Document ID: EPA-HQ-OPP-2007-0364-0020
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-07-06T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

REDLINE VERSION WITH BASF COMMENTS

MEMORANDUM

DATE:	May 10, 2006

SUBJECT:	Glutaraldehyde:  Antimicrobials Division’s Risk Assessment
for Issuance of the Reregistration Eligibility Decision (RED) Document. 
Case No. 2315.  PC Code: 043901.

FROM:	Tim McMahon, Ph.D., Senior Toxicologist

		Najm Shamim, Ph.D., Chemist

		Kathryn Montague, Biologist

		Talia Milano, Chemist

		Cassi Walls, Ph.D., Chemist

		Bob Quick, Chemist 

                   	Antimicrobials Division (7510C)

TO:		Michelle Centra, Chemical Review Manager

		Mark Hartman, Branch Chief 

		Regulatory Management Branch II

		Antimicrobials Division (7510C)     

        

Attached is the Preliminary Risk Assessment for glutaraldehyde for the
purpose of issuing a Reregistration Eligibility (RED) Decision.  The
disciplinary science chapters and other supporting documents for the
glutaraldehyde RED are also included as attachments as follows:  

Glutaraldehyde Toxicology Science Chapter for the Reregistration
Eligibility Decision Document, T. McMahon. April, 2006.

Product Chemistry of  Glutaraldehydeof Glutaraldehyde,  From, From Najm
Shamim, Ph.D. to T. McMahon, Ph.D. April 2005.

Dietary Risk Assessment for Glutaraldehyde Reregistration Eligibility
Decision Memorandum from Najm Shamim,  Ph.D, Ph.D., Chemist. to Michelle
Centra, March , 2006.

Occupational and Residential Exposure Assessment for Glutaraldehyde .
Glutaraldehyde. From T.Dole,  Industrial Hygienist, to Timothy Leighton,
Environmental Health Scientist.  March, 2006.

Ecological Hazard and Environmental Risk Assessment: Glutaraldehyde From
Richard C. Petrie. February, 2006.

Environmental Fate Assessment of Glutaraldehyde for the Reregistration
Eligibility Decision  (RED) Document. From  Srinivas Gowda,
Microbiologist/Chemist, to  Mark Hartman.  March, 2006.

Incident Reports associated with Glutaraldehyde.  From J. Chen, Ph.D.
Toxicologist, to Tim McMahon, Ph.D. Toxicologist.  March, 2006.

Glutaraldehyde: Report of the Antimicrobials Division Toxicology
Endpoint Selection Committee (ADTC).  From Timothy F. McMahon, Chair. 
February 9, 2006.  

		

	

	   

TABLE OF CONTENTS  

1.0  EXECUTIVE
SUMMARY-----------------------------------------------------------------
--------------------4

2.0 PHYSICAL/CHEMICAL PROPERTIES
------------------------------------------------------------------12

 

3.0 HAZARD CHARACTERIZATION
------------------------------------------------------------------------
13 

3.1   Hazard Profile
------------------------------------------------------------------------
------13

3.2  Dose-Response Assessment 
--------------------------------------------------------------14

3.3  FQPA
Considerations----------------------------------------------------------
----------- -18

3.4  Endocrine Disruption
----------------------------------------------------------------------
18

4.0  EXPOSURE ASSESSMENT AND  CHARACTERIZATION
----------------------------------------18

4.1   	Summary of Registered Antimicrobial Uses
--------------------------------------18

4.1.1	Residential Exposure and Risk for antimicrobial uses
---------------------------19

4.2          Dietary Exposure and Risk for Antimicrobial uses
------------------------------23

4.3	Dietary Exposure and Risk from agricultural
uses--------------------------------25

 

 

5.0	AGGREGATE RISK ASSESSMENT AND RISK CHARACTERIZATION ----------------
       25

5.1 Acute and Chronic Dietary Aggregate Risk
--------------------------------------------- 26

5.2 Short- and Intermediate-Term Aggregate Risk
------------------------------------------26

6.0	CUMULATIVE
RISK--------------------------------------------------------------------
----------------------26

7.0   OCCUPATIONAL EXPOSURE
------------------------------------------------------------------------
----27

7.1  Occupational Postapplication Exposure
--------------------------------------------------29

ENVIRONMENTAL RISK
------------------------------------------------------------------------
-----------31

8.1 Ecological
Hazard------------------------------------------------------------------
----------31

8.2 Environmental fate and
transport---------------------------------------------------------- 33

8.3 Environmental exposure and
Risk----------------------------------------------------------33

8.4 Endangered
Species-----------------------------------------------------------------
---------34

INCIDENT REPORT ASSESSMENT
----------------------------------------------------------------------35

9.1  OPP Incident Data
System------------------------------------------------------------------
35

9.2   Poison Control
Center------------------------------------------------------------------
-----35

9.3  California Data
1982-2003---------------------------------------------------------------
---35

9.4   National Telecommunication Pesticide
Network--------------------------------------- 36

9.5  Published Scientific Literature
-------------------------------------------------------------36

9.6 
Conclusions-------------------------------------------------------------
-----------------------38

   
REFERENCES--------------------------------------------------------------
-----------------------------------40

1.0	EXECUTIVE SUMMARY

Glutaraldehyde is registered for use as a disinfectant, biocide,
fungicide, microbicide, sanitizer, sterilizer, tuberculocide and
virucide. antimicrobial in a wide variety of use sites, including  food
handling and food storage establishments such as commercial egg
hatcheries, poultry and swine houses and processing plants, and  animal
feeding and watering equipment.  Nonagricultural commercial and
industrial uses include buildings and truck, construction materials and
laundry equipment.  Approved residential uses include hospital,
veterinary and laboratory premises and equipment in addition to hospital
critical rubber and plastic items.  Glutaraldehyde is used in the
manufacture of a variety of materials as a preservative such as cleaners
adhesives, paper and paperboard (food contact), water based coatings,
paints, inks and dyes.  Industrial process and water system uses include
evaporative condenser water and systems. Glutaraldehyde containing
products are also approved for use in aquatic areas such as ponds, flood
water and sewage water and cooling tower water.

 As an antimicrobial disinfectant agent, glutaraldehyde is applied to
various sites such as, agricultural premises, poultry/livestock
equipment and premises and non-critical care hospital surfaces and
equipment. It is also registered for use as a preservative in latex
paints, oil recovery drilling muds, secondary oil recovery injection
water, metalworking cutting fluids, and as a slimicide in
commercial/industrial water cooling systems, evaporative condenser and
heat exchanger water systems, and pulp/paper mill water systems.,  latex
paints, oil recovery drilling muds, secondary oil recovery injection
water, metalworking cutting fluids, commercial/industrial water cooling
systems, hospitals/hospital equipment, evaporative condenser and heat
exchanger water systems, hospitals/hospitals equipment, industrial
coatings, paper/paper products, pulp/paper mill water systems and
domestic dwelling contents.  It is not registered for any direct food
uses.  Dermal exposure for uses as pour liquid or wipe disinfection and
for pour liquid water cooling systems at the estimated maximum levels
may present a health hazard, assuming comparable toxicity for dermal
absorption and oral administration.

Glutaraldehyde also has non-pesticide uses, including as an
FDA-regulated medical device for Glutaraldehyde is also used as a cold
sterilant to high-level disinfection (sterilization) of disinfect and
clean heat-sensitive critical care medical, surgical and dental
equipment.  It is also Glutaraldehyde is also used as a tissue fixative
in histology and pathology labs and as a hardening agent in the
development of x-rays.

Hazard Characterization

The toxicology database for glutaraldehyde is complete. For a complete
hazard characterization of glutaraldehyde, see the toxicology
disciplinary chapter for glutaraldehyde. 

The Health Effects Division’s Carcinogenicity Assessment Review
Committee (CARC) classified   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1
glutaraldehyde as “Not Likely to be Carcinogenic to Humans” by any
route of exposure.  

A positive carcinogenic response was observed in one carcinogenicity
study in Fischer 344 rats, a strain of rat known to be susceptible to
development of large granular lymphocyte leukemia (LGLL).  A second oral
carcinogenicity study of glutaraldehyde conducted in Wistar rats showed
no carcinogenic response. In addition, inhalation carcinogenicity
studies of glutaraldehyde conducted by the National Toxicology Program
in both Fischer 344 rats showed no evidence of carcinogenicity. 
Although the top dose of the oral carcinogenicity study in Fischer 344
rats showed a significant increase in LGLL tumor incidence, the lower
doses gave no clear indication of a dose-response.  Comparison of the
response at lower doses with the historical control data examined by the
CARC showed that the tumor type in general has a wide variability of
incidence even in untreated animals. Thus, the effect of treatment with
glutaraldehyde on the incidence of this tumor is not clear. This is
supported by the available experimental evidence that has not identified
a clear etiology for LGLL in the rat. Data on the mutagenicity of
glutaraldehyde also show the chemical to be a potent cytotoxicant but
not a mutagenic compound. 

Dose-Response Assessment	

 On  August 24, 2005,  the Antimicrobials Division's Toxicity Endpoint
Selection Committee (ADTC)  evaluated the toxicology data base of
glutaraldehyde,  and selected the toxicological endpoints for acute and
chronic dietary risk assessments as well as for occupational/residential
exposure risk assessments. The ADTC also addressed the potential
enhanced sensitivity of infants and children from exposure to
glutaraldehyde as required by the Food Quality Protection Act (FQPA) of
1996.   

For acute dietary risk assessment to the general population including
infants and children,  the committee selected the NOAEL value of  15
mg/kg/day from a developmental toxicity study in rabbits (MRID 
42154001), based on  the significant decrease in food consumption
observed at 45 mg/kg/day in maternal rabbits. 

