasonable
risk determination. EPA based this determination on an evaluation of potential exposures to the general
population during problem formulation, environmental fate properties, and first tier screening level
analyses. EPA did not assess exposures from drinking water and disposal pathways because they fall
under the jurisdiction of other environmental statutes administered by EPA, i.e., CAA, SDWA, and
RCRA, and CERCLA. EPA has not developed recommended ambient water quality criteria for the
protection of human health for NMP. Exposure to the general population via surface water can occur
through recreational activities (e.g., swimming) and through consuming fish. EPA evaluated the human
health risks of potential acute incidental exposures via oral and dermal routes from recreational
swimming and determined that these risks are not unreasonable.
5.2.2 Environment
6(b)(4)(A) unreasonable risk determination for all conditions of use of NMP: Does not present an
unreasonable risk of injury to the environment (aquatic, sediment dwelling and terrestrial organisms).
For all conditions of use in ambient water, the RQ values (Table 4-2) do not support an unreasonable risk
determination for acute and chronic exposures to NMP for amphibians, fish, and aquatic invertebrates. To
characterize the exposure to NMP by aquatic organisms, modeled data were used to represent surface water
concentrations near facilities actively releasing NMP to surface water, and modeled concentrations were used to
represent ambient water concentrations of NMP. EPA considered the biological relevance of the species to
determine the COCs for the location of surface water concentration data to produce RQs, as well as frequency
and duration of the exposure.
NMP is not expected to partition to or accumulate in soil; rather, based on its physical and chemical
properties, it is expected to volatilize to air or migrate through soil into groundwater. Therefore, risk to
terrestrial organisms is not expected.
In summary, the risk estimates, the environmental effects of NMP, the exposures, physical chemical properties
of NMP and consideration of uncertainties support EPA's determination that there is no unreasonable risk to the
environment from all conditions of use of NMP.
5.3 Changes to the Unreasonable Risk Determination from Draft Risk
Evaluation to Final Risk Evaluation
In this final risk evaluation, EPA made changes to the unreasonable risk determinations for NMP
following the publication of the draft risk evaluation (Table 5-2), as a result of the analysis following
peer review and public comments. The changes are: an updated POD; removal of several processing and
industrial/commercial uses of NMP because they are not conditions of use under TSCA; revisions to the
subcategory of a consumer use; separating conditions of use to provide clearer unreasonable risk
determinations for conditions of use evaluated with multiple exposure scenarios; and addition of a
general population determination. Details of these changes are below.
In the final risk evaluation, EPA updated the POD for acute exposures from the draft risk evaluation
based on updated analyses performed in response to peer review comments. This updated POD for acute
exposures resulted in some changes to acute risk estimates, which impacted unreasonable risk
determinations.
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EPA has also removed several uses of NMP that are not conditions of use under TSCA. While use of
NMP as an inert ingredient in wood preservatives was included in the problem formulation and draft risk
evaluation, upon further analysis of the details of this process, EPA has determined that this use falls
outside TSCA's definition of "chemical substance." Under TSCA Section 3(2)(B)(ii), the definition of
"chemical substance" does not include any pesticide (as defined in the Federal Insecticide, Fungicide,
and Rodenticide Act (FIFRA)) when manufactured, processed, or distributed in commerce for use as a
pesticide. EPA received a public comment describing the use of NMP in wood preservatives. In this
case, NMP is used as an approved inert ingredient under FIFRA. EPA has concluded that this use of
NMP falls within the aforementioned definitional exclusion and NMP, for this use, is not a "chemical
substance" under TSCA.
Similarly, two uses of NMP in pharmaceutical manufacturing were included in the problem formulation
and draft risk evaluation, namely as one of the uses of NMP as a functional fluid in a closed system and
as one of the uses of NMP as an intermediate and reactant. Upon further analysis of the details of these
uses, EPA has determined that these uses fall-outside TSCA's definition of "chemical substance." Under
TSCA Section 3(2)(B)(vi), the definition of "chemical substance" does not include any food, food
additive, drug, cosmetic, or device (as such terms are defined in Section 201 of the Federal Food, Drug,
and Cosmetic Act) when manufactured, processed, or distributed in commerce for use as a food, food
additive, drug, cosmetic, or device. While EPA has identified industrial and commercial use of NMP as
a functional fluid (closed systems) and processing of NMP as a reactant or intermediate as conditions of
use of NMP when under the TSCA definition of chemical substance, EPA has removed mention of
pharmaceutical applications in these conditions of use. EPA has concluded that both uses of NMP fall
within the aforementioned definitional exclusion, and NMP, for these uses, is not a "chemical
substance" under TSCA.
In the draft risk evaluation, EPA made a preliminary determination for the consumer use of NMP as
adhesive and sealant, single component glues and adhesives, including lubricant additives and two-
component glues and adhesives, including some resins. After further review of the consumer products,
EPA has revised the subcategory in the final risk evaluation and renamed the condition of use to be
consumer use of NMP in adhesives and sealants in glues and adhesives, including lubricant adhesives
and sealants.
EPA uses representative Occupational Exposure Scenarios and Consumer Exposure Scenarios to
generate risk estimates. Sometimes the same Exposure Scenario is used for several conditions of use,
and some unreasonable risk determinations are based on multiple exposure scenarios. In the draft risk
evaluation, EPA made single preliminary determinations for several industrial and commercial uses of
NMP when many of these uses were represented by the same Occupational Exposure Scenarios. Based
on peer review, public comments, and data received, EPA has now made final unreasonable risk
determinations based on additional Occupational Exposure Scenarios that more accurately reflect
specific conditions of use of industrial and commercial use of NMP in paints and coatings, adhesives
and sealants, electrical equipment appliance and component manufacturing, semiconductor
manufacturing, and lithium ion battery manufacturing. As a result, two preliminary determinations in the
draft risk evaluation were separated into several unreasonable risk determination in this final risk
evaluation. Specifically, the preliminary unreasonable risk determination for the industrial and
commercial use of NMP in paints and coatings, paint additives and coating additives, and adhesives and
sealants not described by other codes was separated into five unreasonable risk determinations in the
final risk evaluation. The preliminary unreasonable risk determination for the industrial and commercial
use of NMP in solvents (for cleaning and degreasing) and for other uses in manufacturing lithium ion
batteries was separated into several unreasonable risk determinations in the final risk evaluation.
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In the final risk evaluation EPA added additional screening level analyses of general population oral and
dermal exposures to NMP in surface water. Exposure to the general population via surface water can
occur through recreational activities (e.g., swimming).
Table 5-2. Crosswalk of Updates in Presentation of Unreasonable Risk Determinations between
Draft and Final Risk Evaluations
I mviisoiiiihlo Risk l)iMcnnin;ilions in
l-'iiiiil Risk l-'.\iiliiiilion
I mviisoiiiihlo Risk Dolci'iniiiiilions in l)r;il'( Risk ;iln:ili«ui
• Industrial and commercial use in paints and
coatings in lacquers, stains, varnishes, primers
and floor finishes, and powder coatings in surface
preparation
• Industrial and commercial use in paint and coatings (lacquers, stains,
varnishes, primers and floor finishes, and powder coatings, surface
preparation), in paint additives and coating additives not described by other
codes in several manufacturing sectors, and in adhesives and sealants,
several types
• Industrial and commercial use in paint
additives and coating additives not described
by other codes in computer and electronic
product manufacturing in electronic parts
manufacturing.
• Industrial and commercial use in paint
additives and coating additives not described
by other codes in computer and electronic
parts manufacturing for use in semiconductor
manufacturing.
• Industrial and commercial use in paint
additives and coating additives not described
by other codes in multiple manufacturing
sectors
• Industrial and commercial use in adhesives
and sealants including binding agents, single
component glues and adhesives, including
lubricant adhesives, and two-component
glues and adhesives including some resins
• Industrial and commercial use as a solvent
(for cleaning or degreasing) in electrical
equipment, appliance and component
manufacturing
• Industrial and commercial use as a solvent (for cleaning or degreasing)
use in electrical equipment, appliance and component manufacturing and
for other uses in manufacturing lithium ion batteries
• Industrial and commercial use as a solvent
for cleaning and degreasing in electrical
equipment, appliance and component
manufacturing for use in semiconductor
manufacturing
• Industrial and commercial use in other uses
in lithium ion battery manufacturing
• Consumer use in adhesives and sealants in
glues and adhesives, including lubricant
adhesives and sealants
• Consumer use as adhesive and sealant, single component glues and
adhesives, including lubricant adhesives and two-component glues and
adhesives, including some resins
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5.4 Unreasonable Risk Determination Conclusion
5.4.1 No Unreasonable Risk Determinations
TSCA Section 6(b)(4) requires EPA to conduct risk evaluations to determine whether chemical
substances present unreasonable risk under their conditions of use. In conducting risk evaluations, "EPA
will determine whether the chemical substance presents an unreasonable risk of injury to health or the
environment under each condition of use within the scope of the risk evaluation..." 40 CFR 702.47.
Pursuant to TSCA Section 6(i)(l), a determination of "no unreasonable risk" shall be issued by order
and considered to be final agency action. Under EPA's implementing regulations, "[a] determination
made by EPA that the chemical substance, under one or more of the conditions of use within the scope
of the risk evaluations, does not present an unreasonable risk of injury to health or the environment will
be issued by order and considered to be a final Agency action, effective on the date of issuance of the
order." 40 CFR 702.49(d).
EPA has determined that the following conditions of use of NMP do not present an unreasonable risk of
injury to health or the environment:
•	Distribution in commerce (Section 5.2.1.11, Section 5.2.1.38, Section 5.2.2, Section 4, and
Section 3)
•	Industrial and commercial use in ink, toner, and colorant products in printer ink and inks in
writing equipment (Section 5.2.1.19, Section 5.2.1.38, Section 5.2.2, Section 4, and Section 3)
•	Industrial and commercial use in other uses in soldering materials (Section 5.2.1.22, Section
5.2.1.38, Section 5.2.2, Section 4, and Section 3)
•	Industrial and commercial use in other uses in fertilizer and other agricultural chemical
manufacturing, processing aids and solvents (Section 5.2.1.28, Section 5.2.1.38, Section 5.2.2,
Section 4, and Section 3)
•	Consumer use in paint and coating removers (Section 5.2.1.29, Section 5.2.1.38, Section 5.2.2,
Section 4, and Section 3)
•	Consumer use in adhesive removers (Section 5.2.1.30, Section 5.2.1.38, Section 5.2.2, Section 4,
and Section 3)
•	Consumer use in paints and coatings in lacquer, stains, varnishes, primers and floor finishes
(Section 5.2.1.31, Section 5.2.1.38, Section 5.2.2, Section 4, and Section 3)
•	Consumer use in paint additives and coating additives not described by other codes in paints and
arts and crafts paints (Section 5.2.1.32, Section 5.2.1.38, Section 5.2.2, Section 4, and Section 3)
•	Consumer use in other uses in automotive care products (Section 5.2.1.34, Section 5.2.1.38,
Section 5.2.2, Section 4, and Section 3)
•	Consumer use in other uses in cleaning and furniture care products, including wood cleaners,
gasket removers (Section 5.2.1.35, Section 5.2.1.38, Section 5.2.2, Section 4, and Section 3)
•	Consumer use in other uses in lubricant and lubricant additives, including hydrophilic coatings
(Section 5.2.1.36, Section 5.2.1.38, Section 5.2.2, Section 4, and Section 3)
This subsection of the final risk evaluation therefore constitutes the order required under TSCA Section
6(i)(l), and the "no unreasonable risk" determinations in this subsection are considered to be final
agency action effective on the date of issuance of this order. All assumptions that went into reaching the
determinations of no unreasonable risk for these conditions of use, including any considerations
excluded for these conditions of use, are incorporated into this order.
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The support for each determination of "no unreasonable risk" is set forth in Section 5.2 of the final risk
evaluation, "Detailed Unreasonable Risk Determinations by Condition of Use." This subsection also
constitutes the statement of basis and purpose required by TSCA Section 26(f).
5.4.2 Unreasonable Risk Determinations
EPA has determined that the following conditions of use of NMP present an unreasonable risk of injury
to health:
•	Domestic manufacture
•	Import
•	Processing: as a reactant or intermediate in plastic material and resin manufacturing and other
non-incorporative processing
•	Processing: incorporation into a formulation, mixture or reaction product in multiple industrial
sectors
•	Processing: incorporation into articles in lubricants and lubricant additives in machinery
manufacturing
•	Processing: incorporation into articles in paint additives and coating additives not described by
other codes in transportation equipment manufacturing
•	Processing: incorporation into articles as a solvent (which becomes part of product formulation
or mixture), including in textiles, apparel and leather manufacturing
•	Processing: incorporation into articles in other sectors, including in plastic product
manufacturing
•	Processing: repackaging in wholesale and retail trade
•	Processing: recycling
•	Industrial and commercial use in paints, coatings, and, adhesive removers
•	Industrial and commercial use in paints and coatings in lacquers, stains, varnishes, primers and
floor finishes, and powder coatings, surface preparation
•	Industrial and commercial use in paint additives and coating additives not described by other
codes in computer and electronic product manufacturing in electronic parts manufacturing
•	Industrial and commercial use in paint additives and coating additives not described by other
codes in computer and electronic product manufacturing for use in semiconductor manufacturing
•	Industrial and commercial use in in paint additives and coating additives not described by other
codes in several manufacturing sectors
•	Industrial and commercial use as a solvent (for cleaning or degreasing) use in electrical
equipment, appliance and component manufacturing
•	Industrial and commercial use as a solvent (for cleaning or degreasing) in electrical equipment,
appliance and component manufacturing for use in semiconductor manufacturing
•	Industrial and commercial use in processing aids, specific to petroleum production in
petrochemical manufacturing, in other uses in oil and gas drilling, extraction and support
activities, and in functional fluids (closed systems)
•	Industrial and commercial use in adhesives and sealants including binding agents, single
component glues and adhesives, including lubricant adhesives, and two-component glues and
adhesives including some resins
•	Industrial and commercial use in other uses in anti-freeze and de-icing products, automotive care
products, and lubricants and greases
•	Industrial and commercial use in other uses in metal products not covered elsewhere, and
lubricant and lubricant additives including hydrophilic coatings
•	Industrial and commercial use in other uses in laboratory chemicals
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•	Industrial and commercial uses in other uses in lithium ion battery manufacturing
•	Industrial and commercial use in other uses in cleaning and furniture care products, including
wood cleaners and gasket removers
•	Consumer use in adhesives and sealants in glues and adhesives, including lubricant adhesives
and sealants
•	Disposal
EPA will initiate TSCA Section 6(a) risk management actions on these conditions of use as required
under TSCA Section 6(c)(1). Pursuant to TSCA Section 6(i)(2), the "unreasonable risk" determinations
for these conditions of use are not considered final agency actions.
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Page 451 of 576
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APPENDICES
Appendix A REGULATORY HISTORY
- •« av *, •« \ -
-------
SlsiliiU's/Ucgiihilions
Description of Aiilhorily/Ucgiihilion
Description of Ucgiihilion

processed, or imported in the United
States.
review process (60 FR 16309,
March 29, 1995).
Toxic Substances
Control Act (TSCA) -
Section 8(e)
Manufacturers (including importers),
processors and distributors must
immediately notify EPA if they obtain
information that supports the conclusion
that a chemical substance or mixture
presents a substantial risk of injury to
health or the environment.
Seven notifications of substantial
risk (Section 8(e)) received (2007
- 2010) (US EPA, ChemView.
Accessed April 13, 2017).
Toxic Substances
Control Act (TSCA) -
Section 4
Provides EPA with authority to issue
rules and orders requiring manufacturers
(including importers) and processors to
test chemical substances and mixtures.
Six submissions from a test rule
(Section 4) received in the mid-
1990s. (US EPA, ChemView.
Accessed April 13, 2017).
Emergency Planning and
Community Right-To-
Know Act (EPCRA) -
Section 313
Requires annual reporting from facilities
in specific industry sectors that employ
10 or more full time equivalent
employees and that manufacture,
process, or otherwise use a TRI-listed
chemical in quantities above threshold
levels. A facility that meets reporting
requirements must submit a reporting
form for each chemical for which it
triggered reporting, providing data
across a variety of categories, including
activities and uses of the chemical,
releases and other waste management
(e.g., quantities recycled, treated,
combusted) and pollution prevention
activities (under Section 6607 of the
Pollution Prevention Act). This data
includes on-site and off-site data as well
as multimedia data (i.e., air, land and
water).
NMP is a listed substance subject
to reporting requirements under
40 CFR 372.65 effective as of
January 1, 1995.
Federal Food, Drug and
Cosmetic Act (FFDCA)
- Section 408
FFDCA governs the allowable residues
of pesticides in food. Section 408 of the
FFDCA provides EPA with the authority
to set tolerances (rules that establish
maximum allowable residue limits), or
exemptions from the requirement of a
tolerance, for all residues of a pesticide
(including both active and inert
ingredients) that are in or on food. Prior
to issuing a tolerance or exemption from
tolerance, EPA must determine that the
tolerance or exemption is "safe."
NMP is currently approved for
use as a solvent and co-solvent
inert ingredient in pesticide
formulations for both food and
non-food uses and is exempt from
the requirements of a tolerance
limit (40 CFR Part 180.920).
Page 453 of 576
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SlsiliiU's/Ucgiihilions
Description of Aiilhorily/Ucgiihilion
Description of Ucgiihilion

Sections 408(b) and (c) of the FFDCA
define "safe" to mean the Agency has a
reasonable certainty that no harm will
result from aggregate exposures to the
pesticide residue, including all dietary
exposure and all other exposure (e.g.,
non-occupational exposures) for which
there is reliable information. Pesticide
tolerances or exemptions from tolerance
that do not meet the FFDCA safety
standard are subject to revocation. In the
absence of a tolerance or an exemption
from tolerance, a food containing a
pesticide residue is considered
adulterated and may not be distributed in
interstate commerce.

Clean Air Act (CAA) -
Section 111 (b)
Requires EPA to establish new source
performance standards (NSPS) for any
category of new or modified stationary
sources that EPA determines causes, or
contributes significantly to, air pollution
which may reasonably be anticipated to
endanger public health or welfare. The
standards are based on the degree of
emission limitation achievable through
the application of the best system of
emission reduction which (considering
the cost of achieving reductions and non-
air quality health and environmental
impacts and energy requirements) EPA
determines has been adequately
demonstrated.
NMP is subject to CAA Section
111 Standards of Performance for
New Stationary Sources of Air
Pollutants for volatile organic
compound (VOC) emissions from
synthetic organic chemical
manufacturing industry
distillation operations (40 CFR
Part 60, subpart NNN) and
reactor processes (40 CFR Part
60, Subpart RRR).
Clean Air Act (CAA) -
Section 183(e)
Section 183(e) requires EPA to list the
categories of consumer and commercial
products that account for at least 80
percent of all VOC emissions in areas
that violate the National Ambient Air
Quality Standards for ozone and to issue
standards for these categories that
require "best available controls." In lieu
of regulations, EPA may issue control
techniques guidelines if the guidelines
are determined to be substantially as
effective as regulations.
NMP is listed under the National
Volatile Organic Compound
Emission Standards for Aerosol
Coatings (40 CFR part 59,
subpart E).
Clean Air Act (CAA) -
Section 612
Under Section 612 of the CAA, EPA's
Significant New Alternatives Policy
Under EPA's SNAP program,
EPA listed NMP as an acceptable
Page 454 of 576
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Maliilcs/Uegiilalions
Description of Authority/Regulation
Description of Regulation

(SNAP) program reviews substitutes for
ozone depleting substances within a
comparative risk framework. EPA
publishes lists of acceptable and
unacceptable alternatives. A
determination that an alternative is
unacceptable, or acceptable only with
conditions, is made through rulemaking.
substitute for "straight organic
solvent cleaning (with terpenes,
C620 petroleum hydrocarbons,
oxygenated organic solvents such
as ketones, esters, alcohols, etc.)"
for metals, electronics and
precision cleaning and
"Oxygenated organic solvents
(esters, ethers, alcohols, ketones)"
for aerosol solvents (59 FR,
March 18, 1994).
Safe Drinking Water Act
(SDWA) - Section 1412
(b)
Every 5 years, EPA must publish a list of
contaminants (1) that are currently
unregulated, (2) that are known or
anticipated to occur in public water
systems, and (3) which might require
regulations under SDWA. EPA must
also determine whether to regulate at
least five contaminants from the list
every 5 years.
NMP was identified on both the
Third (2009) and Fourth (2016)
Contaminant Candidate Lists (74
FR 51850, October 8, 2009) (81
FR 81099 November 17, 2016).
Other Federal Statutes/Regulations
Occupational Safety and
Health Act (OSHA)
Requires employers to provide their
workers with a place of employment free
from recognized hazards to safety and
health, such as exposure to toxic
chemicals, excessive noise levels,
mechanical dangers, heat or cold stress,
or unsanitary conditions.
Under the Act, OSHA can issue
occupational safety and health standards
including such provisions as Permissible
Exposure Limits (PELs), exposure
monitoring, engineering and
administrative control measures and
respiratory protection.
OSHA has not established a PEL
for NMP.
Federal Food, Drug and
Cosmetic Act (FFDCA)
Provides the U.S Food and Drug
Administration (FDA) with authority to
oversee the safety of food, drugs and
cosmetics.
Food and Drug Administration
identifies NMP as an "Indirect
Additive Used in Food Contact
Substances" specifically as:
1)	an adjuvant substance in the
preparation of slimicides (21 CFR
176.300),
2)	an adjuvant substance in the
production of polysulfone resin
Page 455 of 576
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Maliilcs/Ucgulalions
Description of Aiilhorily/Ucgulalion
Description of Regulation


authorized for use as articles
intended for use in contact with
food (21 CFR 177.1655) and
3) a residual solvent in
polyetherone sulfone resins
authorized as articles for repeated
use in contact with food (21 CFR
177.2440).
FDA also identifies NMP as a
Class 2 solvent, namely a solvent
that "should be limited in
pharmaceutical products because
of their inherent toxicity."
FDA established a Permissible
Daily Exposure (PDE) for NMP
of 5.3 mg/day with a
concentration limit of 530 ppm.
FDA's Center for Veterinary
Medicine developed a method in
2011 for detection of the residues
of NMP in edible tissues of cattle
(21 CFR 500.1410)
Federal Hazardous
Material Transportation
Act
Section 5103 of the Act directs the
Secretary of Transportation to: Designate
material (including an explosive,
radioactive material, infectious
substance, flammable or combustible
liquid, solid or gas, toxic, oxidizing or
corrosive material and compressed gas)
as hazardous when the Secretary
determines that transporting the material
in commerce may pose an unreasonable
risk to health and safety or property.
Issue regulations for the safe
transportation, including security of
hazardous material in intrastate,
interstate and foreign commerce.
The Department of
Transportation (DOT) has
designated NMP as a hazardous
material, and there are special
requirements for marking,
labeling and transporting it (49
CFR Part 171, 49 CFR 172, 40
CFR § 173.202 and 40 CFR §
173.242.
A.2 State Laws and Regulations
Table Apx A-2. State Laws and Regulations
State Actions
Description of Action
State Air
Regulations
New Hampshire (Env-A 1400: Regulated Toxic Air Pollutants) lists NMP as a
regulated toxic air pollutant.
Page 456 of 576
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Slate Actions
Description of Action

Vermont (Vermont Air Pollution Control Regulations, 5261) lists NMP as a
hazardous air contaminant.
Chemicals of
Concern to
Children
Several states have adopted reporting laws for chemicals in children's products that
include NMP including Oregon (OAR 333-016-2000), Vermont (18 V.S.A. Sections
1771 to 1779) and Washington state (WAC 173-334-130). Minnesota has listed
NMP as a chemical of concern to children (Minnesota Statutes 116.9401 to
116.9407).
State
Permissible
Exposure Limits
California PEL is 1 ppm as an 8hr TWA, along with a skin notation (Cal Code Regs,
title 8, Section 5155).
State Right-to-
Know Acts
Massachusetts (454 CMR 21.00), New Jersey (42 N.J.R. 1709(a)) and Pennsylvania
(Chapter 323. Hazardous Substance List).
Other
In California, NMP is listed on Proposition 65 (Cal. Code Regs. Title 27, Section
27001) due to reproductive toxicity. California OEHHA lists a Maximum Allowable
Dose Level (MADL) for inhalation exposure = 3,200 |ig/day MADL for dermal
exposure = 17,000 |ig/day.
The California Department of Toxic Substances Control (DTSC) Safer Consumer
Products Program lists NMP as a Candidate Chemical for development toxicity and
reproductive toxicity. In addition, DTSC is moving to address paint strippers
containing NMP and specifically cautioned against replacing methylene chloride
with NMP. In August 2018 the California DTSC Safer Consumer Products program
proposed to list Paint and Varnish Strippers and Graffiti Removers Containing NMP
as a priority product citing (1) potential for human and other organism exposure to
NMP in paint and varnish strippers and graffiti removers; and (2) the exposure has
the potential to contribute to or cause significant or widespread adverse impacts.
DTSC published a Product-Chemical Profile for Paint and Varnish. Strippers and
Graffiti Removers Containing NMP to support the listing. California Department of
Public Health's Hazard Evaluation System and Information Service (HESIS) issued
a Health Hazard Advisory on NMP in 2006 and updated the Advisory in June 2014.
The Advisory is aimed at workers and employers at sites where NMP is used.
A.3 International Laws and Regulations
Table Apx A-3. Regulatory Actions by Other Governments and Tribes
('oiintrv/Organi/ation
Requirements and Restrictions
European Union
In 2011, NMP was listed on the Candidate list as a Substance of Very High
Concern (SVHC) under regulation (EC) No 1907/2006 - REACH.
In March 2017, NMP was included in the public consultation of chemicals
recommended for inclusion in Annex XIV of the ECHA under Annex
(Authorisation list) of regulation (EC) No 1907/2006 - REACH.
In 2013, the Netherlands submitted a proposal under REACH to restrict
manufacturing and all industrial and professional uses of NMP where
Page 457 of 576
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C'ou ill rv/Orgsinizsil ion
Requirements siihI Restrictions

