NMP TSCA Workplan Risk Assessment
Ethics Information for Human Studies Used to Support NMP PBPK Model
Study
Akesson
and
Paulsson
1997
Akesson
and
Jonsson
2000
Akesson et
al. 2004
Type of human
study
Intentional
dosing
Intentional
dosing
Intentional
dosing
Informed
consent?
Yes
Yes
Yes
Independent
ethics
review?
Yes
Yes
Yes
Selection
Process
Healthy
volunteers were
selected after a
health
examination.
Paper did not
report additional
details about the
recruitment
process.
Healthy
volunteers were
selected after a
health
examination.
Paper did not
report additional
details about the
recruitment
process.
Healthy
volunteers were
selected after a
health
examination.
Pregnant
women were
excluded from
the study.
Risks to subjects
Risks were
minimized by
doing a general
health
examination and
selecting healthy
volunteers.
There were no
reported or
observed
adverse
reactions.
Risks were
minimized by
doing a general
health
examination and
selecting healthy
volunteers.
There were no
reported or
observed
adverse
reactions.
Risks were
minimized by
doing a general
health
examination and
selecting healthy
volunteers.
There were no
reported or
#
Children
Subjects
#
Female
Subjects
#
Male
Subjects
0
0
6
Ages
28-41
yrs
0
0
6
Ages
28-41
yrs
0
6
12
Ages
27-56
yrs
Age
range
Notes
1
Study
Type of human
study
Informed
consent?
Independent
ethics
review?
Selection
Process
Paper did not
report additional
details about the
recruitment
process.
Bader et al.
2005
Bader and
van Thriel,
2006
Intentional
dosing
Intentional
dosing
Yes
Yes
Risks to subjects
#
Children
Subjects
#
Female
Subjects
#
Male
Subjects
Age
range
Notes
observed
adverse
reactions.
Yes
Healthy
volunteers were
selected after a
health
examination.
Selected
subjects had
regular skin
appearance and
did not exhibit
sensitization
toward
chemicals.
Paper did not
report additional
details about the
recruitment
process.
Risks were
minimized by
doing a physical
examination of
the skin.
Subjects
experienced
acute effects
such as feelings
of heat, pricking
and itchiness
during the skin
application.
Moderate
swelling in all
cases and
erythema in one
case were
observed but
were reversible
in 24 hrs.
Yes
Healthy, young
volunteers were
selected after a
medical
examination by
a physician. All
participants were
Caucasians.
Most of the
subjects
participated in a
previously
conducted
study. Paper did
Risks were
minimized by
doing a medical
evaluation
before starting
the study. There
were no
reported or
observed
adverse
reactions.
0
0
4
0
3
8
Average
age:
38±6 yrs
Subjects were
informed about
NMP’s irritating
properties and
its potential to
cause
developmental
toxicity based
on animal
observations.
Ages
23-29
yrs
Volunteers
were informed
about the
possible risks
of the blood
sampling
procedure.
NMP TSCA Workplan Risk Assessment
Study
Type of human
study
Informed
consent?
Independent
ethics
review?
Selection
Process
Risks to subjects
#
Children
Subjects
#
Female
Subjects
#
Male
Subjects
Age
range
Notes
not report
additional details
about the
recruitment
process.
Bader et al.
2007
Bader et al.
2008
Intentional
dosing
Intentional
dosing
Yes
Yes
Yes
Subjects were
recruited at the
University of
Dortmund,
Germany.
Subjects with
respiratory,
cardiovascular
and skin
diseases were
excluded from
the study.
Subjects had to
take a fitness
test. Paper did
not report
additional details
about the
recruitment
process.
Risks were
minimized by
doing a general
fitness test and
excluding
candidates
known to have
respiratory and
skin diseases.
There were no
reported
adverse
reactions.
Yes
Subjects had to
take a fitness
test. Subjects
with respiratory
disorders and
skin diseases
were excluded
from the study.
Paper did not
report additional
details about the
recruitment
process.