An acute dietary risk assessment for females 13-49 is not required for
glutaraldehyde, as there was no appropriate endpoint identified in the
database 

 

For chronic dietary risk assessment, a NOAEL of 16.1 mg/kg/day was
selected from a carcinogenicity study in rats (MRID 46212701), based on 
increases in non-neoplastic lesions (squamous metaplasia, inflammation)
of the respiratory tract and increases in erosions/ulceration of the
glandular stomach mucosa at a dose of 61/87.6 mg/kg/day in males and
females. 

  

For dietary risk assessments, an uncertainty factor of 100 is assigned
to both the acute and chronic reference dose values (10x inter-species
extrapolation, 10x intra-species variation).  As the FQPA factor was
reduced to 1x, the resulting acute and chronic reference dose values are
0.15 and 0.16 mg/kg/day,  respectively. 

For short-term (1-30 days) and intermediate-term (30 days- 6months)
incidental oral risk assessments, the NOAEL value of 15 mg/kg/day was
selected  from the developmental toxicity study in rabbits (MRID 
42154001), based on  the significant decrease in food consumption
observed at 45 mg/kg/day in maternal rabbits. 

 

For short-term dermal risk assessment (1-30 days), a NOAEL of 50
mg/kg/day was selected  from the 28-day dermal toxicity study in rats
(MRID  43259101),  based on dermal irritation (erythema, scaling) at the
site of test substance application at the next highest dose of 100
mg/kg/day. This is a route-specific study and is also appropriate for
the time frame of the risk assessment. For risk assessments, an
uncertainty factor of 100 was assigned (10x inter-species extrapolation,
10x intra-species variation).  

For intermediate-term and long-term dermal risk assessments, there was
no appropriate endpoint identified in the database.  There were no 
systemicno systemic effects observed in the 90-day dermal toxicity study
(MRID 46046801) at the highest  dosehighest dose tested(tested (150
mg/kg/day) and dermal toxicity was observed at the lowest dose tested
(50 mg/kg/day).  This is similar to the effect levels in the 28-day
dermal toxicity. Thus, use of the 50 mg/kg/day value as an endpoint for
short-term dermal exposure would also be protective of effects occurring
from any intermediate-term dermal exposure, as irritation is protected
against and systemic effects do not occur at this dose level.  

For short-term inhalation risk assessments (1-30 days), the NOAEL of 0.7
mg/m3 was selected from the 2-week inhalation toxicity study conducted
with glutaraldehyde as published in the NTP Technical Report (NTP
Technical report on toxicity studies of glutaraldehyde: Administration
by inhalation to F344/n rats and B6C3F1 mice, NIH Publication 93-3348.
March 1993) based on histopathological changes of the nasal passages,
larynx, trachea, and lungs at the LOAEL of 2.0 mg/m3 and above in rats
and mice. 

 

For intermediate-term inhalation risk assessments, the NOAEL of 0.512
mg/m3 was selected from the 13-week inhalation toxicity studies
conducted with glutaraldehyde as published in the NTP Technical Report
(NTP Technical report on toxicity studies of glutaraldehyde:
Administration by inhalation to F344/n rats and B6C3F1 mice, NIH
Publication 93-3348. March 1993) based on histopathological changes of
the nasal and respiratory tract epithelium in rats and mice at the LOAEL
of 1.02 mg/m3 and above. 

For long-term inhalation risk assessments, the LOAEL of 0.26 mg/m3 was
selected from a chronic toxicity and carcinogenicity study in rats and
mice (MRID 44842202, NTP Technical Report #490), based on increased
incidence of hyaline degeneration in female mice. 

 

EPA’s selection of inappropriate endpoints and animal studies must be
reconsidered.  Application of the HEC/RfC methodology for compounds that
are sensory irritants and corrosive at high does levels must be
reevaluated because it is resulting in RfCs that are orders of magnitude
lower than levels that decades of experience have indicated are safe for
use.  EPA needs to carefully and thoughtfully review its approach before
making regulatory decisions that are unsupported by actual experience
with the glutaraldehyde.

As discussed in Spencer, PJ, The Utility of Human Chemesthectic
Thresholds for Establishing Inhalation Reference Concentrations (RfCs)
for Sensory Irritants, June 12, 2006, (incorporated here by reference),
the RfCs derived by EPA in this risk assessment are unrealistically low,
being below global occupational exposure limits (OELs) by one or two
orders of magnitude.  This disparity is largely attributable to use of
secondary effects of irritation in animal studies.  Instead, EPA should
rely on RfCs calculated on sensory irritation as the critical effect and
focus on studies in humans.  BASF and Dow have provided data to EPA for
use in this assessment that provides a reliable, objective endpoint in
humans and establishes a realistic, protective and scientifically
credible RfC.

FQPA Considerations

 The ADTC concluded that the special hazard-based FQPA factor can be
reduced to 1x.  The available developmental  and reproductive toxicity
data for glutaraldehyde show no evidence of teratogenicity or
reproductive toxicity.  The studies are conducted according to
guidelines and show no evidence of increased susceptibility of
offspring.  There is no evidence for neurotoxicity of glutaraldehyde. 

Dietary Exposure and Risk

Glutaraldehyde can be used as a disinfectant or sanitizer on hard
food-contact surfaces in food processing plants, on conveyor belts in
food processing plants, on hard surfaces and equipment in farm premises,
hatcheries, and animal/poultry housing facilities, on hatching eggs, in
adhesives, mineral slurries, pigments and fillers for food-contact
paper, in process water systems of papermillspaper mills as a slimicide,
and in process water systems of sugar beet mills. The use of
antimicrobials on food or feed contact surfaces, agricultural
commodities, and in animal premises and poultry premises including
hatcheries may result in pesticide residues in human food.  The Agency
must determine the risk to human health that may occur from exposure to
glutaraldehyde from these direct (there are no direct food uses) and
indirect food contact uses. In the absence of data for residues of
glutaraldehyde on treated food and food contact surfaces, the Agency has
estimated residue levels that may occur in food using maximum
application rates from product labels and a variety of FDA models and
assumptions. Using the residue estimates, Estimated Daily Intake
(mg/person/day) and Dietary Daily Dose (mg/kg/day) values were
calculated for each scenario. These daily estimates were conservatively
used to assess  dietary risks by calculating the %  chronic RfD (cPAD). 

Of all scenarios quantitatively evaluated, none of the calculated % cPAD
values exceeded 100%.  For application to hard surfaces in food
processing plants, the % cPAD values assuming a 10% transfer rate from
the treated hard surface to food (from FDA Sanitizing Guidelines) were
0.96% for adult males, 1.12% for adult females, and 4.47% for children.
Assuming a 100% transfer rate, the % cPADs were 9.57 for adult males,
11.17% for adult females, and 44.67% for children. For application to
adhesives in papermaking, the % cPAD values were 0.00019% for adult
males, 0.00022% for adult females, and 0.00044% for children.  For
application to papermillpaper mill process water systems as a slimicide,
the % cPAD values were 10.0% for adult males, 11.7% for adult females,
and 23.4% for children. At this time, therefore, the Agency has no risk
concerns from  the indirect food uses of  glutaraldehdye glutaraldehyde,
as indicated by the application rates for the scenarios listed.

 

Drinking Water Exposure and Risk

When glutaraldehyde is introduced into the environment, it is most
likely to remain in the aquatic compartment, given the small air/water
partition and soil/water partition coefficients.  Aquatic metabolism,
under aerobic and anaerobic conditions, and aerobic soil metabolism are
major routes of dissipation of glutaraldehyde.  The calculated aerobic
and anaerobic pseudo first-order half-lives of glutaraldehyde in flooded
river sediment are 10.6 and 7.7 hours, respectively.  Glutaraldehyde
meets the OECD criteria for classification as readily biodegradable in
freshwater environments and as having the potential to be biodegradable
in marine environments.  In addition, the metabolism of glutaraldehyde
is rapid and proceeds via the formation of glutaric acid as an
intermediate to complete mineralization.  Because of its biodegradation,
glutaraldehyde is not likely to contaminate surface and ground waters.

Residential Handler Exposure and Risk  See comments in ORE chapter for
detailed explanations and comments on this section.

All of the GA products appear to be intended for use only in industrial
or medical areas, however, the residential population may be exposed to
household items such as laundry detergents and paints that have been
treated with GA as a material preservative. and emissions from cooling
towers that have been treated with GA as a slimicide

Residential handler inhalation exposures were assessed for use of paint
and laundry detergent treated with 100 ppm or 1000 ppm GA as a
preservative.  The painter inhalation exposures were assessed using the
EPA’s Wall Paint Exposure Model (WPEM) and laundry detergent
inhalation exposures were assessed using the EPA’s Consumer Exposure
Module (CEM).    Both the paint and laundry detergent scenarios were
assessed as short term exposures because the uses occur intermittently. 
 At the minimum treatment rate (100 ppm) the 24 hour average air
concentration for the painter is 2.2 ppb which exceeds the RfC of 0.12
ppb and the paint user inhalation exposures are of concern.  For the
handlers of laundry detergent treated at 100 ppm, the 24 hour average
air concentration of 0.26 ppb also exceeds the RfC. .  [All values must
be recalculated because the wrong vapor pressure was used and there was
no recognition of rapid degradation of glutaraldehyde in air.]

Residential handler dermal exposures were assessed by comparing the
concentration in the paints and the laundry detergents with the
concentrations used in the dermal toxicity studies.  The dermal
exposures are of concern at the high treatment rate of 1000 ppm (0.1
percent) because the Margin of Exposure (MOE) of 25 is less than the
target MOE of 100.  The dermal exposures are not of concern when the
treatment rate is 250 ppm (0.025 percent) because the MOE is equal to
100.  [EPA has not provided information on how it partitioned available
glutaraldehyde between the dermal and inhalation routes of exposure,
and, in fact, may have double counted glutaraldehyde exposures in its
risk assessment.