workers' exposure exceeds a level specified in the restriction ECHA
database. Accessed April 18, 2017).
On April 18, 2018, the European Union added NMP to REACH Annex
XVII, the restricted substances list. The action specifies three conditions of
restriction. The conditions are: 1) NMP shall not be placed on the market
as a substance on its own or in mixtures in concentrations greater than
0.3% after May 9, 2020, unless manufacturers, importers and downstream
users have included chemical safety reports and SDSs with Derived No-
Effect Levels (DNELs) relating to workers' exposures of 14,4 mg/m3 for
exposure by inhalation and 4,8 mg/kg/day for dermal exposure; 2) NMP
shall not be manufactured, or used, as a substance on its own or in mixtures
in a concentration equal to or greater than 0.3% after May 9, 2020 unless
manufacturers and downstream users take the appropriate risk management
measures and provide the appropriate operational conditions to ensure that
exposure of workers is below the DNELs specified above: and 3) the
restrictions above shall apply from May 9, 2024 to placing on the market
for use, or use, as a solvent or reactant in the process of coating wires.
Australia
NMP was assessed under Human Health Tier III of the Inventory Multi-
tiered Assessment and Prioritisation (IMAP) (National Industrial
Chemicals Notification and Assessment Scheme, NICNAS, 2017, Human
Health Tier III assessment for 2-Pyrrolidinone, 1 methyl-. Accessed
April, 18 2017).
Japan
NMP is regulated in Japan under the following legislation:
•	Act on the Evaluation of Chemical Substances and Regulation of
their Manufacture, etc. (Chemical Substances Control Law)
•	Industrial Safety and Health Act
(National Institute of Technology and Evaluation (NITE) Chemical Risk
Information Platform (CHIRP). Accessed April 18, 2017).
European Union and
Australia, Austria,
Belgium, Canada
(Ontario), Denmark,
Finland, France,
Germany, Ireland, Italy,
Latvia, New Zealand,
Poland, Spain, Sweden,
Switzerland, The
Netherlands, Turkey and
the United Kingdom.
Occupational exposure limits (OELs) for NMP (GESTIS International
limit values for chemical agents (OELs) database. Accessed April 18,
2017).
Page 458 of 576
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Appendix B LIST OF SUPPLEMENTAL DOCUMENTS
1.	Associated Systematic Review Data Quality Evaluation and Data Extraction Documents -
Provides additional detail and information on individual study or data evaluations and data
extractions including criteria and scoring results.
a.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Systematic Review Supplemental
File: Data Quality Evaluation of Environmental Fate and Transport Studies. Docket
EPA-HQ-OPPT-2019-0236 (U.S. EPA. 202010
b.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Systematic Review Supplemental
File: Data Quality Evaluation of Physical and Chemical Properties Studies. Docket EPA-
HQ-OPPT-2019-0236 (U.S. EPA... 2020a)
c.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Systematic Review Supplemental
File: Data Quality Evaluation of Environmental Release and Occupational Exposure
Data. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA... 2020i)
d.	Final Risk Evaluation for n-Methylpyrrolidone (NMP) Systematic Review Supplemental
File: Data Quality Evaluation of Environmental Release and Occupational Exposure
Data - Common Sources. Docket EPA-HQ-OPPT-2019-0236. (U.S. EPA. 2020k)
e.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Systematic Review Supplemental
File: Data Quality Evaluation of Consumer and General Population Exposure Studies.
Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2020g)
f.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Systematic Review Supplemental
File: Data Quality Evaluation of Ecological Hazard Studies. Docket EPA-HQ-OPPT-
2019-0236 Q ^ \ \l \ J020i)
g.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Systematic Review Supplemental
File: Data Quality Evaluation of Human Health Hazard Studies - Animal and In Vitro
Studies. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 20200
h.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Systematic Review Supplemental
File: Data Quality Evaluation of Human Health Hazard Studies - Epidemiological
Studies. Docket EPA-HQ-OPPT-2019-0236 (	»20m)
i.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Systematic Review Supplemental
File: Updates to the Data Quality Criteria for Epidemiological Studies. (U.S. EPA.
2020o)
j. Final Risk Evaluation for n-Methylpyrrolidone (NMP), Systematic Review Supplemental
File: Data Extraction Tables for Epidemiological Studies. Docket EPA-HQ-OPPT-2019-
0236 (U.S. EPA. 2020ir)
2.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Supplemental Information on
Occupational Exposure Assessment. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2020F) -
Provides additional details and information on the occupational exposure assessment including
PBPK modeling inputs and air concentration model equations, inputs, and outputs.
3.	Final Risk Evaluation for n-Methylpyrrolidone (NMP), Supplemental Information on Consumer
Exposure Assessment. Docket EPA-HQ-OPPT-2019-0236 (	20b) - Provides
additional details and information on the consumer exposure assessment, including Consumer
Exposure Model (CEM) approach, inputs and sensitivity analysis.
Page 459 of 576
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Final Risk Evaluation for n-Methylpyrrolidone (2-Pyrrolidinone, 1-Methyl-) (NMP), Benchmark
Dose Modeling Supplemental File. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2020e) -
Provides additional details and results of the benchmark dose modeling of the human health
hazard endpoints.
Final Risk Evaluation for n-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP),
Supplemental Information File on Occupational Risk Calculations. Docket EPA-HQ-OPPT-
2019-0236 (U.S. EPA. 2.020s)
Final Risk Evaluation for n-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP),
Supplemental Information on Consumer Exposure Assessment, Consumer Exposure Model and
Multi-Chamber Concentration and Exposure Model Input Parameters. Docket EPA-HQ-OPPT-
2019-0236 (U.S. EPA. 2020c)
Final Risk Evaluation for n-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP),
Supplemental Information File on Consumer Exposure Assessment, Consumer Exposure Model
and Multi-Chamber Concentration and Exposure Model Outputs. Docket EPA-HQ-OPPT-2019-
0236 (	)20d)
Final Risk Evaluation for n-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP),
Supplemental Information File on Consumer Exposure Assessment PBPK Model Inputs and
Outputs, and Consumer Risk Calculations. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA.
Final Risk Evaluation for n-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP),
Supplemental Information File on PBPK Model Code. Docket EPA-HQ-OPPT-2019-0236 (U.S.
EPA. 2020v)
Page 460 of 576
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Appendix C MASS BALANCE
EPA attempted to develop a mass balance to account for the amount of NMP entering and leaving all
facilities in the United States. EPA attempted to quantify the amount of NMP associated with each of its
life cycle stages from introduction into commerce in the U.S. (from both domestic manufacture and
import), processing, use, release, and disposal using 2016 CDR, 2015 TRI, literature, and public
comments. Due to limitations in the reasonably available data (e.g., reporting thresholds, CBI, data from
different years), the mass balance may not account for all of the NMP in commerce in the U.S. or could
potentially allocate portions of the production volume incorrectly. The following subsections described
EPA's approach to developing the mass balance and the result of the mass balance.
C.l Approach for Developing the Mass Balance
EPA used the reported aggregated production volume of 160,818,058 lbs from the 2016 CDR data as the
amount of NMP manufactured and imported to the U.S. (U.S. EPA. 2016a). Starting with this volume,
EPA attempted to estimate the portion of the volume used domestically versus or exported. The export
volume was estimated to be 14,601,983 lbs in 2015; however, this does not account for export volumes
claimed as CBI in the 2016 CDR (U.S. EPA. 2016a). The domestic use volume was assumed to be
anything not reported as exported in the 2016 CDR plus any volume reported as transferred for off-site
recycling in the 2015 TRI. EPA only considered the off-site recycling volume as EPA assumes any
volume reported for on-site recycling is reused at the site with consumption, disposal, and treatment of
the recycled volume accounted for in the facility's other reported TRI values and thus already accounted
for in the mass balance. EPA assumed the volume reported for off-site recycling is reintroduced into
commerce similar to virgin (i.e., unused directly from manufacturer or importer) NMP. This resulted in
a total of 158,320,923 lbs, or 98% of the total PV, being used domestically.
Use volumes were determined based on 2016 CDR (U.S. EPA. 2016a). EPA's 2015 TSCA Work Plan
Chemical Risk Assessment n-Methylpyrrolidone: Paint Stripper Use (U.S. EPA. ), public
comments (EaetePicfaer Technologies. 2020a; Fuiifilm Holdings America Corporation. 2020; Celanese
Engineer i i , Saft American. 2017; Thomas. 2017). and 2015 TRI releases for sites that use NMP
as a reactant (calculated with assumed reaction extent) (	). Based on these sources, an
estimated 25% of the domestic use volume (38,587,620 lbs) is used as a reactant, 9% (14,248,883 lbs) is
used for paint stripping, 1.5% (2,425,000 lbs), is used for chemical processing excluding formulation,
1.2% (1,847,567 lbs) is used in the electronics industry, 0.46% (728,000 lbs) is used in paints and
coatings, 0.33% (521,000 lbs) is used as a solvent for cleaning and degreasing, 0.11% (181,000 lbs) is
used in ink, toner, and colorant products, 0.002% (3,080 lbs) is used as a processing aid specific to
petroleum production, and 0.001% (1,760 lbs) is used in adhesives and sealants. Because some of these
estimates are from 2016 CDR (and does not account for CBI volumes) or from individual companies
and trade associations (as opposed to the entire industry), they may not represent the entire volume of
NMP for these uses. Therefore, the remaining 63% of the domestic use volume (99,507,013 lbs) is used
in miscellaneous uses, including those already mentioned.
During manufacture, processing, and use, a portion of volume of NMP at a given site may be released to
the environment or end up in waste streams that are ultimately sent for on- or off-site treatment,
disposal, energy recovery, or recycling. EPA used data from the 2015 TRI to quantify volumes
associated with each end-of-life activities (	016b). 2015 TRI data was grouped into the
following categories of end-of-life activities: wastewater discharges, water discharges, land disposal, air
emissions, off-site recycling, energy recovery, and waste treatment.
Page 461 of 576
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The volume estimated for wastewater discharges includes the total volume reported by facilities as
transferred to off-site wastewater treatment (non-POTW) and off-site POTW treatment. It does not
account for subsequent removal from wastewater streams into air or sludge that may occur at such
treatment sites. The volume estimated for water discharges includes volumes reported by facilities for
on-site surface water discharges. The amount calculated for land disposal includes the releases from all
on-site and off-site underground injection, surface impoundment, land application, landfills, and any
other land disposal reported in the 2015 TRI (U.S. EPA. 2016b). The volume estimated for air emissions
includes the total reported fugitive air emissions and stack air emissions from 2015 TRI reporters (U.S.
EPA. 2016bY
For recycling, TRI includes volumes for both on- and off-site recycling. As stated above, EPA assumed
that any volume reported for on-site recycle is reused at the site with consumption, disposal, and
treatment of the recycled volume accounted for in the facility's other reported TRI values and not further
considered for the mass balance. EPA assumed the volume reported for off-site recycling is reintroduced
into commerce similar to virgin {i.e., unused directly from manufacturer or importer) NMP.
Any unused, spent, or waste NMP not accounted for above is expected to be sent for further waste
treatment. These methods can be reported to TRI specifically as energy recovery or generally as waste
treatment. However, volumes reported as sent for off-site energy recovery or treatment can be double
counted if the site receiving the waste NMP is also required to report to TRI for NMP. To attempt to
account for these transfers, EPA mapped reported off-site transfers for treatment or energy recovery
using RCRA IDs and subtracted out any volume reported as transferred to another NMP reporter. The
treatment and energy recovery volumes also assume 100% destruction/removal efficiencies which is
likely unrealistic. Therefore, some portion of these values may also be counted in releases.
The end-of-life stage also accounts for NMP that is consumed in a reaction from reactant uses. To
estimate the amount that is consumed in reaction, EPA identified in the sites in TRI that report NMP
uses as a reactant and subtracted out the volume reported as released, disposed of, or otherwise managed
as waste at each site from the intermediate use volume and assumed the remainder was consumed. EPA
acknowledges that some portion of the intermediate use volume may remain as unintended impurities in
products from the reaction; however, this volume cannot be quantified.
C.2 Results and Uncertainties in the Mass Balance
FigureApx C-l shows the result of the mass balance. The overall percentage of NMP accounted for at
the end-of-life is 83% of the 2016 CDR production volume. The 17% of the volume that is unaccounted
for is most likely due to limitations in reporting requirements (e.g., reporting thresholds) for TRI
resulting in certain sites not being required to report. Other sources of uncertainty include comparison of
data from different years, calculated volume of NMP used as a reactant based on 2015 TRI data and
assumed reaction extent, CBI on exported volumes, double counting of treatment and energy recovery
volumes, and unknown volumes of unreacted NMP remaining in products.
Page 462 of 576
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PRODUCTION
USES
Manufacture and Import
Volume (lbs): 160.818,058
Total Domestic Manufacture.
Import, and Off-Site Recycle
Volume (lbs):
°/o of Total PV:
Volume (lbs):
% of Total PV:
Volume (lbs):
Paint Stripping
°/o of Total PV:
Volume (lbs):
Ink- toner, and Colorant products
0.110/6
181,000
°/o of Total PV:
Volume (lbs):
Intermediates
Paints and Coatings
% of Total PV:
Volume (lbs):
Adhesives and Sealants
°/o of Total PV:
Volume (lbs):
o/o of Total PV:
Volume (lbs):
Chemical processing, excluding
formulation
o/o of Total PV:
Volume (lbs):
Processing Aids, Specific to
Petroleum Production
o/o of Total PV:
Volume (lbs):
Solvents (for cleaning and
decreasing)
% of Total PV:
Volume (lbs):
Figure Apx C-l. NMP Mass Balance
Page 463 of 576
END OF LIFE
Unreacted NMP Remaining in Products
°/o of Total PV: Unknown
Volume (lbs):	Unknown	
o/o of Total PV
Volume (lbs):
Waste Treatment (Incineration)
7 J %
11*71,836
Water Discharges
°/0 of Total PV
Volume (lbs):
Wastewater Discharges
O/o of Total PV
Volume (lbs):
o/o of Total PV
Volume (lbs):
Land Disposal
% of Total PV
Volume (lbs):
O/b of Total PV
Volume (lbs):
Aii* Emissions
°/o of Total PV
Volume (lbs):
Off-site Recycled
Total Exported
% of Total PV	9.10/6
Volume (lbs): 14.601.983
Consumed in Reaction

o/o of Total PV 239 o
Volume (lbs): 36,914,739


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Appendix D FATE AND TRANSPORT
EPI Suite™ Model Inputs
To set up EPI Suite™ for estimating fate properties of NMP, NMP was identified using the "Name
Lookup" function. The physical and chemical properties were input based on the values in Table 1-1.
EPI Suite™ was run using default settings {i.e., no other parameters were changed or input).
EPI Suite
MPBPVP
wSKuW
WATERNT
KOCWIN
BCFBAF
oioHLwin
ECOSAR
EPI Links
File
Edit
Functions
Batch Mode
Show
Structure
Output
Fugacity
STP
Help
-|q|x
EPI Suite - Welcome Screen
PhysProp
Draw
Input CAS tt
Input Smiles:
Clear Input Fields
Output
Full
Summary
Input Chen, Name: N-METHYLPYRROLIDONE
Name Lookup
3.20E-09
Water Solubility
Henry LC
atm-m /mole
vapor Pressure:
25 Celsius
Melting Point:
Log Kow
202 Celsius
Boiling Point:
Water Depth:
meters/sec
Wind Velocity:
Current Velocity:
1E+006 mg/L
0.345 mm Hg
The Estimation Programs Interface (EPI) SuiteTM was developed by the US Environmental Protection Agency's Office of Pollution Prevention
and Toxics and Syracuse Research Corporation (SRC). It is a screening-level tool, intended for use in applications such as to quickly screen
chemicals for release potential and "bin" chemicals by priority for future work. Estimated values should not be used when experimental
(measured) values are available.
EPI SuiteTM cannot be used for all chemical substances. The intended application domain is organic chemicals. Inorganic and organometallic
chemicals generally are outside the domain.
Important information on the performance, development and application of EPI SuiteTM and the individual programs within it can be
found under the Help tab. Copyright 2000-2012 United States Environmental Protection Agency for EPI SuiteTM and all component
programs except BioHCWIN and KOAWIN.
FigureApx D-l. EPI Suite™ Model Inputs for Estimating NMP Fate and Transport Properties
Page 464 of 576
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Table Apx D-l. Biodegradation Study Summary for NMP
Sinclj Tjpe (jesir)
Inilisil
( onccnlrsilion
Inoculum
Source
(An isicrohic
Sisilus
Dursilion
Kcsull
( ommcnls
AITilisilcri
Reference
Dsilsi Qu;ilil\
l-'.\si In si 1 icin resn lis of
l ull Sinclj Report
\\ silcr
Other; Degradation
kinetics of NMP in
liquid culture under
various parameters
>500 to <2000
mg/L
activated sludge,
industrial,
adapted
aerobic
28h
Biodeeradation
Daramctcr: half-
lift:
50%/5.05h
The reviewer agreed
with this study's
overall quality level.
Cai et al.
High
Other; Semi-
continuous activated
sludge test following
ASTM (1975)
procedure for
biodegradation of
synthetic detergents
100 ppm
activated sludge,
domestic
(adaptation not
specified)
aerobic
7d
Biodeeradation
Daramctcr:
Dcrccnt removal:
95%/7d after 5-
day incremental
acclimation
period (primary
biodegradation;
complete
mineralization
not observed)
The reviewer agreed
with this study's
overall quality level.
Chow and Ng
High
Other; Static die-
away test similar to
the method
recommended by the
British Standard
Technical Committee
of Synthetic
Detergents
100 ppm
activated sludge,
domestic
(adaptation not
specified)
aerobic
14d
Biodeeradation
Daramctcr:
COD: 45%/14d;
Biodeeradation
Daramctcr:
Dcrccnt removal:
95%/14d
The reviewer agreed
with this study's
overall quality level.
Chow and Ng
(1983)
High
Coupled-units test
(adaptation of the
OECD Confirmatory
Test; OECD, 1976)
>12 mg C/L
Communal
sewage
treatment plant
effluent
(adaptation not
specified)
Aerobic
4-12 weeks
Biodeeradation
Daramctcr:
DOC: 99%
The reviewer agreed
with this study's
overall quality level.
Gerike and
Fischer (1979)
High
OECD-screening,
OECD 30IE
3-20 mg C/L
Surface water
Aerobic
19 days
Biodeeradation
Daramctcr:
DOC: 99%/l
day
The reviewer agreed
with this study's
overall quality level.
Gerike and
Fischer (1979)
High
Page 465 of 576
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EPA OPPTS
835.3200 (Zahn-
Wellens / EMPA
Test OECD 302B)
400 mg C/L
Industrial
sewage
treatment plant
Aerobic
14 days
Biodeeradation
Daramctcr:
DOC: 98%
The reviewer agreed
with this study's
overall quality level.
Gerike and
Fischer (1979)
High
EPA OPPTS
835.3110 (Ready
Biodegradability);
STURM OECD
30IB (C02
Evolution)
10 mg C/L
Surface water
Aerobic
28 days
Biodeeradation
Daramctcr:
DOC: 97%
The reviewer agreed
with this study's
overall quality level.
Gerike and
Fischer (1979)
High
EPA OPPTS
835.3100 (Aerobic
Aquatic
Biodegradation;
MITI OECD 301C)
50 mg C/L
Sewage
treatment plant
Aerobic
4 days
Biodeeradation
Daramctcr:
DOC: 95%
The reviewer agreed
with this study's
overall quality level.
Gerike and
Fischer (1979)
High
EPA OPPTS
835.3100 (Aerobic
Aquatic
Biodegradation;
Closed bottle OECD
301D)
1 mg C/L
Surface water
Aerobic
30 days
Biodeeradation
Daramctcr:
BODT30: 88%
The reviewer agreed
with this study's
overall quality level.
Gerike and
Fischer (1979)
High
Other; Method based
on Chow & Ng
(1983) The
biodegradation of n-
methyl-2-pyrrolidone
in water by sewage
bacteria. Water
Research 17, 117—
118.
50 g/L
Activated sludge
from municipal
wastewater
treatment plant
in Zlin, Czech
Republic and
from an
industrial WTP
in Slovenska
Lupca, Slovak
Republic
Aerobic
10 days
Biodeeradation
Daramctcr: test
material:
100%/4days
The reviewer agreed
with this study's
overall quality level.
Knzek et al.
(2015)
High
Other; semi-
continuous system
92-200 mg/L
Activated sludge
(adaptation not
specified) from
the Fukashiba
Joint Waste
Water Treatment
Plant
aerobic
24h
Biodeeradation
Daramctcr: TOC:
92%
Biodeeradation
Daramctcr:
oercent DOC:
94%
The reviewer agreed
with this study's
overall quality level.
Also reviewed in
HERO ID 4140473.
Matsui et al.
(1975)
High
Page 466 of 576
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Biodeeradation
Daramctcr:
Dcrccnt removal:
>98%



OECD Guideline 301
C (Ready
Biodegradability:
Modified MITI Test
(I)); Reported as
Japanese MITI test
Not reported in
secondary
source
activated sludge,
domestic
(adaptation not
specified)
aerobic
28d
Biodeeradation
Daramctcr:
BOD:
73%/28d
The reviewer agreed
with this study's
overall quality level.
and
Regulatory
Medium
Other;
Biodegradation of
NMP in municipal
sewage under static
and flow-through
conditions and
influence of NMP
concentrations on
non-adapted sludge
>50 to <20000
g/L
activated sludge,
adapted
aerobic
<206h
Biodeeradation
Daramctcr:
theoretical
oxveen uotake:
52-93%/<206h
The reviewer
downgraded this
study's overall
quality rating. They
noted: Analytical
methods were
unclear which limits
interpretation of the
study results.
Go mo Ilea and
Gomolka
Medium
Soil
Other; Non-guideline
laboratory test
1.7 mg/kg
three types of
soils (clay, loam,
and sand)
Not
specified
3 months
Biodeeradation
Daramctcr:
elimination half-
lift:
4.0 to 11.5d
(soil);
4.0, 8.7, and
11.5d (clay,
loam and sand)
Biodeeradation
Daramctcr:
Dcrccnt removal:
>90%/21d
The reviewer agreed
with this study's
overall quality level.
Shaver (1984)
Medium
Page 467 of 576
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Table Apx D-2. Photolysis Study Summary for n-Methyl-2-pyrrolidone
Sliiily Type (year)
\Ya\elen»th
R;m»e
Duration
Result
Comments
AITilialed
Reference
Data Quality K\aluation results of
l ull Study Report
Air
Other; Rate
constants for
atmospheric
reactions of 1-
methyl-2-
pyrrolidinone with
OH radicals, NO3
radicals, and O3
measured and
products of the OH
radical and NO3
radical reactions
investigated
>300 nm
8-25 min
Photodceradation
parameter: indirect
photolysis: rate constant:
for reaction with OH
radicals:
(2.15 ± 0.36)E-11 cm3
molecule"1 s"1;
Reaction with NO3
radicals: (1.26 ± 0.40)E-
13 cm3 molecule"1 s"1
The reviewer
agreed with this
study's overall
quality level.
Aschmann
and
Atkinson
(1999)
High
Water
Photocatalytic
decomposition in
aqueous solution
using light sources
of UVA, UVC, and
UVLED
254 nm to
385 nm
120 min
Photodeeradation
parameter: indirect
photolysis w/ and w/o
catalyst: rate constant:
0.0125 min"1 to 0.0454
min"1
Study performed
in the presence of
catalyst or at
wavelengths not
relevant to
environmental
conditions.
Aliabadi et
al. (2012)
Unacceptable
Page 468 of 576
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Appendix E RELEASES TO THE ENVIRONMENT
Systematic Review for Environmental Exposures
During problem formulation, it was determined that the aquatic exposure pathway would not be further
analyzed for NMP. The PECO was updated accordingly and all of the "on-topic" studies that entered the
process were screened out at Level 3, prior to data evaluation. However, "on-topic" exposure literature
for NMP did follow the systematic review process. 132 references were identified as "on-topic" and
subjected to an initial title/abstract screen (Level 1) and proceeded to full-text screening (Level 2 and 3).
29 references proceeded to a "Gateway" screen (Level 3), intended to consider alignment with the
current PECO. Only 22 references that entered Level 3 moved forward to data evaluation (Level 4).
First-tier Aquatic Exposure Assessment for NMP
EPA used data from EPA's TRI to estimate NMP concentrations released to ambient water by
discharging facilities. This "first-tier" exposure assessment was used to derive conservative estimates of
NMP surface water concentrations near facilities that reported the highest NMP water releases. EPA
identified the top 12 industries reporting the highest NMP water releases and used the reported
information to estimate surface water concentrations based on the 2015 TRI data and EPA's Exposure
and Fate Assessment Screening Tool, Version 2014. The environmental release data used for this first-
tier aquatic exposure assessment and reported in the NMP Problem Formulation can be found in Table
1-4 (U.S. EPA. 2018c). For this final risk evaluation, EPA also used updated, 2018 TRI release data.
Surface Water Concentrations
Surface water concentrations were estimated for multiple scenarios using E-FAST 2014, which can be
used to estimate site-specific surface water concentrations based on estimated loadings of NMP into
receiving water bodies. For TRI, the facilities' reported release quantities can be based on estimates
from monitoring data or measurements (i.e., continuous, random, or periodic), mass balance
calculations, published or site-specific emission factors, or other approaches such as engineering
calculations or best engineering judgment. E-FAST 2014 incorporates stream dilution at the point of
release using stream flow distribution data contained within the model. Site-specific stream flow data
are applied using a National Pollutant Discharge Elimination System (NPDES) code. If a specific
discharger's NPDES code could not be identified within the E-FAST database, a surrogate site or
generic Standard Industrial Classification (SIC) code was applied.
EPA considered multiple scenarios to estimate NMP concentrations in surface water resulting from
industrial discharges. EPA used the first-tier, PDM within EPA's Exposure and Fate Assessment
Screening Tool (E-FAST), and 2015 and more recent 2018 TRI facility release data, facilities reporting
the largest releases of NMP were modeled based on the assumption of 12 or 250 days of release. The 12-
day release scenario represents an acute exposure scenario wherein periodic maintenance and cleaning
activities could result in monthly releases. The 250-day release scenario represents a chronic exposure
scenario in which standard operations may result in continuous, or more protracted discharges of NMP.
Six facilities reported direct discharges of NMP to surface waters and seven facilities reported transfer
of NMP to a municipal treatment facility also known as a POTW facility for treatment and discharge
into surface waters.
EPA did not identify water monitoring data for NMP during its review of the national surface water
monitoring database. The 2015 and 2018 TRI data on direct and indirect environmental releases were
used to estimate NMP concentrations in surface water. Direct releases represent environmental releases
of NMP that are discharged directly from a facility into a receiving water body (after treatment),
Page 469 of 576
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whereas indirect releases are releases from the POTW where the facility has transferred NMP. The
POTW releases are discharges to surface water that occur following treatment. EPA used an estimated
removal rate of 92% in estimating NMP remaining in treated wastewater from indirect POTW
discharges. Because TRI reported facility direct releases are the amounts at discharge, EPA estimates of
surface water concentrations did not account for any additional treatment by an onsite system. The
predicted surface water concentrations presented in below in Table Apx E-l are associated with a low
flow - 7Q10, which is an annual minimum seven-day average stream flow over a ten-year recurrence
interval. No post-release degradation or removal mechanisms (e.g., hydrolysis, aerobic degradation,
photolysis, volatilization) are applied in the calculation of the modeled surface water concentrations.
For the facility transferring NMP waste to the POTW in Pensacola, Florida, the POTW diverts 85% of
its treated wastewater for reuse in other industrial facilities as process water. Only 15% of the treated
wastewater is discharged into the receiving water of Perdido Bay. EPA therefore, estimated the NMP
stream/receiving water concentration based on 15% of total NMP-containing treated wastewater
discharged.
To capture "high-end" surface water concentrations, EPA compiled the release data for nine facilities
that reported the largest NMP direct water releases. This represented 100 % of the total volume of NMP
reported as a direct discharge to surface water during the 2015 and 2018 TRI reporting periods. Since
there were many more facilities reporting indirect releases of NMP to surface water, seven of the
facilities reporting the largest indirect water releases (representing ~ 11% of the total number of facilities
reporting indirect discharges) were compiled. The volume of NMP released from these facilities
encompassed more than 87% of the total volume of NMP reported as an indirect discharge to surface
water.
The "high-end" surface water concentrations (i.e., those obtained assuming a low stream flow for the
receiving water body) from all PDM runs ranged from 4.2 |ig/L to 228 |ig/L, for the acute (i.e., fewer
than 20 days of environmental releases per year) and 1.6E-04 |ig/L to 1,022 |ig/L chronic exposure
scenario (i.e., more than 20 days of environmental releases per year assumed), respectively. The
maximum acute scenario concentration was 228 |ig/L and the maximum chronic scenario concentration
was 1,022 |ig/L. Comparing these concentrations with the respective aquatic ecological COCs of
100,000 |ig/L for acute and 1,770 |ig/L for chronic results in no exceedances for the acute scenario and
no exceedances for the chronic scenario > 20 days (see Table 4-2). EPA does not anticipate a concern to
aquatic organisms from NMP discharges to surface waters.
Page 470 of 576
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Table Apx E-l. Releases of NMP to Surface Waters


Onsilc NMP


l op l-'acililv Discharges
Waslew siler
NMP Transfers lo OITsile POTW'1'
(2015/2018)

Releases" (Ibs/vr)

(Ibs/vr)
l-'acililv
Si ale
2015
2018
2015
2018
Foilron Industries
iNC
8,987
250
0
0
Spruance Plant
VA
4,602
4,672
0
0
GlobalFoundries
VT
451
736
0
0
BASF Corp.
AL
N/A
550

0
American Refining Group
PA
26.83
13
0
0
Essex Group, Fort Wayne
IN
22.1
44
0

GlobalFoundries
NY
N/A
14

0
BASF Corp.
MI
2
11
269
304
Essex Group, Franklin
IN
N/A
2

0
Koch Membrane
MA


533,525
957,817
Pall Corp.,
FL


154,798
171,762
Air Products
MO


150,011
151,780
GVS; GE Healthcare:





Westborough POTW
MA


154,651
141,758
Intel, Aloha; Intel, Ronler





Acres: Rock Creek STP,





Hillsborob
OR


680,000
348,000
VeoliaES Technical





Solutions, LLC
NJ



395,169
Intel Corp
AZ



163,000
Caterpillar, Inc
IL



144,672
Cree, Inc
NC



142,605
Pall Filtration
CA



125,631
a GVS and GE Healthcare facilities both discharge to the same Massachusetts (MAO 100412) POTW. These releases
(89,958 lbs/yr and 51,800 lbs/yr, respectively in 2018 and 100,606 lbs/yr and 54,045 lbs/yr, respectively in 2015) were
combined to reflect POTW inflows.
b Intel-Aloha and Intel Ronler Campus both discharge to the Hillsboro POTW (Rock Creek STP, NPDES: OR0029777) so
their releases (98,0001b/yr and 250,000, respectively in 2018 and 170,000 and 510,000, respectively in 2015) were
combined to reflect the POTW inflows.
Table Apx E-2. Estimated NMP Surface Water Concentrations





PD.M: Si ream NMP
l op Kacililv Discharges
PD.M: Si ream NMP
('onccnlralions
(2015/2018)

('onccnlralions (2015)

(2018)





# Dsivs


# Dsivs




( (K

Chronic
( (K


Acule
Chronic
Kxceeded
Acule
250 or
Kxceeded


12 (lav
250 (lav
(1.770
12 dav
300 dav
(1.770
l-'acililv
Si ale
(MK/I-)
(ug/l.)
mk/i.)
(MS/I.)
(MK/I.)
mk/i.)
Direct Discharger Facilities
Fortran Industries,
NC
224.00
10.75
0
6.2
2.5E-01
0
Page 471 of 576
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l op Kacilitv Discharges
(2015/2018)
PD.M: Stream NMP
Concentrations (2015)
PD.M: Stream NMP
Concenl rat ions
(20IS)
l-'acilitv
State
Acute
12 (lav
(Mg/I.)
Chronic
250 (lav
(Mg/I.)
# Davs
(¦<>(¦
Kxceeded
(1.770
Mg/I.)
Acute
12 dav
(Mg/I-)
Chronic
250 or
300 day
(Mg/I.)
# Davs
COC
Kxceeded
(1.770
Mg/I )
Spruance Plant,
VA
119.70
5.75
0
121
4.9
0
GlobalFoundries
VT
44.49
2.14
0
73
3.4
0
BASF, Mcintosh
AL



7.6
2.9E-01
0
American Refining
Group
PA
8.49
4.0E-01
0
4.2
1.7E-01
0
Essex Group, Fort
Wayne
IN
5.56
2.7E-01
0
228
9.2
0
GlobalFoundries
NY



49
2.3
0
BASF Corp
MI
1.1E-03
4.9E-04
0
6.2E-03
5.4E-04
0
Essex Group
Franklin
IN



