NIOSH: Carbonless Copy Paper Review Exec Summary

Gary Greenberg Gary.Greenberg at Duke.edu
Sat Jan 6 01:42:16 EST 2001


Carbonless Copy Paper

NIOSH Hazard Review December, 2000 DHHS (NIOSH) Publication No. 2001-107 

This document is available as 2001-107.pdf (155 pages, 718K)
http://www.cdc.gov/niosh/pdfs/01-107.pdf

Executive Summary

In 1987, the Occupational Safety and Health Administration (OSHA)
requested that the National Institute for Occupational Safety and Health
(NIOSH) investigate the validity of reported adverse health effects in
workers occupationally exposed to chemicals contained in or released
from carbonless copy paper (CCP). Because of limited published
information, NIOSH issued a Federal Register notice soliciting
information about possible adverse health effects from CCP exposure [52
Fed. Reg. * 22534 (1987)]. * Federal Register. See Fed. Reg. in
references.

On the basis of information available at that time, no strong conclusion
could be reached concerning a consistent link between CCP and major
health effects. Between 1987 and 1997, additional reports involving
health problems potentially related to CCP were identified. Therefore,
in 1997 NIOSH issued a second Federal Register notice soliciting new
information [62 Fed. Reg. 8023 (1997)]. This report contains a review of
the published literature on CCP and the submissions to the NIOSH docket
from the two Federal Register notices.

CCP was introduced in 1954 by the National Cash Register Company as
no-carbon-required (NCR) paper—an alternative to separate sheets of
carbon paper [Sandberg 1955; Green 1955; Miller and Phillips 1972;
Calnan 1979; Buring and Hennekens 1991]. A given CCP can vary greatly as
to its constituents, weight and types of paper coatings, paper color,
dye colors and combinations of dyes used on coatings, solvents and
solvent mixtures (including variations from different suppliers),
physical form of the paper (rolls versus sheets), and final form of the
product (i.e., bound with adhesives). Thus the product known as CCP is
not a single product but includes thousands of different and often
unique products [Mead Corporation 1997]. This fact needs to be
considered when interpreting the findings from the scientific
literature.

About 10 years after the introduction of CCP, medical complaints began
to be reported by office workers [North Carolina Medical Journal 1982;
Magnusson 1974; Göthe et al. 1981; Buring and Hennekens 1991]. Since
1965, various health effects associated with exposure to CCP have been
reported in the literature appearing from Denmark, Finland, England,
Sweden, Germany, the Netherlands, France, Italy, Belgium, Japan, Norway,
and the United States.

NIOSH has reviewed the published and unpublished literature on CCP. The
following paragraphs summarize the findings from this review regarding
the primary health effects associated with CCP exposure.

Irritation of the Skin, Eyes, and Upper Respiratory Tract

The most common findings from the human studies are symptoms consistent
with irritation of the skin, eyes, and upper respiratory system
following exposure to some types of CCP. These symptoms have also been
described in numerous case reports and case series of persons exposed to
CCP, and associations between these symptoms and CCP exposure have been
observed in several cross-sectional epidemiologic studies. A positive
exposure-response relationship between these symptoms and CCP exposure
has also been observed in those studies that examined this relationship.

The cross-sectional epidemiologic studies have several major
methodologic limitations that make them difficult to interpret. One
major potential source of bias in these studies is overreporting of
symptoms by workers who are already aware of a potential association
between CCP exposure and irritative symptoms. This form of bias is often
referred to as “recall bias” and is well recognized to be a potentially
important factor in epidemiologic studies in which symptoms or exposures
are identified by questionnaires administered to the study subjects.
Selection bias is also a major concern— particularly in studies with a
low participation rate, where subjects with symptoms may have been more
likely to return the questionnaires. These studies may also have been
biased toward observing no effects by (1) analyzing a mix of workers
with high and low potential for CCP exposures and (2) including only
active workers and thus excluding workers who may have left the
workforce as a result of adverse health effects related to CCP exposure.

The strongest evidence for an association between symptoms and CCP
exposure comes from the studies of indoor air quality. These studies
report a positive (and in several cases statistically significant)
association between CCP exposure and symptoms of skin, eye, and upper
respiratory tract irritation. Of the studies reviewed in this document,
the indoor air quality studies are the least susceptible to recall bias
because they were not conducted in workplaces where specific concerns
about CCP or other indoor pollutants were heightened by previous
complaints. None of these indoor air studies were designed primarily to
address the CCP question, hence investigator bias is also less likely.