Residential Post-application Exposure and Risk

Residential postapplication exposure scenarios include inhalation
exposures from paints and cooling tower emissions.  [Conducting a
residential post-application exposure assessment for use in cooling
towers is unnecessary and inappropriate.  There is no support for an
assumption that residents of apartment buildings or other facilities
would be exposed to glutaraldehyde associated with cooling tower usage,
given siting considerations and that the measurements relied on by EPA
were within 30 cms of the slats. This portion of the risk assessment
must be deleted.]  Typically, paints used in a residential setting
result in short term exposure durations (1 to 30 days) while cooling
tower emissions can result in long term exposures.   The WPEM model was
used to estimate air concentrations resulting from the use of paint
preserved with GA with the assumption that the resident is located in a
non-painted part of the house while a bedroom is being painted by a
professional painter.   The 24 hour average air concentration of 3.7 ppb
exceeds the short term RfC of 0.12 ppb when paint treated at the minimum
rate of 100 ppm is used.   Cooling tower potential emissions were
evaluated using a proprietary model (CT-EVAP) which was validated with
air sampling at a representative cooling tower.  The results of the
modeling and air sampling suggest that GA air concentrations exceed the
long term RfC of 0.005 ppb.  .  [All values must be recalculated because
the wrong vapor pressure was used and there was no recognition of rapid
degradation of glutaraldehyde in air.]

Occupational Exposure and Risk  .  [All values must be recalculated
because the wrong vapor pressure was used and there was no recognition
of rapid degradation of glutaraldehyde in air.  Moreover, EPA must
explain how it partitioned glutaraldehyde with regard to inhalation and
dermal exposure in its various assessments.]

Occupational Handler Exposures

There are several occupational handler exposure scenarios that involve
GA products.  These scenarios either involve the manual or automatic
addition of GA products to industrial processes or they involve the
application of dilution solutions of GA to interior surfaces or spaces
such a medical hard surfaces or poultry houses.  Because GA has a
relatively high vapor pressure (0.1 mm hg at 50% solution
concentration), the unit exposure data from PHED and CMA are not
applicable because these data are based upon chemicals that have a much
lower vapor pressure (less than 1.0 x 10-4 mm Hg).    [This comment must
be reassessed in light of the fact that EPA has improperly used this
vapor pressure for glutaraldehyde levels at which the vapor pressure is
orders of magnitude lower.  There is no basis for EPA stating that
exposures from generic data cannot be extrapolated to glutaraldehyde at
typical use rates in occupational and residential settings.]  When the
vapor pressure is less than 1.0 x 10-4, chemicals are airborne primarily
as aerosols, while at a higher vapor pressure, chemicals are airborne
primarily as vapors.  Instead of calculating exposures using the CMA or
PHED data, GA air sampling data were reviewed to determine if GA
exposures exceed the RfC.   Most of the available exposure data are from
short term samples of approximately 15 minutes in duration and they were
taken as a comparison to the ACGIH TLV of 50 ppb.    Although many of
the short term samples exceeded the RfC of 0.32 ppb, these samples are
not comparable to the RfC because the un-sampled periods probably had
lower exposures than the sampled period.  A few of the drumming samples
reported by Dow Chemical were taken over a full shift and the results of
these samples ranged from 10 to 170 ppb.   All of these samples exceeded
the short term RfC of 0.32 ppb.

There are three products which are used to clean non-critical hard
surfaces in medical clinics, dental clinics and veterinary offices.  
HED utilized the CEM model to estimate air concentrations resulting from
these uses.   Input values included a weight fraction of 0.00275 and
ventilation rates of 0.45 and 4 air changes per hour.  Since medical
surface cleaners can be used on a year round basis, only long term
exposures were assessed.   The 8 hour average air concentrations exceed
the long term RfC of 0.063 ppb at both the minimum and maximum
ventilation rates and are of concern.  The daily peak exposure of 130
ppb at the minimum ventilation rate is also of concern because it
exceeds the ACGIH TLV of 50 ppb.

Occupational Post Application Exposures 

Post application GA inhalation exposures were assessed for professional
painters using paint preserved with GA and for workers entering poultry
houses after fogging with GA.    Post application dermal exposures were
also assessed for machinists using metal working fluids treated with GA.

Professional painter inhalation exposure to GA vapors was assessed using
the WPEM Model with the standard assumption that two professional
painters would paint an entire 7350 ft3 apartment in a work day.   Since
professional painters can paint indoors on a year round basis, only long
term exposures were assessed.   The WPEM calculations indicated that the
daily average GA air concentration of 54 ppb exceeded the long term RfC
of 0.015 ppb at the low treatment rate, therefore, the inhalation
exposures are of concern.

Inhalation exposures to GA following poultry house fogging were assessed
using the Multi-Chamber Concentration and Exposure Model (MCCEM v1.2). 
The initial concentration of 25 ppm was based upon the parameters listed
in the Virocide Label 

(71355-1) and it was assumed that the ventilation rate was 4 air changes
per hour.  The MCCEM calculations indicate that the air concentrations
declined to the TLV of 50 ppb in 95 minutes and to the RfC of 0.32 ppb
in 170 minutes. 

Dermal exposures to GA in metal working fluids were assessed by
comparing the concentrations in the metal working fluids with the
concentrations used in the dermal toxicity studies.  The dermal
exposures are of concern at the high application rate of 270 ppm (0.027
percent) because the MOE of 92 is less than the target MOE of 100.  The
dermal exposures are not of concern at the low application rate of 36
ppm (0.0036 percent) because the MOE exceeds 100.

Aggregate Exposure and Risk

	

An aggregate risk assessment was not required for glutaraldehyde. With
the exception of the incidental oral endpoint, the chronic dietary
endpoint, dermal endpoint, and inhalation endpoints are all based upon
different studies and toxicological effects. There are no incidental
oral exposure scenarios identified for glutaraldehyde.  On this basis,
no aggregation of exposures areaggregation of exposures is performed and
risks are as expressed for each scenario identified already in this risk
assessment.  

Environmental Fate Assessment

When glutaraldehyde is introduced into the environment, it is most
likely to remain in the aquatic compartment, given the small air/water
partition and soil/water partition coefficients.  Aquatic metabolism,
under aerobic and anaerobic conditions, and aerobic soil metabolism are
major routes of dissipation of glutaraldehyde.  The calculated aerobic
and anaerobic pseudo first-order half-lives of glutaraldehyde in flooded
river sediment are 10.6 and 7.7 hours, respectively.  Glutaraldehyde
meets the OECD criteria for classification as readily biodegradable in
freshwater environments and as having the potential to be biodegradable
in marine environments.  I addition, the metabolism of glutaraldehyde is
rapid and proceeds via the formation of glutaric acid as an intermediate
to complete mineralization.  Because of its biodegradation,
glutaraldehyde is not likely to contaminate surface and ground waters.

Glutaraldehyde’s tendency to bind with agricultural soils varies
according to soil type.  Glutaraldehyde is highly mobile in sandy
sediment and moderately mobile in sandy loam, silt loam, silty clay
loam, and loamy sand soils.  The Freundlich adsorption coefficients
ranged from 0.59 in sandy sediment to 4.96 in silty clay loam.  Based on
its adsorptions coefficients, and the tendency for glutaraldehyde to
partition into the water phase, glutaraldehyde is not likely to
contaminate soils.  There may be a water/sediment partitioning issue and
acute adverse impacts on benthic organisms.  However, glutaraldehyde
degrades fairly rapidly in freshwater and soils, and the impacts may be
short-lived.

The tendency of glutaraldehyde to bioaccumulate is low, based on its
high water solubility and low n-octanol/water partition coefficient. 
Glutaraldehyde should not pose a concern for bioconcentration in aquatic
organisms.

Ecological/Environmental Risk Assessment

Freshwater and estuarine/marine aquatic animals and plants could
potentially be exposed to glutaraldehyde discharged into the aquatic
environment.  Screening level modeling was conducted to estimate the
exposure and environment risk resulting from industrial wastewater
releases of glutaraldehyde into surface water following registered use
in once-through cooling towers.  This site was selected as having
maximum potential for environmental exposure of all labeled
glutaraldehyde sites.  

Nontarget plants are most sensitive to glutaraldehyde (EC50=310 ppb,
NOAEC=42 ppb), followed by freshwater aquatic invertebrates (LC50=750
ppb, NOAEC=560 ppb), followed by the oyster (EC50=780 ppb, NOAEC=160
ppb), followed by freshwater fish (LC50=9,500 ppb, NOAEC=1,700 ppb). 
The chronic freshwater fish value is NOAEC=1,600 ppb.    Based on Log
Kow, glutaraldehyde is highly hydrophilic and no bioaccumulation is
expected that could lead to secondary poisoning.  No persistent
breakdown products are expected to occur.                 

Tier I model results indicate the following:  no chronic risks to fish
are expected to occur even from the worst case scenario (highest initial
dosage, lowest stream flow).  No acute effects to non-target fish are
expected to occur except for the worst case scenario of high initial
dosage, low stream flow. Freshwater/marine invertebrates and green algae
are at high acute risk from all scenarios modeled.  No chronic
invertebrate data are available.  

For endangered/threatened species, freshwater/marine invertebrates and
green algae are at risk from all modeled scenarios.  Glutaraldehyde is
expected to be acutely toxic to endangered/threatened fish, all modeled
scenarios, except for the low maintenance dosage having medium stream
flow.  This risk assessment is incomplete and should not be used for
regulatory purposes without further consideration of the half-life and
degradation rates of glutaraldehyde in soil and water.  MRID 466737-01
indicates that glutaraldehyde is classified by OECD as readily
biodegradable in both freshwater and marine environments.  Under aerobic
conditions, glutaraldehyde metabolism in water and sediment is rapid and
proceeds to glutaric acid as an intermediate, and then ultimately to CO2
and H20 degradation products.  Confirmatory data is suggested as a next
step.