30
1.4
0
Indirect Discharger Facilities
Koch Membrane
MA

60
0

90
0
Pall Corp.a
FL

878
0

812
0
Air Products
MO

636
0

427
0
GVS; GE
Healthcareb
MA

1,327
0

1,012
0
Intel, Aloha; Intel,
Ronler Acres:
Rock Creekc
OR

1,995
2

1,022
0
Veolia ES
Technical
Solutions, LLC d
NJ




28
0
Intel Corp.6
AZ




0
0
Caterpillar, Inc
IL




8.6E-01
0
Cree, Inc d
NC




22
0
Pall Filtration
CA




36
0
a Surface water concentration represents 15% of Pall Corporation wastewater sent to POTW for treatment and release.
Remaining 85% of Pall Corporation discharges are sent to other industries for beneficial use.
b The total predicted NMP surface water concentration resulting from Westborough POTW releases is listed. The contribution
from GVS is 643 ug/L and GE Healthcare is 369ug/L in 2018 and 863 ug/L and 464 ug/L, respectively, in 2015.
0 The total predicted NMP surface water concentration resulting from Hillsboro POTW releases is listed. The contribution
from Intel, Aloha is 288 ug/L and Intel, Ronler Acres is 734 ug/L in 2018 and 499 ug/L and 1,496 ug/L, respectively in
2015.
d The Veolia and Cree facilities transfer wastewater to a wastewater treatment facility that treats and removes 92% NMP and
then is assumed to discharge remaining wastewater to the local POTW for treatment and discharge to surface waters
e The Intel, Chandler, Arizona facility discharges to several water reclamation facilities. These facilities do not discharge to
surface waters, instead treated wastewaters are used for groundwater recharge and/or beneficial use per Arizona state permit
requirements.
Page 472 of 576
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Appendix F OCCUPATIONAL EXPOSURES
Section F.l contains information gathered by EPA in support of understanding glove use for pure NMP
and for using NMP-containing formulations. For more information, including the results of an NMP
glove permeability study, refer to the Crook and Simpson (2007) citation noted below as Health Safety
Laboratory (2007).
F.l Information on Gloves for Pure NMP and for Formulations
containing NMP
Section F.l.l contains information gathered by EPA in support of understanding glove use for pure
NMP and for paint and coatings removal using NMP formulations. Section F.l.2 contains information
on gloves and respirators from SDSs for NMP and NMP-containing Products.
F.l.l Specifications for Gloves for Pure NMP and in Paint and Coating Removal
Formulations containing NMP
Section F.l.l contains information gathered by EPA in support of understanding glove use for pure
NMP and for paint and coatings removal using NMP formulations (EP A-HQ-OPPT-2016-C X'O).
This information may be generally useful for a broader range of uses of NMP and is presented for
illustrative purposes.
Summary on Suitable Gloves for Pure NMP and in Formulations
For scenarios where gloves can provide protection to achieve benchmark MOEs, gloves should be tested
to determine whether they are protective against the specific formulation of the product that contains
NMP. Several studies found in the literature indicate that the best types of glove material to protect
against dermal exposure to pure NMP are Silver Shield, Butyl Rubber and Ansell Barrier laminate film.
The next best types of glove among those studied to use for NMP exposure would be Neoprene and
Natural Rubber/Latex. Among the studies, Silver Shield provided the best protection against NMP,
whether it was in pure form or part of a tested formulation. Detailed information on these and other
glove types which were evaluated for their permeation characteristics against NMP are provided below.
The cited studies' results may be a good starting point for determining glove types to consider for glove
testing.
Gloves for Pure NMP
There are many factors that determine proper chemical-resistant glove selection. In addition to the
specific chemical(s) utilized, the most important factors include duration, frequency, and adversity of
chemical exposure. The degree of dexterity required for the task and associated physical stress to the
glove are also significant considerations. The manner in which employees are able to doff the various
glove types to best prevent skin contamination is also important but sometimes overlooked.
Generally, dermal exposures to the solvents in paint and coating removal formulations may be assumed
to be frequent or lengthy and may result in significant exposure. These assumptions affect the proper
choice of glove type and errs on the side of caution, which is advised for any PPE decision since PPE is
the last line of defense against exposure in an industrial hygienist's hierarchy of controls.
Table Apx F-l below summarizes commonly used industrial hygiene literature (e.g., glove selection
guides, manufacturer publications, etc.) and capture the highest rated glove types from each reference.
Consideration of all factors (breakthrough time, qualitative indicator (QI), and other issues raised in the
comments field) allow an overall determination of effectiveness.
Page 473 of 576
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Table Apx F-l. Glove Types Evaluated for Pure NMP
Reference
(ilo\e Type
Uresi kth rou »li
lime
Qn:ilil:ilne liuliciilor
Comments
1
Ansell Barrier
(Laminate Film)
Glove
>480 mins
Very well suited
Degradation rate: Good-
Excellent.
Permeation rate: Excellent
Natural Rubber
75 mins
Very well suited
Degradation rate: Excellent.
Permeation rate: Very Good
Butyl
>480 mins
Very well suited
Degradation rate: Excellent
2
Neoprene over
Natural Rubber (Best
Chem Master)
>480 mins
Safest, best selection
Highest rating attainable
Butyl
>480 mins
Safest, best selection
Highest rating attainable
Neoprene
(Chloroflex)
>480 mins
Safest, best selection
Highest rating attainable
4
Butyl
8 hrs
Good for total immersion
Degradation rate: Excellent
Natural Rubber
1.26 hrs
Good for accidental
splash protection and
intermittent contact
Degradation rate: Fair
Nitrile
1.45 hrs
Good for accidental
splash protection and
intermittent contact
Degradation rate: Fair
8
Neoprene
226 mins
Used for high chemical
exposure
Specific glove evaluated is
Chem Ply N-440
Natural Latex /
Neoprene / Nitrile
50 mins
Used for repeated
chemical contact
Specific glove evaluated is
Trionic 0-240
10
Silver Shield (North)
Not Provided
Recommended
Silver Shield and Butyl rubber
gloves are the only two glove
types recommended by this
source
Butyl
Not Provided
Recommended
Based on the information from Table Apx F-l, the three best types of glove material to protect against
pure NMP dermal exposure are Silver Shield, Butyl Rubber and Ansell Barrier laminate film. The next
best types of glove to use for pure NMP exposure would be Neoprene and Natural Rubber/Latex. As
mentioned previously, Silver Shield gloves do not provide acceptable dexterity for most workers, so
they are commonly worn as a base glove with a tighter-fitting glove (e.g., latex) over the top.
Alternatively, Butyl Rubber or Ansell Barrier laminate film gloves could be worn and would provide
significant protection.
Key Points and Examples for Paint and Coating Removal Formulations
The U.S. EPA's Safety, Health and Environmental Management Division's (SHEMD) Guideline 44
(Personal Protective Equipment) states that when working with mixtures and formulated products, the
chemical component with the shortest break-through time must be considered when determining the
appropriate glove type for protection against chemical hazards unless specific test data are available
(SHEMD. 2004). Additionally, an industrial hygienist will consider the formulation's chemical
Page 474 of 576
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properties, including the highest hazard component of the formulation, and whether individual
components produce synergistic degradation effects. Typically, specific test data for formulations are
not available and best judgment, based on these considerations provides the basis for glove type
selection. However, in this case there are a few publications that specifically address glove types for use
with methylene chloride and NMP as part of paint and coating removal formulations.
In early 2002, an article entitled "A Comparative Analysis of Glove Permeation Resistance to Paint
Stripping Formulations" (Stull et al. 2002) specifically examined which glove types provide the best
protection to users of commercial paint and coating removal products. Twenty different glove types
were evaluated for degradation and resistance to permeation under continuous and/or intermittent
contact with seven different paint and coating removal formulations in a multiple-phase experiment.
Paint and coating removal formulations included some that were methylene chloride-based and others
that were NMP-based. The study found that gloves made of Plastic Laminate (e.g., Silver Shield)
resisted permeation by the majority of paint and coating removal while Butyl Rubber provided the next
best level of permeation resistance against the majority of formulations. However, Butyl Rubber gloves
did show rapid permeation for methylene chloride-based formulations and would not be recommended
for methylene chloride. It should be noted that PVA gloves, shown to be effective against pure
methylene chloride, were not evaluated. Interestingly, more glove types resisted permeation of NMP -
based formulations than conventional solvent-based products such as methylene chloride. The results
showed that relatively small-molecule, volatile, chemical-based solvents cause somewhat more
degradation and considerably more permeation of glove types as compared with NMP-based
formulations against the same gloves. Key conclusions include the following: "However, paint stripper
formulations represent varying multichemical mixtures and, ultimately, commercial paint strippers must
be individually evaluated for permeation resistance against selected gloves" (Stull et al.. 2002). and,
"because of several potential synergistic effects well established in the literature and in this study for
mixture permeation, it is highly recommended that glove selection decisions be based on testing of the
commercial paint stripper against the specific glove in question" (Stull et al.. 2002).
Another study from in 2007 entitled "Protective Glove Selection for Workers using NMP-Containing
Products: Graffiti Removal" essentially came to the same conclusion; of the gloves studied Silver Shield
gloves provide the best protection against NMP-based paint and coating removal formulations (Health
Safety Laboratory. 2007). The study states that "Butyl gloves, used with caution would be a second
choice" (Health Safety Laboratory. 2007). The increased dexterity and robustness of Butyl gloves were
noted as an advantage of Butyl over Silver Shield. Key recommendations include that gloves should be
"tested against all relevant chemical formulations as a matter of routine in order to inform glove
selection" (Health Safety Laboratory. 2007) and "assumptions of glove choice based on the use of model
compounds or similar formulations should be made with extreme caution (Health Safety Laboratory.
2007)." Additionally, Crook recommended that "The BS EN 374-3 continuous contact test and its
successors should remain the benchmark for chemically protective glove type decisions" (Health Safety
Laboratory. 2007).
In summary, these studies indicate that glove permeation continuous contact testing of each
formulation is necessary to provide proper protection. These studies' results may be a good starting
point for determining glove types to consider for permeation testing. The studies found that among
gloves tested Silver Shield provide the best protection against both methylene chloride and NMP,
whether they are in pure form or as part of a tested formulation. The best alternative for protection
against methylene chloride would be PVA gloves, while the best alternative for NMP protection would
be Butyl Rubber gloves. A more task-specific decision on appropriate glove type selection could be
Page 475 of 576
-------
made through employee interviews and observation of tasks using methylene chloride- or NMP-
containing products.
F.1.2 Information on Gloves and Respirators from SDSs for NMP and NMP-containing
Products
EPA reviewed SDSs for neat NMP and products containing NMP for information on glove and
respiratory protection. Specifically, EPA reviewed SDSs for each occupational exposure scenario
assessed in Section 2.4.1.2. EPA compiled the recommended glove materials and respiratory protection
for each occupational exposure scenario from the reviewed SDSs (total of 21 SDSs were reviewed) in
Table Apx F-2. For neat NMP and NMP-containing products, the SDSs recommend a variety of glove
materials, including butyl rubber (8 SDSs), nitrile rubber (9 SDSs), neoprene (8 SDSs), natural rubber (4
SDSs), polyvinyl chloride (PVC) (4 SDSs), latex (2 SDSs), and Teflon (1 SDS). Note that many of the
reviewed SDSs included multiple glove material recommendations. Almost half of the reviewed SDSs
indicated that respiratory protection was not needed under normal conditions with adequate ventilation,
unless exposure limits are exceeded or workers experience irritation or other symptoms (10 of 21 SDSs).
Three SDSs recommend the use of respirators with organic vapor cartridges. Four SDSs recommend the
use of particulate filters in instances where mist or dusts may form while using the NMP-containing
product. Four SDSs recommend the use of a self-contained breathing apparatus (SCBA) for emergency
situations, such as spills, that can create intensive or prolonged exposure. Note that many of the
reviewed SDSs included respiratory protection recommendations, based on the exposure scenario (i.e.,
normal use, emergency, potential for mist or dust).
Page 476 of 576
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Table Apx F-2. Recommended Glove Materials and Respiratory Protection for NMP and N1V
P-Containing Products from SDSs
Applicable ()cciip;ition;il Kxposnre
SiTiiiirio
Mnlvrial. \MI>*\1.%
Recommended (Jo\e Mitleriitl
Recommended
Respii itloi x Protect ion
Source
Manufacturing; Repackaging; Chemical
Processing, Excluding Formulation;
Incorporation into a Formulation,
Mixture or Reaction Product;
Laboratory Use
Neat, 99-100%
Butyl rubber
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
Tedia High
Purity Solvents
(2011)
Manufacturing; Repackaging; Chemical
Processing, Excluding Formulation;
Incorporation into a Formulation,
Mixture or Reaction Product;
Laboratory Use
Neat, 99%
Nitrile rubber, neoprene, butyl
rubber
Industrial uses: Organic
gases and vapors filter
Type A Brown
conforming to EN14387.
Laboratory Use: Half
mask, Valve filtering; or,
Half mask, plus filter
I'hcimo Fisher
Scientific.
(2019)
Application of Paints, Coatings,
Adhesives and Sealants
Mixture, >85%
Butyl rubber or Teflon gloves
If vapors or mists are
generated, wear a
NIOSH/MSHA
approved organic
vapor/mist respirator or
an air supplied respirator
as appropriate. Use only
self-contained breathing
apparatus for
emergencies.
:K (2015)
Application of Paints, Coatings,
Adhesives and Sealants
Mixture, <1%
Polymer laminate; nitrile gloves
may be worn over polymer
laminate gloves to improve
dexterity
Half facepiece or full
facepiece air-purifying
respirator suitable for
organic vapors and
particulates.
3M (2018)
Application of Paints, Coatings,
Adhesives and Sealants
Mixture, <1%
Nitrile gloves
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
TLS (2013)
Page 477 of 576
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Applicable Occupntioiiiil Kxposure
Scenario
Malerial. \MI>*\1.%
Recommended (Jo\e M;ilcri;il
Reco m m ended
Resp i r:i (o r\ P rot eel i on
Source



exposure limits are
exceeded.

Printing and Writing
Mixture, >15%
Neoprene, butyl, or nitrile
rubber
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
Voxel Inc
(2015)
Printing and Writing
Mixture, 0-5%
Neoprene, butyl, or nitrile
rubber gloves with cuffs
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
Novaeemtrix
( )
Metal Finishing a
Mixture, 1-5%
Rubber gloves
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
U.S. Chemical
(2012)
Metal Finishing a; Automotive Car
Servicing (aerosol use)b
Mixture, unspecified NMP
concentration
Nitrile or polyvinyl chloride
(PVC) gloves
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
Simoniz USA
(2012)
Removal of Paints, Coatings, Adhesives,
and Sealants
Mixture, 20-30%
Butyl Rubber
Half facepiece or full
facepiece air-purifying
respirator suitable for
organic vapors.
3M (2014)
Removal of Paints, Coatings, Adhesives,
and Sealants
Mixture, 41%
Use gloves chemically resistant
to this material (Neoprene,
Nitrile, PVC)
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
ILS (2016)
Page 478 of 576
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Applicable Occupntioiiiil Kxposure


Reco m m ended

Scenario
Malerial. \MI>*\1.%
Recommended (Jo\e M;ilcri;il
Resp i r:i (o r\ P rot eel i on
Source



exposure limits are
exceeded.




Normal use: Use NIOSH




approved respiratory

Cleaning
Mixture, 90-95%
PVC-lined, latex, orNitrile
gloves
protection.
Emergency: Self-
contained breathing
apparatus, air-line
respirator, full-face
respirator
Crest (2011)




Normal use: not

Cleaning
Mixture, 1-5%
Natural Latex or Rubber
required.
Emergency: A2P2 -
Combo filter: gas filter
type A with medium
capacity and a class P2
particle filter.
Prestige (2010)



No specific respirator
recommended. SDS

Automotive Car Servicing (aerosol use)
b
Mixture, 30-40%
Neoprene
indicates to use an
approved respirator if
exposure limits are
exceeded.
Slide (2018)



In case of low exposure,

Electronics Manufacturing
Mixture, unspecified NMP
concentration
Butyl rubber
use cartridge respirator.
In case of intensive or
longer exposure, use
self-contained breathing
apparatus.
MicroChem
(2012)
Electronics Manufacturing
Mixture, 0-1%
Neoprene or natural rubber
gloves if handling an open or
leaking battery
Not necessary under
normal conditions.
Lenmar Battery
(2014)
Soldering
Mixture, 1-3%
Nitrile rubber or natural rubber
When ventilation is not
sufficient to remove
Kester (2017)
Page 479 of 576
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Applicable Occupntioiiiil Kxposure
Scenario
Malerial. \MI>*\1.%
Recommended (Jo\e Material
Reco in in ended
Resp i r:i (o r\ P rot eel i on
Source



fumes from the breathing
zone, a safety approved
respirator or self-
contained breathing
apparatus should be
worn.

Fertilizer Application
Mixture, <1%
Neoprene gloves
Wear air supplied
respiratory protection if
exposure concentrations
are unknown. In case of
inadequate ventilation or
risk of inhalation of dust,
use suitable respiratory
equipment with particle
filter.
Koch
(2011)
Fertilizer Application
Mixture, <10%
Chemical resistant gloves
Wear air supplied
respiratory protection if
exposure concentrations
are unknown. In case of
inadequate ventilation or
risk of inhalation of mist,
use suitable respiratory
equipment with particle
filter.
Koch
Agronomic
(2018)
Wood Preservatives
Mixture, <1%
Chemical-resistant gloves (such
as barrier laminate, butyl
rubber, nitrile rubber, neoprene
rubber, polyvinyl chloride,
vitro)
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
Osmose
Utilities (2015)
Page 480 of 576
-------
Applicable Occupntioiiiil Kxposure
Scenario
Malerial. \MI>*\1.%
Recommended (Jo\e M;ilcri;il
Reco m m ended
Resp i r:i (o r\ P rot eel i on
Source
Recycling and Disposalc
Reclaimed neat NMP, 99-
100%
Chemical resistant gloves
Use NIOSH-certified,
air-purifying respirators
with organic vapor
cartridges when
concentration of vapor or
mist exceeds applicable
exposure limits.
Protection provided by
air-purifying respirators
is limited.
Safetv-KJeen
(2015)
11 These products are recommended for use on metal parts, but EPA does not know the extent to which these products may be used within the six operations listed under
metal finishing at 40 CFR 433.10.
b These SDSs are for aerosol cleaning products. EPA does not know the extent to which these products are used in the automotive service industry.
0 Safety-Kleen is a waste management company; however, this SDS does not explicitly state that the NMP has been reclaimed.
Page 481 of 576
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Appendix G CONSUMER EXPOSURES
G.l Overview of the E-FAST/CEM Model
The Exposure and Fate Assessment Screening Tool Version 2 (E-FAST2) Consumer Exposure Module
(CEM) was selected for the consumer exposure modeling as the most appropriate model to use due to
the lack of reasonably available emissions and monitoring data for NMP uses other than paint removers
under consideration. Moreover, EPA did not have the input parameter data from specific NMP product
chamber studies required to run more complex indoor air models for the consumer products under the
scope of this assessment. CEM uses high-end input parameters/assumptions to generate conservative,
upper-bound inhalation exposure estimates for aerosol spray products. The advantages of CEM are the
following:
1.	CEM model has been peer-reviewed.
2.	CEM accommodates the inputs reasonably available for the products containing NMP in the indoor
air model.
3.	CEM uses the same calculation engine to compute indoor air concentrations from a source as the
Multi-Chamber Concentration and Exposure Model (MCCEM) but does not require measured emission
values (e.g., chamber studies).
Modeling Air Concentrations
The model used a two-zone representation of a house to calculate the potential acute dose rate (mg/kg-
bw/day) of NMP for users and non-users. Zone 1 represents the area where the consumer is using the
product, whereas Zone 2 represents the remainder of the house. Zone 2 can be used for modeling passive
exposure to non-users in the home (bystanders), such as children.
The general steps of the calculation engine within the CEM model included:
1.	Introduction of the chemical (i.e., NMP) into the room of use (Zone 1),
2.	Transfer of the chemical to the rest of the house (Zone 2) due to exchange of air between the different
rooms,
3.	Exchange of the house air with outdoor air and,
4.	Summation of the exposure doses as the modeled occupant moves about the house
The chemical of concern (i.e., NMP) enters the room air through two pathways: (1) overspray of the
product and (2) evaporation from a thin film. Six percent (6%) of the product was assumed to become
instantly aerosolized (i.e., product overspray) and was available for inhalation.
The CEM model uses data from the evaporation of a chemical film to calculate the rate of the mass
evaporating from the application surface covered during product use (Chinn. 1981). The model assumes
air exchanges from the room of use (Zone 1) and the rest of the house (Zone 2) according to interzonal
flow. The model also allows air exchange from the house (Zone 1 & 2) with the outdoor air.
EPA used the default activity pattern in CEM based on the occupant being present in the home for most
of the day. As the occupants moved around the house in the model, the NMP air concentration would
vary. The exposure to the calculated air concentrations were summed using CEM to estimate a potential
24-hr dose.
The user's exposure to NMP depends on their activity pattern (i.e., how much time using the product, as
well as the time in the room of use or in the rest of the house) as to the concentration of NMP in the air
Page 482 of 576
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within each of these areas. Based on the varying air concentrations estimated by the CEM model over a
24-hour period, EPA then used the PBPK model to estimate internal dose of NMP from inhalation.
Chronic exposure assessments were not performed for any of the consumer COUs because the frequency
of product used is unlikely to present a concern for chronic exposure.
Modeling Dermal Exposure
Since consumers do not always wear gloves when using consumer products, EPA modeled dermal
exposures for all NMP-containing products. Though CEM can estimate dermal exposures using a
chemical permeability coefficient, EPA used the PBPK model to estimate the internal dose of NMP as it
is absorbed through the skin both from direct contact of the liquid product and through absorption of
vapor through skin. The PBPK model thus, estimated the total internal dose of NMP through combined
routes of exposure: inhalation, dermal and vapor through skin and was used to estimate exposures in the
Paint Remover Risk Assessment.
Page 483 of 576
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G.2 Supplemental Consumer Exposure and Risk Estimation Technical
Report for NMP in Paint and Coating Removal
c/EPA
United States	July 2016
Environmental Protection	Office of Chemical Safety and
Agency	Pollution Prevention
Supplemental Consumer Exposure and Risk Estimation
Technical Report for NMP in Paint and Coating Removal
[RIN 2070-AK07]
July 2016
Page 484 of 576
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1. Introduction
EPA performed this technical analysis of consumer exposure scenarios for the use of n-
methylpyrrolidone (NMP) in paint and coating removal. Consistent with its final TSCA Work Plan
Chemical Risk Assessment for NMP (EPA, 2015), this analysis adds additional exposure scenarios
associated with the use of NMP in consumer paint and coating removal.
2.Executive	Summary
In 2015, EPA completed a risk assessment for NMP in paint and coating removal (EPA, 2015)10. The
NMP risk assessment found risks of concern for occupational use and certain consumer uses of NMP in
paint and coating removal. EPA conducted exposure modeling and risk analyses to investigate additional
exposure parameters to those included in the NMP risk assessment.
The NMP risk assessment evaluated risks based on emissions data from a brush-applied product. This
supplemental analysis used the same modeling methods to evaluate exposures and estimate risks from
larger projects. This additional exposure modeling describes the same product type (paint and coating
removal product) as in the NMP risk assessment, but with extended application times, increased product
use and altered user behavior.
The expanded consumer exposure modeling used the Multi-Chamber Concentration and Exposure
Model (MCCEM) (EPA 2010), the same model used in the NMP risk assessment. MCCEM was used to
estimate 24-hr indoor air concentrations of NMP (i.e., acute exposure) for the additional consumer
exposure modeling scenarios described here. These air concentrations were calculated for both users11
and bystanders12 of paint and coating removal products containing NMP in a residential setting.
Generally, the modeling reported in this document adopted many of the input parameters and
assumptions described in the NMP risk assessment, with the exception of those variations necessary to
evaluate additional consumer exposure scenarios.
The risk calculations used physiologically based pharmacokinetic (PBPK) modeling to incorporate both
the airborne exposure, calculated in this document, and the dermal exposures resulting from product use.
This is the same methodology as was applied in the NMP risk assessment. The results of the risk
calculations are discussed in the Section 6 of this document. As expected, the larger projects modeled in
this analysis resulted in larger indoor air concentrations and longer dermal exposures and based on those
higher exposures, concerns for developmental effects were found for some of the additional exposure
scenarios evaluated.
3.	Background of Consumer Exposure Analysis for Paint and Coating
Removal Products Presented in EPA's NMP Risk Assessment
10	EPA (U.S. Environmental Protection Agency). 2015. TSCA Work Plan Chemical Risk Assessment, n-Methylpyrrolidone:
Paint Stripper Use, CASRN: 872-50-4. Office of Pollution Prevention and Toxics, Washington, DC.
https://www.epa.gov/sites/production/files/2015-ll/documents/nmp_ra_3_23_15_final.pdf.
11	Users are directly involved of the application of the painter remover to a painted surface.
12	Non-users are other inhabitants of the home that spend most of their day inside but do not enter the room where the paint
remover is used.
Page 485 of 576
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The assessment of consumer use of paint and coating removal products in the NMP risk assessment used
information from products containing NMP and surveys of users to estimate concentrations of NMP in
indoor air due to product use (EPA, 2015). The parameters and their origins are explained in the NMP
risk assessment, specifically in Section 2.2 and Appendix E (EPA, 2015).
In the NMP risk assessment and in this supplemental analysis, EPA used MCCEM to estimate NMP
inhalation exposures for the consumer use scenarios (EPA 2010). This modeling approach was selected
because emission data were reasonably available from chamber studies for a product containing NMP.
The model used a multi-zone representation of a house to calculate the NMP exposure levels for
consumers (users) and bystanders (non-users). In this model, the room in which the product was used
was represented by one or two zones, and the rest of the house (ROH) volume represents another zone.
The user was assumed to spend time in the room of use on the day of use, whereas the non-user was
modeled as spending the day in the rest of the house or outside (EPA, 2015).
The modeling approach integrated assumptions and input parameters about the chemical emission rate
over time, the volume of the house and the room of use, the air exchange rate and interzonal airflow rate.
The model also considered the exposed individual's location during and after product use (EPA 2010).
MCCEM was used to calculate minute by minute air concentrations based on the behavior patterns
assumed in the model. A description of the original modeled inputs and their sources as well as a
description of how MCCEM was implemented for paint removers is also in the NMP risk assessment
(EPA, 2015).
4. Additional Exposure Analysis for Consumer Paint and Coating
Removal
Modeling using the same methodology was conducted for additional consumer exposure scenarios to aid
in understanding how exposures and risk might change by varying certain user behaviors or product
application techniques. The same consumer exposure model, MCCEM, used for the NMP risk
assessment was also used for the additional modeling described in this document.
The parameters that were varied in the new modeling runs are (1) the size of the paint and coating
removal project, (2) the type of project undertaken (furniture, flooring and bathtub) and (3) time lapsed
prior to when the paint scrapings were removed from the house. Tables 2-5 of the NMP risk assessment
contain a list of other parameters used in the consumer exposure modeling.
The consumer exposure scenarios in the NMP risk assessment were based on the mass of paint and
coating removal product that was used by the 50th and 80th percentile consumers from a survey of
consumers that reported the use of a paint and coating removal product. This mass of paint and coating
removal product was used to determine the amount of painted surface area from which paint could be
removed, which was converted into a representative project. In the NMP risk assessment, this was
described as, for example a set of shelves, coffee table, bathtub, or a chest of drawers. For this
supplemental analysis, consideration was expanded to include the potential for larger consumer projects
involving paint and coating removal, such as a dining set (table and chairs) and an entire room floor. An
additional model run for the bathtub scenario was included to evaluate exposures if the product was used
twice to completely remove paint from the surface of the tub.
Page 486 of 576
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Finally, the scenarios modeled in the NMP risk assessment described a consumer that removed the
scrapings to an outdoor garbage bin after the second scraping event. A model scenario, or run, was
added in this supplemental analysis to evaluate the impact of removing the scrapings more promptly.
Removing the scrapings from the room of use could reduce the mass of NMP volatilizing in the room
and consequently could reduce exposures for both the user and bystanders.
The minute by minute outputs of these MCCEM runs were entered into a PBPK model developed for
the NMP risk assessment.
TableApx G-l and TableApx G-2 summarize the variants in modeling parameters for the additional
exposure model runs.
Page 487 of 576
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' 'able Apx G-l. NMP Consumer Brush- and Roller-Applied Paint Removal Scenario Descriptions and Parameters

NMP Released

Room of Use
Rest of House
User

Case
ID
Wt. Fract.
Area
Treated, ft2
App
Rate,
sf/min
Release
Fraction
Removal Method
Volume,
m3
ACH, hr1
Volume
m3
ACH,
hr1
Location
During Wait
and Break
Period
Non-User
Location
1
A —
2

10
2

5-min. brush application, 30-min. wait, and 10-min.
scrape per application; process repeated after

Open
windows
1.26





Coffee table

completion of first scrape. Scrapings removed from
house after last scrape.

Closed
Windows
0.45




1
B —
2

25
Chest of
drawers
2

12.5-min. brush application, 30-min. wait, and 25-min.
scrape per application; process repeated after

Open
windows
1.26






completion of first scrape. Scrapings removed from
house after last scrape.

Closed
Windows
0.45




1




82-min. brush application, 18-min. wait, and 125-min.
scrape per application; process repeated after 30-min.
break. Scrapings removed from house after 2ntl scrape.
54
Open
windows
1.26
438
0.45


C 2
0.5
100
Dining table
and 8 chairs
2 (Table)
1 (Chairs)
0.8695

Closed
Windows
0.45


ROH
ROH
(entire time)
3




Same as Scenario CI except scrapings removed after
each scrape.

Open
windows
1.26




1
D —
2

240
4

1-hour roller-application, 1-hour wait, 1.5-hour scrape;
process repeated after 1-hour break. Scrapings
removed from house after each scrape.

Open
windows
1.26





Floors


Closed
Windows
0.45




1
E

36
2

18-min. brush application, 30-min. wait, and 36-min.
scrape per application; process repeated with no break.
Scrapings removed from house after 2nd scrape.
Source
Cloud 1 m3
0.18
483
0.18


2

bathtub


Same as Scenario El except entire process is repeated
after 1-hour break.
Bathroom
9 m3





Page 488 of 576
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' 'able Apx G-2. NMP Consumer Spray-Applied Paint Removal Scenario Descriptions and Parameters

NMP Released

Room of Use
Rest of House
User











Location

Case
ID


App

Removal Method "




During
Wait and
Non-User
Location

Wt.
Area
Rate,
Release

Volume,

Volume,
ACH, hr
Break


Fract.
Treated, ft2
sf/min
Fraction

m3
ACH, hr1
m3
i
Period

1

100
Dining table


41-min. spray application, 30-min. wait, and 125-min.
scrape per application; process repeated after 1-hour
break. Scrapings removed from house after 2ntl scrape.

Open
windows
1.26




F 2

and
8 chairs
4 (Table)
2 (Chairs)


Closed
Windows
0.45




3

Table (36 sf)
Chairs (64 sf)


Same as Scenario F1 except scrapings removed after each
scrape.
54
Open
windows
1.26
438
0.45


1
G —
2
0.5
240
4*
0.8695
1-hour spray application, 1-hour wait, 1.5-hour scrape;
process repeated after 1-hour break. Scrapings removed
from house after last scrape.