Other information supports the plausibility of the findings from the
experimental studies in humans. The plausibility of signs and symptoms
of irritation associated with CCP exposure is supported by the presence
of several known irritants and allergens (e.g., formaldehyde, kerosene,
phthalates, acrylates, glutaraldehyde, amines, and isocyanates) in some
types of CCP and by similar effects in experimental studies of animals.
For example, in seven studies of CCP and formaldehyde, nearly all
exposure measurements exceeded the NIOSH REL (but not the OSHA PEL) for
formaldehyde [Norbäck 1983b; Gockel et al. 1981; Hazelton Laboratories
1985; Apol and Thoburn 1986; Chovil et al. 1986; Omland et al. 1993;
Zimmer and Hadwen 1993]. Finally, laboratory experiments in humans
support the plausibility of the associations between irritative symptoms
and exposure to CCP. Signs consistent with irritation of the skin and/or
the upper respiratory tract have been noted in a few of the experimental
laboratory studies in humans. However, most of these studies failed to
demonstrate any effects or showed extremely mild reactions to CCP
exposure. Inconsistencies in the findings of these studies might easily
be explained by differences in study design and particularly by
differences in the types of CCP tested.

Allergic Contact Dermatitis

Several authors have reported cases of allergic contact dermatitis that
appear to have been associated with CCP or its components [Marks 1981;
Kannerva et al. 1990a,b, 1993; Shehade 1987]. Development of
sensitization to CCP or its components was also reported in a few
persons in several industry-sponsored repeated insult patch test (RIPT)
studies (Report 77–512–70 and Supplemental Report 79–512b–70, Report
77–896–71, and Report 79–0085–73, all from Hill Top Research, Inc.; and
Project SH–72–4, dated April 18, 1972, performed by the Shelanski
Holding Company, Conshohocken, Pennsylvania, for Monsanto Co., St.
Louis, Missouri). In 8 of 217 test materials, study investigators
indicated that skin sensitization occurred in some human subjects.
However, these studies were mostly judged to be negative for irritation
by the investigators. Thus in a small proportion of the population, CCP
or its components appear capable of inducing cell-mediated (type IV)
immune response and allergic contact dermatitis, particularly under the
intensive exposures associated with RIPT protocols. Cases of allergic
contact dermatitis were reported only in RIPT studies from the 1970s
that were submitted to the 1987 NIOSH docket; no cases were reported in
the studies submitted to the 1997 docket. This fact indicates that the
CCP component( s) responsible for the allergic contact dermatitis
observed in the early studies may have been removed from current
formulations of CCP.

Systemic Reactions

Three patients with systemic reactions clinically suggestive of mast
cell and/or basophil degranulation after cutaneous challenge with CCP or
its components have been reported in two published case reports [Marks
et al. 1984; LaMarte 1988]. These reports suggest that some CCPs or
their components can induce reactions clinically compatible with those
caused by mast cell and/or basophil mediator release. Immunologic
sensitization was not adequately evaluated in these studies, and thus it
is unclear whether an immunologic mechanism underlies these reactions.
However, no additional reports were located in the peer-reviewed
literature over the last 12 years. Thus, even if the reported reactions
were referable to CCP exposure, systemic reactions of this type appear
to be exceedingly rare. Furthermore, the relevance of these reports to
current CCP exposures is uncertain.

Conclusions

On the basis of a NIOSH review of the scientific literature and
information submitted in response to its 1987 and 1997 Federal Register
notices, NIOSH concludes the following:

- The weight of the evidence supports the conclusion that exposure to
certain types of CCP or its components has, under some conditions,
resulted in symptoms of irritation of the skin and of the mucosal
membranes of the eyes and upper respiratory tract.

This conclusion is based primarily on interpretation of the evidence
from the epidemiologic studies. Although the magnitude of the effects
observed in these studies was only weak to moderate, these studies were
reasonably consistent in reporting an association and evidence of an
exposure-response relationship between CCP exposure and irritative
symptoms of the eyes, skin, and upper respiratory tract. The
plausibility of the epidemiologic evidence is supported by the presence
of known irritants in some types of CCP, toxicologic studies that
demonstrate mild irritation in laboratory animals exposed to CCP, and
the evidence for respiratory and skin irritation in some of the
experimental laboratory studies in humans. Some of the epidemiologic
studies may have been biased, particularly by overreporting from study
subjects who were already concerned about the potential effects of CCP
exposure (i.e., recall bias). However, it is unlikely that recall bias
could explain the associations observed between CCP exposure and
irritative symptoms of the eyes, skin, and upper respiratory tract in
the indoor air quality studies, since these studies were not conducted
in an atmosphere of concern regarding the health effects of CCP.