There should be no requirement for confirmatory data given that
glutaraldehyde used in once-through cooling towers is subjects to NPDES
permitting pursuant to the Clean Water Act.  The likelihood that
glutaraldehyde would be used in a cooling tower where discharges would
impact endangered or threatened species is miniscule.  It makes no sense
for the Agency to require an unneeded macro assessment for a product
regulated at site-specific levels by a sister office within EPA.

Endangered Species

PDM4 modeling indicates that glutaraldehyde discharges under a number of
modeled scenarios and may adversely affect endangered/threatened fish
and aquatic invertebrates (both freshwater and marine).  For
endangered/threatened species, freshwater/marine invertebrates and green
algae are at risk from all modeled scenarios.  Glutaraldehyde is
expected to be acutely toxic to endangered/threatened fish, all modeled
scenarios, except for the low maintenance dosage having medium stream
flow.  The Agency is not currently aware of any endangered or threatened
green alga species,species; however, the non-target plant risk
assessment is incomplete due to outstanding data for other aquatic plant
species.  

Factors that serve to reduce discharge impacts on aquatic species
include the NPDES permitting process, rapid glutaraldehyde breakdown in
the environment, and relatively short term impacts on aquatic ecosystems
from currently registered uses.  The PDM4 model does not account for
degradation rates of glutaraldehyde in soil or water.  An endangered
species determination cannot be made at this time and will be deferred
until confirmatory data are made available.  

Incident Reports

For assessment of human incidents, several databases were searched for
available information, including the Office of Pesticides Programs (OPP)
Incident Data System (IDS), Poison Control Centers, the California
Department of Pesticide Regulation, the National Pesticide
Telecommunications Network (NPTN), and the published scientific
peer-reviewed literature.  

Dermal exposure is considered a significant  route of exposure.  The
most common symptoms reported for cases of dermal exposure were skin
irritation/burning, rash, itching, skin discoloration/redness.  Allergic
type reactions have also been reported. Published scientific literature
also indicates that health care workers using glutaraldehyde in
FDA-regulated high-level disinfection applications at levels exceeding
those in most industrial and other EPA regulated applications are more
than 8 times more likely to be allergic to glutearaldehyde than
non-health care working peers.

Eye pain, burning of eyes, conjunctivitis, blurring vision, and acute
inflammation are the primary symptoms associated with ocular exposure
incidents.

The most common symptoms reported for cases of inhalation exposure were
respiratory irritation/burning, irritation to mouth/throat/nose,
coughing/choking, shortness of breath, dizziness.  There is evidence as
well that glutaraldehyde can cause occupational asthma. .  

Other systemic effects associated with glutaraldehyde include headache,
dizziness, nausea, stomach ache, sore throats, numbness of limbs, and
cardiac effects (heart palpitations and tachycardia).

 

2.0	PHYSICAL/CHEMICAL PROPERTIES AND CHARACTERIZATION

Table 1. Chemical Characteristics for Glutaraldehyde

Table 1 - Physical and Chemical Properties of GA

	Parameter	Source

Molecular Weight	100.1	Product Chemistry Data1

Color	Colorless	Product Chemistry Data1

Physical State	Liquid at about 7 F	Product Chemistry Data1

Specific Gravity	1.13 at 20 C	Product Chemistry Data1

Dissociation Constant	n/a	Product Chemistry Data1

pH	3.7 to 4.5	Product Chemistry Data1

Stability	Stable at proper conditions	Product Chemistry Data1

Melting Point	-6 C	Product Chemistry Data1

Boiling Point	100.5 C	Product Chemistry Data1

Water Solubility	167 gram/liter	Product Chemistry Data1

Kow	0.66	Product Chemistry Data1

Vapor Pressure (1 torr = 1 mm Hg)	0.102 torr (50% solution)

0.003 torr (2% solution)	ACGIH2

1. Data Evaluation Records (DER) for Product Chemistry of
Glutaraldehyde, A. Najm Shamim, 4/12/05 

2. Documentation of Glutaraldehyde TLV, ACGIH 2001.

	

                         

		

3.0	HAZARD CHARACTERIZATION

3.1	Hazard Profile

Acute Toxicity

      The acute toxicity data for glutaraldehyde is summarized below in
Table 2.

 

Table 2:  Acute Toxicity Profile for Glutaraldehyde

Guideline Number	Study Type/Test substance (% a.i.)	MRID Number/

Citation	Results	Toxicity Category

870.1100

(§81-1)	Acute Oral- Rat

Glutaraldehyde 50%

Acceptable - Guideline	00117061,

00164370	LD50 = 180 mg/kg (male)

LD50 = 210 mg/kg (female)

LD50 = 230 mg/kg (combined)	II

870.1200

(§81-2)	Acute Dermal- Rabbit

Glutaraldehyde 50.2%	44691606	LD50 > 2000 mg/kg (combined)	III

870.1300

(§81-3)	Acute Inhalation - rat.	00060275	LC50 > 4.16 mg/L	IV

870.2500

(§81-5)	Primary Eye Irritation- Rabbit

Glutaraldehyde 1.5%	0017064	A maximum irritating score of 26.4 for
unrinsed eyes and 30 for rinsed eyes in 24 hours; “moderately
irritating.”	I

870.2400

(§81-4)	Primary Eye Irritation – Rabbit

Glutaraldehyde 1.5%	00117065	Maximum mean score in first 24 hours was
3.33 at 24 hours, “minimally irritating.”	I

870.2400

(§81-4)	Primary Eye Irritation – Rabbit

Glutaraldehyde 0.5%	00117066	Maximum mean score in first 24 hours was 12
at 24 hours, “minimally irritating.”	I

870.2400

(§81-4)	Primary Eye Irritation – Rabbit

Glutaraldehyde 1.0%	00117067	Within 24 hours, treated eye showed mild
irritation.	I

870.2400

(§81-4)	Primary Eye Irritation – Rabbit

Glutaraldehyde 1.5%	00117068	Maximum mean score in first 24 hours was 36
at 24 hours, “moderately irritating.”	I

870.2500

(§81-5)	Primary Dermal Irritation- Rabbit

Glutaraldehyde 25%	00117060	Primary Irritant	I

870.2500

(§81-5)	Primary Dermal Irritation- Rabbit

Glutaraldehyde 50%	00117061	PIS = 6.34

(14-day average)	I

870.2600

(§81-6)	Dermal Sensitization –LLNA assay in mice	43330201	SI > 3 ;
positive sensitizer	 

Complete information on the non-acute mammalian toxicity of
glutaraldehyde can be found in the Toxicology disciplinary chapter for
glutaraldehyde. 

 

  SEQ CHAPTER \h \r 1 In accordance with the EPA Final Guidelines for
Carcinogen Risk Assessment (March 29, 2005), the Health Effects
Division’s Carcinogenicity Assessment Review Committee (CARC)  
classified glutaraldehyde as “Not Likely to be Carcinogenic to
Humans” by any route of exposure.  

A positive carcinogenic response was observed in one carcinogenicity
study in Fischer 344 rats, a strain of rat known to be susceptible to
development of large granular lymphocyte leukemia (LGLL).  A second oral
carcinogenicity study of glutaraldehyde conducted in Wistar rats showed
no carcinogenic response. In addition, inhalation carcinogenicity
studies of glutaraldehyde conducted by the National Toxicology Program
in both Fischer 344 rats showed no evidence of carcinogenicity. 
Although the top dose of the oral carcinogenicity study in Fischer 344
rats showed a significant increase in LGLL tumor incidence, the lower
doses gave no clear indication of a dose-response.  Comparison of the
response at lower doses with the historical control data examined by the
CARC showed that the tumor type in general has a wide variability of
incidence even in untreated animals. Thus, the effect of treatment with
glutaraldehyde on the incidence of this tumor is not clear. This is
supported by the available experimental evidence that has not identified
a clear etiology for LGLL in the rat. Data on the mutagenicity of
glutaraldehyde also show the chemical to be a potent cytotoxicant but
not a mutagenic compound. 

Dose-Response Assessment

On  August 24, 2005,  the Antimicrobials Division's Toxicity Endpoint
Selection Committee (ADTC)  evaluated the toxicology data base of
glutaraldehyde,  and selected the toxicological endpoints for acute and
chronic dietary risk assessments as well as for occupational/residential
exposure risk assessments. The ADTC also addressed the potential
enhanced sensitivity of infants and children from exposure to
glutaraldehyde as required by the Food Quality Protection Act (FQPA) of
1996A summary of the results are presented in Table 3. 

[See previous comments, supra, comments in individual science chapters
and paper submitted by Dow (Spencer, PJ, The Utility of Human
Chemesthectic Thresholds for Establishing Inhalation Reference
Concentrations (RfCs) for Sensory Irritants, June 12, 2006,
(incorporated here by reference).]  As noted, he RfCs derived by EPA in
this risk assessment are unrealistically low, being below global
occupational exposure limits (OELs) by one or two orders of magnitude. 
This disparity is largely attributable to use of secondary effects of
irritation in animal studies.  Instead, EPA should rely on RfCs
calculated on sensory irritation as the critical effect and focus on
studies in humans.  BASF and Dow have provided data to EPA on human
chemesthetic thresholds for use in establishing RfCs for glutaraldehyde
for use in this assessment that provide a reliable, objective endpoint
in humans and establish a realistic, protective and scientifically
credible RfC.

Table 3.  Toxicology Dose and Endpoint Selection for Glutaraldehyde

  SEQ CHAPTER \h \r 1 Exposure

Scenario	Dose Used in Risk Assessment

(mg/kg/day) 	Target MOE, UF, 

Special FQPA SF* for Risk Assessment	Study and Toxicological Effects

Dietary Risk Assessments

Acute Dietary

(general population and females 13-49) 	No appropriate endpoints were
identified that represent a single dose effect.  

Therefore, this risk assessment is not required.