Open
windows
1.26


ROH
ROH
(entire time)

Floors


Closed
Windows
0.45




1
H 	

36
bathtub
4

9-min. spray application, 30-min. wait, and 36-min.
scrape per application; process repeated with no break.
Scrapings removed from house after 2nd scrape.
Source
Cloud 1 m3
0.18
483
0.18


2



Same as Scenario HI except entire process is repeated
after 1-hour break.
Bathroom
9 m3





* The application rate for spray-on floors was kept the same as for roll-on floors (Professional Judgment).
** All spray-applied cases use the "high" volatility model, which assumes the first exponential mass increases by 10-fold.
Wt. Fract. = Weight Fraction, ROH=Rest of House
Page 489 of 576
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5. Exposure Modeling Results
As in the NMP risk assessment, the indoor air concentrations generated by MCCEM were combined
with dermal exposures in a PBPK model. The outputs of that model are the basis for the risk findings for
the consumer use of NMP for paint and coating removal in the following scenarios. Calculations are in a
reference spreadsheet in a separate appendix titled Appendix B - Spreadsheet: Details of NMP Exposure
Model Results.
For the purpose of comparing these higher-end consumer exposures to occupational exposures
calculated in the NMP Risk Assessment, EPA also calculated indoor air concentrations using an 8-hour
time weighted average (TWA) exposure (see Table D-l in Appendix D). The PBPK model used the
minute-by-minute values generated by MCCEM, not these 8-hour values.
6. Risk Estimation
Risks for acute exposures were estimated for the minute-by-minute exposure concentrations generated
by MCCEM and dermal exposures with the PBPK model. The same methodology as was used for the
NMP risk assessment with additional risk estimates assuming dermal exposure to NMP during the time
of application and scraping. The risks for developmental effects were evaluated with a margin of
exposure (MOE) approach using the health hazard value derived in the NMP risk assessment. The
hazard value is the peak blood concentration of 216 mg/L and the benchmark MOE (the total of the
uncertainty factors) is 30. The evaluation hazard values, their origins, and application to risk estimation
are explained in the NMP risk assessment, specifically in Sections 3 and 4 (EPA, 2015). The risk
estimates for the exposure concentrations in this supplemental analysis are shown in TableApx G-3.
Risks for acute exposures for developmental effects were found for users during larger projects in the
additional scenarios evaluated. Risks were only found for non-users in the ROH in the largest project
(G2).
Table Apx G-3. Risk Estimates for Additional Scenarios for Users Assuming Dermal Exposure
During Application and Scrapping	
Scenario
Clove I se
MOK lor POD C"		 216
nig/I.
benchmark MOT. = 30
('mux (lllg/l.)
moi:
Al. Coffee Table, Brush Application in Workshop,
Windows Open
Gloves
0.27
796
No Gloves
1.99
108
A2. Coffee Table, Brush Application in Workshop,
Windows Closed
Gloves
0.30
718
No Gloves
2.02
107
Bl. Chest, Brush Application in Workshop, Windows Open
Gloves
0.65
332
No Gloves
3.76
58

Gloves
0.77
282
Page 490 of 576
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Sronsirio
B2. Chest, Brush Application in Workshop, Windows
Closed
Clove I so
MOK lor POD C"		 216
mg/l.
hciichmnrk MOT. = 30
('mux (lllg/l.)
moi:
No Gloves
3.88
55.7
CI. Dining table and chairs, Brush Application in Workshop,
Windows Open
Gloves
3.37
64.1
No Gloves
13.31
16.2
C2. Dining table and chairs, Brush Application in Workshop,
Windows Closed
Gloves
4.40
49.0
No Gloves
14.50
14.9
C3. Dining table and chairs, Brush Application in Workshop,
Windows Open, Scrapings removed after each scrap
Gloves
2.60
83.2
No Gloves
12.44
17.4
Dl. Floors, Roller Application in Workshop, Windows Open
Gloves
4.40
49.1
No Gloves
11.76
18.4
D2. Floors, Roller Application in Workshop, Windows
Closed
Gloves
5.58
38.7
No Gloves
13.36
16.2
El. Bathtub, Brush Application in Bathroom, Csat = 1,013
mg/m3, 2 Applications
Gloves
4.17
52
No Gloves
7.81
28
E2. Bathtub, Brush Application in Bathroom, Csat = 1,013
mg/m3, 4 Applications
Gloves
6.39
34
No Gloves
10.02
22
Fl. Dining table and chairs, Spray Application in Workshop,
Windows Open
Gloves
9.39
23
No Gloves
14.72
15
F2. Dining table and chairs, Spray Application in Workshop,
Windows Closed
Gloves
12.02
18.0
No Gloves
18.42
11.7
F3. Dining table and chairs, Spray Application in Workshop,
Windows Open
Gloves
9.27
23.3
No Gloves
14.21
15.2
Gl. Floors, Spray Application in Workshop, Windows Open
Gloves
23.03
9.4
No Gloves
26.19
8.2
G2. Floors, Spray Application in Workshop, Windows
Closed
Gloves
30.11
7.2
No Gloves
33.61
6.4

Gloves
22.72
9.5
Page 491 of 576
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Sccnsirio
HI. Bathtub, Spray Application in Bathroom, Csat = 1,013
mg/m3, 2 Applications
Clove I so
MOK lor POD C"		 216
mg/l.
hciichmnrk MOT. = 30
('mux (lllg/l.)
moi:
No Gloves
25.32
8.5
H2. Bathtub, Spray Application in Bathroom, Csat = 1,013
mg/m3, 4 Applications
Gloves
33.64
6.4
No Gloves
38.62
5.6
7. Uncertainties and Data Limitations
The modeling of additional scenarios described here has all the same uncertainties listed in the final
NMP risk assessment document.
Furthermore, it may be unlikely that a spray-applied paint and coating removal product would be used
on projects as large as those modeled in this document. Spray-applied paint and coating removal
products may be more useful for surfaces that are curved or irregular and are difficult to cover with a
brush or roller. However, this does not prevent the potential use of spray-applied products in the manner
modeled.
8.	Conclusions
As expected, the larger projects resulted in larger indoor air concentrations of NMP. New 8-hour TWA
air concentrations were calculated based on the user's pattern of moving in the home. These updated
user behavior adjusted TWA air concentrations are many times larger than those presented in the NMP
risk assessment.
The modeling results showed a small decline in exposure when scrapings from the room of use were
removed more promptly {i.e., removed after each scrape and within 4 hours rather than at the completion
of the project up to 8 hours). However, this variable is not a primary factor in the calculated values from
MCCEM.
As expected, the larger projects resulted in higher NMP peak blood concentrations. Risks were
identified for developmental effects for the larger projects.
9.	References
EPA (US Environmental Protection Agency). 2010. Multi-Chamber Concentration and Exposure Model
(MCCEM) Version 1.2. https://www.epa.gov/tsca-screening-tools/forms/mccem-multi-chamber-
concentration-and-exposure-model-download-and-install (accessed on April 29, 2016).
EPA (U.S. Environmental Protection Agency). 2015. TSCA Work Plan Chemical Risk Assessment, n-
Methylpyrrolidone: Paint Stripper Use, CASRN: 872-50-4. Office of Pollution Prevention and Toxics,
Washington, DC. https://www.epa.gov/assessing-and-managing-chemicals-imder4sca/tsca-work-plan-
chemical-risk-assessment-n-0
Page 492 of 576
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10. Appendix A
Types of Paint Removal Modeling Scenarios:
A.	Coffee table (surface area = 10 ft2; App. rate = 2 sf/min; Total duration = 90 minutes)
1.	Brush-On, Workshop, User in rest of house (ROH) during wait time, ROH=0.45 Air changes per
hour (ACH), Workshop = 1.26 ACH, Interzonal air flow (IZ) = 107 m3/hr., 0.5 Weight Fraction,
Scrapings removed after 2nd scrape (WINDOWS OPEN)
2.	Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 0.45 ACH
(= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape
(WINDOWS CLOSED)
B.	Chest of drawers (surface area = 25 ft2; App. rate = 2 sf/min; Total duration = 135 min)
1.	Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26 ACH,
IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape (WINDOWS OPEN)
2.	Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 0.45 ACH
(= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape
(WINDOWS CLOSED)
C.	Dining table and chairs (surface area = 100 ft2 (36 ft2 for table and 64 ft2for chairs,
8 @ 8 ft2); App. rate = 2 sf/min table (18 min), 1 sf/min chairs (64 min); 18 minute wait, Scrape rate
0.8 sf/min (125 min), 30 minute break; Total duration = 8 hours)
1.	Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26 ACH,
IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape (WINDOWS OPEN)
2.	Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 0.45 ACH
(= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape
(WINDOWS CLOSED)
3.	Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26 ACH,
IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape (WINDOWS OPEN)
D.	Floor paint removal (surface area = 240 ft2; App. rate = 4 sf/min; 1 hour wait, Scrape rate = 2.67
(1.5 hour), 1 hour break; Total duration = 8 hours)
1.	Roll-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26 ACH, IZ
= 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape (WINDOWS OPEN)
2.	Roll-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 0.45 ACH (=
24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape
(WINDOWS CLOSED)
E.	Bathtub paint removal (surface area = 36 ft2; App. rate = 2 sf/min; Total duration = 2.8 hours (2
apps); 6.6 hours (4 apps))
1.	Brush-On, Bathroom + Source Cloud, User in ROH during wait time, ROH=0.18 ACH,
Bathroom = 0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80/35 m3/hr., 0.5 Weight
Fraction (Csat =1013 mg/m3), Scrapings removed after 2nd scrape (NO WINDOWS, 2
applications)
2.	Brush-On, Bathroom + Source Cloud, User in ROH during wait time, ROH=0.18 ACH,
Bathroom =0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80/35 m3/hr., 0.5 Weight
Fraction (Csat = 1013 mg/m3), Scrapings removed after 2nd and 4th scrapes (NO WINDOWS, 4
applications)
F.	Dining table and chairs (surface area = 100 ft2 (36 ft2 for table and 64 ft2for chairs,
8 @ 8 ft2); App. rate = 4 sf/min table (9 min), 2 sf/min chairs (32 min); 30 minute wait, Scrape rate
0.8 sf/min (125 min), 1 hour break; Total duration = 7 hours)
1.	Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26 ACH,
IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape (WINDOWS OPEN)
2.	Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 0.45 ACH
(= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape
(WINDOWS CLOSED)
Page 493 of 576
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3. Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26 ACH,
IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape (WINDOWS OPEN)
G.	Floor paint removal (surface area = 240 ft2; App. rate = 4 sf/min; 1 hour wait, Scrape rate = 2.67
sf/min (1.5 hour), 1 hour break; Total duration = 8 hours)
1.	Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26 ACH,
IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape (WINDOWS OPEN)
2.	Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 0.45 ACH
(= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape
(WINDOWS CLOSED)
H.	Bathtub paint removal (surface area = 36 ft2; App. rate = 4 sf/min; Total duration = 2.5 hours (2
apps); 6 hours (4 apps))
1.	Spray-On, Bathroom + Source Cloud, User in ROH during wait time, ROH=0.18 ACH,
Bathroom = 0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80/35 m3/hr., 0.5 Weight
Fraction (Csat = 1013 mg/m3), Scrapings removed after 2nd scrape (NO WINDOWS, 2
applications)
2.	Spray -On, Bathroom + Source Cloud, User in ROH during wait time, ROH=0.18 ACH,
Bathroom =0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80/35 m3/hr., 0.5 Weight
Fraction (Csat = 1013 mg/m3), Scrapings removed after 2nd and 4th scrapes (NO WINDOWS, 4
applications)
Unchanged modeling parameters for all scenarios
•	House volume = 492 m3
•	Paint stripper consumer weight fraction = 0.5 (upper end)
•	Non-user location = ROH (entire time)
Page 494 of 576
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Table Apx G-4. Time Schedule for Brush- and Roller-Applied Paint and Coating Removal with Repeat Application
Scenario
l-'.liipsed Time I'roin Time Zero. Minnies (Product I ser l.nc;ilinn)
Apply 1
11 ail I
Scrape 1
Break
Apply 2
W ail 2
Scrape 2
A. Brush application to coffee table in workshop, central tendency scenario
(App rate = 2 sf/min)
0-5
(Workshop)
5-35
(ROH)
35-45
(Workshop)
0
45-50
(Workshop)
50-80
(ROH)
80-90
(Workshop)
B. Brush application to chest in workshop, upper-end scenario for user &
non-user
(App rate = 2 sf/min)
0-12.5
(Workshop)
12.5-42.5
(ROH)
42.5-67.5
(Workshop)
0
67.5-80
(Workshop)
80-110
(ROH)
110-135
(Workshop)
C. Brush application to dining table and chairs in workshop, central tendency
scenario
(App rate = 2 sf/min for table; 1 sf/min for chairs)
0-82
(Workshop)
82-100
(ROH)
100-225
(Workshop)
225-255
(ROH)
255-337
(Workshop)
337-355
(ROH)
355-480
(Workshop)
D. Roller application to floor
(App rate = 4 sf/min)
0-60
(Workshop)
60-120
(ROH)
120-210
(Workshop)
210-270
(ROH)
270-330
(Workshop)
330-390
(ROH)
390-480
(Workshop)
E. Brush application to bathtub
(App rate = 2 sf/min)
El = 2 applications
E2 = 4 apps (repeat 1st 2 apps after 1 hour break, total time = 396 min.)
0-18
(Src Cloud)
228-246
(Src Cloud)
18-48
(ROH)
246-276
(ROH)
48-84
(Src Cloud)
276-312
(Src Cloud)
0
84-102
(Src Cloud)
312-330
(Src Cloud)
102-132
(ROH)
330-360
(ROH)
132-168
(Src Cloud)
360-396
(Src Cloud)
Table Apx G-5. Time Schedule for Spray-Applied Paint ant
Coating Removal with Repeat Application