- Exposure to CCP or its components may rarely cause allergic contact
dermatitis.

This conclusion is based on published case reports of allergic contact
sensitization and results reported in several industry- sponsored RIPT
studies. Cases of allergic contact dermatitis were reported only in RIPT
studies from the 1970s that were submitted to the 1987 NIOSH docket; no
cases were reported in the studies submitted to the 1997 docket. This
fact may indicate that the CCP component responsible for the allergic
contact dermatitis observed in the early studies was removed from the
more recent formulations of CCP.

- Systemic reactions have occurred in a few persons exposed to CCP. This
conclusion is based on the finding that three such cases have been
reported in the peer-reviewed medical literature. No cases have been
reported in the last 7 years, and thus there is no evidence that current
exposures to CCP present a risk for this health outcome.

- Data are insufficient to evaluate claims of other adverse health
effects (such as neurologic effects and reports of multiple chemical
sensitivity [MCS]) that have been suggested in some of the clinical
reports submitted to the NIOSH docket.

In conclusion, although the weight of the evidence indicates that
exposure to CCP in the past has resulted in adverse health effects, it
is uncertain whether current formulations of CCP represent a significant
risk to exposed workers. Only a few cases of systemic reactions and
allergic contact dermatitis have been reported in the United States or
in Europe, which suggests that the risk of these serious outcomes is
extremely low given the large number of people who have been exposed to
CCP over a period of many years. Recently conducted experimental studies
in humans (RIPT studies) suggest that the potential for skin irritation
from exposure to current formulations of CCP is nonexistent, or at most
slight. However, it is unclear how well these experimental studies
simulate the exposures and potential responses of CCP users—particularly
heavy users. Data from industry reporting systems suggest no widespread
problem and in fact indicate a decrease in health-related complaints in
recent years despite an increase in CCP production. However, these
passive reporting systems are unlikely to capture all or even most cases
of CCP-related health effects, and changes in publicity about CCP may
have caused fluctuations in the reporting of cases. Since the 1980s, no
epidemiologic studies have been conducted to determine irritative
symptoms among U.S. workers exposed to CCP [Mendell et al. 1991]. A
positive epidemiologic study was conducted in Finland in 1991 [Jaakkola
and Jaakkola 1999]. However, the relevance of these findings for U.S.
workers may be limited because of differences between the CCP products
used in Europe and the United States. Thus information is lacking about
the prevalence of irritation of the eyes, skin, and upper respiratory
tract among workers currently handling CCP in the United States.

Recommendations

NIOSH recognizes that it may occasionally be necessary to limit CCP
exposure in certain workers through administrative controls (such as job
rotation). But in most cases, implementing normal precautions and
recommendations for maintaining acceptable indoor air quality should be
adequate to reduce or eliminate symptoms. Good industrial hygiene and
work practices are likely to prevent symptoms from potent irritants
(such as formaldehyde) that may be emitted from CCP. These include
adequate ventilation, humidity, and temperature controls; proper
housekeeping; minimal hand-to-mouth and hand-to-eye contact; and
periodic cleansing of hands.

In addition, NIOSH recommends the following:

- CCP manufacturers and their suppliers are encouraged to follow best
practices, such as the Product Stewardship Code of Management Practices
[American Chemistry Council 2000]; they should also consider enhancing
their product guidance to reflect that published studies indicate that
irritative symptoms appear to increase with increasing exposure to CCP.

- CCP manufacturers and their suppliers should also consider how human
test procedures (e.g., RIPT) can be modified by the use of standardized
protocols that include proper controls (e.g., bond paper), tests that
mimic high-use situations, and meaningful criteria for scoring and
interpreting these tests to assess safety from skin contact (e.g., ASTM
D 6355–98) [ASTM 1999]. Current best practices in the field of product
testing may not be sensitive enough to identify mild skin irritants.

- As part of ongoing surveillance, CCP manufacturers and their suppliers
may want to evaluate the frequency and severity of irritation in workers
using CCP.


-- 
Gary N. Greenberg, MD MPH    Sysop / Moderator Occ-Env-Med-L MailList
Free subscription enrollment at http://subscribe.occhealthnews.com
gary.greenberg at duke.edu     Duke Occupat, Environ, Int & Fam Medicine


---






More information about the Toxicol mailing list