Chronic Dietary

(all populations)	NOAEL = 

16.1 mg/kg/day

	FQPA SF = 1

UF = 100 (10x inter-species extrapolation, 10x intra-species variation)

Chronic RfD (cPAD) = 0.16 mg/kg/day	Carcinogenicity Study (drinking
water) in the Rat (MRID 46212701)

LOAEL = 61 mg/kg/day based on increases in non-neoplastic lesions
(squamous metaplasia, foreign body granuloma, pirulent inflammation) of
the respiratory tract and erosion/ulceration in the mucosa of the
glandular stomach.

Non-Dietary Risk Assessments

Incidental Oral Short-Term 

(1-30 days)

	NOAEL (maternal)  =  15 mg/kg/day	Target MOE = 100

(10x inter-species extrapolation, 10x intra-species variation) 

FQPA SF = 1

	Prenatal Developmental Toxicity Study in the Rabbit (MRID 42154001)

LOAEL (maternal) = 45 mg/kg/day based on maternal death (4/15),
decreased food consumption, body weight and body weight gain and
increased incidence of soft stool, diarrhea or no defecation.

Incidental Oral Intermediate-Term 

 (1- 6 months)

	NOAEL (maternal)  =  15 mg/kg/day	Target MOE = 100

(10x inter-species extrapolation, 10x intra-species variation) 

FQPA SF = 1	 Prenatal Developmental Toxicity Study in the Rabbit (MRID
42154001)

LOAEL (maternal) = 45 mg/kg/day based on maternal death (4/15),
decreased food consumption, body weight and body weight gain and
increased incidence of soft stool, diarrhea or no defecation.

Dermal

Short-Term (1 to 30 days)	NOAEL = 

50 mg/kg/day (2.5% @ 40 µl/cm2)a

(1000 µg/cm2)b

	Target MOE = 100 

(10x inter-species extrapolation, 10x intra-species variation)

	28-day dermal toxicity study in the rat (MRID 43259101)

NOAEL   = 50 mg/kg/day based on erythema, edema and skin lesions
observed at 100 mg/kg/day

Dermal Intermediate-Term (1 to 6 months)	An intermediate-term endpoint
not required for glutaraldehyde  

Dermal

Long-Term (>6 months)	A long-term dermal endpoint is not required for
glutaraldehyde. 

Inhalation

(short-term occupational / residential)	NOAEL (rat, mouse) = 0.7 mg/m3

HECocc = 0.041 mg/m3  

HECres = 0.014 mg/m3  

RfCocc =  0.0013 mg/m3  

RfCres =  0.0005 mg/m3  

	UF = 30

(3x inter-species extrapolation, 10x intra-species variation)	Two-week
inhalation toxicity study in rats and mice (NIH publication 93-3348)

NOAEL = 0.7 mg/m3, based on histopathological alterations of the nasal
passages, larynx, trachea, and lung at 2.0 mg/m3 and above.

Inhalation (intermediate-term) 	NOAEL (rat, mouse) = 0.512 mg/m3

 HECocc = 0.03 mg/m3  

HECres = 0.01mg/m3  

RfCocc =  0.001 mg/m3  

RfCres =  0.0003 mg/m3  

  	UF = 30

(3x inter-species extrapolation, 10x intra-species variation)	Thirteen
week inhalation toxicity study in rats and mice (NIH publication
93-3348). 

NOAEL = 0.512 mg/m3, based on histopathological changes of the nasal and
respiratory tract epithelium at 1.02 mg/m3. 

Inhalation

(long-term)

	LOAEL (mouse) = 

0.26 mg/m3

 HECocc = 0.019 mg/m3  

HECres = 0.004 mg/m3  

RfCocc =  0.00006 mg/m3  

RfCres =  0.00002 mg/m3  

 	UF = 300 

(3x inter-species extrapolation, 10x intra-species variation; 10x for
use of LOAEL)	Two-Year Inhalation Toxicity Study in the Rat and the
Mouse (MRID 44842202)

LOAEL = 0.26 mg/m3, based on squamous epithelial
hyperplasia/inflammation and turbinate necrosis in the nose.

Cancer	 In accordance with the EPA Final Guidelines for Carcinogen Risk
Assessment (March 29, 2005),   the Health Effects Division’s
Carcinogenicity Assessment Review Committee concluded that
glutaraldehyde was “not likely to be carcinogenic to humans” by any
route of exposure. 

UF = uncertainty factor, DB UF = data base uncertainty factor, FQPA SF =
special FQPA safety factor, NOAEL = no observed adverse effect level,
LOAEL = lowest observed adverse effect level, PAD = population adjusted
dose (a = acute, c = chronic), RfD = reference dose, MOE = margin of
exposure 

 a  0.2ml/kg x 0.2 kg/rat = 0.4 ml/rat   ( 2 sq. in x 2.54 cm/in)2 = 10
cm2

0.4 ml/10cm2 x 1000 ul/ml = 40 µl/cm2

b   TGAI-based dermal endpoint = (50 mg/kg rat x 0.2 kg rat x 1000
ug/mg) / 10 cm2  area of rat dosed = 1000 µg/cm2  



HECocc/res = NOAELadj x RGDR

FQPA Considerations

From the available data on reproductive and developmental toxicity of
glutaraldehyde, there was no evidence to suggest that offspring are more
sensitive to the toxic effects of glutaraldehyde than parental animals.
In addition,  there was no evidence to suggest a neurotoxic effect of
glutaraldehyde from the available toxicology data on this chemical. 
Based on this assessment, the Antimicrobials Division’s ADTC committee
concluded that the special hazard-based FQPA factor can be reduced to 1x
for risk assessments involving the FQPA safety factor. 

 Endocrine Disruption

EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as
amended by FQPA, to develop a screening program to determine whether
certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine
effects as the Administrator may designate."  Following the
recommendations of its Endocrine Disruptor Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there was scientific
basis for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system.  EPA also
adopted EDSTAC(s recommendation that the Program include evaluations of
potential effects in wildlife.  For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA has authority to
require the wildlife evaluations.  As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).

When the appropriate screening and/or testing protocols being considered
under the Agency(s EDSP have been developed, glutaraldehyde may be
subjected to additional screening and/or testing to better characterize
effects related to endocrine disruption.

 EXPOSURE ASSESSMENT AND CHARACTERIZATION

Summary of Registered  Antimicrobial Uses

GA is an active ingredient in numerous disinfecting products and is also
used as a materials preservative.  A summary of GA uses is given in
Table 2.  GA is used for slimicide treatment of cooling towers,
industrial process water, metal working fluids and oil field muds. As a
materials preservative, GA is used in paints, laundry detergents and
paper.   Medical uses of GA include RTU sprays and wipes that are used
to clean non-critical surfaces and medical waste treatment products that
are used to disinfect medical waste such as fluid in suction canisters
(46781-10) and general medical waste (71814-1).  GA is also widely used
to disinfect endoscopy equipment, however, that use is under the purview
of the FDA because it is considered an FDA critical use and therefore it
is not included in this assessment. Table 4 presents the uses of GA.

Table 4.  Summary of GA Registered Uses

Use Category	Use Sites	Application Rate 	Addition Method

Process and Waste Water	Air Washers, Recirc and Once thru cooling, 
Service and Aux water	20 to 100 ppm 	Open and Auto

	Waste Water

Beet Sugar	225 to 1125 ppm

15 to 250 ppm	Auto

Pulp and Paper	Process Water

Slurries and Coatings	50 to 750 ppm

50 to 300 ppm	Auto 

Fluids Preservation	Heat Transfer

Metal Working

Water Based Conveyor	20 to 100 ppm

36 to 270 ppm

50 to 300 ppm	Open and Auto

Other Preservation	Reverse Osmosis

General Preservative Use

Preservative for Concentrates

Concrete Admixtures	0.1 to 1.0%

100 to 1000 ppm 

100 to 1000 ppm

0.1 to 0.4%	Open and Auto

Oil Field	Water Floods

Drilling and workover fluids

Packer fluids

Pipelines

Storage Wells

Pipeline pigging

Hydro-testing	10 to 2500 ppm

25 to 500 ppm

25 to 300 ppm

250 to 2500 ppm

250 to 2500 ppm

500 to 5000 ppm

50 to 2000 ppm	Open and Auto

Animal and Poultry Housing	Mopping

Spraying

Fogging	0.1 to 0.25 %	Open Pour and Hand Held Application

Medical	Surface Treatment Spray

Surface Treatment Wipe

Medical Waste TreatmentA

Medical Waste TreatmentB	0.275%

0.275%

9.6%

7.8%	RTU

RTU

RTU

RTU

A. Is a RTU suction canister used to collect blood and other fluids
discharged from suction systems.

B.  Is used in a container system used to collect general medical waste.

The routes of exposure evaluated in the present assessment are:
short-term (ST), intermediate-term (IT), and long-term (LT) dermal and
inhalation exposures.  

4.1.1	Residential Exposure/Risk   [See previous comments and comments in
ORE Chapter.]

All of the glutaraldehdyyde (GA) products appear to be intended for use
only in industrial or medical areas.  There is one product (55195-3)
containing GA that has labeling which could be interpreted to mean that
it could be used in residential areas, however, it appears to be
primarily intended for use in medical areas.   This product is a RTU
surface spray which can be applied to hard surfaces such as counter
tops, table surfaces and office furniture in medical clinics.  In
addition, the residential population may be exposed to household items
such as laundry detergents and paints that have been treated with GA as
a material preservative and emissions from cooling towers that have been
treated with GA as a slimicide.  Table 4-2 identifies the residential
exposure scenarios assessed for GA.

Table 5.  Glutaraldehyde Residential Exposure Scenarios

Use	

Exposure Scenario	

Exposure Duration	Exposure Pathway	

Application Rate

Material Preservation of  Laundry Detergent	

Handler Exposure While Using Treated Laundry Detergent	

Short Term	Dermal and Inhalation	

100 to 1000 ppm

Material Preservation of Latex Paint	Handler Exposure While Using
Treated Paint	Short Term	Dermal and Inhalation	100 to 1000 ppm

	Post Application Exposure to Treated Paint	Short Term	Inhalation

	Cooling Towers	Post Application Exposure to Cooling Tower Emissions
Long Term	Inhalation	20 to 100 ppm

 

[Delete cooling tower assessment.]