l-'.hipsed rime l"rom l ime Zero. Minnies (Product I scr locution)
Scenario
Apply 1
Wail 1
Scrape 1
Iircuk
Apply 2
H ail 2
Scrape 2
F. Spray application to dining table and chairs in workshop, central
tendency scenario
(App rate = 4 sf/min for table; 2 sf/min for chairs)
0-41
(Workshop)
41-71
(ROH)
71-196
(Workshop)
196-256
(ROH)
256-297
(Workshop)
297-327
(ROH)
327-452
(Workshop)
G. Spray application to floors
(App rate = 4 sf/min)
0-60
(Workshop)
60-120
(ROH)
120-210
(Workshop)
210-270
(ROH)
270-330
(Workshop)
330-390
(ROH)
390-480
(Workshop)
H. Spray application to bathtub
(App rate = 4 sf/min)
HI = 2 applications
H2 = 4 apps (repeat 1st 2 apps after 1 hour break, total time = 360 min.)
0-9
(Src Cloud)
210-219
(Src Cloud)
9-39
(ROH)
219-249
(ROH)
39-75
(Src Cloud)
249-285
(Src Cloud)
0
75-84
(Src Cloud)
285-294
(Src Cloud)
84-114
(ROH)
294-324
(ROH)
114-150
(Src Cloud)
324-360
(Src Cloud)
Src Cloud = Source Cloud
Page 495 of 576
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D.5 MCCEM Inhalation Modeling Case Summaries
NMP Summaries
Formula:
CASRN:
Molecular Weight:
Density:
Appearance:
Melting Point:
Boiling Point:
Conversion units: 1 ppm =
C5H9NO
872-50-4
99.13 g/mol
1.028 g/cm2 (liquid)
clear liquid
-24 °C = -11 °F = 249 K
203 °C = 397 °F = 476 K
4.054397 mg/m3
Saturation Concentration: -1,013 mg/m3 (equivalent to a vapor pressure of 0.190 Torr at
25 °C, used in Scenario 5, based on ("OECD. 2007a). See Section D.3)
Saturation Concentration: -640 mg/m3 (representing the upper end of the saturation concentration
values associated with "normal humidity conditions." See Section D.3)
Page 496 of 576
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NMPScenario Al. Coffee Table, Brush-On, Workshop, User in ROHduring wait time, ROH=0.45
ACH, Workshop = 1.26 ACH (= 68 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed
after 2nd scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method:
Brush-on'
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Coffee table = 10 sq. ft. surface area
Applied product mass =108 g/sq. ft. = 1,080 g
Applied NMP = 1,080 g x 0.5 (wt. fraction) = 540 g
Total NMP mass released (theoretical, both exponentials) = 1,080 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) = 469.53 g
Mass released per app = 234.77 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*234.77*32.83 = 61.7 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*234.77*0.00237 = 0.55 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
Al) Coffee Table, Brush-On,
Workshop, User ROH during wait
time, 0.45 ACH, 0.5 Weight
Fraction, WINDOWS OPEN
0-5
(Wkshp)
5-35
(ROH)
35-45
(Wkshp)
45-50
(Wkshp)
50-80
(ROH)
80-90
(Wkshp)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (22 hours, 30 minutes)
Model Run Time:
0-24 hours
User takes out scrapings after 90 minutes; emissions truncated.
Page 497 of 576
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NMPScenario A2. Coffee Table, Brush-On, Workshop, User in ROHduring wait time, ROH=0.45
ACH, Workshop = 0.45 ACH (= 24.3 inVhr.), IZ = 107 mVhr., 0.5 Weight Fraction, Scrapings
removed after 2nd scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Coffee table = 10 sq. ft. surface area
Applied product mass =108 g/sq. ft. = 1,080 g
Applied NMP = 1,080 g x 0.5 (wt. fraction) = 540 g
Total NMP mass released (theoretical, both exponentials) = 1,080 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) = 469.53 g
Mass released per app = 234.77 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*234.77*32.83 = 61.7 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.862*234.77*0.00237 = 0.55 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
A2) Coffee Table, Brush-On,
Workshop, User ROH during wait
time, 0.45 ACH, 0.5 Weight
Fraction, WINDOWS CLOSED
0-5
(Wkshp)
5-35
(ROH)
35-45
(Wkshp)
45-50
(Wkshp)
50-80
(ROH)
80-90
(Wkshp)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (22 hours, 30 minutes)
Model Run Time:
0-24 hours
User takes out scrapings after 90 minutes; emissions truncated.
Page 498 of 576
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NMPScenario Bl. Chest, Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH,
Workshop = 1.26 ACH (= 68 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after
2nd scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Chest = 25 sq. ft. surface area
Applied product mass = 2,700 g
Applied NMP = 2,700 g x 0.5 (wt. fraction) = 1,350 g
Total NMP mass released (both exponentials) = 2,700 g x 0.5 (wt. fraction) x 0.8695 (release fraction,
theoretical) =1173.8 g	
Mass released per app = 586.9 g
For each of the 2 applications:
ki = 32.83/hr
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*586.9*32.83 = 154.1 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*586.9*0.00237 = 1.38 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
Bl) Chest, Brush-On, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-12.5
(Wkshp)
12.5-
42.5
(ROH)
42.5-
67.5
(Wkshp)
67.5-80
(Wkshp)
80-110
(ROH)
110-135
(Wkshp)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (21 hours, 45 minutes)
Model Run Time:
0-24 hours
Page 499 of 576
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User takes out scrapings after 135 minutes; emissions truncated.
NMPScenario B2. Chest, Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH,
Workshop = 0.45 ACH (= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after
2nd scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Chest = 25 sq. ft. surface area
Applied product mass = 2,700 g
Applied NMP = 2,700 g x 0.5 (wt. fraction) = 1,350 g
Total NMP mass released (both exponentials) = 2,700 g x 0.5 (wt. fraction) x 0.8695 (release fraction,
theoretical) =1173.8 g	
Mass released per app = 586.9 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*586.9*32.83 = 154.1 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*586.9*0.00237 = 1.38 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
B2) Chest, Brush-On, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-12.5
(Wkshp)
12.5-
42.5
(ROH)
42.5-
67.5
(Wkshp)
67.5-80
(Wkshp)
80-110
(ROH)
110-135
(Wkshp)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (21 hours, 45 minutes)
Page 500 of 576
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Model Run Time:
0-24 hours
User takes out scrapings after 135 minutes; emissions truncated.
NMP Scenario CI. Dining table and chairs, Brush-On, Workshop, User in ROH during wait time,
ROH=0.45 ACH, Workshop = 1.26 ACH (= 68 nrVhr.), IZ = 107 m Vhr., 0.5 Weight Fraction,
Scrapings removed after 2nd scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method: Brush-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 10,800 g
Applied NMP = 10,800 g x 0.5 (wt. fraction) = 5,400 g
Total NMP mass released (both exponentials) = 10,800 g x 0.5 (wt. fraction) x 0.8695 (release fraction,
theoretical) =4695.3 g	
Mass released per app = 2347.65 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*2347.65*32.83 = 616.6 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*2347.65*0.00237 = 5.52 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
CI) Dining table and chairs,
Brush-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-82
(Wkshp
)
82-100
(ROH)
100-225
(Wkshp
)
225-255
(ROH)
255-337
(Wkshp
)
337-355
(ROH)
355-480
(Wkshp
)
User in ROH at the end of Scraping 2
Page 501 of 576
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User in ROH for the remainder of the run (16 hours)
Model Run Time:
0-24 hours
User takes out scrapings after 480 minutes; emissions truncated.
NMP Scenario C2. Dining table and chairs, Brush-On, Workshop, User in ROH during wait time,
ROH=0.45 ACH, Workshop = 0.45 ACH (= 24.3 mVhr.), IZ = 107 nrVhr., 0.5 Weight Fraction,
Scrapings removed after 2nd scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 10,800 g (Application rate = 108 g/sf)
Applied NMP = 10,800 g x 0.5 (wt. fraction) = 5,400 g
Total NMP mass released (both exponentials) = 10,800 g x 0.5 (wt. fraction) x 0.8695 (release fraction,
theoretical) =4695.3 g	
Mass released per app = 2347.65 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*2347.65*32.83 = 616.6 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*2347.65*0.00237 = 5.52 g/hr. (NOTE: only k and Mass are needed as inputs)
Page 502 of 576
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Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
C2) Dining table and chairs,
Brush-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-82
(Wkshp
)
82-100
(ROH)
100-225
(Wkshp
)
225-255
(ROH)
255-337
(Wkshp
)
337-355
(ROH)
355-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Model Run Time:
0-24 hours
User takes out scrapings after 480 minutes; emissions truncated.
NMP Scenario C3. Dining table and chairs, Brush-On, Workshop, User in ROH during wait time,
ROH=0.45 ACH, Workshop = 1.26 ACH (= 68 m Vhr.), IZ = 107 m Vhr., 0.5 Weight Fraction,
Scrapings removed after each scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 10,800 g (Application rate = 108 g/sf)
Applied NMP = 10,800 g x 0.5 (wt. fraction) = 5,400 g
Total NMP mass released (both exponentials) = 10,800 g x 0.5 (wt. fraction) x 0.8695 (release fraction,
theoretical) =4695.3 g	
Mass released per app = 2347.65 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eoi = Mass * ki = 0.008*2347.65*32.83 = 616.6 g/hr. (NOTE: only k and Mass are needed as inputs)
Page 503 of 576
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k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*2347.65*0.00237 = 5.52 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
C3) Dining table and chairs,
Brush-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-82
(Wkshp
)
82-100
(ROH)
100-225
(Wkshp
)
225-255
(ROH)
255-337
(Wkshp
)
337-355
(ROH)
355-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Model Run Time:
0-24 hours
User takes out scrapings after 225 and 480 minutes; emissions truncated.
NMP Scenario Dl. Floor, Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH,
Workshop = 1.26 ACH (= 68 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after
each scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Floor = 240 sq. ft. surface area
Applied product mass = 25,920 g (Application rate = 108 g/sf)
Applied NMP = 25,920 g x 0.5 (wt. fraction) = 12,960 g
Total NMP mass released (both exponentials) = 25,920 g x 0.5 (wt. fraction) x 0.8695 (release fraction,
theoretical) =11,268.7 g	
Mass released per app = 5634.4 g
Page 504 of 576
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For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*5634.4*32.83 = 1479.8 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*5634.4*0.00237 = 13.25 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
Dl) Floor, Roll-on, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-60
(Wkshp
)
60-120
(ROH)
120-210
(Wkshp
)
210-270
(ROH)
270-330
(Wkshp
)
330-390
(ROH)
390-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Model Run Time:
0-24 hours
User takes out scrapings after 210 and 480 minutes; emissions truncated.
NMP Scenario D2. Floor, Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH,
Workshop = 0.45 ACH (= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after
each scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Floor = 240 sq. ft. surface area
Applied product mass = 25,920 g (Application rate = 108 g/sf)
Applied NMP = 25,920 g x 0.5 (wt. fraction) = 12,960 g
Page 505 of 576
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Total NMP mass released (both exponentials) = 25,920 g x 0.5 (wt. fraction) x 0.8695 (release fraction,
theoretical) =11,268.7 g	
Mass released per app = 5634.4 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*5634.4*32.83 = 1479.8 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*5634.4*0.00237 = 13.25 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
D2) Floor, Roll-on, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-60
(Wkshp
)
60-120
(ROH)
120-210
(Wkshp
)
210-270
(ROH)
270-330
(Wkshp
)
330-390
(ROH)
390-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Model Run Time:
0-24 hours
User takes out scrapings after 210 and 480 minutes; emissions truncated
NMP Scenario El. Bathroom, Brush-On, Bathroom + Source Cloud, User in ROH during wait time,
R()ll=0.18 A CI I, Bathroom = 0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80, 35
m3/hr., 0.5 Weight Fraction (Csat = 1013 mg/m3), Scrapings removed after 2nd scrape (WINDOWS
CLOSED, 2 applications)
MCCEM Input Summary
MCCEM saturation concentration constraint invoked at 1013 mg/m3
Application Method: Brush-on
Volumes:
Bathroom Volume = 9 m3 (8 m3 after subtracting source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 - 9 = 483 m3
Airflows:
Bathroom-outdoors
1.6 m3/h
Source cloud - bathroom
80 m3/h
Page 506 of 576
-------
Source cloud - outdoors
0
ROH-outdoors
86.9 m3/h (0.18 ACH)
Bathroom-ROH
35 m3/h
NMP Mass Released:
Bathtub = 36 sq. ft. surface area
Applied product mass = 3,888 g (Application rate = 108 g/sf)
Applied NMP = 3,888 g x 0.5 (wt. fraction) = 1,944 g
Total NMP mass released (both exponentials) = 3,888 g x 0.5 (wt. fraction) x 0.8695 (release fraction,
theoretical) = 1690.3 g	
Mass released per app = 845.15 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*845.15.4*32.83 = 222.0 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*845.15*0.00237 = 1.99 g/hr. (NOTE: only k and Mass are needed as inputs)
Ap
alication Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
El) Bathtub, Brush-On,
Bathroom + Source Cloud, User
in ROH during wait time, 0.18
ACH, 0.5 Wt. Fract.
0-18
(SrcClou
d)
18-48
(ROH)
48-84
(SrcClou
d)
84-102
(SrcClou
d)
102-132
(ROH)
132-168
(SrcClou
d)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (21 hours, 12 minutes)
Model Run Time:
0-24 hours
User takes out scrapings after 168 minutes; emissions truncated.
NMP Scenario E2. Bathroom, Brush-On, Bathroom + Source Cloud, User in ROH during wait time,
R()ll=0.18 A CI I, Bathroom = 0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80, 35
m3/hr., 0.5 Weight Fraction (Csat = 1013 mg/m3), Scrapings removed after 2nd and 4th scrapes
(WINDOWS CLOSED, 4 applications)
MCCEM Input Summary
MCCEM saturation concentration constraint invoked at 1013 mg/m3
Application Method: Brush-on
Volumes:
Page 507 of 576
-------
Bathroom Volume = 9 m3 (8 m3 after subtracting source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 - 9 = 483 m3
Airflows:
Bathroom-outdoors
1.6 m3/h
Source cloud - bathroom
80 m3/h
Source cloud - outdoors
0
ROH-outdoors
86.9 m3/h (0.18 ACH)
Bathroom-ROH
35 m3/h
NMP Mass Released:
Bathtub = 36 sq. ft. surface area
Applied product mass = 3,888 g (Application rate = 108 g/sf)
Applied NMP = 3,888 g x 0.5 (wt. fraction) = 1,944 g
Total NMP mass released (both exponentials) = 3,888 g x 0.5 (wt. fraction) x 0.8695 (release fraction,
theoretical) = 1690.3 g	
Mass released per app = 845.15 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 = |0.8% of released NMP
Eqi = Mass * ki = 0.008*845.15.4*32.83 = 222.0 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*845.15*0.00237 = 1.99 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply
1&3
Wait
1&3
Scrape
1&3
Apply
2&4
Wait
2&4
Scrape
2&4
E2) Bathtub, Brush-On, Bathroom + Source Cloud, User in
ROH during wait time, 0.18 ACH, 0.5 Weight Fraction
1st and 2nd Application
0-18
(SrcClou
d)
18-48
(ROH)
48-84
(SrcClou
d)
84-102
(SrcClou
d)
102-132
(ROH)
132-168
(SrcClou
d)
3rd and 4th Application
228-246
(SrcClou
d)
246-276
(ROH)
276-312
(SrcClou
d)
312-330
(SrcClou
d)
330-360
(ROH)
360-396
(SrcClou
d)
User in ROH at the end of Scraping 2 and 4
User in ROH for the remainder of the run (17 hours, 24 minutes)
Model Run Time:
0-24 hours
User takes out scrapings after 168 and 396 minutes; emissions truncated.
Page 508 of 576
-------
NMP Scenario Fl. Dining table and chairs, Spray-On, Workshop, User in ROH during wait time,
ROH=0.45 ACH, Workshop = 1.26 ACH (= 68 m Vhr.), IZ = 107 m Vhr., 0.5 Weight Fraction,
Scrapings removed after 2nd scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 8,100 g (Application rate = 81 g/sf)
Overspray = 0.05*8,100 g = 405 g
Total Product Mass = 8,100 + 405 = 8,505 g
Total NMP Mass = 8,505 g x 0.5 (wt. fraction) = 4,252.5 g
Total NMP mass released (both exponentials) = 4,252.5 x 0.8695 (release fraction, theoretical) = 3697.5
Mass released per app = 1848.8 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eqi = Mass * ki = 0.08*1848.8*32.83 = 4855.7 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released NMP
E02 = Mass * k2 = 0.919*1848.8*0.00237 = 4.03 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
Fl) Dining table and chairs,
Spray-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-41
(Wkshp
)
41-71
(ROH)
71-196
(Wkshp
)
196-256
(ROH)
256-297
(Wkshp
)
297-327
ROH)
327-452
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours, 28 minutes)
Page 509 of 576
-------
Model Run Time:
0-24 hours
User takes out scrapings after 452 minutes; emissions truncated.
NMP Scenario F2. Dining table and chairs, Spray-On, Workshop, User in ROH during wait time,
ROH=0.45 ACH, Workshop = 0.45 ACH (= 24.3 inVhr.), IZ = 107 inVhr., 0.5 Weight Fraction,
Scrapings removed after 2nd scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 8,100 g (Application rate = 81 g/sf)
Overspray = 0.05*8,100 g = 405 g
Total Product Mass = 8,100 + 405 = 8,505 g
Total NMP Mass = 8,505 g x 0.5 (wt. fraction) = 4,252.5 g
Total NMP mass released (both exponentials) = 4,252.5 x 0.8695 (release fraction, theoretical) = 3697.5
Mass released per app = 1848.8 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eqi = Mass * ki = 0.08*1848.8*32.83 = 4855.7 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released NMP
E02 = Mass * k2 = 0.919*1848.8*0.00237 = 4.03 g/hr. (NOTE: only k and Mass are needed as inputs)
Page 510 of 576
-------
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
F2) Dining table and chairs,
Spray-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-41
(Wkshp
)
41-71
(ROH)
71-196
(Wkshp
)
196-256
(ROH)
256-297
(Wkshp
)
297-327
ROH)
327-452
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours, 28 minutes)
Model Run Time:
0-24 hours
User takes out scrapings after 452 minutes; emissions truncated.
NMP Scenario F3. Dining table and chairs, Spray-On, Workshop, User in ROH during wait time,
ROH=0.45 ACH, Workshop = 1.26 ACH (= 68 m Vhr.), IZ = 107 m Vhr., 0.5 Weight Fraction,
Scrapings removed after each scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 8,100 g (Application rate = 81 g/sf)
Overspray = 0.05*8,100 g = 405 g
Total Product Mass = 8,100 + 405 = 8,505 g
Total NMP Mass = 8,505 g x 0.5 (wt. fraction) = 4,252.5 g
Total NMP mass released (both exponentials) = 4,252.5 x 0.8695 (release fraction, theoretical) = 3697.5
Mass released per app = 1848.8 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eoi = Mass * ki = 0.08*1848.8*32.83 = 4855.7 g/hr. (NOTE: only k and Mass are needed as inputs)
Page 511 of 576
-------
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released NMP
E02 = Mass * k2 = 0.919*1848.8*0.00237 = 4.03 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
F3) Dining table and chairs,
Spray-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-41
(Wkshp
)
41-71
(ROH)
71-196
(Wkshp
)
196-256
(ROH)
256-297
(Wkshp
)
297-327
ROH)
327-452
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours, 28 minutes)
Model Run Time:
0-24 hours
User takes out scrapings after 196 and 452 minutes; emissions truncated.
NMP Scenario Gl. Floor, Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH,
Workshop = 1.26 ACH (= 68 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after
each scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Floor = 240 sq. ft. surface area
Applied product mass = 19,440 g (Application rate = 81 g/sf)
Overspray = 0.05*19,440 g = 972 g
Total Product Mass = 19,440 + 972 = 20,412 g
Total NMP Mass = 20,412 g x 0.5 (wt. fraction) = 10,206 g
Total NMP mass released (both exponentials) = 10,206 x 0.8695 (release fraction, theoretical) = 8,874.1
Mass released per app = 4437.1 g
For each of the 2 applications:
Page 512 of 576
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ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eqi = Mass * ki = 0.08*4437.1*32.83 = 11,653.6 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released NMP
E02 = Mass * k2 = 0.919*4437.1*0.00237 = 9.66 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
Gl) Floor, Spray-on, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-60
(Wkshp
)
60-120
(ROH)
120-210
(Wkshp
)
210-270
(ROH)
270-330
(Wkshp
)
330-390
(ROH)
390-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Model Run Time:
0-24 hours
User takes out scrapings after 210 and 480 minutes; emissions truncated.
NMP Scenario G2. Floor, Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH,
Workshop = 0.45 ACH (= 24.3 m Vhr.), IZ = 107 nrVhr., 0.5 Weight Fraction, Scrapings removed after
each scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop -outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Floor = 240 sq. ft. surface area
Applied product mass = 19,440 g (Application rate = 81 g/sf)
Overspray = 0.05*19,440 g = 972 g
Total Product Mass = 19,440 + 972 = 20,412 g
Total NMP Mass = 20,412 g x 0.5 (wt. fraction) = 10,206 g
Total NMP mass released (both exponentials) = 10,206g x 0.8695 (release fraction, theoretical) =8,874.1
g
Page 513 of 576
-------
Mass released per app = 4437.1 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eqi = Mass * ki = 0.08*4437.1*32.83 = 11,653.6 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released NMP
E02 = Mass * k2 = 0.919*4437.1*0.00237 = 9.66 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
G2) Floor, Spray-on, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-60
(Wkshp
)
60-120
(ROH)
120-210
(Wkshp
)
210-270
(ROH)
270-330
(Wkshp
)
330-390
(ROH)
390-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Model Run Time:
0-24 hours
User takes out scrapings after 210 and 480 minutes; emissions truncated
NMP Scenario HI. Bathroom, Spray-On, Bathroom + Source Cloud, User in ROH during wait time,
R()ll=0.18 A CI I, Bathroom = 0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80, 35
m3/hr., 0.5 Weight Fraction (Csat = 1013 mg/m3), Scrapings removed after 2nd scrape (WINDOWS
CLOSED, 2 applications)
MCCEM Input Summary
MCCEM saturation concentration constraint invoked at 1013 mg/m3
Application Method: Spray-on
Volumes: Bathroom Volume = 9 m3 (8 m3 after subtracting source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 - 9 = 483 m3
Airflows:
Bathroom-outdoors
1.6 m3/h
Source cloud - bathroom
80 m3/h
Source cloud - outdoors
0
ROH-outdoors
86.9 m3/h (0.18 ACH)
Bathroom-ROH
35 m3/h
Page 514 of 576
-------
NMP Mass Released:
Bathtub = 36 sq. ft. surface area
Applied product mass = 2,916 g (Application rate = 81 g/sf)
Overspray = 0.05*2,916 g = 145.8 g
Total Product Mass = 2,916 + 145.8 = 3,061.8 g
Total NMP Mass = 3,061.8 g x 0.5 (wt. fraction) = 1,530.9 g
Total NMP mass released (both exponentials) = 1530.9 x 0.8695 (release fraction, theoretical) =1331.1 g
Mass released per app = 665.6 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eqi = Mass * ki = 0.08*665.6*32.83 = 1748.1 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.919*665.6*0.00237 = 1.45 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
HI) Bathtub, Spray-On,
Bathroom + Source Cloud, User
in ROH during wait time, 0.18
ACH, 0.5 Wt. Fract.
0-9
(Src
Cloud)
9-39
(ROH)
39-75
(Src
Cloud)
75-84
(Src
Cloud)
84-114
(ROH)
114-150
(Src
Cloud)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (21 hours, 30 minutes)
Model Run Time:
0-24 hours
User takes out scrapings after 150 minutes; emissions truncated.
NMP Scenario H2. Bathroom, Spray-On, Bathroom + Source Cloud, User in ROH during wait time,
R()ll=0.18 A CI I, Bathroom = 0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80, 35
m3/hr., 0.5 Weight Fraction (Csat = 1013 mg/m3), Scrapings removed after 2nd and 4th scrapes
(WINDOWS CLOSED, 4 applications)
MCCEM Input Summary
MCCEM saturation concentration constraint invoked at 1013 mg/m3
Application Method: Spray-on
Volumes: Bathroom Volume = 9 m3 (8 m3 after subtracting source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 - 9 = 483 m3
Airflows:
Bathroom-outdoors	|l.6m3/h
Page 515 of 576
-------
Source cloud - bathroom
80 m3/h
Source cloud - outdoors
0
ROH-outdoors
86.9 m3/h (0.18 ACH)
Bathroom-ROH
35 m3/h
NMP Mass Released:
Bathtub = 36 sq. ft. surface area
Applied product mass = 2,916 g (Application rate = 81 g/sf)
Overspray = 0.05*2,916 g = 145.8 g
Total Product Mass = 2,916 + 145.8 = 3,061.8 g
Total NMP Mass = 3,061.8 g x 0.5 (wt. fraction) = 1,530.9 g
Total NMP mass released (both exponentials) = 1530.9 x 0.8695 (release fraction, theoretical) =1331.1 g
Mass released per app = 665.6 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eqi = Mass * ki = 0.08*665.6*32.83 = 1748.1 g/hr. (NOTE: only k and Mass are needed as inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.919*665.6*0.00237 = 1.45 g/hr. (NOTE: only k and Mass are needed as inputs)
Application Times and Activity Patterns:
Episode
Bathtub, Spray-On, Bathroom +
Source Cloud, User in ROH
during wait time, 0.18 ACH, 0.5
Wt. Fract
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply
1&3
Wait
1&3
Scrape
1&3
Apply
2&4
Wait
2 &4
Scrape
2&4
E2) Bathtub, Brush-On, Bathroom + Source Cloud, User in
ROH during wait time, 0.18 ACH, 0.5 Weight Fraction
1st and 2nd Application
0-9
(Wkshp)
9-39
(ROH)
39-75
(Wkshp)
75-84
(Wkshp)
84-114
(ROH)
114-150
(Wkshp)
3rd and 4th Application
210-219
(Wkshp)
219-249
(ROH)
249-285
(Wkshp)
285-294
(Wkshp)
294-324
(ROH)
324-360
(Wkshp)
User in ROH at the end of Scraping 2 and 4
User in ROH for the remainder of the run (18 hours)
Model Run Time:
0-24 hours
User takes out scrapings after 150 and 360 minutes; emissions truncated.
Appendix B - Spreadsheet: Details of NMP Exposure Model Results
See the separate spreadsheet loaded into this docket (EPA-HQ-OPPT-2016-0231) for the zone-specific
and exposure concentrations predicted by MCCEM.
Appendix C - Spreadsheet: NMP Risk Estimation
See the separate spreadsheet loaded into this docket (EPA-HQ-OPPT-2016-0231) for risk calculations.
Page 516 of 576
-------
Appendix D
Table D-l. Eight-hour TWA exposures for additional scenarios
Scenario
Individual
8-1 lour TWA exposure
m«/in!
ppm
Al. Coffee Table, Brush Application in Workshop,
Windows Open
User
2.2
0.5
Non-User
1.5
0.4
A2. Coffee Table, Brush Application in Workshop,
Windows Closed
User
3.1
0.8
Non-User
2.2
0.5
Bl. Chest, Brush Application in Workshop, Windows Open
User
7.7
1.9
Non-User
4.3
1.1
B2. Chest, Brush Application in Workshop, Windows
Closed
User
10.7
2.6
Non-User
6.1
1.5
CI. Dining table and chairs, Brush Application in Workshop,
Windows Open
User
70.2
17.3
Non-User
24.7
6.1
C2. Dining table and chairs, Brush Application in Workshop,
Windows Closed
User
97.7
24.1
Non-User
35.0
8.6
C3. Dining table and chairs, Brush Application in Workshop,
Windows Open, Scrapings removed after each scrap
User
54.5
13.4
Non-User
19.1
4.7
Dl. Floors, Roller Application in Workshop, Windows Open
User
110.9
27.4
Non-User
45.0
11.1
D2. Floors, Roller Application in Workshop, Windows
Closed
User
150.6
37.1
Non-User
63.7
15.7
El. Bathtub, Brush Application in Bathroom, Csat = 1,013
mg/m3, 2 Applications
User
78.8
19.4
Non-User
20.4
5.0
E2. Bathtub, Brush Application in Bathroom, Csat = 1,013
mg/m3, 4 Applications
User
148.9
36.7
Non-User
35.7
8.8
Fl. Dining table and chairs, Spray Application in Workshop,
Windows Open
User
227.1
56.0
Non-User
94.8
23.4
F2. Dining table and chairs, Spray Application in Workshop,
Windows Closed
User
319.3
78.8
Non-User
133.8
33.0
Page 517 of 576
-------
Seensirio
1 ikI i\ icl mil
S-11 onr TWA exposure
m«/in!
ppm
F3. Dining table and chairs, Spray Application in Workshop,
Windows Open
User
218.4
53.9
Non-User
92.1
22.7
Gl. Floors, Spray Application in Workshop, Windows Open
User
540.1
133.2
Non-User
214.2
52.8
G2. Floors, Spray Application in Workshop, Windows
Closed
User
724.6
178.7
Non-User
303.1
74.8
HI. Bathtub, Spray Application in Bathroom, Csat = 1,013
mg/m3, 2 Applications
User
339.4
83.7
Non-User
109.2
26.9
H2. Bathtub, Spray Application in Bathroom, Csat = 1,013
mg/m3, 4 Applications
User
640.9
158.1
Non-User
192.8
47.6
Csat = Saturation Concentration
Page 518 of 576
-------
Appendix H ENVIRONMENTAL HAZARDS
EPA has reviewed acceptable ecotoxicity studies for NMP according to the data quality evaluation
criteria found in The Application of Systematic Review in TSCA Risk Evaluations (U.S. EPA. 2018a).
The results of these ecotoxicity study evaluations can be found in the Systematic Review Supplemental
File: Data Quality Evaluation of Ecological Hazard Studies. Docket EPA-HQ-OPPT-2019-0236 (U.S.
201). The data quality evaluation indicated these studies are of high confidence and are used to
characterize the environmental hazards of NMP. These studies support that hazard of NMP to aquatic
organisms is low and that no further evaluation is required.
The acceptable aquatic studies that were evaluated for NMP are summarized in Table Apx H-l. The
hazard of these studies has been reported (	)Q6b; OECD. 2007; Danish Ministry of the
Environment, 2015; U.S. EPA. 2015c and Environment Canad ) as stated in the NMP Problem
Formulation (U.S. EPA. 2018cY
Table Apx H-l. On-topic aquatic toxicity studies that were evaluated for NMP
Tesl Species
Ircsli /
Siili
Wilier
Diii'iilion
I'.ndpoinl
( onceiil r;i 1 ion(s)
Tesl
An;il\sis
r.lTccl(s)
References
Diilii
Qu;ili(>
r.\;iliiiiliun
Fish
Fathead
minnow
(Pimephales
promelas)
Fresh
96-h
LCso = 1072
mg/L
389, 648, 1080, 1800,
3000, 5000 mg/L
Static,
Nominal
Mortality
>79)
High
Rainbow trout
(Salmo
Gairdneri)
Fresh
96-h
LCso = 3048
mg/L
778, 1296, 2160, 3600,
6000, 10,000 mg/L
Static,
Nominal
Mortality
>79)
High
Rainbow trout
(Oncorhynchus
mykiss)
Fresh
96-h
LC50 > 500
mg/L
0, 500 mg/L
Static,
Nominal
Mortality
IV'xVF (1983)
High
Orfe (Leuciscus
idus)
Fresh
96-h
LCso = 4030
mg/L
100, 215, 464, 1000,
2150, 4640, 10,000 mg/L
Static,
Nominal
Mortality
BASF (1.986)
High
Aquatic Invertebrates
Water flea
(Daphnia
magna)
Fresh
48-h
LCso = 4897
mg/L
389, 648, 1080, 1800,
3000, 5000, 8333 mg/L
Static,
Nominal
Mortality
GAF (1979)
High
Water flea
(.Daphnia
magna)
Fresh
21-day
NOEC=12.5
mg/L
LOEC= 25
mg/L
0.39,0.78, 1.56,3.13,
6.25, 12.5, 25, 50, 100
mg/L
Static,
Nominal
Reproduct
ion
BASF (2001)a
High
Grass shrimp
(Palaemonetes
vulgaris)
Salt
96-h
LCso= 1107
mg/L
360, 600, 1000, 1667,
2775 mg/L
Static,
Nominal
Mortality
GAF (1979)
High
Scud
(Gammarus sp)
Fresh
96-h
LCso= 4655
mg/L
389, 648, 1080, 1800,
3000, 5000, 8333 mg/L
Static,
Nominal
Mortality
GAF (1979)
High
Mud crabs
(Neopanope
texana sayi)
Salt
96-h
LCso= 1585
mg/L
360, 600, 1000, 1667,
2775 mg/L
Static,
Nominal
Mortality
>79)
High
-------
Tesl Species
Ircsli/
Siili
Wilier
Diii'iilion
I'.ndpoinl
( onceiil r;i 1 ion(s)
Tesl
An;il\sis
r.lTccl(s)
References
Diilii
Qu ;il it.\
l'\iiliiiilion
Algae
Algae
(Scenedemus
subspicatus)
Fresh
72-h
EbCso- 600
ErC50=673
mg/L
7.8, 15.6, 31.3,62.5,
125, 250, 500 mg/L
Static,
Nominal
Biomass
Growth
rate
BASF (1989)
High
Algae
(Scenedemus
subspicatus)
Fresh
72-h
LOEC=250
NOEC=125
7.8, 15.6, 31.3,62.5,
125, 250, 500 mg/L
Static,
Nominal
Growth
F (1989)
High
aReservation of Rights: BASF has agreed to share this toxicity study report ("Study Report") with US EPA, at its written
request, for EPA's use in implementing a statutory requirement of the Toxic Substances Control Act ("TSCA "). Every
other use, exploitation, reproduction, distribution, publication or submission to any other party requires BASF's written
permission, except as otherwise provided by law. The submission of this Study Report to a public docket maintained by
the United States Environmental Protection Agency is not a waiver of BASF's ownership rights. No consent is granted for
any other third-party use of this Study Report for any purpose, in any jurisdiction. Specifically, and by example, no
consent is granted allowing the use of this Study Report by a private entity in requesting any regulatory status, registration
or other approval or benefit, whether international, national, state or local, including but not limited to the Registration,
Evaluation, Authorisation and Restriction of Chemicals ("REACH") regulation administered by European Chemicals
Agency ("ECHA"), an agency of the European Union.
Page 520 of 576
-------
Appendix I HUMAN HEALTH HAZARDS
LI Hazard and Data Evaluation Summaries
1.1.1 Hazard and Data Evaluation Summary for Acute and Short-term Oral Exposure Studies
Table Apx 1-1. Hazard and Data Evaluation Summary for Acute and Short-term Oral Exposure Studies
I iii Sid
Origin/
S\stem
Siudj
Tj pe
Spocios.
Si r;iin.
Sex
(N ii in her
/liroup)
Doses/
C onceii I r;i (ions
Diii'iilion
Author
Reported
NOAI'.I./
I.OA Ml.
IP A
Identified
NOAII./
I.OAl'.l.
IITecl
Reference
Diilii
Qu;ilil\
l'.\iiliiiilion
Body
Weight
Short-
term
(1-30
days)
Rat,
Other,
Male (5)
0, 149, 429,
1234, 2019
mg/kg-bw/day
(0, 2000, 6000,
18,000, and
30,000 ppm)
4 weeks
NOAEL =
429 mg/kg -
bw/day
NOAEL=
429 mg/kg -
bw/day
Decreased body weight and
altered testes and liver weights
were observed at 1234 mg/kg-
bw/day and above.
Degeneration/atrophy of testicular
seminiferous tubules were
observed 1/5 males at 1234
mg/kg-bw/day and in 5/5 at 2019
mg/kg-bw/day. Increased
incidence of centrilobular
hepatocellular hypertrophy and
decreased serum glucose were
observed at 1234 mg/kg-bw/day
and above.
Malek et al.
(1QQ7\
High
Body
Weight
Short-
term
(1-30
days)
Rat,
Other
Female
(5)
0, 161,493,
1548, 2268
mg/kg-bw/day
(0, 2000, 6000,
18,000, and
30,000 ppm)
4 weeks
NOAEL=
1548 mg/kg
- bw/day
NOAEL =
1548 mg/kg ¦
bw/day
Decreased body weight and body
weight gain were observed at
2268 mg/kg-bw/day. Increased
serum total protein, albumin, and
cholesterol levels and increased
incidence of centrilobular
hepatocellular hypertrophy,
hypocellular bone marrow, and
thymic atrophy were also
observed at 2268 mg/kg-bw/day.
Malek et al.
(.1.997)
High
Page 521 of 576
-------
T;ir»c(
Orjiiin/
Sjslcm
Sludj
Tj |>c
Spocios.
Si r;iin.
Sox
(Nil m her
/liroup)
Doses/
(oiicciilnilions
Diii'iilion
Author
Reported
NOAF.I./
1.OA l-'.l.
IP A
Identified
NOAF.I./
1.OA F.I.
Filed
Reference
Diilii
Qu;ili(\
F\ ;ilu;ilion
Body
Weight
Short-
term
(1-30
days)
Mouse,
B6C3F1,
Female
(5)
0, 180, 920,
2970,4060
mg/kg-bw/day
(0, 500, 2500.
7500, 10,000
ppm)
4 weeks
Not
Reported
NOAEL =
4060 mg/kg -
bw/day
No exposure-related effects
NMP
Producers
Group
(.1.994)
High
Body
Weight
Short-
term
(1-30
days)
Mouse
B6C3F1,
Male (5)
0, 130, 720,
2130,2670
mg/kg-bw/day
(0, 500, 2500.
7500, 10,000
ppm)
4 weeks
Not
Reported
NOAEL=
2670 mg/kg -
bw/day
No exposure-related effects
NMP
Producers
Group
(.1.994)
High
Clinical
Chemistry/
Biochemica
1
Short-
term
(1-30
days)
Rat
Sprague-
Dawley,
Male (5)
0, 250, 500,
1000 mg/kg-
bw/day
5 days/ week
for 5 weeks
Not
Reported
NOAEL=
250 mg/kg -
bw/day
Decreased serum creatinine
Gopinathan
etal. (20.1.3)
Medium
Endocrine
Short-
term
(1-30
days)
Rat,
Other,
Female
(5)
0, 161,493,
1548, 2268
mg/kg-bw/day
(0, 2000, 6000,
18000, and
30000 ppm)
4 weeks
NOAF.I. =
1548 mg/kg
- bw/day
NOAEL=
1548 mg/kg -
bw/day
Decreased body weight and body
weight gain were observed at
2268 mg/kg-bw/day. Increased
serum total protein, albumin, and
cholesterol levels and increased
incidence of centrilobular
hepatocellular hypertrophy,
hypocellular bone marrow, and
thymic atrophy were also
observed at 2268 mg/kg-bw/day.
Malek et al.
(.1.997)
High
Hemato-
logical and
Immune
Short-
term
(1-30
days)
Rat,
Sprague-
Dawley,
Male (5)
0, 250, 500,
1000 mg/kg-
bw/day
5 days/ week
for 5 weeks
Not
Reported
NOAEL=
1000 mg/kg -
bw/day
No mortalities occurred and no
changes were reported for
hematology parameters or liver or
spleen weights.
Gopinathan
et al. (20.1.3)
Medium
Hepatic
Short-
term
(1-30
days)
Rat,
Sprague-
Dawley,
Male (5)
0, 250, 500,
1000 mg/kg-
bw/day
5 days/ week
for 5 weeks
Not
Reported
NOAEL=
1000 mg/kg -
bw/day
No mortalities occurred and no
changes were reported for
hematology parameters or liver or
spleen weights.
Gopinathan
et al. (20.1.3)
Medium
Page 522 of 576
-------
T;ir»c(
Orjiiin/
Sjslcm
Sludj
1 J |)C
Spocios.
Si r;iin.
Sox
(Nil m her
/iiroii|))
Doses/
(oiicciilnilions
Diii'iilion
Author
Reported
NOAF.I./
1.OA l-'.l.
IP A
Identified
NOAF.I./
1.OA F.I.
FITcci
Reference
Diilii
Qu;ili(\
F.\;ilu;ilion
Hepatic
Short-
term
(1-30
days)
Rat,
Other
Female
(5)
0, 161,493,
1548, 2268
mg/kg-bw/day
(0, 2000, 6000,
18,000, and
30,000 ppm)
4 weeks
NOAF.I. =
1548 mg/kg
- bw/day
NOAEL =
1548 mg/kg -
bw/day
Decreased body weight and body
weight gain were observed at
2268 mg/kg-bw/day. Increased
serum total protein, albumin, and
cholesterol levels and increased
incidence of centrilobular
hepatocellular hypertrophy,
hypocellular bone marrow, and
thymic atrophy were also
observed at 2268 mg/kg-bw/day.
Malek et al.
High
Hepatic
Short-
term
(1-30
days)
Mouse,
B6C3F1,
Female
(5)
0, 180, 920,
2970,4060
mg/kg-bw/day
(0, 500, 2500.
7500, 10,000
ppm)
4 weeks
Not
Reported
NOAEL=
4060 mg/kg -
bw/day
No exposure-related effects
NMP
Producers
Group
(1994)
High
Hepatic
Short-
term
(1-30
days)
Mouse,
B6C3F1,
Male (5)
0, 130, 720,
2130,2670
mg/kg-bw/day
(0, 500, 2500.
7500, 10,000
ppm)
4 weeks
Not
Reported
NOAEL=
2670 mg/kg -
bw/day
No exposure-related effects
NMP
Producers
Group
(.1.994)
High
Mortality
Short-
term
(1-30
days)
Rat,
Sprague-
Dawley,
Male (5)
0, 250, 500,
1000 mg/kg-
bw/day
5 days/ week
for 5 weeks
Not
Reported
NOAEL=
1000 mg/kg -
bw/day
No mortalities occurred and no
changes were reported for
hematology parameters or liver or
spleen weights.
Gopinathan
et al. (2013)
Medium
Mortality
Short-
term
(1-30
days)
Mouse,
B6C3F1,
Male (5)
0, 130, 720,
2130,2670
mg/kg-bw/day
(0, 500, 2500,
7500, 10000
ppm)
4 weeks
NOAF.I. =
0.048
NOAEL=
1125 mg/kg -
bw/day
Mortality in a male mouse that
also showed renal effects. Death
was considered related to
treatment.
Malek et al.
High
Page 523 of 576
-------
T;ir»c(
Orjiiin/
Sjslcm
Sludj
1 \ |)C
Spocios.
Si r;iin.
Sox
(Nil m her
/iiroii|))
Doses/
(oiicciilnilions
Diii'iilion
Author
Reported
NOAF.I./
1.OA l-'.l.
IP A
Identified
NOAF.I./
1.OA F.I.
Filed
Reference
Diilii
Qu;ili(\
F.\ ;ilu;ilion
Mortality
Short-
term
(1-30
days)
Mouse,
B6C3F1,
Female
(5)
0, 180, 920,
2970,4060
mg/kg-bw/day
(0, 500, 2500.
7500, 10,000
ppm)
4 weeks
Not
Reported
NOAEL =
4060 mg/kg -
bw/day
No exposure-related effects
NMP
Producers
Group
(.1.994)
High
Mortality
Short-
term
(1-30
days)
Mouse,
B6C3F1,
Male (5)
0, 130, 720,
2130,2670
mg/kg-bw/day
(0, 500, 2500.
7500, 10,000
ppm)
4 weeks
Not
Reported
NOAEL=
2670 mg/kg -
bw/day
No exposure-related effects
NMP
Producers
Group
(.1.994)
High
Not
Reported
Short-
term
(1-30
days)
Rat,
Sprague-
Dawley,
Male (5)
0, 250, 500,
1000 mg/kg-
bw/day
5 days/ week
for 5 weeks
Not
Reported
NOAEL=
250 mg/kg -
bw/day
Decreased serum creatinine
Gopinathan
etal. (20.1.3)
Medium
Not
Reported
Short-
term
(1-30
days)
Rat,
Sprague-
Dawley,
Male (5)
0, 250, 500,
1000 mg/kg-
bw/day
5 days/ week
for 5 weeks
Not
Reported
NOAEL=
250 mg/kg -
bw/day
Decreased serum creatinine
Gopinathan
et al. (20.1.3)
Medium
Renal
Short-
term
(1-30
days)
Rat,
Sprague-
Dawley,
Male (5)
0, 250, 500,
1000 mg/kg-
bw/day
5 days/ week
for 5 weeks
Not
Reported
Not
Reported
Mottled kidneys were reported
bilaterally with a combined
incidence in all dose groups (250,
500, and 1000 mg/kg-bw/day) of
8/15. This was not observed in
controls. No changes were
reported for urine chemistry
parameters or kidney weights.
Incidences of mottled kidneys for
each dose group were not
reported, so I did not assign a
NOAEL or LOAEL for renal
effects.
Gopinathan
et al. (20.1.3)
Medium
Page 524 of 576
-------
T;ir»c(
Orjiiin/
Sjslcm
Sludj
1 \ |)C
Spocios.
Si r;iin.
Sox
(Nil m her
/iiroii|))
Doses/
(oiicciilnilions
Diii'iilion
Author
Reported
NOAKI./
1.OA l-'.l.
IP A
Identified
NO A HI./
1.OA l-'.l.
I'.ITect
Reference
Diilii
Qu;ili(\
l-'.\;ilu;ilion
Renal
Short-
tenn
(1-30
days)
Mouse,
B6C3F1,
Female
(5)
0, 180, 920,
2970,4060
mg/kg-bw/day
(0, 500, 2500.
7500, 10,000
ppm)
4 weeks
NOAF.I. =
920 mg/kg -
bw/day
NOAEL=
920 mg/kg -
bw/day
Dark yellow urine in all animals at
Dose 3, 4, and 5. Cloudy swelling
of the distal renal tubule in 3/5
females at Dose 5
NMP
Producers
Group
(.1.994)
High
Renal
Short-
term
(1-30
days)
Mouse,
B6C3F1,
Male (5)
0, 130, 720,
2130,2670
mg/kg-bw/day
(0, 500, 2500.
7500, 10,000
ppm)
4 weeks
NOAEL =
720 mg/kg -
bw/day
NOAEL=
720 mg/kg -
bw/day
Dark yellow urine in all animals at
Dose 3, 4, and 5. Cloudy swelling
of the distal renal tubule in 2/5
males at Dose 4. and 4/5 males at
Dose 5
NMP
Producers
Group
(1994)
High
Page 525 of 576
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1.1.2 Hazard and Data Evaluation Summary for Reproductive and Developmental Oral Exposure Studies
Table Apx 1-2. Hazard and Data Evaluation Summary for Reproductive and Developmental Oral Exposure Studies
Tsir»et
()r»;m/
System
Study Type
Species.
St miii.
Sex
(Number
/group)
Doses/
(onccn-
tr:itious
Duriitioii
Author
Ueporteil
NOAKI./
I.OAEI.
i:i»a
1 den ti lied
NOAKL/
I.OAKI.
KITecl Measured
Reference
l):it:i
Qiiiilitv
K\:ilu:ilion
Body
Weight
Two-
generation
reproduction
study
Rat,
Sprague-
Dawley
(30/sex/
group)
0, 50, 160,
500
mg/kg/day
10 weeks prior to
mating, throughout
mating, gestation,
lactation, and rest
periods between
pregnancies over
two generations
NOAEL=
160
mg/kg-
bw/day
NOAEL=
160
mg/kg-
bw/day
Reduced maternal body
weight gain from gestational
day 0-20 during both litters of
the parental generation in the
high dose group
Exxon
(1991)
High
Body
Weight
Developmental
Rat,
Sprague-
Dawley
(25/
group)
0, 40, 125,
400
mg/kg/day
Daily exposure on
gestational days
(GD) 6-15
NOAEL=
125
mg/kg-
bw/day
NOAEL=
125
mg/kg-
bw/day
Reduced maternal body
weight gain at 400 mg/kg-
bw/day
Exxon
(1992)
High
Body
Weight
Two-
generation
reproduction
study
Rat,
Sprague-
Dawley
(30/sex/
group)
0, 50, 160,
350/500
mg/kg/day
10 weeks prior to
mating, throughout
mating, gestation,
lactation, and rest
periods between
pregnancies over
two generations
NOEL=
350
mg/kg-
bw/day
NOAEL =
350
mg/kg-
bw/day
Reduced maternal body
weight gain from gestational
day 0-20 during the first litter
of the parental generation in
the high dose group (500
mg/kg-bw/day)
NMP
Producers
Group,
(1999a)
High
Body
Weight
Two-
generation
reproduction
study
Rat,
Wistar
(25/sex/
group)
0, 50, 160,
350/500
mg/kg/day
10 weeks prior to
mating, throughout
mating, gestation,
lactation, and rest
periods between
pregnancies over
two generations
NOAEL=
160
mg/kg-
bw/day
NOAEL =
160
mg/kg-
bw/day
Reduced maternal body
weight gain from gestational
day 0-20 during both litters of
the parental generation in the
high dose group
NMP
Producers
Group
(1999c)
High
Page 526 of 576
-------
T:ir»et
()r»;iu/
System
Sliuly Type
Species,
Si m in.
Sex
(Nil in her
/group)
Doses/
C'ouceii-
Inilions
Duration
Author
Keported
\oai:i./
I.OAEI.
i:i»a
1 ileu (i lied
\oai:l/
I.OAKI.
KITect Mesisured
Reference
l):il:i
Qiiiilitv
K\:ilu:ilion
Body
Weight
Reproductive
Rat, Male
(22-24)
0, 100,
300, 1000
mg/kg-
bw/day
5 days/ week for
10 weeks prior to
mating and 1 week
during mating
Not
Reported
NOAEL =
300 mg/kg
- bw/day
Significant body weight
decrement of at least 10% in
paternal rats exposed prior to
mating in the high dose group
Sitarek et
al. (2008)
High
Offspring
Survival,
Growth,
and
Develop-
ment
Two-
generation
reproduction
study
Rat,
Sprague-
Dawley
(30/sex/
group)
0, 50, 160,
500
mg/kg/day
10 weeks prior to
mating, throughout
mating, gestation,
lactation, and rest
periods between
pregnancies over
two generations
NOAEL=
160
mg/kg-
bw/day
NOAEL=
160
mg/kg-
bw/day
Significant decrease in
offspring survival indices and
growth rates and increase in
the number of stillborn pups
in both generations in the high
dose group
Exxon
(1991)
High
Offspring
Survival,
Growth,
and
Develop-
ment
Developmental
Rat,
Sprague-
Dawley
(25/
group)
0, 40, 125,
400
mg/kg/day
Daily exposure on
gestational days
(GD) 6-15
NOAEL=
125
mg/kg-
bw/day
NOAEL=
125
mg/kg-
bw/day
Reduced fetal body weights,
reduced ossification sites in
proximal phalanges of the
hindpaw, at 400 mg/kg-
bw/day
Exxon
(1992)
High
Offspring
Survival,
Growth,
and
Develop-
ment
Two-
generation
reproduction
study
Rat,
Sprague-
Dawley
(30/sex/
group)
0, 50, 160,
350/500
mg/kg/day
10 weeks prior to
mating, throughout
mating, gestation,
lactation, and rest
periods between
pregnancies over
two generations
NOEL=
160
mg/kg-
bw/day
NOAEL =
50 mg/kg-
bw/day
Significant decrease in pup
survival through PND4 and
decrease in pup body weights
in both generations in the high
dose group; significant
decrease in pup body weights
at PND 7-21 in the second
litter of the second generation
in the 160 mg/kg/day dose
group; significant increase in
stillborn pups in the first litter
of the first generation in the
high dose group
NMP
Producers
Group
(1999a)
High
Page 527 of 576
-------
T:ir»et
()r»;iu/
System
Sliuly Type
Species,
Si m in.
Sex
(Nil in her
/group)
Doses/
C'ouceii-
Inilions
Duration
Author
Keported
\oai:i./
I.OAEI.
i:i»a
1 ileu (i lied
\oai:l/
I.OAKI.
KITect Mesisured
Reference
l):il:i
Qiiiilitv
K\:ilu:ilion
Offspring
Survival,
Growth,
and
Develop-
ment
Two-
generation
reproduction
study
Rat,
Wistar
(25/sex/
group)
0, 50, 160,
350/500
mg/kg/day
10 weeks prior to
mating, throughout
mating, gestation,
lactation, and rest
periods between
pregnancies over
two generations
NOAEL=
160
mg/kg-
bw/day
NOAEL=
160
mg/kg-
bw/day
Significant increase in the
number of stillborn pups in
the first generation high dose
group and decrease in pup
survival through PND4 in
both generations in the high
dose group
NMP
Producers
Group
(1999c)
High
Offspring
Survival,
Growth,
and
Develop-
ment
Developmental
Rat,
Sprague-
Dawley
(15-16)
0, 125,
250, 500,
750
mg/kg-
bw/day
Daily exposure on
gestational days
(GD) 6-20
NOAEL=
125
mg/kg-
bw/day
NOAEL=
125
mg/kg-
bw/day
Significant increase in
resorptions/ post-implantation
losses, increased skeletal
malformations, and decreased
fetal body weights
Saillenfait
et al.
(2002)
High
Offspring
Survival,
Growth,
and
Develop-
ment
Reproductive
Rat,
Other,
Male (22-
24)
0, 100,
300, 1000
mg/kg-
bw/day
5 days/ week for
10 weeks prior to
mating and 1 week
during mating
Not
Reported
NOAEL =
100 mg/kg
- bw/day
Significant decrease in
offspring viability through
PND4 following paternal
exposure prior to mating
Sitarek et
al. (2008)
High
Offspring
Survival,
Growth,
and
Develop-
ment
Reproductive
Rat,
Wistar,
Female
(22-28)
0, 150,
450,1000
mg/kg-
bw/day
5 days/ week for
two weeks before
mating, during
gestation and
lactation
LOAEL =
150
mg/kg-
bw/day
LOAEL =
150
mg/kg-
bw/day
Significant decrease in pup
survival within three weeks of
birth at all doses; number of
live pups was reduced at
1 OOOmg/kg-bw/day
Sitarek et
al. (2012)
High
Page 528 of 576
-------
T:ir»et
Or»;iu/
System
Study Type
Species,
Si m in.
Sex
(Nil m her
/group)
Doses/
C'ouceii-
Inilions
Duration
Author
Keported
noael/
I.OAEI.
i:i»a
1 ileu (i lied
NOAEL/
I.OAKI.
Effect Mesisured
Reference
l):il:i
Quality
E\:ilu:ilion
Repro-
ductive
Subchronic
(30-90 days)
Dog,
Beagle,
Both
(6/sex)
0, 24, 75,
246
mg/kg-
bw/day in
males; 0,
24, 76, 246
mg/kg-
bw/day in
females
(actual
concentrati
ons)
13 weeks
Not
Reported
NOAEL =
246 mg/kg
- bw/day
No effects on reproductive
organs, hematological/
immune, body weight, relative
organ (liver, kidney, spleen,
heart, thyroid, adrenal glands,
brain, and pituitary) weights.
Becci et al.
(1983)
High
Repro-
ductive
Two-
generation
reproduction
study
Rat,
Sprague-
Dawley
(30/sex/
group)
0, 50, 160,
500
mg/kg/day
10 weeks prior to
mating, throughout
mating, gestation,
lactation, and rest
periods between
pregnancies over
two generations
NOAEL
= 160
mg/kg -
bw/day
LOAEL =
50 mg/kg -
bw/day
Significant reductions in male
fertility, female fecundity at
all doses tested in both litters
of the second generation;
increased numbers of second
generation females with
microscopic changes in the
uterus and ovaries, including
decreased numbers of corpora
lutea and decreased
implantation sites in the high
dose group; increased
incidence of smaller than
normal testes in second
generation parental males in
the high dose group
Exxon
(1991)
High
Page 529 of 576
-------
T:ir»et
()r»:in/
System
Study Type
Species,
Si m in.
Sex
(Nil m her
/group)
Doses/
C'ouceii-
Inilions
Duration
Author
Keported
NOAEL/
I.OAEI.
i:i»a
1 ileu (i lied
NOAEL/
I.OAKI.
Effect Mesisured
Reference
l):il:i
Quality
L\:ilu:ilion
Repro-
ductive
Short-term (1-
30 days)
Mouse,
B6C3F1,
Male (5)
0, 130,
720,2130,
2670
mg/kg-
bw/day (0,
500, 2500.
7500,
10,000
ppm)
4 weeks
Not
Reported
NOAEL =
2670 mg/kg
- bw/day
No exposure-related effects
NMP
Producers
Group/
BASF
(1994)
High
Repro-
ductive
Short-term (1-
30 days)
Rat,
Other,
Male (5)
0, 149,
429, 1234,
2019
mg/kg-
bw/day (0,
2000,
6000,
18,000,
30,000
ppm)
4 weeks
NOAEL
= 429
mg/kg -
bw/day
NOAEL =
429 mg/kg
- bw/day
Decreased body weight and
altered testes and liver
weights were observed at
1234 mg/kg-bw/day and
above. Degeneration/atrophy
of testicular seminiferous
tubules were observed 1/5
males at 1234 mg/kg-bw/day
and in 5/5 at 2019 mg/kg-
bw/day. Increased incidence
of centrilobular hepatocellular
hypertrophy and decreased
serum glucose were observed
at 1234 mg/kg-bw/day and
above.
Malek et
al. (1997)
High
Page 530 of 576
-------
T:ir»et
()r»:in/
System
Study Type
Species,
Si m in.
Sex
(Nil m her
/group)
Doses/
C'ouceii-
Inilions
Duration
Author
Keported
noael/
I.OAEI.
i:i»a
1 ileu (i lied
NOAEL/
I.OAKI.
Effect Mesisured
Reference
l):il:i
Qiiiilitv
E\:ilu:ilion
Repro-
ductive
Two-
generation
reproduction
study
Rat,
Sprague-
Dawley
(30/sex/
group)
0, 50, 160,
350/500
mg/kg/day
10 weeks prior to
mating, throughout
mating, gestation,
lactation, and rest
periods between
pregnancies over
two generations
NOEL=
350
mg/kg-
bw/day
NOAEL =
350
mg/kg-
bw/day
No significant reduction
reported in male or female
fertility; no significant
difference from controls
reported on estrous cycles,
sperm parameters,
reproductive organ weights or
histopathological findings in
ovaries or testes
NMP
Producers
Group
(1999a)
High
Repro-
ductive
Two-
generation
reproduction
study
Rat,
Wistar
(25/sex/
group)
0, 50, 160,
350/500
mg/kg/day
10 weeks prior to
mating, throughout
mating, gestation,
lactation, and rest
periods between
pregnancies over
two generations
NOAEL
for
fertility =
350
mg/kg-
bw/day
NOAEL
for fertility
= 350
mg/kg-
bw/day;
NOEAL
for testes
weights =
50 mg/kg-
bw/day
No significant reduction
reported in male or female
fertility; no significant
difference from controls
reported on estrous cycles,
sperm parameters, or
histopathological findings in
ovaries or testes; Significant
change in testes weights
relative to body weight in mid
and high dose groups in both
generations.
NMP
Producers
Group
(1999c)
High
Repro-
ductive
Subchronic
(30-90 days)
Rat,
Other,
Male (10)
0, 1, 169,
433,1057
mg/kg-
bw/day (0,
3000,
7500,
18,000
ppm)
90 days
Not
Reported
NOAEL =
1057
mg/kg -
bw/day
No adverse effects.
Malley et
al. (1999)
High
Page 531 of 576
-------
T:ir»et
()r»;iu/
System
Study Type
Species,
Si m in.
Sex
(Nil m her
/group)
Doses/
C'ouceii-
Inilions
Duration
Author
Keported
\oai:i./
I.OAKI.
i:i»a
1 ileu (i lied
\oai:l/
I.OAKI.
KITect Measured
Reference
l):il:i
Quality
K\:ilu:ilion
Repro-
ductive
Subchronic
(30-90 days)
Mouse,
Both
(20/sex)
0, 277,
619,1931
mg/kg-
bw/day (0,
1000,
2500,7500
ppm)
90 days
Not
Reported
NOAEL =
1931
mg/kg -
bw/day
No adverse effects.
Malley et
al. (1999)
High
Repro-
ductive
Chronic (>90
days)
Rat,
Other,
Male (62)
0, 66.4,
207, 678
mg/kg-
bw/day (0,
1600,
5000,
15,000
ppm)
2 years
Not
Reported
NOAEL =
207 mg/kg
- bw/day
Biliateral
degeneration/atrophy of
seminiferous tubules in the
tests, bilateral
oligospermia/germ cell debris
in the epididymites,
centrilobular fatty change in
the liver
Malley et
al. (2001)
High
Repro-
ductive
Chronic (>90
days)
Rat,
Other,
Female
(62)
0, 87.8,
283,939
mg/kg-
bw/day (0,
1600,
5000,
15,000
ppm)
2 years
Not
Reported
NOAEL =
939 mg/kg
- bw/day
No exposure-related adverse
effects
Malley et
al. (2001)
High
Repro-
ductive
Chronic (>90
days)
Mouse,
B6C3F1,
Male (50)
0, 89, 173,
1089
mg/kg-
bw/day (0,
600, 1200,
7200 ppm)
18 months
Not
Reported
NOAEL =
1089
mg/kg -
bw/day
No adverse effects
Malley et
al. (2001)
High
Page 532 of 576
-------
T:ir»et
()r»:in/
System
Study Type
Species,
Si m in.
Sex
(Nil m her
/group)
Doses/
C'ouceii-
Inilions
Duration
Author
Keported
noael/
I.OAEI.
i:i»a
1 ileu (i lied
NOAEL/
I.OAKI.
Effect Mesisured
Reference
l):il:i
Quality
E\:ilu:ilion
Repro-
ductive
Chronic (>90
days)
Mouse,
B6C3F1,
Female
(50)
0, 115,
221, 1399
mg/kg-
bw/day (0,
600, 1200,
7200 ppm)
18 months
Not
Reported
NOAEL =
1399
mg/kg -
bw/day
No adverse effects
Malley et
al. (2001.)
High
Repro-
ductive
Reproductive
Rat,
Other,
Male (22-
24)
0, 100,
300, 1000
mg/kg-
bw/day
5 days/ week for
10 weeks prior to
mating and 1 week
during mating
Not
Reported
NOAEL =
300 mg/kg
- bw/day
Significant increase in male
infertility, damage to
seminiferous epithelium and
significant reduction in
thyroid weight at 1000 mg/kg -
bw/day
Sitarek et
al (2008)
High
Repro-
ductive
Reproductive
Rat,
Wistar,
Female
(22-28)
0, 150,
450,1000
mg/kg-
bw/day
5 days/ week for
two weeks before
mating, during
gestation and
lactation
NOAEL
= 150
mg/kg-
bw/day
NOAEL =
150
mg/kg-
bw/day
Significant decrease in female
fertility index
Sitarek et
al. (2012)
High
Page 533 of 576
-------
1.1.3 Hazard and Data Evaluation Summary for Reproductive and Developmental Inhalation Exposure Studies
Table Apx 1-3. Hazard and Data Evaluation Summary for Reproductive and Developmental Inhalation Exposure Studies
Tsir»et
Oriiiin/
System
Sluilv Type
Species.
Si rsiin. Sex
(Nil m her/
»roup)
Doses/
(onccn-
I l ilt ions
Dumlion
Author
Report eil
noaei./
I.OAEI.
EPA
1 den tilled
noaei./
I.OAEI.
Effect Mesisured
Reference
Diitii
Qiiiility
E\ iiliiiition
Body
Weight
Developmental
Rat,
Sprague-
Dawley,
Female (25-
26)
0, 122,
243,487
mg/m3
6	hours/ day;
7	days/ week
for 15 weeks
NOAEL=
122 mg/m3
NOAEL =
122 mg/m3
LOAEL for decreased
maternal weight gain at 243
mg/m3. Maternal food intake
also decreased at 487 mg/m3.
Saillenfait
et al. (2003)
High
Neuro-
logical/
Behavior
Reproductive
Rat, Other,
Both (10M
and 20F)
0, 42,
206, 472
mg/m3
6 hours/ day 7
days/ week
for 143 weeks
Not
Reported
NOAEL =
42 mg/m3
F0 dams exhibited decreased
response to auditory stimuli at
the highest dose.
Solomon et
al. (1995)
High
Offspring
Survival,
Growth,
and
Develop-
ment
Developmental
Rat, Other,
Female (25)
0, 100,
360
mg/m3
6 hours/ day 7
days/ week
for 10 weeks
Not
Reported
NOAEL =
360 mg/m3
No effects on uterine or litter
parameters, fetal weight or
length, or incidence of gross,
soft tissue, or skeletal
anomalies
Lee et al.
(1987)
High
Offspring
Survival,
Growth,
and
Develop-
ment
Reproductive
Rat, Other,
Both (10M
and 20F)
0, 42,
206, 472
mg/m3
6	hours/ day;
7	days/ week
for 143 weeks
Not
Reported
NOAEL =
42 mg/m3
Decreased F1 offspring
weights per litter from PND 1
to PND 21, and decreased
fetal body weight in
developmental phase of study,
at highest dose
Solomon et
al. (1995)
High
Offspring
Survival,
Growth,
and
Develop-
ment
Developmental
Rat,
Sprague-
Dawley,
Female (25-
26)
0, 122,
243,487
mg/m3
6	hours/ day;
7	days/ week
for 15 weeks
NOAEL=
243 mg/m3
NOAEL=
243 mg/m3
Reduced fetal weight at 487
mg/m3 exposure
Saillenfait
et al. (2003)
High
Page 534 of 576
-------
Tsir»et
Oriiiin/
System
Study Type
Species,
Si rsiin. Sex
(Nil m her/
»roup)
Doses/
(onceii-
I l ilt ions
Dumlion
Author
Report ed
noaei./
I.OAEI.
EPA
1 den tilled
noaei./
I.OAEI.
Effect Mesisured
Reference
Diitii
Qiiiility
E\ iiliiiition
Repro-
ductive
Chronic (>90
days)
Rat, Cij:
CD(SD),
Both (120)
0,41,405
mg/m3
6 hours/
day 5 days/
week
Not
Reported
NOAEL =
41 mg/m3
Mammary gland hyperplasia
DuPont
(1982)
Medium
Repro-
ductive
Chronic (>90
days)
Rat, Cij:
CD(SD),
Both (120)
0,41,405
mg/m3
6 hours/ day 5
days/ week
Not
Reported
NOAEL =
405 mg/m3
No adverse effects reported
based on histopathology of
epididymites and prostate
DuPont
(1982)
Medium
Repro-
ductive
Reproductive
Rat, Other,
Both (10M
and 20F)
0, 42,
206, 472
mg/m3
6 hours/ day 7
days/ week
for 143 weeks
NOAEL =
472 mg/m3
NOAEL =
472 mg/m3
No significant difference in
reproductive performance or
adult body weight. Study
notes condensation on inside
of high dose chambers, which
precluded achieving target
concentration of 527 mg/m3.
Solomon et
al. (1995)
High
Page 535 of 576
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1.1.4 Hazard and Data Evaluation Summary for Reproductive and Developmental Dermal Exposure Studies
Table Apx 1-4. Hazard and Data Evaluation Summary for Reproductive and Deve
T:ir»ct
()r»:in/
System
Sliiily Type
Species.
Strsiin.
Sex
(Nil in her/
»roup)
Doses/
Coiicen-
l r;il ions
Diinilion
Author
Reported
\oai:i./
I.OAEI.
i:i»a
1 clenti I'iecl
\oai:l/
I.OAEI.
Effect Measured
Reference
l):it:i
Qiiiililv
K\:ilu;ition
Growth
and
develop
ment
Developmental
Sprague-
Dawley,
Female
(25)
0, 75,237
and 750
mg/kg-
bw/day
Days 6-15 of
gestation
Not
reported
NOAEL=
237
mg/kg-
bw/day
Decreased number of live
fetuses per dam and
increased percentage of
resorption sites and
skeletal abnormalities as
well as maternal toxicity
indicated by reduced body
weight gain at the highest
dose
Becci et al.
(1982)
Medium
opmental Dermal Exposure Studies
Page 536 of 576
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1.1.5 Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Inhalation Exposure Studies
Table Apx 1-5. Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Inhalation Exposure Studies
Tsir»et
Oriiiin/
System
Sluilv
Type
Species, Si niin.
Sex (Nilmher/
»roup)
Doses/
('onccn-
Imlions
Diimlion
Author
Reported
noael/
LOAM.
EPA
1 den tilled
NOAEL/
LOAEL
Effect Measured
Reference
l):it;i
Quality
L\ ;i In :it ion
Body
Weight
Chronic
(>90 days)
Rat, Crj:
CD(SD), Both
(120)
0,41,405
mg/m3
6 hours/ day
5 days/week
Not
Reported
NOAEL =
405 mg/m3
Body weight was significantly
decreased in 405 mg/m3 males
(but only 6% lower than controls).
Effects on mortality, hematology
and clinical chemistry parameters,
the kidney, and cancer incidence
were not temporally- and/or
concentration-related, and/or were
not toxicologically relevant (e.g.,
decreased cancer incidence).
DuPont
(1982)
Medium
Clinical
Chem-
istry/
Biochem-
ical
Chronic
(>90 days)
Rat, Crj:
CD(SD), Both
(120)
0,41,405
mg/m3
6 hours/ day
5 days/week
Not
Reported
NOAEL =
405 mg/m3
Body weight was significantly
decreased in 405 mg/m3 males
(but only 6% lower than controls).
Effects on mortality, hematology
and clinical chemistry parameters,
the kidney, and cancer incidence
were not temporally- and/or
concentration-related, and/or were
not toxicologically relevant (e.g.,
decreased cancer incidence).
DuPont
(1982)
Medium
Hemato-
logical
and
Immune
Chronic
(>90 days)
Rat, Crj:
CD(SD), Both
(120)
0,41,405
mg/m3
6 hours/ day
5 days/week
Not
Reported
NOAEL =
405 mg/m3
Body weight was significantly
decreased in 405 mg/m3 males
(but only 6% lower than controls).
Effects on mortality, hematology
and clinical chemistry parameters,
the kidney, and cancer incidence
were not temporally- and/or
concentration-related, and/or were
not toxicologically relevant (e.g.,
decreased cancer incidence).
DuPont
(1982)
Medium
Page 537 of 576
-------
Tsir»et
Oriiiin/
System
Study
Type
Species, Si niin.
Sex (Nilmher/
»roup)
Doses/
C'oncen-
Imlions
Diimlion
Author
Reported
noael/
LOAM.
EPA
1 den ti lied
NOAEL/
LOAEL
Effect Measured
Reference
l):it;i
Quality
L\ iihiiition
Mortality
Chronic
(>90 days)
Rat, Crj:
CD(SD), Both
(120)
0,41,405
mg/m3
6 hours/ day
5 days/week
Not
Reported
NOAEL =
405 mg/m3
Body weight was significantly
decreased in 405 mg/m3 males
(but only 6% lower than controls).
Effects on mortality, hematology
and clinical chemistry parameters,
the kidney, and cancer incidence
were not temporally- and/or
concentration-related, and/or were
not toxicologically relevant (e.g.,
decreased cancer incidence).
DuPont
(1982)
Medium
Not
Reported
Chronic
(>90 days)
Rat, Crj:
CD(SD), Both
(120)
0,41,405
mg/m3
6 hours/ day
5 days/week
Not
Reported
NOAEL =
405 mg/m3
Body weight was significantly
decreased in 405 mg/m3 males
(but only 6% lower than controls).
Effects on mortality, hematology
and clinical chemistry parameters,
the kidney, and cancer incidence
were not temporally- and/or
concentration-related, and/or were
not toxicologically relevant (e.g.,
decreased cancer incidence).
DuPont
Medium
Page 538 of 576
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1.1.6 Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Oral Exposure Studies
Table Apx 1-6. Hazard and Data Eva
uation Summary for Sub-chronic and Chronic Non-cancer Oral Exposure Studies
Tsir»et Or»:in/
System
Sluilv
Typo
Species, Si ruin.
Sex (Nil in her/
group)
Doses/
Coiiceiilriilioiis
Dunilioii
Author
Reported
noaei./
I.OAEI.
EPA
Identified
NOAEL/
I.OAEI.
Effect Measured
Reference
Diitii
Qiiiililv
E\ iihiiition
Body Weight
Sub-
chronic
(30-90
days)
Mouse, Both
(20/sex)
0, 277,619,
1931 mg/kg-
bw/day (0, 1000,
2500, 7500 ppm)
90 days
Not
Reported
NOAEL =
1931 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Body Weight
Sub-
chronic
(30-90
days)
Rat, Other, Male
(20-26)
0, 169, 433,
1057 mg/kg-
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
NOAEL =
0.048
NOAEL =
1057 mg/kg
- bw/day
Body weight effects not
considered adverse
(associated with decreased
food consumption, indicating
palatability issue)
Malley et al.
(1999)
High
Body Weight
Sub-
chronic
(30-90
days)
Rat, Other,
Female (20-26)
0,217,565,
1344 mg/kg -
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
NOAEL =
0.048
NOAEL =
1344 mg/kg
- bw/day
Body weight effects within
10% of control
Malley et al.
(1999)
High
Body Weight
Chronic
(>90 days)
Rat, Other, Male
(62)
0, 66.4, 207, 678
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
NOAEL =
207 mg/kg -
bw/day
NOAEL =
207 mg/kg -
bw/day
Study authors report a study
NOAEL of 207 mg/kg/day in
male rats based on 25%
decrease in terminal body
weight and increased
incidence of severe chronic
progressive nephropathy.
Malley et al.
(2001)
High
Body Weight
Chronic
(>90 days)
Rat, Other,
Female (62)
0, 87.8, 283,939
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
NOAEL =
283 mg/kg -
bw/day
NOAEL =
283 mg/kg -
bw/day
Study authors report a study
NOAEL of 283 mg/kg/day in
female rats based on 35%
decrease in terminal body
weight.
Malley et al.
(2001)
High
Page 539 of 576
-------
Tsir»cl ()r»:in/
System
Sluilv
Typo
Species, Si ruin.
Sex (\u in her/
group)
Doses/
C'oiiceiilriilious
Dunilioii
Author
Reported
noael/
I.OAEI.
EPA
Identified
noael/
LOAM.
Effect Measured
Reference
Diilii
Qiiiililv
E\ iihiiilion
Body Weight
Chronic
(>90 days)
Mouse, B6C3F1,
Male (50)
0, 89, 173, 1089
mg/kg-bw/day
(0, 600, 1200,
7200 ppm)
18 months
Not
Reported
NOAEL =
1089 mg/kg
- bw/day
No adverse effects
Malley et al.
(2001)
High
Body Weight
Chronic
(>90 days)
Mouse, B6C3F1,
Female (50)
0, 115,221,
1399 mg/kg-
bw/day (0, 600,
1200, 7200 ppm)
18 months
Not
Reported
NOAEL =
1399 mg/kg
- bw/day
No adverse effects
Malley et al.
(2001)
High
Hematological
and Immune
Sub-
chronic
(30-90
days)
Dog, Beagle
Both (6/sex)
0, 24, 75, 246
mg/kg-bw/day in
males; 0, 24, 76,
246 mg/kg-
bw/day in
females
13 weeks
Not
Reported
NOAEL =
246 mg/kg -
bw/day
No effects on reproductive
organs,
hematological/immune ,
body weight, relative organ
(liver, kidney, spleen, heart,
thyroid, adrenal glands,
brain, and pituitary) weights.
Becci et al.
(1983)
High
Hepatic
Sub-
chronic
(30-90
days)
Rat, Other, Male
(10)
0, 169, 433,
1057 mg/kg-
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
Not
Reported
NOAEL =
1057 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Hepatic
Sub-
chronic
(30-90
days)
Rat, Other,
Female (20-26)
0,217,565,
1344 mg/kg-
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
Not
Reported
NOAEL =
1344 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Hepatic
Sub-
chronic
(30-90
days)
Mouse, Both
(20/sex)
0, 277,619,
1931 mg/kg-
bw/day (0, 1000,
2500, 7500 ppm)
90 days
Not
Reported
NOAEL =
1931 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Page 540 of 576
-------
Tsir»cl ()r»:in/
System
Sluilv
Typo
Species, Si ruin.
Sex (\u in her/
group)
Doses/
C'oiiceiilriilious
Dunilioii
Author
Reported
noael/
I.OAEI.
EPA
Identified
NOAEL/
I.OAEL
Effect Measured
Reference
Diilii
Qiiiililv
E\ iihiiilion
Hepatic
Chronic
(>90 days)
Rat, Other, Male
(62)
0, 66.4, 207, 678
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
Not
Reported
NOAEL =
207 mg/kg -
bw/day
Biliateral
degeneration/atrophy of
seminiferous tubules in the
tests, bilateral
oligospermia/germ cell
debris in the epididymites,
centrilobular fatty change in
the liver
Malley et al.
(2001)
High
Hepatic
Chronic
(>90 days)
Rat, Other,
Female (62)
0, 87.8, 283,939
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
Not
Reported
NOAEL =
939 mg/kg -
bw/day
No exposure-related adverse
effects
Malley et al.
(2001)
High
Hepatic
Chronic
(>90 days)
Mouse, B6C3F1,
Female (50)
0, 115,221,
1399 mg/kg-
bw/day (0, 600,
1200, 7200 ppm)
18 months
NOAEL =
221 mg/kg -
bw/day
NOAEL =
221 mg/kg -
bw/day
Study authors reported a
study NOAEL of 221
mg/kg/day for female mice
based on increased liver
weight, increased incidence
of hepatocellular basophilic
foci, eosinophilic foci, and
cellular alterations in liver,
and increased hepatocellular
adenoma and carcinoma.
Malley et al.
(2001)
High
Page 541 of 576
-------
Tsir»cl ()r»:in/
System
Sluilv
Typo
Species, Si ruin.
Sex (\u in her/
group)
Doses/
C'oiiceiilriilious
Dunilioii
Author
Reported
noaei./
I.OAEI.
EPA
Identified
NOAEL/
I.OAEL
Effect Measured
Reference
Diilii
Qiiiililv
E\ iihiiilion
Hepatic
Chronic
(>90 days)
Mouse, B6C3F1,
Male (50)
0, 89, 173, 1089
mg/kg-bw/day
(0, 600, 1200,
7200 ppm)
18 months
NOAEL =
89 mg/kg -
bw/day
NOAEL =
89 mg/kg -
bw/day
Study authors report a study
NOAEL of 89 mg/kg/day in
male mice based on
increased liver weight in the
mid- and high-dose groups.
At the high dose, additional
effects included increased
incidence of hepatocellular
hypertrophy, clear cell foci,
eosinophilic foci, and
cellular alterations in the
liver.
Malley et al.
(2001)
High
Mortality
Sub-
chronic
(30-90
days)
Rat, Other, Male
(10)
0, 169, 433,
1057 mg/kg-
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
Not
Reported
NOAEL =
1057 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Mortality
Sub-
chronic
(30-90
days)
Rat, Other,
Female (20-26)
0,217,565,
1344 mg/kg-
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
Not
Reported
NOAEL =
1344 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Mortality
Sub-
chronic
(30-90
days)
Mouse, Both
(20/sex)
0, 277,619,
1931 mg/kg-
bw/day (0, 1000,
2500, 7500 ppm)
90 days
Not
Reported
NOAEL =
1931 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Mortality
Chronic
(>90 days)
Rat, Other, Male
(62)
0, 66.4, 207, 678
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
NOAEL =
0.048
NOAEL =
66.4 mg/kg
- bw/day
Decreased survival at 207
mg/kg/day (21%) compared
with control (32%)
Malley et al.
(2001)
High
Page 542 of 576
-------
Tsir»cl ()r»:in/
System
Sluilv
Typo
Species, Si ruin.
Sex (\u in her/
group)
Doses/
C'oiiceiilriilious
Dunilioii
Author
Reported
noael/
I.OAEI.
EPA
Identified
noael/
LOAM.
Effect Measured
Reference
Diilii
Qiiiililv
E\ iihiiilion
Mortality
Chronic
(>90 days)
Rat, Other,
Female (62)
0, 87.8, 283,939
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
Not
Reported
NOAEL =
939 mg/kg -
bw/day
No exposure-related adverse
effects
Malley et al.
(2001)
High
Mortality
Chronic
(>90 days)
Mouse, B6C3F1,
Male (50)
0, 89, 173, 1089
mg/kg-bw/day
(0, 600, 1200,
7200 ppm)
18 months
Not
Reported
NOAEL =
1089 mg/kg
- bw/day
No adverse effects
Malley et al.
(2001)
High
Mortality
Chronic
(>90 days)
Mouse, B6C3F1,
Female (50)
0, 115,221,
1399 mg/kg-
bw/day (0, 600,
1200, 7200 ppm)
18 months
Not
Reported
NOAEL =
1399 mg/kg
- bw/day
No adverse effects
Malley et al.
(2001)
High
Renal
Sub-
chronic
(30-90
days)
Rat, Other, Male
(10)
0, 169, 433,
1057 mg/kg-
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
Not
Reported
NOAEL =
1057 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Renal
Sub-
chronic
(30-90
days)
Rat, Other,
Female (20-26)
0,217,565,
1344 mg/kg-
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
Not
Reported
NOAEL =
1344 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Renal
Sub-
chronic
(30-90
days)
Mouse, Both
(20/sex)
0, 277,619,
1931 mg/kg-
bw/day (0, 1000,
2500, 7500 ppm)
90 days
Not
Reported
NOAEL =
1931 mg/kg
- bw/day
No adverse effects.
Malley et al.
(1999)
High
Page 543 of 576
-------
Tsir»cl ()r»:in/
System
Sluilv
Typo
Species, Si ruin.
Sex (\u in her/
group)
Doses/
C'oiiceiilriilious
Dunilioii
Author
Reported
noael/
I.OAEI.
EPA
Identified
NOAEL/
I.OAEL
Effect Measured
Reference
Diilii
Qiiiililv
E\ iihiiilion
Renal
Chronic
(>90 days)
Rat, Other, Male
(62)
0, 66.4, 207, 678
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
NOAEL =
207 mg/kg -
bw/day
NOAEL =
207 mg/kg -
bw/day
Study authors report a study
NOAEL of 207 mg/kg/day in
male rats based on 25%
decrease in terminal body
weight and increased
incidence of severe chronic
progressive nephropathy.
Malley et al.
(2001)
High
Renal
Chronic
(>90 days)
Rat, Other
Female (62)
0, 87.8, 283,939
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
Not
Reported
NOAEL =
939 mg/kg -
bw/day
No exposure-related adverse
effects
Malley et al.
(2001)
High
Renal
Chronic
(>90 days)
Mouse, B6C3F1
- Male (50)
0, 89, 173, 1089
mg/kg-bw/day
(0, 600, 1200,
7200 ppm)
18 months
Not
Reported
NOAEL =
1089 mg/kg
- bw/day
No adverse effects
Malley et al.
(2001)
High
Renal
Chronic
(>90 days)
Mouse, B6C3F1
- Female (50)
0, 115,221,
1399 mg/kg-
bw/day (0, 600,
1200, 7200 ppm)
18 months
Not
Reported
NOAEL =
1399 mg/kg
- bw/day
No adverse effects
Malley et al.
(2001)
High
Page 544 of 576
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1.1.7 Hazard and Data Evaluation Summary for Cancer Studies
Table Apx 1-7. Summary of Tumor Incidence Data from Animal Cancer Bioassays
Species/ St rsiin/
Sex
(Nil in her/» roup)
Exposure
Route
Doses/
(oiicenlmtions
Diimlion
("sincer
Incidence
Effect
Reference
l):i(;i
Qiuililv
E\ nliiitlion
Rat/Cij: CD(SD)/
Both (120)
Inhalation,
whole body
0, 41, 405 mg/m3
6 hours/day
5 days/week
for 2 years
Data not
presented
Increased piluilarx
adenocarcinomas at 41
but not 405 mg/m3 and
at 18 but not 24
months
DuPont
(1M2)a
Medium
(1.8)
Rat/Other/
Female (62)
0, 87.8, 283,939
mg/kg-bw/day (0,
1600, 5000, 15,000
ppm)
2 years
0, 2, 3, 3
At least one mammary
neoplasm
Mouse/B6C3F1/
Male (50)
Oral,
dietary
0, 89,173,1089
mg/kg-bw/day (0,
600,1200, 7200
ppm)
5, 2, 4, 12
Increased incidence of
hepatocellular
adenoma
4, 1,3, 13
Increased incidence of
hepatocellular
carcinoma
Malley et al.
(200 nb
18 months
Mouse/B6C3Fl/
Female (50)
0, 115,221, 1399
mg/kg-bw/day (0,
600,1200, 7200
ppm)
2, 2, 1,7'
Increased
hepatocellular
adenoma and
carcinoma
0, 0, 0, 3
Increased
hepatocellular
carcinoma
High (1.2)
This is the unpublished study of the published study identified as Lee et al. (1987)
b Unpublished study of the results in rats is available as NMP Producers Group (1997)
P < 0.05 by Cochran-Armitage trend test	
Page 545 of 576
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1.1.8 Hazard and Data Evaluation Summary for Genotoxicity and Mechanistic Studies
Table Apx 1-8. Summary of Genotoxicity and Mechanistic Data
Species
KxpOSIII'C
Route
Kxposure
l)ose/l)n I'iition
Outcome
Comments
Reference
Ditlit Qiiiililv
K\ iiliiiition
Mice: NMRI
Oral gavage
Single dose of 0,
950, 1900, or 3800
mg/kg-bw
No increase in
multinucleated
erythrocytes
Authors report indications of systemic
toxicity from NMP exposure. Authors
conclude that results indicate a lack of
clastogenic effect or spindle poison
effect of NMP in vivo. Positive
control responses demonstrate that the
assay was able to detect such effects.
Eneelhardt and
High
Chinese Hamster
Oral gavage
Single dose of 0,
1900, or 3800
mg/kg-bw
No increase in the
number of mitoses
containing structural or
numerical chromosomal
aberrations in bone
marrow.
Authors report indications of systemic
toxicity from NMP exposure. Authors
conclude that results indicate a lack of
clastogenic or aneugenic effect of
NMP. Positive control responses
demonstrate that the assay was able to
detect structural and numerical
chromosomal aberrations.