Risks were
minimized by
doing a general
fitness test and
excluding
candidates
known to have
respiratory and
skin diseases.
Medical staff
supervised the
conduct of the
experiment.
There were no
reported
0
0
0
0
16
16
Average
age:
26.5±2.
4 yrs
Study was
conducted
following the
principles of
the Declaration
of Helsinki.
Ages
22-30
yrs
Study was
conducted
following the
principles of
the Declaration
of Helsinki.
3
Study
Type of human
study
Informed
consent?
Independent
ethics
review?
Selection
Process
Risks to subjects
#
Children
Subjects
#
Female
Subjects
#
Male
Subjects
Age
range
Notes
adverse
reactions.
Xiaofei et al.
2000
Observational
study as well
as intentional
dosing
Yes
Not
reported.
The candidates’
medical records
were evaluated.
None of the
participants had
medical
concerns that
would prevent
them to
participate in the
study. One of
the workers had
dermatitis after
direct skin
contact with
NMP. Paper did
not report
additional details
about the
recruitment
process of
workers and
volunteers and
how the factory
was identified for
the study.
Risks were
minimized by
evaluating the
candidates’
medical records.
There were no
reported
adverse
reactions.
0
17
Ages
20-56
yrs
The
observational
study
monitored
NMP in plasma
or urine while
workers were
performing
their daily
tasks. The
study also
enrolled 5
volunteers who
observed the
workers.
Informed
consent was
obtained from
all participants
in the study.
Both workers
and volunteers
were exposed
to NMP at
comparable
dose levels.
NMP TSCA Workplan Risk Assessment
References
*References were obtained from Dr. Poet’s paper (Torka et al. 2010, Quantitative risk analysis
for N-methyl pyrrolidone using physiologically-based pharmacokinetic and benchmark dose
modeling, Toxicological Sciences 113 (2), 468-482)
Akesson, B., Carnerup, M. A., and Jonsson, B. A. (2004). Evaluation of exposure biomarkers from
percutaneous absorption of N-methyl-2-pyrrolidone. Scand. J. Work Environ. Health 30, 306–
312.
Akesson, B., and Jonsson, B. A. (2000). Biological monitoring of N-methyl-2-pyrrolidone using 5hydroxy-N-methyl-2-pyrrolidone in plasma and urine as the biomarker. Scand. J. Work Environ.
Health 26, 213–218.
Akesson, B., and Paulsson, K. (1997). Experimental exposure of male volunteers to N-methyl-2pyrrolidone (NMP): Acute effects and pharmacokinetics of NMP in plasma and urine. Occup.
Environ. Med. 54, 236–240.
Bader, M., Keener, S. A., and Wrbitzky, R. (2005). Dermal absorption and urinary elimination of
N-methyl-2-pyrrolidone. Int. Arch. Occup. Environ. Health 78, 673–676.
Bader, M., and van Thriel, C. (2006). Human volunteer study on biomarkers of N-methyl-2pyrrolidone (NMP) after inhalation exposure. Report for the NMP Producers Group,
Washington, DC.
Bader, M., Wrbitzky, R., Blaszkewicz, M., Schaper, M., and van Thriel, C. (2008). Human
volunteer study on the inhalational and dermal absorption of N-methyl-2-pyrrolidone (NMP)
from the vapour phase. Arch. Toxicol. 82, 13–20.
Bader, M., Wrbitzky, R., Blaszkewicz, M., and van Thriel, C. (2007). Human experimental
exposure study on the uptake and urinary elimination of N-methyl-2-pyrrolidone (NMP) during
simulated workplace conditions. Arch. Toxicol. 81, 335–346.
Xiaofei, E., Wada, Y., Nozaki, J., Miyauchi, H., Tanaka, S., Seki, Y., and Koizumi, A. (2000). A linear
pharmacokinetic model predicts usefulness of N-methyl-2-pyrrolidone (NMP) in plasma or urine
as a biomarker for biological monitoring for NMP exposure. J. Occup. Health 42, 321–327.
5