Because GA has a relatively high vapor pressure (0.1 mm hg at 50%
solution concentration), the unit exposure data from PHED and CMA are
not applicable because these data are generally based upon chemicals
that have a much lower vapor pressure (less than 1.0 x 10-4 mm Hg).   
[See previous comments on use of inappropriate vapor pressure, failure
to adjust for glutaraldehyde half-life in air, etc.]  When the vapor
pressure is less than 1.0 x 10-4, chemicals are airborne primarily as
aerosols, while at a higher vapor pressure, chemicals are airborne
primarily as vapors.  The painter inhalation exposures to the GA vapors
were assessed using the EPA’s Wall Paint Exposure Model (WPEM) and
laundry detergent inhalation exposures were assessed using the EPA’s
Consumer Exposure Module (CEM).  The dermal exposures were assessed by
comparing the concentration in the paints and the laundry detergents
with the concentrations used in the dermal toxicity studies.

Residential Painter Inhalation Exposure and Risk   [See previous
comments on use of inappropriate vapor pressure, failure to adjust for
glutaraldehyde half-life in air, etc.]  

The Agency’s Health Effects Division utilized EPA’s Wall Paint
Exposure Model (WPEM) version 3.2 to estimate air concentrations
resulting from the use of paint preserved with glutaraldehyde.  WPEM was
developed under a contract by Geomet Technologies for EPA OPPT to
provide estimates of potential air concentrations and consumer/worker
exposures to chemicals emitted from wall paint which is applied using a
roller or a brush.  WPEM uses mathematical models developed from small
chamber data to estimate the emissions of chemicals from oil-based
(alkyd) and latex wall paint.  The emission data can then be combined
with detailed use, workload and occupancy data (e.g., amount of time
spent in the painted room, etc,) to estimate exposure.  Specific input
parameters include: the type of paint (latex or alkyd) being assessed,
density of the paint (default values available), and the chemical weight
fraction, molecular weight, and vapor pressure.   Detailed information
and the executable model can be downloaded from
http://www.epa.gov/opptintr/exposure/docs/wpem.htm.  

The results of modeling were converted from mg/m3 to ppb using a
conversion factor of 0.00409 mg/m3 per ppb.  Since a homeowner or
do-it-yourself painter typically paints on an intermittent basis (i.e.,
once or twice a year), only short term exposures were assessed.   At the
maximum application rate, the 24 hour average air concentration of 22
ppb exceeds the RfC of 0.12 ppb by a factor of 180 and the inhalation
exposures are of concern.  At the minimum application rate, the 24 hour
air concentration of 2.2 ppb exceeds the RfC of 0.12 ppb by a factor of
18 and is also of concern.   Results are shown in Table 6.

Table 6.  Short-Term Inhalation Risk Summary for Residential Painters

Application Rate	Painted Surface AreaA	Air Exchange Rate per hour
C24-hourB	Short Term RfC

1000 ppm	452 ft2	0.45	22 ppb	0.12 ppb

100 ppm

	2.2 ppb

	A.  Assuming the walls of one room are painted as specified in the
RESDIY scenario of WPEM.

B.  The 24 hour average air concentration experienced by the residential
painter on the day of painting.

Air concentrations in bold font indicate risks of concern because they
exceed the RfC.

Residential Laundry Detergent Handler Inhalation Exposure Assessment    
[See previous comments on use of inappropriate vapor pressure, failure
to adjust for glutaraldehyde half-life in air, etc.]  

For the laundry detergent handler inhalation exposure to GA vapor from
laundry detergent, .  HED utilized EPA’s Consumer Exposure Module
(CEM) to estimate air concentrations resulting from the use of laundry
detergent preserved with GA.    Detailed information and the executable
model can be downloaded from http://www.epa.gov/opptintr/exposure  

Since a resident does laundry on an intermittent basis (i.e., a few
times per week), only short term exposures were assessed.   The results
of the CEM model run are included in Table 7. 

Table 7.  Short-Term Inhalation Risk Summary for Laundry Detergent
Handlers

Application Rate	Amount of Laundry Detergent Used Per Day/ Duration of
Use 	Air Exchange Rate per hour	C24-hourA	Short Term RfC

1000 ppm	400 grams/0.667 hours	0.45	2.6 ppb	0.12 ppb

100 ppm

	0.26 ppb

	A. The 24 hour average air concentration experienced by the laundry
detergent handler on the day of detergent use.

*Air concentrations in bold font indicate risks of concern because they
exceed the RfC.

Residential Handler Dermal Exposure Assessment      [See previous
comments on use of inappropriate vapor pressure, failure to adjust for
glutaraldehyde half-life in air, etc.]  

The residential handler dermal exposures were assessed by comparing the
concentrations in the paints and the laundry detergents with the
concentrations used in the dermal toxicity studies.  This comparison is
shown in Table 8 below and indicates that the dermal exposures are of
concern at the high application rate of 1000 ppm (0.1 percent) because
the Margin of Exposure (MOE) of 25 is less than the target MOE of 100. 
The dermal exposures are not of concern when the application rate is 250
ppm (0.025 percent) because the MOE is equal to 100.

Table 8.  Residential Handler Dermal Exposures

Application Rate (ppm)	Application Rate 

(Percent)	Glutaraldehyde NOAEL	NOAEL ConcentrationA	MOEB

1000

250

100	0.1

0.025

0.01	50 mg/kg/day	2.5%	25

100

250

A. The concentration of glutaraldehyde in the test solution applied at
the NOAEL dose.

B. MOE =  NOAEL Concentration (percent) / Application Rate (percent)

Residential Painting Post Application Exposure Assessment tc \l4
"4.4.2.5		Paints 

The Agency’s Health Effects Division utilized EPA’s Wall Paint
Exposure Model (WPEM) to estimate air concentrations resulting from the
use of paint preserved with GA.  For this exposure assessment, WPEM
default scenarios were used to determine exposure to adults (RESADULT)
and children (RESCHILD).  This WPEM default scenario assumes that the
home occupants are exposed to the chemical in paint in adjacent rooms
(Zone 2) during painting and in the painted room (Zone 1) after
painting.  This default scenario includes 7 hours in Zone 2, 8 hours in
Zone 1 and 6 hours outside of the house.  The air concentrations are
given in Table 9 and indicate that risks are of concern at both the
maximum and minimum application rates because the 24 hour average air
concentrations exceed the short term RFC.

Table 9.  Post Application Risk Summary for Glutaraldehyde Treated Paint

Application Rate	Area Painted	Air Exchange Rate 	C24 in Zone 1 (ppb)	C24
in Zone 2 (ppb)	C24 at personA (ppb)	Short Term RfC (ppb)

1000 ppm	452 ft2 

(one room)	0.45 ACH	98	33	37	0.12

100 ppm

	9.8	3.3	3.7

	.  A. Average air concentration experienced by the resident person for
the first 24 hours during and after painting.

Air concentrations in bold font indicate risks of concern because they
exceed the RfC.

Cooling Tower Emissions Exposure Assessment   [Delete]

Because some cooling towers service apartment and office buildings,
there is a potential for residential exposure to cooling tower emissions
of GA.  These potential emissions were evaluated using a model (CT-EVAP)
which was validated with air sampling at a representative cooling tower
that was treated with 100 ppm GA.   The results of the modeling and air
sampling are listed in Table 10 and suggest that GA air concentrations
are greater than the long term RfC of 0.005 ppb when considered as a
daily or weekly average.

 

Table 10.  Air Concentrations from Glutaraldehyde Cooling Tower
Emissions

Cooling Tower 	Application RateA	Water Capacity (Gallons)	Drift Rate
Maximum Predicted Concentration 

(ppb)	Maximum Measured 15 Minute Air ConcentrationB

(ppb)	Average Air Concentration 

(ppb)

B96 	63 ppm	14,400	0.005%	3.4 @ 1 hour	N/A	1.3C

B203	100 ppm	9,000	0.005%	7.1 @ 10 min	4.9 	2.2C

Hospital California	60 ppm	2,000	0.005%	4.9	N/A	0.049D

A.  The label application rate is 20 to 100 ppm as listed in Table 2.

B.  This sample was collected 30 cm downwind of the eliminator slots. 
Several other samples were also collected and           were below the
LOD of 4.9 ppb.

C. Averaged over one day (1440 minutes).

D. Averaged over one week (10080 minutes).

Air concentrations in bold font are concern because they exceed the RfC
of 0.005 ppb.

Dietary Exposure/Risk for Antimicrobial Uses  	[See comments in Dietary
Risk Assessment Chapter for complete information.]

Glutaraldehyde can be used as a disinfectant or sanitizer on hard
food-contact surfaces in food processing plants, on conveyor belts in
food processing plants, on hard surfaces and equipment in farm premises,
hatcheries, and animal/poultry housing facilities, on hatching eggs, in
adhesives, mineral slurries, pigments and fillers for food-contact
paper, in process water systems of papermillspaper mills as a slimicide,
and in process water systems of sugar beet mills. 

The use of antimicrobials on food or feed contact surfaces, agricultural
commodities, and in animal premises and poultry premises including
hatcheries may result in pesticide residues in human food.  The Agency
must determine the risk to human health that may occur from exposure to
glutaraldehyde from these direct and indirect food contact uses. The
dietary scenarios selected by the Agency for quantitative assessment
include: application to hard surfaces in food processing plants,
application to adhesives used in papermaking, application to pigments
and fillers used in papermaking, and application to papermillpaper mill
process water systems as a slimicide.  These scenarios are believed to
represent worst-case estimates of indirect food contact dietary
exposure.  