High
Salmonella
(strains TA1535,
TA1537, TA98,
TA97, and
TA100) and
mammalian
microsomes
In vitro
Ames assay
0, 100, 333, 1000,
3333, or 10000
Hg/plate
(± S9 mix)
No mutagenic response
reported for NMP with
or without metabolic
activation.
Salmonella mutagenicity was tested
with and without mammalian
microsomes. Arochlor-1254 induced
S9 liver fractions were obtained from
male Sprague-Dawley rats and male
Syrian hamsters. Positive control
responses demonstrate that the assay
was able to detect mutagenic effects.
Mortelmans et at
High
Salmonella
(strains TA100,
TA102, TA104,
TA97, TA98,
TA2638,
UTH8413,
UTH8414)
In vitro
Ames assay
(standard
plate
incorporation
assay)
0,0.01,0.1, 1.0,
10, 100, or 1000
nM/plate
(± S9 mix)
No mutagenic response
reported for NMP with
or without metabolic
activation.
Test were performed using strains
capable of detecting frameshifts,
base-pair substitution, and excision
repair. ; Arochlor-1254 induced S9
liver fractions were obtained from
male Sprague-Dawley rats. In strains
TA102 and TA104,, an increase in
revertant numbers was reported but
the increase was less than two-fold
greater than background and did not
demonstrate a linear dose-response.
Wells et al (1988)
High
Page 546 of 576
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Species
Kxposure
Route
Kxposurc
Dosc/Diii'iilion
Outcome
Comments
Reference
l);it:i Qiiiility
K\ iiliiiition
Salmonella
(strains TA98,
TA104)
In vitro
Ames assay;
(pre-
incubation
assay)
0.01 - 1000
nM/plate
(± S9 mix)
No mutagenic response
reported for NMP
Tests were performed following pre-
incubation of NMP, S9 mix, and
bacteria. Following pre-incubation,
NMP was cytotoxic to Salmonella at
the highest test concentrations

Midi
Not applicable
In vitro cell
free binding
assay
25 mMNMP
Percentage competition
of NMP vs. control
binding to each of the
two BRDT binding
domains was reported as
2.6% and 4.4% (where
0% indicates strongest
binding interaction and
100% indicates absent
binding)
BromoMax screening assay provides
competitive binding data for a panel
of bromodomain-containing proteins,
including the testis-specific BRDT as
well as BRD1, BRD2, BRD3, BRD4,
BAZ2B, CREBBP, and TAF1. NMP
binding to bromodomains contained
in these proteins ranged from 0-8%.
Shortt (20.1.4)
High
Not applicable
In vitro cell
free binding
assay
10 concentrations
across 5 log units
IC50 for BRD2 = 3.3
mM
IC50 for BRD4 = 3.4
mM
AlphaScreen binding assay was used
to determine the effect of NMP on
bromodomain binding ability for a
panel of bromodomain-containing
proteins. IC50s for BRD2 and BRD4
bromodomains were calculated from
AlphaScreen results across a range of
concentrations
Gjoksi (20.1.5a):
Gjoksi (20.1.6)
High
Page 547 of 576
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Appendix J NMP PBPK MODELING
The PBPK models of Poet et al. (2010) (Figure_Apx J-l) describe the toxicokinetics of NMP in rats and
humans. EPA has revised the models for use in this risk evaluation, and the models underwent scientific
and technical evaluations consistent with those outlined in An umbrella Quality Assurance Project Plan
(QAPP) for PBPK models (EPA 2018e). These PBPK models were initially evaluated and revised by
EPA in 2013 ( S EPA 2013b). Further modifications and calibration were conducted by Dr. Torka
Poet in 2014 (personal communication). In this update, additional data were considered to further
calibrate and validate the model. Model calibration consists of using data to optimize parameters when
those parameters are unknown or approximated, validation is used to show the fits of the model to other
datasets. EPA then evaluated the version submitted by Dr. Poet in 2014 and made some additional
corrections and modifications as described below.
NMP
Inhalation
Exposui e
Dei ma
Urine
Metabolites
max
Liver
Fetus
Mammary
Fat
Placenta
5-HNMP
skin
slowly Perfusei
	Tissues
Richly Perfused
	Tissues
Alveolar Air
Lung Blood
Oral
Exposure
FigureApx J-l. PBPK model structure.
PBPK model used to describe the disposition of NMP and its major metabolite 5-HNMP in rats and
humans following oral, dermal, or inhalation exposures. Lines represent blood flow between
compartments (QC, cardiac output [L/h]); Qi, blood flow to "i" tissue (L/h). The NMP parent model
consists of seven parental tissue compartments, along with arterial and venous blood. (Figure from Poet
et al. (2010)).
-------
These PBPK models simulate the pharmacokinetics of NMP and its metabolite 5-HNMP in rats and
humans, described briefly below. The models consist of nine main compartments: lung, richly perfused
tissues, slowly perfused tissues, skin, fat, mammary, placenta, fetus and liver for NMP with a submodel
for 5H-NMP. The model can simulate NMP exposures via the oral, inhalation and dermal routes.
Dermal absorption occurs for contact with NMP liquid and vapor. Distribution of NMP to tissues is
assumed to be flow-limited. The model includes mathematical descriptions of the growth of fetal and
maternal tissues during gestation based on a previous PBPK model of pregnancy (Gentry et al.. 2002).
Due to extensive differences between rat and human gestation periods, separate rat and human models
were developed. NMP metabolism was assumed to occur in the liver. NMP was assumed to be
eliminated in exhaled air and urine. 5-HNMP was assumed to be eliminated by further metabolism and
in urine. The physiological parameter values used in the model were obtained from the literature (Gentn
et al.. 2002; Brown et a 7b) and biochemical constants for absorption, metabolism and elimination
were fit to the reasonably available toxicokinetic data (Payan. et al.. 2002; Akesson and Paulsson. 1997;
NMP Producers Group. 1995a; Midgtey et al.. 1992; Wells and Digenis. 1988). Further description of
the PBPK model are available in Poet et al. ( ),	), and the modifications described
below. In this risk evaluation, EPA used a modified version of the PBPK models. Partition coefficients
and parameters used in the EPA model are summarized in TableApx J-l and TableApx J-2.
TableApx J-l. TissuerBlood Partition Coefficients Used in the Rat and Human NMP PBPK
Models
Tissue
I'euiiilo U:il11
11 ii in :i n
NMP
Blood:air
450
450
Slowly-perfused:blood
0.74
0.46
Fat:blood
0.62
0.49
Liverblood
1.02
0.82
Rapidly-perfused: blood
1.02
0.10
Skin: saline
0.42
0.42
Skin: blood
0.12
0.099
Skin: air
55
44.5
Lung:blood
0.1
0.10
Mammary:blood
1.0
0.49
Uterus: blood
0.34
0.08
Placenta: blood
0.309
0.1
Fetus:placenta
1.0
1.0
5-HNMP
Liverblood
3.0
NAb
Fat:blood
0.4
NAb
Placenta: blood
1.07
NAb
Fetus:placenta
1.0