In the absence of data for residues of glutaraldehyde on treated food
and feed contact surfaces, the Agency has estimated residue levels that
may occur in food using maximum application rates from product labels
and a variety of FDA models and assumptions (Table 11). Using the
residue estimates, Estimated Daily Intake (mg/person/day) and Dietary
Daily Dose (mg/kg/day) values were calculated for each scenario. These
daily estimates were conservatively used to assess chronic dietary risks
by calculating the % cPAD (chronic population-adjusted dose).  Risks
exceed the Agency’s level of concern when the % cPAD exceeds 100%. The
cPAD selected by the Agency is 0.16 mg/kg/day which is based on a NOAEL
of 16.1 mg/kg/day, an uncertainty factor of 100 (10x inter-species
extrapolation and 10x intra-species variation), and a FQPA 1X Safety
Factor. The NOAEL of 16.1 mg/kg/day is from a carcinogenicity study
(drinking water) in the rat where increases in non-neoplastic lesions
(squamous metaplasia, foreign body granuloma, pirulent inflammation) of
the respiratory tract and erosion/ulceration in the mucosa of the
glandular stomach was observed at the LOAEL of 61 mg/kg/day. An acute
dietary assessment was not conducted by the Agency because no
appropriate endpoints were identified that represent a single dose
effect.  

Of all scenarios quantitatively evaluated, none of the calculated % cPAD
values exceeded 100%.  For application to hard surfaces in food
processing plants, the % cPAD values assuming a 10% transfer rate from
the treated hard surface to food (from FDA Sanitizing Guidelines) were
0.96% for adult males, 1.12% for adult females, and 4.47% for children.
Assuming a 100% transfer rate, the % cPADs were 9.57 for adult males,
11.17% for adult females, and 44.67% for children. For application to
adhesives in papermaking, the % cPAD values were 0.00019% for adult
males, 0.00022% for adult females, and 0.00044% for children.  For
application to papermillpaper mill process water systems as a slimicide,
the % cPAD values were 10.0% for adult males, 11.7% for adult females,
and 23.4% for children. At this time, therefore, the Agency has no
concerns for the use of  glutaraldehdye, as indicated by the application
rates for the scenarios listed.

	

Dietary exposures from general agricultural premise use and poultry
hatcheries (including egg sanitization) are expected to be much lower
than the dietary exposures resulting from representative uses
quantitatively assessed.  Agricultural premise uses involve the
application of a pesticide chemical to hard surfaces in barns and animal
houses. These uses involve application to the physical structure of the
premises (including floors and walls) and also include, but not limited
to, empty watering troughs and feed troughs, animal halters, ropes and
forks. Poultry hatcheries are not used in the production of eggs for
food-grade eggs for human consumption. Hatchery eggs are used for the
production of chicks.  Sanitizer chemicals could penetrate the egg shell
and become a residue in the developing chick.  Due to growth dilution in
growing birds, any residues that penetrate the egg shell and occur in
the chick would not be expected to be detectable in birds that are ready
for consumption. In the absence of any adverse data at this time, the
Agency has no concerns for the agricultural uses listed.  [Delete.  Note
food use, based on current agency guidance and regulation.  See Dietary
Risk Assessment Chapter,]

Glutaraldehyde can also be used on conveyor belts in food processing
plants. This use was determined to be a non food-contact use and,
therefore, was not quantitatively assessed.  

Table 11. Cumulative Estimated Dietary Intake (EDI)/ Daily Dietary Dose
(DDD) and % cPADs for GA from INDIRECT Food uses

Use	Dietary Concentration (ppm)	Estimated Daily Intake (mg/person/day
Daily Dietary Dose(mg/kg/day)	% cPAD

Counter top/ disinfectant	536	0.112 (adult)

0.112 (child)	0.001 (adult)

0.007 (child)	1.0

4.67

Adhesives 	1000	2.10E-05 (adult)

 1.05E-05 (child)	 3.00E-07  (adult)

  7.00E-07 (child)	 0.00019

 0.00044

Pulp/Paper slimicide use 	 750	 0.021 (adult)

  0.0105 (child)	 0.0003 (adult)

  0.0007 (child)	 0.185

 0.438

Pigment/filler paper and paperboard	 300	 0.0015 (adult)

 0.00075 (child)	 0.000022 (adult)

 0.000051 (child)	 0.014

0.032

Paper coatings	300	0.045 (adult)

  0.0225 (child)	 0.00064 (adult)

 0.0015 (child)	 0.4

0.94

 

Cumulative	2886	0.179 (adult)

 0.145 (child)	 0.0019  (adult)

 0.009  (child)	 1.1

 5.62

DIETARY EXPOSURE ASSESSMENT FOR CONVENTIONAL (AGRICULTURAL) Uses of GA 
[The use of the term “conventional (agricultural)” is not consistent
with any Agency guidance, regulation, or practice.   This term and this
whole following section should be deleted.]

Dietary exposures from general agricultural premise use and poultry
hatcheries (including egg sanitization) are expected to be much lower
than the dietary exposures resulting from representative uses
quantitatively assessed.  Agricultural premise uses involve the
application of a pesticide chemical to hard surfaces in barns and animal
houses. These uses involve application to the physical structure of the
premises (including floors and walls) and also include, but not limited
to, empty watering troughs and feed troughs, animal halters, ropes and
forks. Poultry hatcheries are not used in the production of eggs for
food-grade eggs for human consumption. Hatchery eggs are used for the
production of chicks.  Sanitizer chemicals could penetrate the egg shell
and become a residue in the developing chick.  Due to growth dilution in
growing birds, any residues that penetrate the egg shell and occur in
the chick would not be expected to be detectable in birds that are ready
for consumption. In the absence of any adverse data at this time, the
Agency has no concerns for the agricultural uses listed.

Glutaraldehyde can also be used on conveyor belts in food processing
plants. This use was determined to be a non food-contact use and,
therefore, was not quantitatively assessed.  

		

5.0 AGGREGATE RISK ASSESSMENT 

In order for a pesticide registration to continue, it must be shown
“that there is reasonable certainty that no harm will result from
aggregate exposure to pesticide chemical residue, including all
anticipated dietary exposures and other exposures for which there are
reliable information.”   Aggregate exposure is the total exposure to a
single chemical (or its residues) that may occur from dietary (i.e.,
food and drinking water), residential, and other non-occupational
sources, and from all known or plausible exposure routes (oral, dermal,
and inhalation).  

In performing aggregate exposure and risk assessments, the Office of
Pesticide Programs has published guidance outlining the necessary steps
to perform such assessments (General Principles for Performing Aggregate
Exposure and Risk Assessments, November 28, 2001; available at
http://www.epa.gov/pesticides/trac/science/aggregate.pdf).  Steps for
deciding whether to perform aggregate exposure and risk assessments are
listed, which include: identification of toxicological endpoints for
each exposure route and duration; identification of potential exposures
for each pathway (food, water, and/or residential);  reconciliation of
durations and pathways of exposure with durations and pathways of health
effects; determination of which possible residential exposure scenarios
are likely to occur together within a given time frame; determination of
magnitude and duration of exposure for all exposure combinations;
determination of the appropriate technique (deterministic or
probabilistic) for exposure assessment; and determination of the
appropriate risk metric to estimate aggregate risk

With the exception of the incidental oral endpoint, the chronic dietary
endpoint, dermal endpoint, and inhalation endpoints are all based upon
different studies and toxicological effects. There are no incidental
oral exposure scenarios identified for glutaraldehyde.  On this basis,
no aggregation of exposures areaggregation of exposures is performed and
risks are as expressed for each scenario identified already in this risk
assessment.  

5.1 Acute and Chronic Dietary Aggregate Risk

As noted, there was no acute dietary endpoint identified for
glutaraldehyde and only a chronic dietary endpoint was selected.
Drinking water exposure is not expected to be of concern. Therefore,
dietary risks are as identified for the antimicrobial and agricultural
uses of glutaraldehyde already discussed in this risk assessment. There
are no aggregate exposures and risks necessary for acute or chronic
dietary exposures 

 

5.2 Short-and Intermediate-Term Aggregate Risk

 As noted, there were no incidental oral exposure scenarios identified
for glutaraldehyde in this risk assessment. Further, dermal and
inhalation endpoints were selected from different studies. Thus, no
aggregation is necessary.

 

6.0  	CUMULATIVE RISK

FQPA (1996) stipulates that when determining the safety of a pesticide
chemical, EPA shall base its assessment of the risk posed by the
chemical on, among other things, available information concerning the
cumulative effects to human health that may result from dietary,
residential, or other non-occupational exposure to other substances that
have a common mechanism of toxicity.  The reason for consideration of
other substances is due to the possibility that low-level exposures to
multiple chemical substances that cause a common toxic effect by a
common mechanism could lead to the same adverse health effect as would a
higher level of exposure to any of the other substances individually.  A
person exposed to a pesticide at a level that is considered safe may in
fact experience harm if that person is also exposed to other substances
that cause a common toxic effect by a mechanism common with that of the
subject pesticide, even if the individual exposure levels to the other
substances are also considered safe.

AD did not perform a cumulative risk assessment as part of this RED for
GA because AD has not yet initiated a review to determine if there are
any other chemical substances that have a mechanism of toxicity common
with that of GA.  Some published experimental evidence regarding
carcinogenicity of glutaraldehyde (Hester et al., 2005) suggests that
glutaraldehyde may act differently than related aldehydes with respect
to carcinogenicity.  For purposes of this RED, EPA has assumed that GA
does not have a common mechanism of toxicity with other substances.

On this basis, the Registrant must submit, upon EPA’s request and
according to a schedule determined by the Agency, such information as
the Agency directs to be submitted in order to evaluate issues related
to whether GA shares a common mechanism of toxicity with any other
substance.   If AD identifies other substances that share a common
mechanism of toxicity with GA, AD will perform aggregate exposure
assessments on each chemical, and will begin to conduct a cumulative
risk assessment. 