Page 549 of 576
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Tissue
l-'cmsilc K:il11
1 In 111:111 ''
Rest-of-body:blood
0.73
NAb
aThe PBPK models was developed specifically for female rats and humans, to simulate pregnancy. Hence, to the
extent available, tissue partition data for females from CPoet et al, 2010) were used.
b The human PBPK model only has a single compartment for the amount of 5-HNMP in the body, hence does not
have tissue:blood partition coefficients for this metabolite.
Table Apx J-2. Summary of PBPK Model Parameters
I'iiniiiielor
K«il
1 In ill ;i 11 ''
Source
Body weight (kg)
Variable
Variable
Data set-specific
Tissue volumes (% body weight)
Liver
3..66 b
3.1
Gentry et al. (2002); Brown et al. (1997a)
Lung
0.5 b
NA
Gentry et al. (2002); Brown et al.
7a)
Blood (total)
6.7 b
0.79 b
Gentry et al. (2002); Brown et al.
la)
Rapidly perfused
7.1
4.2
Gentry et al. (2002); Brown et al. (1997a)
Slowly perfused
calculated
calculated
91%- (sum of othertissue %) Centre et
al. (2002); Brown et al. (1997a)
Fat
9.0
23
Gentry et al. (2002); Brown et al. (1997a)
Skin d
19.0
5.1
Brown et )7a)
Flows (l/h/kg0 75)
Alveolar ventilation
15 e
16 b,e
Brown et >7a)
Cardiac output
15 e
15 e
Brown et >7a)
Percentage of cardiac output
Liver
18.3
25.0
Gentry et al. (2002); Brown et al. (1997a)
Richly perfused
51.2
48.0
Gentry et al. (2002); Brown et al. (1997a)
Slowly perfused
calculated
calculated
100% - (sum of other flow %) Gentry et
al. (2002); Brown et al. (1997a)
Fat
7.0
5.0
Gentry et al. (2002); Brown et al. (1997a)
Skin d
5.8 b
5.8 b
Gentry et al. (2002); Brown et al. (1997a)
Biochemical constants f
NMP: FmaxC (mg/h/kg0 75)
9 c
19.3 c
Optimized
NMP: Km (mg/1)
225 c
150 c
Optimized
5-HNMP FmaxC (mg/h/kg0 75)
0.009 c
NA
Optimized
5-HNMP: Km (mg/1)
4.9 c
NA
Optimized
5-HNMP 1st order: Vk2 (L/h/kg°75)
NA
0.0359 c
Optimized
First order urinary elimination - not scaled
Page 550 of 576
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I'simmclcr
Kill '
1 III 111 2111 ''
Source
\\ll» /v (1. h)
Y\
1) |(>;
Oplinu/.ed
5-HNMP. Kme
NA
2.75 c
Optimized
First order urinary elimination- scaled
KlC NMP (L-kg° 25/h)8
1.61 c
0.103 c
Optimized
KlnC 5-HNMP (L-kg° 25/h)8
3.0E-4 c
NA
Optimized
Absorption
Dermal liquid: Kpl,Pvl (cm/h)
4.6E-3 c
4.78E-4 -
2.04E-3 c'h
Optimized
Dermal vapor: Pv (cm/h)
NA
16.4 c
Optimized
Stomach to liver (h1)
1.5 c
1.36 b
Optimized
Stomach to intestines (h1)
0.85 c
NA
Optimized
Intestines to liver (h1)
0.006 c
NA
Optimized
Pregnancy-specific parameters
Mammary tissue volume (% body
weight)
1
0.62
Clewell et al. (2002); O'Flahertv et al.
1)
Uterus tissue volume (% body
weight)
0.2
0.14
O'Flahertv et al. (1992); ICRP (1975)
Mammary % of cardiac output
0.1 b
2.7
Clewell et al. (2002); O'Flahertv et al.
1)
Uterus % of cardiac output
0.5
0.5 b
O'Flahertv etal. (1992): ICRP (1975)
Table modified from Poet et al. 2010.
a Values are for non-pregnant females (at start of gestation). Pregnancy-related changes are as described by Poet et
al. (2010).
b Values in model code/scripts of Poet et al. (2010) that did not match values listed or were not reported in the
publication. Since results of Poet et al. (2010) (figures, model output tables) were replicated using these values,
they are considered the correct parameter values.
0 Indicates parameters that have been revised since Poet et al 2010 based on recalibration described below
d Values are for total skin. The skin compartment simulated in the PBPK model was comprised solely of the area of
the skin (and underlying volume) exposed to liquid. The remainder of the skin was included in the slowly
perfused compartment
e Ventilation and cardiac rates are body-weight (B W) specific. Values shown here are the scaling constants. Given
standard BW values of 0.25 kg for rats and 70 kg for humans, the resulting total flows (L/h) match those in Poet
etal. (2010).
f Fmax (mg/h) = VmaxC X BW075
bKl (L/h) = KlC / BW0 25
h Increases with NMP weight fraction above 0.5.
J.l Rat Model
Several corrections were made to the model code (.csl file) and supporting scripts (.m) files as received
from Dr. Torka Poet (personal communication). The first few of these are general and described here.
Page 551 of 576
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Blood Flows
Since the placenta is a separate compartment for the 5-HNMP model, its blood-flow and volume were
subtracted from the sums used for the 'rest of body' for 5-HNMP. Also, the term for blood flow from
the placenta was added to the mixed-venous blood mass balance for 5-HNMP.
To assure flow mass balance, instead of calculating cardiac output (QC) as an initial amount plus the
change from initial for each compartment, it was just calculated as the sum over all the compartments:
Equation J-l Cardiac Output
! QC = QCINIT + (QFAT - QFATI) + (QMAM - QMAMI) + QPLA+ (QUTR - QUTRI)
QC = QFAT+QLIV+QSLW+QRAP+QSKN+QMAM+QPLA+QUTR ! PMS, 8-13-13
Parameter Consolidation
In the provided files, some physiological and chemical-specific parameter were set in separate scripts;
e.g., skin transport parameters in the dermal exposure scripts. This approach creates the potential for
inconsistent parameters between different exposure simulations. Therefore, most parameters are now set
in the ratparam.m script except those which are experimental control variables (e.g., air concentration,
duration of exposure) and pregnancy-specific parameters set in preg_rat_params.m. The final set of
parameters used and any inconsistencies with previous values in ratparam.m that may have differed are
noted in that script.
Recalibration (performed by T. Poet)
Additional data were used to calibrate and validate the intravenous, oral and dermal routes of exposure
in rats. While plasma and urinary excretion data for major metabolite (5-HNMP) have also been
reevaluated, primary attention has been paid to NMP, since the dose measure of interest are for the
parent chemical. Model parameters for rats are set in the preg_rat_params.m and ratparam.m code
scripts (preg_rat_params first calls ratparam), included in the acslX code package available with this
assessment. Specific data and modeling choices for the rat are as follows.
Intravenous Data
All reasonably available intravenous data were obtained from studies that administered radiolabeled
NMP. Most of the reasonably available studies only provided peak measured concentration and
pharmacokinetic parameters. The study chosen to calibrate the model was that described by Pay an et al.
(2002). in which nulliparous rats were exposed to NMP doses ranging from 0.1 to 500 mg/kg. However,
the authors only reported plasma NMP data for the lowest dose. This time-course data set was used to
optimize metabolic rate parameters (VmaxC and Km) to describe the clearance of NMP from plasma.
Unchanged NMP has only been found at very low levels in rat urine, so urinary elimination was set at a
nominal value using a BW-scaled constant of KLNC= 0.0001 kg0.25/h. KLN = KLNC/(BW0.25) =
0.00014 h-1 for a 0.25-kg rat.
Pay an et al. (2002) estimated the post-distribution metabolic rates of NMP from the disappearance of
NMP from plasma in their studies. These estimated rates (Km=200 mg/L and VmaxC=1.5
mg/hr/kg0.75) were used as the seed values for the optimization carried out using the optimization
routines supplied in acslX (v3.0.2.1; The AEgis Technologies Group, Inc, Huntsville, AL) in which the
model was created. By starting with these values, it was hoped that the dose-range in that study would
be represented and the optimized model would fit across doses. The final optimized parameters were
Km= 225 mg/1 and VmaxC=9 mg/hr/kg0 75. Wells (1988) administered an intravenous dose of 45 mg/kg
Page 552 of 576
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to rats, which is 450x higher than the dose used for optimization and this was used to validate the
metabolic rates over a large range (Figure_Apx J-2).
^	i a
£	(	45 mg/kg simulation
^	¦ Wells & Digenis (1988)
"O	0.1 mg/kg simulation
§	Q Payan et al. (2002)
100
-O 1
c
cl
T
Z 0.1
0.01
o
0
2
4
6
8
10
12
Time (h)
Figure Apx J-2. Model Fits to IV Injection Data in Rats
Oral Data
All reasonably available oral exposure data were obtained from studies that administered radiolabeled
NMP. The most valuable data sets are those that specifically measured NMP in blood (dose measure
used in the assessment). NMP is highly metabolized and generally not found in urine as unchanged
NMP. The study chosen to calibrate the oral absorption rate was described by Midglev et al. (1992). In
this study, male and female rats received an oral gavage of 105 mg/kg (22.5 mg in rats weighing 192-
239 g) NMP, co-exposed with 2-pyrrolidinone in a water vehicle. The authors concluded that 94.5% of
the administered radiolabel was absorbed. However, when a constant (FRACOR) was fit to the data
using the PBPK model the optimal value was found to be 93%.
The data indicate a rapid uptake and a slow elimination of NMP from plasma. Using the metabolic rate
constants optimized to fit the intravenous dosing and the oral bioavailability measurements of Midglev
et al. (1992). the model estimates of plasma NMP clearance resulted in a much higher AUC than the
data indicated (Figure_Apx J-3). There is no suggestion of extra-hepatic (i.e., intestinal) metabolism, so
another mechanism to describe this absorption pattern was investigated. NMP is readily absorbed across
membranes (see dermal absorption data discussion below) and for some chemicals absorption has been
proposed to occur either in the stomach or quickly in the intestine, then more slowly during later phases
of transport (Timchalk et al.. 2002; Levitt et al.. 1.997; Staats et al.. 1991). Therefore the original PBPK
model was altered to include primary (stomach) and secondary (intestine) GI compartments to describe
oral absorption following the description from Staats (1991). The resulting model predictions are vastly
improved (Figure_Apx J-3). Using dual oral absorption results in -75% of the absorbed dose (after
multiplying by 93% bioavailability) being absorbed via the faster process and the remaining -25% being
more slowly absorbed. Also, an unusually high fraction of the radioactivity was found in the feed
residue for the females in the NMP Producers Group (1995a) study, 4.5%, so the simulated dose for that
group was decreased proportionately.
Page 553 of 576
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80
70
60
o>
E
CL
2
z
flj
E
en
Q.
50
40
30
~ 20
10
6	8
Time (hr)
10
12
14
— 112 mg/kg simulation
	50 mg/kg (female) simulation
¦ Midgley 112 mg/kg data
V Ghantous 50 mg/kg female data
0	20	40	60	80	100	120
Time (hr)
FigureApx J-3. Model Fits to Rat Oral PK Data
Dermal Model & Data
Corrections to the mass balance equations for the rat skin are as indicated in the commented code copied
below. RASK is the rate of changes in the skin compartment. The equation for the amount in the
compartment, ASK, includes the initial condition, ASK0, for the initial dermal application, but
otherwise the correction to RASK makes it the standard format for PBPK models. As received the code
112 mg/kg simulation
Midgley 112 mg/kg data
50 mg/kg (male) simulation
Ghantous 50 mg/kg male data
50 mg/kg (female) simulation
Ghantous 50 mg/kg female data ^
~
A
Page 554 of 576
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had multiplied CSK rather than CSKV (skin venous blood concentration) by the blood flow (QSKN) for
the rate of efflux in blood and had not separately calculated CSKV.
Equation 3-2 Rat Skin Model Equations
RASK = QSKN*(CA - CSKV) + RADL ! NOW MINUS CSKV, NOT CSK; PMS 8-21-13
ASK = INTEG(RASK,ASKO) ! Initial value, ASKO, added for Becciettil , l»S2)
! exposures; pms 8-14-13
CSK = ASK/VSK !'NMP IN SKIN, MG/L'
CSKV = CSK/PSKB ! NMP IN VENOUS BLOOD, PMS 8-22-13
The corresponding flow term for transfer from the skin to the mixed venous blood compartment was
also corrected (i.e., to use CVSK instead of CSK).
While these changes to the skin compartment equations initially degraded the fits to the dermal exposure
considerably, it also appeared that the associated partition coefficients were not consistent with the
measured values reported by Poet et al. Q ), Table 5. They were recalculated as follows:
Equation J-3 Rat Skin Partition Coefficients
Skin:liquid, PSKL = 0.42: % value as measured for skin:saline, vs. 450
Skin:blood, PSKB = 0.12: % (skin:saline)/(blood:saline)
Skin:air, PSKA = 55:
% (skin:saline)*(blood:air)/(blood:saline) = (skin:blood)*(blood:air)
Developmental studies for NMP have been conducted by the dermal route (Becci et al.. 1982.). In the
original PBPK model publication (Poet et al.. 2010). the dermal route was assessed using a permeability
coefficient (Kp) of 4.7x 10"3 cm/hr that was approximated from in vitro studies (Payan et al.. 2003). For
the current assessment, the in vivo dermal exposure studies described by Payan (2003) were used to
optimize Kp. In this study, rats were exposed to 200 |il of neat NMP. According to Payan et al., by
24 hrs after dosing, 80% of the NMP applied had penetrated the skin. The Kp value optimized to these
data was estimated to be 4.6x 10"3 cm/hr (Figure_Apx J-4), which is consistent with the range of Kp
values estimated from the in vitro studies (from 2.0 x 10"3 to 7.7 / 10"3cm/hr: Payan et al. (2002)).
Page 555 of 576
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600
500
	 Model
O Payan et al. (2003) data
-I
Oi 400
Q.
£ 300
z
(U
I 200
JO
Q.
100
0	4	8	12	16	20	24	28	32
Time (hr)
FigureApx J-4. Model Fits to Dermal PK Data from Payan et al. (2003) in Rats
Inhalation
No parameters were optimized to simulate the inhalation exposures of female rats to 104 ppm NMP for
6 hr ( I P Producers Group. 1995a), 100% inhalation bioavailability was assumed. These data, like the
oral exposure data from the same source, appear to be more variable than from other studies. The model
fits to the data are shown in Figure Apx J-5.
Page 556 of 576
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—	100 ppm (female) simulation
—	100 ppm (male) simulation
• Ghantous (1995) female data
~ Ghantous (1995) male data
0	3	6	9
Time (hr)
FigureApx J-5. Model Simulations vs. Inhalation PK Data from Ghantous (1995a) for NMP
Inhalation in Rats
Exposure Control for Bioassav Simulations
Because both Becci et al. (1982 and Saillenfait et al. (2002) explicitly stated that the animal BWs were
measured every 3rd day of gestation and the dermal/oral doses were adjusted accordingly on those days
(as BW increases during pregnancy), corresponding conditional (if/then) statements were added to the
'GAVD' and 'REAPPLY' discrete blocks, to re-calculate the doses on those days.
The code for the dermal discrete blocks follows. ASK0 is the total absolute amount applied; DSK is the
dose/kg BW. Because Becci et al. (1982) rubbed the material into the skin, it is assumed to be added
directly into the skin compartment (ASK), rather than as a liquid on top. Hence the dose is given as an
addition of ASK0 (mg/day applied) to ASK.
Equation J-4 Dermal Dosing Equations
DISCRETE SKWASH ! PMS, 8-14-13
ASK = 0.0 ! Assume skin washing in Becci et al. (1982) removes all NMP IN skin
if (DAYS.LT.15.0) SCHEDULE REAPPLY.AT.(T+DOSEINTERVAL-TWASH)
END
DISCRETE REAPPLY ! PMS, 8-14-13
IF (ROUND(DAYS) EQ.9.0) ASKO=DSK*BW
IF (ROUND(DAYS).EQ.12.0) ASKO=DSK*BW
IF (ROUND(DAYS).EQ. 15.0) ASKO=DSK*BW
ASK = ASK + ASKO
SCHEDULE SKWASH. AT.(T+TWASH)
END
Also, because Becci et al. (1982) washed the skin area exposed to dermal application at the end of a set
time interval, a "SKWASH" discrete block was introduced at which time the amount in that patch of
Page 557 of 576
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skin was assumed to be momentarily reduced to zero. During periods of dermal application, transport
from the liquid to the skin was turned on using the pulse function, DZONE. After removal of the liquid
it was assumed that NMP in the skin patch could volatilize into the otherwise clean air, with the rate
defined by the same permeability constants, but using the skin:air partition coefficient.
The rate of transfer to/from the skin area is then defined by:
Equation J-5 NMP Dermal Transport
RADL=(KPL*SA/1000.0)*((CSURF-(CSK/PSKL))*DZONE - (1.0-DZONE)*(CSK/PSKA))
! 2ND term, (1.0-DZONE)*(CSK/PSKA), allows for evaporative loss when DZONE=0
The primary part of this equation for transfer when liquid is in contact with the skin,
(KPL*SA/1000.0)*(CSURF-(CSK/PSKL)), is identical to that used previously by McDougal (1986).
Finally, a constant, CONCMGS, was introduced so that the air concentration could be set directly in
mg/m3. This is converted to the concentration in mg/L (CONCMG) in the code and added to the
inhalation exposure, turned on and off using the switch, CIZONE, which is turned on and off using
SCHEDULE/DISCRETE statements:
Equation J-6 NMP Vapor Exposure Control
CI = CCH*PULSE(0., DOSEINTERVAL,TCHNG) + CIZONE*CONCMG ! MG/L
! Added CIZONE*CONCMG, PMS, 8-13-13
J.2 Human Model
Human exposures to NMP will be primarily via the inhalation route; contribution from the dermal route
(vapors or liquid) may also be significant if not primary for some scenarios. Ingestion of NMP is not
expected to be a significant pathway in human populations. Both controlled and occupational human
exposure data are reasonably available from the published literature. Controlled human biomonitoring
studies were used to calibrate NMP and 5-HNMP metabolic rates and a workplace exposure assessment
study was used to validate the model and exposure scenarios.
3.2.1 Corrections to Human Model Structure
NMP Metabolism and Urinary Elimination
Since the human PK data were consistent with a nearly linear model (first-order kinetics, including
metabolism) estimation of a metabolic saturation constant, Km, using the traditional Michaelis-Menten
equation for metabolism of NMP, was difficult. In particular as estimates of Km became larger, model
fits became less sensitive to variation in its value. Therefore, equation was changed from the standard
form, rate = Vmax*C/(Km + C), where C is the concentration of NMP in the liver, to the equivalent
form, rate = VK1*C/(1 + AF1*C), where VK1 = Vmax/Km and AF1 = 1/Km. These two forms are
mathematically identical given the relationship between parameters just shown. The affinity constant,
AF1, can be easily bounded to be non-negative and possibly converge to zero, corresponding to an
indeterminately large Km. Since VK represents hepatic metabolism, it was assumed to scale with BW
the same as Vmax; i.e., VK1 = VK1C*BW075. The values of VmaxC and Km reported in Table 1-2 are,
correspondingly, VmaxC = VK1C/AF1 and Km = 1/AF1. The urinary elimination of NMP was assumed
to be first order, rather than saturable, using a rate constant (KUMNE) that was not scaled by BW.
5-HNMP
Since 5-HNMP is not being considered as an internal metric for toxicity and its volume-of-distribution
(VOD) appeared to be over-estimated using the original PBPK model structure and measured tissue
Page 558 of 576
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partition coefficients, its description was replaced with a classical one-compartment PK model. Further,
as the metabolism of 5-HNMP also appeared to be linear and the data for estimating a Km value even
weaker, a transformation of its metabolic rate equation like that for NMP described just above was
assumed, but with the affinity assumed to be effectively zero, resulting in a first-order metabolic rate
equation. As with NMP, the urinary elimination of 5-HNMP was also assumed to be first-order. The
resulting model then becomes:
Equation 3-1 5-HNMP Metabolism and Elimination
d A5H/dt = RAMETl*STOCH - RAMETM1 - RAUHP
(rate of change of amount of 5-HNMP)
CVEN1 = A5H/VOD5H (concentration of 5-HNMP in venous blood)
VOD5H = VOD5HC*BW (volume of distribution assumed to scale with BW)
RAMETM1 = -CVEN1 *VK2, where VK2 = VK2C*BW0.75
(rate of metabolism of 5-HNMP)
RAUHP = KME*CVEN1 (rate of urinary elimination of 5-HNMP)
RAMET1 = rate of NMP metabolism to 5-HNMP (mg NMP metabolized/h)
STOCH = ratio of 5-HNMP to NMP molecular weights.
Exposure and Timing Control
A table function, RESLVL, was added as a place-holder for reading in defined (consumer) inhalation
exposure time-courses; specifically from EPA exposure assessment modeling.
A constant, GDstart, the day of gestation on which the simulation starts and a variable Gtime, the hrs
into gestation, were added to facilitate separating exposure control from gestation timing.
A second set of DISCRETE/SCHEDULE blocks were added to allow for split exposure scenarios
(morning/afternoon worker exposure; dual-episode consumer exposures). DZONE, set in the
DISCRETE/SCHEDULE blocks, controls the time within a day when discontinuous exposure occurs.
Czone is the product of DZONE and a pulse function used to control for days/week exposure in
workplace scenarios:
Equation J-8 Vapor Exposure Scheduling
Czone = pulse(0.0,full week,hrsweek)*DZONE ! pms 8-20-13
! for a 5 day/wk exposure, use fullweek=7*24, hrsweek=5*24 (Dayswk=5)
! for a single day, fullweek=lel6, hrsweek=24 (Dayswk=l)
A binary constant, BRUSH, was added to set exposure scenarios when dermal contact with liquid
occurs. For workplace scenarios, exposure to vapor and liquid are assumed to be simultaneous; i.e., the
worker leaves the location with NMP vapor and washes his/her hands when he/she has finished applying
the material.
Skin Compartment
The original skin compartment which is coded to include uptake from liquid-dermal contact was
renamed by adding "L" to the end, SK -> SKL and a second skin compartment to account for concurrent
vapor-skin uptake, SKV, was added. This was done because when the human model was calibrated for
inhalation exposure, an exposed skin surface area of 6700 cm2 was used. When this surface is reduced to
~ 0, predicted blood levels of NMP are reduced ~ 45%. Thus vapor uptake through the skin is a
significant component of inhalation exposure and there is no reason to assume, a priori, that this uptake
Page 559 of 576
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(or desorption) does not occur through a similar area of exposed skin during workplace and consumer
exposures, except for any area that would have liquid contact or otherwise be occluded (e.g., by
protective equipment). So, the SKV compartment allows for simultaneous absorption of vapor-through-
skin that does not have liquid contact and from areas of skin with liquid contact. The surface area of
SKV and SKL are SAV and SAL, respectively. SAL can set directly for different exposure scenarios.
To account for variations with individual BW, a parameter for the fraction of skin area exposed to vapor
was introduced: SAVC, with SAV = SAVC*TSA, where TSA is the total body surface area. TSA is
calculated for each individual based on BW and height. For EPA simulations, SAVC was set to 0.25,
representing the head, neck, arms and hands, minus any area assumed to have liquid contact or covered
with protective gloves or a facemask.
The rate for delivery from a liquid film to the 'SKL' skin compartment (also see further below) is then
defined by:
Equation J-9 NMP Liquid Rate of Delivery to Skin
P VLU=P VLF (WF )
RADL = (PVLU* SAL/1000.0) * (C SURF-(C SKL/P SKL)) * Czone*BRU SH
! Net rate of delivery to "L" skin from liquid, when liquid is there
PVLF is a linear interpolation TABLE function which supplies the permeability for liquid NMP (PVLU)
as a function of the weight fraction (WF). In particular, PVLF is parameterized such that PVLU =
4.78xl0"4 cm/h for WF < 0.5, increasing linearly from that value to 2.05xl0"3 cm/h for 0.5 < WF < 1.0.
(Derivation of these values is described below, with human dermal absorption data.)
The equations for transfer of vapor (air concentration = CI) to the SKL compartment, which occurs
during periods with no liquid/spray contact for the SKL compartment are similarly:
Equation J-10 NMP Vapor Rate of Delivery to Skin
RADVL = (PV*SAL/1000.0)*(CI - (CSKL/PSKA))*(1.0-Czone*BRUSH)
! Net rate of delivery to "L" skin from air, when liquid not present
Since the dermal exposures are to neat or highly concentrated preparations of NMP, it would not be
appropriate to assume that the residual liquid volume on the skin remains constant as absorption occurs.
Further assuming that water penetration of the skin is minimal, the amount of water in the liquid solution
is assumed to remain constant. The initial volume on the skin is defined by a new constant VLIQ0 and
the density of NMP at 40C (~ skin temperature) = DENSITY = 1.02xl06 mg/L. To avoid potential
divide-by-zero errors, the nominal initial concentration (CONCL) is reduced by 1 mg/L (1 ppm) when
computing the initial amount of NMP and water in the liquid:
Equation J-ll NMP Unabsorbed Fraction Remaining on Skin
DDN = (CONCL - 1 0)*VLIQ0*FAD
! Subtract 1 mg/L, ~ 1 ppm, from initial conc. to avoid VLIQ —> 0
AH20 = (DENSITY+1 0-CONCL)*VLIQ0 ! ... and add it to H20. pms 9-16-14
A mass-balance equation was then added to attract the remaining amount and volume on the skin
surface, which is then used to calculate the concentration:
ASURF = INTEG(-RADL, DDN) ! Amount in liquid. DDN is the initial amount.
VLIQ = (AH20 + ASURF)/DEN SIT Y
Page 560 of 576
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CSURF = ASURF/VLIQ
This volume balance is important for analysis and calibration of the dermal PK studies where small
volumes (5 or 10 ml) were applied at the beginning of the exposure and not replenished. However, in
workplace and consumer user exposures, it is assumed that fresh liquid is constantly replacing any NMP
that is absorbed, keeping the surface concentration essentially constant. Therefore, the initial volume,
VLQO, is set to a large value (106 L) for those scenarios.
The skin partition coefficients were also recalculated as was done for the rat, with rat parameters for
skin:saline and blood:air, but human blood:saline.
Tissue and Blood-Flow Mass Balances
The model had been previously coded with an alveolar blood compartment (ALV), but this was
commented out in the DYNAMIC section. Therefore this volume fraction should not be subtracted when
calculating the slowly-perfused volume. The fraction of blood-flow to slowly perfused tissue was
updated to also account for the SKV compartment; on the other hand a separate skin compartment is not
used for 5-HNMP, so the skin blood flow is NOT subtracted for the metabolite-slowly-perfused
compartment (SLW5). These have all been corrected.
QSKCC (original fractional flow to the skin) had been subtracted twice, both in calculating QSLWC and
then in the calculation of QSLW. The 2nd subtraction created a mass balance error and hence was
removed. On the other hand, placental blood flow is now subtracted, so the total flow to slowly-perfused
continues to total cardiac output minus all other tissue/group flows.
For tissues for which the volume changes with gestation day, the initial values were corrected to match
the calculation in the DYNAMIC section, which apply at the first time-step. In the dynamic section, the
calculation of QC was corrected to include the increase* in placental flow (QPLA - QPLAI) rather
than the total placental flow (QPLA), since QCINIT includes QPLAI. QSLW5 and VSLW5 (5-HNMP
slow compartment flow and volume) are now calculated in the DYNAMIC section by subtraction. The
calculation of QC was otherwise left in its original form, in contrast to the rat PBPK model.
Parameter Consolidation
Like the rat model, the human model physiological and biochemical parameters are now primarily set in
a single script, human_params.m. Initial values for the metabolic and vapor-absorption (KPV)
parameters were obtained by fitting Bader et al. (2006) inhalation data with the exception of the high-
concentration data from one individual, but the data otherwise grouped without distinction between
individuals (further details below). An alternate set of fitted parameters was obtained by fitting the data
for each individual separately, focused on the low-concentration data and then calculating the average of
each parameter across the individually-fitted values. This subset of parameters is selected by using
human_avg_params.m. Since further analysis of the dermal absorption of liquid NMP showed that this
uptake differed between neat (100%) NMP and diluted (50%) NMP, separate value of PVL were
obtained for neat vs. diluted NMP (also see below). Hence only constants which define specific
exposure scenarios (include skin areas exposed) and PVL are defined in the specific simulation scripts.
Inhalation Data
A study conducted by the Hannover Medical School, University of Dortmund, Germany (Bader and Van
Thriet. 2006) was used to calibrate inhalation parameters of the model. In this study, 8 healthy, non-
smoking, male volunteers were exposed to 10, 40 or 80 mg/m3 NMP in an environmental chamber. Over
Page 561 of 576
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the course of several weeks, each volunteer was exposed sequentially to all 3 concentrations. The 8
volunteers were separated into 2 groups of 4 and each group was exposed in a shared chamber. The
exposures were carried out in ascending concentrations, with a 1-week period between each session.
Volunteers wore slacks and T shirts and thus had arms exposed to vapor. Blood was collected from each
volunteer in the middle of the 6-hr exposure period, at the end of exposure (6 hr) and 1, 2, 3, 18 and 42
hrs after the end of exposure. Urine was also collected from each volunteer at times up to 42 hrs after the
end of exposure. Because it is relatively rare to have blood and urine data for multiple exposure levels,
multiple time points, in individuals, efforts were made to ensure the exposure scenarios for these data
were modeled as accurately as possible.
To collect the mid-exposure blood samples, volunteers left the chamber one at a time and moved to
another room to have blood drawn and to give a urine sample. The data are consistent with a sharp drop
in concentration for the mid-exposure blood sampling, when the peak NMP concentration measured at
the end of the exposures are considered. In the report, the time taken to leave the chamber, walk to the
new room, donate blood and urine was suggested to be about 10 minutes. However, exact times were not
recorded. The notes indicate that the time between blood collection and urine collection was at least 5
minutes. In addition, the recorded times for collection of blood from first collected sample to last {i.e.,
between the first and fourth volunteers to leave the chamber) was up to 55 minutes. If the times were
equivalent for each subject and the volunteers only left the chamber as the previous volunteer returned,
this would indicate an average of 12 minutes was needed for sample collection from each volunteer.
Based on a careful review of the data tables in Bader and van Thriel (2006) and personal communication
with Dr. Michael Bader and Dr. Christoph van Thriel, it was determined that each subject entered and
left the exposure chamber at different times as described just above and were likely not sampled at
exactly the same time after the beginning and end of each exposure segment. While the total exposure
time for each subject was monitored and kept to exactly 6 h on each exposure day, based on the timing
of the blood and urine samples (taken outside the exposure chamber), it is clear that the study design
was not exactly followed. In particular, while the morning and afternoon exposures were supposed to be
3 h each, the time between the mid-day and first afternoon blood samples was less than 3 h for some
individuals in some exposures (and the mid-day sample was taken much later after noon for such
samples). In these cases it seemed likely that the individual spent slightly more than 3 h in the chamber
in the morning and slightly less in the afternoon, for that exposure. Based on the recorded data and
communications, the exposure timing used for modeling and simulation was set to 3.1 h for the morning
exposure, a mid-day break of 0.2 h (12 min) and 2.9 h for the afternoon exposure. Since individual
subjects did not enter and exited the chamber at exactly the same time, the time of their entrance to the
chamber for each exposure was estimated based on the recorded times of the blood and urine samples.
The sample times used for modeling were then calculated relative to the estimated entry times.
It was also clear that a number of the measurements, especially those of 5-HNMP for the low-
concentration exposure, were recorded as the limit of detection (LOD), when the measured value fell
below this limit. This was confirmed with Dr. Bader (personal communication). Therefore all
measurements at/below the LOD were removed from the data set to avoid the bias they would otherwise
introduce.
It also appeared that the high-concentration-exposure (80 mg/m3) for one subject deviated substantially
from the other subjects; see Figure Apx J-6 below. Since the blood concentration at 6 h was well below
those of the other subjects and that at 24 h well above (4 subjects had levels below the LOD), this
individual's high concentration set was excluded from analysis of the grouped data. Blood
Page 562 of 576
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concentrations at the middle and low exposure for this individual were among the range of the other
subjects, hence included in the group data.
With this one data set removed, the revised model was fit to the group data for exposures at 9.7 and 80
mg/m3, by adjusting the following parameters: PV, VK1C, AF1, KUMNE, VK2C, VOD5HC and KME.
Since the data for the 40 mg/m3 exposure were consistent with the 80 mg/m3, but the data for 9.7 mg/m3
appeared not to be and it was considered especially important to describe low-concentration exposures,
the 40 mg/m3 data were excluded from this exercise. The resulting parameter values are as follows, with
model fits to the group data shown in Figure_Apx J-7, left side. These fits are compared to ones
obtained by fitting the data for each individual separately, where possible using only the low-
concentration exposure data and then calculating the average across the individual fits for each
parameter (right side of Figure_Apx J-7; details below).
B
CO 0.9
~
nCl n
15	20	25
Time (h)
Figure Apx J-6. NMP Blood Concentration Data from Bader and van Thriel (2006)
Curves are simulations for 9.7, 40 and 80 mg/m3 exposures. Squares are individual blood concentration
data for the 80 mg/m3 exposure. Solid squares are from the one individual with the highest BW and
height (102 kg, 190 cm), compared to the other subjects (65-80 kg, 168-183 cm).
Page 563 of 576
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0
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FigureApx J-7. Alternate Fits to Collective Data from Bader and van Thriel (2006)
Left panels show fits to the groped data for 9.7 and 80 mg/m3 (data shown). Simulations in right panel
used average of parameters fit to each individual separately, primarily for 9.7 mg/m3 (see text for
details).
Page 564 of 576
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Piinimelers rilled lo "roup d;it;i
lor 9.7 iiiul SO mo/nr4 exposures
A\erii»e of p:ir;iinelers lit to d;il;i lor e;u-h iiulix idu;il
sep:ir:ilel\, priniiirilv ().7 m»/iir(
PV =1.6 (cm/h)
VK1C = 0.47 (L/(h*kg0 75))
AF1 = 0.02 (L/mg)
VK2C = 0.035 (L/(h*kg°75))
VOD5HC = 0.26 (L/kg)
KME = 2 .3 (L/h)
KUMNE = 0.092 (L/h)
PV= 16.4 (cm/h)
VK1C = 0.386 (L/(h*kg0 75))
AF1 = 0.02 (L/mg) [fixed at group-fit value]
VK2C = 0.0359 (L/(h*kg°75))
VOD5HC = 0.243 (L/kg)
KME = 2.75 (L/h)
KUMNE = 0.103 (L/h)
In their summary statistics, Bader and van Thriel (2006) reported group-averages of the peak NMP
blood levels as being 0.293 mg/L for the 9.7 mg/m3 and 1.585 mg/m3. The ratio of these two
(1.585/0.293 = 5.4), is considerably less than one would expect assuming linearity with exposure level
(80/9.7 = 8.25) and is the opposite of what one would expect due to metabolic saturation of the
conversion of NMP to 5-HNMP. This is not true for the ratio peak 5-HNMP levels in blood (8.08),
however, which is comparable to the relative exposure level. If the nonlinearity in NMP blood levels
were due to more efficient metabolism at the higher exposure level, then ratio of 5-HNMP blood levels
would have been greater than expected.
Since the mechanism for the nonlinearity in blood NMP levels is unclear and it would be undesirable to
under-estimate NMP blood levels and hence human risks at lower exposure levels, it was decided to
estimate parameters using only the low-exposure data, if possible or with minimal use of the high-
exposure data. (For two of the subjects the blood levels of 5-HNMP did not rise above the LOD for the
low exposure, making it impossible to estimate VOD5HC for them. Hence the 80 mg/m3 blood 5-
HNMP data were also needed to estimate their parameters.) Given the observation that the high-
exposure data for one subject was disparate from the other subjects, it also seemed possible that the
apparent nonlinearity in the average PK data was due to the mixing of data from the 8 subjects in the
study. Therefore, fits focused on the low-exposure data were conducted separately for each subject.
Since limiting to the low-exposure data would provide almost no information on metabolic saturation
and the affinity (AF1) obtained from the fits to the group data was quite low (0.02 L/mg), AF1 was held
at that group-fit value for this exercise. The resulting parameter values are listed in Table Apx J-3 and
fits to the individual data shown in FigureApx J-8 through FigureApx J-l 1. In order to allow one to
see the fit to the low concentration and otherwise compare the fits across individuals, the y-axis scale
was held constant for each analyte across the individuals, though this meant that the simulation curves
for the higher exposure data sometimes went off the top of the plot.
Page 565 of 576
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TableApx J-3. Estimated PBPK Parameters for Each Subject of the Bader and van Thriel (2006)
Experiments
Subject
YKIC
ki mm:
PV
YK2C
kmi:
VOI)5ll(
1
0.25
0.11
19
0.017
3.2
0.2
4
0.17
0.042
34
0.004
3
0.14
10
0.22
0.069
35
0.027
2.8
0.12
12
0.63
0.046
12
0.044
1.9
0.39
14
0.57
0.2
10
0.08
2.5
0.4
16
0.45
0.06
0
0.08
1.9
0.2
17
0.38
0.2
20
0.02
4.3
0.26
25
0.42
0.1
1.5
0.015
2.4
0.23
average
0.386
0.103
16.4
0.0359
2.75
0.243
It is interesting to note that for half of the subjects (#12, #14, #16 and #25), the fits and data for NMP in
blood show that the data are quite consistent with the essentially linear PBPK model, while for the other
half the simulations with parameters fitted to the low-concentration data over-predict the high-
concentration NMP data.
Page 566 of 576
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1.8
w
c
'l
D
C
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4
3.5
3
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0.8
0.6
0.4
0.2
0
140
120
100
80
60
40
20
0
Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
0.6
12 18
Time (h)
12
Time (h)
24 36
Time (h)
» 3.5
J. 3
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2
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	 Model 80 mg/m3
Model 40 mg/m3
	Model 9.7 mg/m3
~ Exp obs 80 ppm
A Exp obs 40 mg/m3
V Exp obs 9.7 mg/m3
Time (h)
12
Time (h)
24 36
Time (h)
24 36
Time (h)
Figure Apx J-8. Model Fits to Subjects 1 and 4 of Bader and van
Model fit separately to each subject. See text for details.
24 36
Time (h)
Thriel (2006)
Page 567 of 576
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V
c
L
D
C
Q.
T
Z
X
in
Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
Time (h)
Time (h)
/
12
Time (h)
Time (h)
~ ~ ~ ~
V V
24 36
Time (h)
24 36
Time (h)
~ ~ ~ ~
24 36
Time (h)
24 36
Time (h)
Figure Apx J-9. Model Fits to Subjects 10 and 12 of Bader and van Thriel (2006)
Model fit separately to each subject. See text for details.
Page 568 of 576
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Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
Model 80 mg/m3
Model 40 mg/m3
	Model 9.7 mg/m3
~ Exp obs 80 ppm
A Exp obs 40 mg/m3
V Exp obs 9.7 mg/m3
12 18
Time (h)
24
12 18
Time (h)
AA
wvv
v v-
12
24 36
Time (h)
48
24 36 48	0 12
Time (h)
Figure Apx J-10. Model Fits to Subjects 14 and 16 of Bader and
Model fit separately to each subject. See text for details.
24
Time (h)
12 18
Time (h)
~ ~ ~ ~
A	A	A_
12 24 36 48
Time (h)
24 36
Time (h)
van Thriel (2006)
48
Page 569 of 576
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Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
Model 80 mg/m3
Model 40 mg/m3
	Model 9.7 mg/m3
~ Exp obs 80 ppm
A Exp obs 40 mg/m3
V Exp obs 9.7 mg/m3
12 18
Time (h)
24
Time (h)
Time (h)
24 36
Time (h)
12 18
Time (h)
cm ~~ ~~ ~
A A A A
24 36
Time (h)
24 36
Time (h)
Figure Apx J-ll. Model Fits to Subjects 17 and 25 of Bader and
Model fit separately to each subject. See text for details.
W
24 36
Time (h)
van Thriel (2006)
48
Page 570 of 576
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Dermal Data: Vapor and Liquid
Volunteers in the study described by Akesson and Paulsson (1997) wore shorts and t-shirts and thus also
had dermal (vapor) exposures, as well as inhalation exposures, to NMP. The exposure concentrations for
this study were similar to those of Bader et al (2005). With only inhalation exposures, the model under-
predicted plasma NMP by about 25%, a vapor permeability coefficient, which accounts for both the skin
permeability and the vapor/skin surface interaction, (PV) of 1.5 cm/hr was optimized to fit these data
and is equivalent to the previously optimized value (Poet et al.. 2010) (Figure_Apx J-12).
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0 3	6 9 12 15 18 21 24
Time (hr)
Figure Apx J-12. Model Fits to Human Inhalation Data of Akesson and Paulsson (1997), With
and Without Dermal Absorption of Vapors
Model parameters were as obtained previously using the data of Bader and van Thriel (2006).
Simulations are shown with dermal absorption of vapors included ("with dermal"; 25% of total surface
area assumed exposed) or turned off ("no dermal").
Akesson et al. (2004) exposed 12 volunteers (6 male and 6 female) to 300 mg NMP either neat or
diluted 50:50 in an aqueous solution. Blood and urine 5-HNMP concentrations were monitored for up to
9 days. The plasma 5-HNMP concentration was extracted from the figure using Digitizlt
(Braunschweig, Germany). Urinary 5-HNMP concentrations were extrapolated to total amount
eliminated using the assumption that the average urinary flow for an adult is 18 ml/kg-day (Heffernan et
al.. 2014). Aqueous dilution resulted in a slower time to reach peak plasma 5-HNMP and a reduction in
peak plasma concentration. Because the urinary elimination constant (KME) for 5-HNMP was seen to
vary among subjects when fitting the Bader and van Thriel (2006) data and we did not want a lack-of-fit
to the urinary elimination data (which establish the mass balance, hence total amount absorbed) to
adversely impact the fitting of the 5-HNMP blood levels, KME was also fit to each data set then. The
optimized liquid permeability constant (PVL) for neat NMP was 2.05 x 10"! cm/hr (with KME =
4.54L/hr). To fit the data from the diluted exposures, a lower PVL of 4.78xl0"4 cm/h was needed (with
KME = 2.10 L/hr) (Figure_Apx J-13). In the absence of absorption data for other concentrations, below
and between 0.5 and 1.0, it was assumed that PVL is constant at the value estimated for 50% NMP when
the NMP concentration is < 50% and that it increases linearly from that value to the value estimated for
53 mg/m3 simulation, with dermal
¦ 24 mg/m3 simulation, with dermal
-	10 mg/m3 simulation, with dermal
-	53 mg/m3 simulation, no dermal
• 24 mg/m3 simulation, no dermal
-	10 mg/m3 simulation, no dermal
53 mg/m3 data
24 mg/m3 data
10 mg/m3 data	
Page 571 of 576
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100% NMP for intermediate concentrations. The resulting PVL function was used in estimating human
dermal absorption for neat and diluted NMP absorption, with KME kept at the value estimated with 50%
NMP (2.1 L/hr). (Note that KME does not impact NMP blood levels and hence estimates of risk.)
Workplace Observer Study
In a biomonitoring study Xiaofei (2000) followed 4 workers and 5 observers in a lens manufacturing
facility. The workers washed lenses with NMP, working 11-hr shifts with a 1-hr lunch break (total 12
hrs within the facility). Observers were stated to be in the facility from 8 am to 5 pm for a single day, but
the tabulated exposure metrics indicated only 8 h of exposure, so it was assumed that they also took a 1-
hr break (at noon). The mean exposures for the observers was 0.28 ppm, with a range from 0.24 to 0.32
ppm. The PBPK model underestimated plasma NMP concentrations for the workers (data not shown)
and observer by ~3x when no dermal exposure is assumed (Figure Apx J-14). However, droplets of
NMP were noted on the lenses as the workers were moving those lenses to drying racks. Just assuming
that these droplets were due to some aerosolized NMP and that the observers had a small surface area of
skin exposed to such droplets, 0.2 cm2, gave results that better fitted the blood data during the exposure,
but the clearance after exposure appeared to be too rapid. Assuming that the average metabolic rate was
V2 of that identified from the Bader and van Thriel (2006) data (i.e., VK1C = 0.193 L/h-kg0.75) with an
even smaller exposure to aerosol (0.1 cm2 of exposed skin) resulted in simulations that matched the data
well (Figure Apx J-14). The lowest individual VK1C estimated for the Bader and van Thriel (2006)
data was 0.17 L/h-kg0.75, so the value used here is not unreasonable. In summary, the un-adjusted
model gave simulations that were within a factor of three of this data set and the discrepancy can be
explained by a reasonable level of metabolic variability between the two study populations and a small
amount of dermal contact.
Page 572 of 576
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Time (h)
Model simulation, men, neat NMP
Model simulation, women, neat NMP
Moodel simulation, men, 50% NMP
Akesson et al 2004 men, neat NMP
Akesson et al 2004 women, neat NMP
Akesson et al 2004 men, 50% NMP
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Model simulation, women, neat NMP
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Akesson et al 2004 men, neat NMP
Akesson et al 2004 women, neat NMP
Akesson et al 2004 men, 50% NMP
r
10	20	30	40	50	60
Time (h)
FigureApx J-13. Model Fits to Human Dermal Exposure Data of Akesson et al. (2004)
Upper panel shows simulation and data for metabolite 5H-NMP concentration in blood plasma and
lower panel shows simulation and data for the cumulative total 5H-NMP excretion in urine.
T
50
Page 573 of 576
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— 0.32 ppm simulation
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¦ Volunteer B
A Volunteer C
O Volunteer D
jK Volunteer E	^
FigureApx J-14. Workplace Observer Simulations Representing Subjects of Xioafei et al. (2000)
* Metabolic elimination was reduced to that estimated from Bader and van Thriel (2006) data and
0.1 cm2 of skin was assumed exposed to liquid aerosol.
J.2.2 Changes in Blood Concentrations Predicted Over the Course of a Work Week
EPA evaluated the potential for NMP to accumulate in workers from week to week. To do this, EPA
used the human PBPK model to predict blood concentrations over the course of a work week followed
by a weekend with no exposure using several occupational exposure scenarios as examples to cover a
range of exposure levels. Results are illustrated in the following figures. Even in the workers with the
highest levels of exposure (Example scenario #1), the PBPK model predicts that blood concentrations of
NMP may increase over the course of the work week but will be eliminated over the course of a
weekend. Hence, no week-to-week accumulation is expected in humans under any anticipated
workplace exposures.
Page 574 of 576
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—	Venous blood cone
—	Air cone (mg/m3)
72 96
Time (h)
FigureApx J-15. Blood Concentrations Modeled for an Occupational Exposure Scenario with a
High-end AUC prediction - 12 h shift.
Blood concentrations of NMP are shown over the course of a five-day work week followed by two days
off This plot shows model predictions for the 'lithium ion- drum handling' occupational exposure
scenario based on a 12-hour shift (an OES representing a high-end AUC prediction).
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Time (h)
Figure Apx J-16. Blood Concentrations Modeled for an Occupational Exposure Scenario with a
High-end AUC prediction - 8 h shift.
This plot shows model predictions for the 'capacitor, resistor, coil, transformer and other inductor
manufacturing' occupational exposure scenario based on an 8-hour shift (an OES representing a high-
end AUC prediction).
Example scenario #2
Page 575 of 576
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Example scenario #3
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FigureApx J-17. Blood Concentrations Modeled for an Occupational Exposure Scenario with a
Mid-Range AUC.
Blood concentrations of NMP are shown over the course of a five-day work week followed by two days
off This plot shows model predictions for the 'recycling and disposal' occupational exposure scenario
(an OES representing mid-range AUC prediction).
Example scenario #4
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Figure Apx J-18. Blood Concentrations Modeled for Occupational Exposure Scenario with Low-
end AUC prediction.
Blood concentrations of NMP are shown over the course of a five-day work week followed by two days
off. This plot shows model predictions for the 'printing and writing' occupational exposure scenario (an
OES representing a low-end AUC prediction).
Page 576 of 576
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