The Health Effects Division, Office of Pesticide Programs, has recently
developed a framework proposed for conducting cumulative risk
assessments on substances that have a common mechanism of toxicity. 
This guidance was issued for public comment on January 16, 2002 (67 FR
2210-2214) and is available from the OPP Website at: 
http://www.epa.gov/pesticides/trac/science/cumulative_guidance.pdf.  In
the guidance, it is stated that a cumulative risk assessment of
substances that cause a common toxic effect by a common mechanism will
not be conducted until an aggregate exposure assessment of each
substance has been completed.

Before undertaking a cumulative risk assessment, AD will follow
procedures for identifying chemicals that have a common mechanism of
toxicity as set forth in the (Guidance for Identifying Pesticide
Chemicals and Other Substances that Have a Common Mechanism of Toxicity(
(64 FR 5795-5796, February 5, 1999).

7.0	OCCUPATIONAL EXPOSURE AND RISK   [See comments in previous sections
and in ORE Chapter.  EPA has used inaccurate vapor pressure values,
failed to account for glutaraldehdye’s short-half life in air, relied
on an incorrect endpoint, and inappropriate data.  The risk assessments
all must be redone.]

A complete explanation of the occupational exposure and risk assessment
can be found in the supporting disciplinary chapter entitled
Occupational and Residential Exposure Assessment for Glutaraldehyde
(D324565). Summary information is provided in this section.

 

There are several occupational handler exposure scenarios that involve
glutaraldehyde (GA) products.  The mixer/loader scenarios   involve the
manual or automatic addition of GA products to industrial processes. 
The mixer/loader/applicator handler   involvehandler   involves the
mixing/loading and/or application of dilute solutions of GA to poultry
houses or medical hard surfaces.

Most of the available exposure data are from short term samples of
approximately 15 minutes in duration and they were taken as a comparison
to the ACGIH TLV of 50 ppb.    Although many of the short term samples
exceeded the RfC of 0.32 ppb, these samples are not comparable to the
RfC because the un-sampled periods probably had lower exposures than the
sampled period.

The drumming samples prior to 1989 were taken over a full shift and the
results ranged from 10 to 170 ppb.   All of these samples exceeded the
short term RfC of 0.32 ppb.

Professional Painter Inhalation Exposure Assessment

In this section, the professional painter inhalation exposure to GA
vapors during paint activities was assessed (Table 12).  HED utilized
EPA’s WPEM Model to estimate air concentrations resulting from the use
of paint preserved with GA.  For this professional painter exposure
assessment, the WPEM default scenario (RESPROF) for the professional
painter was used.  This RESPROF scenario assumes that two professional
painters are exposed to a chemical in paint while painting an entire
apartment in a work day.  A detailed description of the RESPROF scenario
is in the WPEM User’s Guide.  The following chemical-specific inputs
were used:

The molecular weight of GA is 100 amu and the vapor pressure is 0.10 mm
Hg. [Inaccurate.]

The weight fractions of Glutaraldehyde in paint are 0.0001 or 0.001
based upon the application rates of 100 or 1000 ppm.

No factoring of short half-life.

Since professional painters can paint indoors on a year round basis only
long term exposures were assessed.   Because the C-8hour air
concentrations exceed the long term RfC of 0.015 ppb, the inhalation
exposures are of concern at both the maximum and minimum application
rate.  The C15-min air concentrations also exceed the TLV of 50 ppb.

Table 12.   Inhalation Risk Summary for Occupational Painters

Application Rate	Painted Surface Area	Air Exchange Rate 	Hours per Day
C15-minA

(ppb)	ACGIH TLV

(ppb)	C-8hourB

(ppb)	Long Term RfC (ppb)

1000 ppm	2131 f2

(one apartment)	0.45 per hour	8	680	50	540	0.015

100 ppm

68

54

	A.  Maximum 15 minute average air concentration.

B.  Maximum 8 hour average air concentration.

Air concentrations in bold font are concern because they exceed the TLV
and the RfC. 

Medical Clinic Hard Surface Cleaning Inhalation Exposure Assessment

There are three products (15136-9, 55195-3 and 55194-5) which are used
to clean non-critical hard surfaces in medical clinics, dental clinics
and veterinary offices.  Two of theses products are RTU sprays and one
is an RTU wipe.  In this section, worker inhalation exposure to GA
vapors during hard surface cleaning with these products was assessed   
HED utilized EPA’s Consumer Exposure Module (CEM) to estimate air
concentrations resulting from the use of glutaraldehyde as a general
purpose cleaner (Table 13).    Detailed information and the executable
model can be downloaded from http://www.epa.gov/opptintr/exposure  

 

The following chemical-specific inputs were used in the model:

The molecular weight of GA is 100 and the vapor pressure is 0.10 mm Hg. 
[Inaccurate.]

The weight fraction of GA is 0.00275 (0.275%) as stated on the product
labels.

The mass of product used is 123 grams which is a default assumption in
CEM.

The minimum air exchange rate of 0.45 air changes per hour (ACH) is
based upon the assumption that a clinic would be located in a residence.

The maximum air exchange rate of 4 ACH based upon the assumption that a
clinic would be located in a well ventilated hospital building.

No recognition of short-half life in air.

It should be noted that CEM calculates daily exposures as a 24 hour
TWAs.  The 24 TWAs were converted to 8 hour TWAs by assuming that all of
the exposure occurs during the workday.  Since medical surface cleaners
can be used on a year round basis, only long term exposures were
assessed.  Because the 8 hour time weighted average (TWA) air
concentrations exceed the long term RfC of 0.015 ppb, the inhalation
exposures are of concern at both the low and high air exchange rates. 
The peak exposure is also of concern at the low air exchange rate
because it exceeds the ACGIH TLV of 50 ppb.

Table 13.  Inhalation Risk Summary for Medical Hard Surface Cleaning

Weight Fraction	Amount of Product Used	Duration of Use	Air Exchange Rate
Peak Concentration (ppb)	ACGIH TLV (ppb)	24 Hour TWA (ppb)	8 Hour TWA
(ppb) 	Long Term RfC (ppb)

0.00275	123 grams	1.42 hours	0.45	130	50	26	78	0.015

	4	21

0.033	10

	

Air concentrations in bold font are of concern because they exceed the
TLV and/or the RfC.

Occupational Post-application Exposures   

Fogging Exposure Assessment

 tc \l3 "6.2.3	Fogging 

GA is used for fogging poultry houses in preparation for a new flock of
birds.   Exposures to GA can occur after fogging when the workers
re-enter the fogged area to finish cleanup.  Only inhalation exposures
were assessed, because dermal post application exposures are  presumed
to be negligible because the GA evaporates rapidly from the fog as
predicted by the Aero-Evap model presented in MRID 468822-07 (McCready,
2004).   The inhalation exposure assessment was conducted using the
single chamber decay formula from the Multi-Chamber Concentration and
Exposure Model (MCCEM v1.2).   This assessment was based upon the
application parameters listed in the Virocide Label (EPA Reg #71355-1)
because this label has the most explicit instructions for fogging
application.  The following assumptions were made:

The area being fogged is a one-chamber barn with dimensions of 300 ft
x50 ft x10 ft (AD standard assumption).  

The air exchange rate is 4 air changes per hour. (Jacobson, 2005).  

Fogging occurs instantaneously, so that the entire mass of product is
mixed homogeneously with the indoor air as soon as fogging commences. 

The concentration of the fogging solution is 2.1 percent GA.  This is
based upon the dilution rate of 1 part product per 4 parts water times
from label #71355-1 which contains 10.725% GA.

The application rate of fogging solution is 125 ounces per 1000 cubic
yards (yd3) based upon label #71355-1.

The application rate in terms of ai is 0.17 lb ai per 1000 yd3 based
upon the following: 

	(125 oz applied per 1000 yd3 / 128 oz per gallon) x (8.35 lb per gallon
* 2.1% ai)

The initial concentration is 101 mg/m3 (25,000 ppb) based upon the
following:

	(0.17 lb ai * 454,000 mg per lb) / (1000 yd3 * 0.764 m3 per yd3)

The calculations show that  thethat the air concentrations decline to
less than the TLV in 94 minutes and to less than the RfC in 170 minutes
(Table 14). 

Table 14.  Glutaraldehyde Air Concentrations After Fogging a Poultry
House

Elapsed Time (minutes)	Air Concentration 

(ppb)	Relevant Standard 

(ppb)

0	25,000 	50 - ACGIH TLV 

94 	47 	50 - ACGIH TLV of 50

170 	0.030 	0.032 - EPA Short Term RfC 

Metal Working Fluids Exposure Assessment tc \l3 "6.2.2	Metal Working
Fluids, Machinist 

Dermal Exposure

	

There is a potential for dermal exposure when a machinist handles
treated metalworking fluids.  This exposure occurs after the
glutaraldehyde has been added to the metal working fluid which is used
by a machinist.  The dermal exposures were assessed by comparing the
concentrations in the treated metal working fluids with the
concentrations used in the dermal toxicity studies.  This comparison is
shown in Table 15 below and indicates that the dermal exposures are of
concern at the high application rate of 270 ppm (0.027 percent) because
the MOE of 92 is less than the target MOE of 100.  The dermal exposures
are not of concern at the low application rate of 36 ppm (0.0036
percent) because the MOE exceeds 100.

Table 15.  Dermal Risks from Machining Fluids Treated with
Glutaraldehyde

Application Rate (ppm)	Application Rate 

(Percent)	Glutaraldehyde NOAEL	NOAEL ConcentrationA	MOEB

270 	0.027	50 mg/kg/day

	2.5%	92

690

36 	0.0036

	A. The concentration of glutaraldehyde in the test solution applied at
the NOAEL dose.

B. MOE =  NOAEL Concentration (percent) / Application Rate (percent)

8.0      ENVIRONMENTAL RISK

8.1 Ecological Hazard

Detailed information on the  ecological hazard and environmental risk
assessment for glutaraldehhyde can be found in the ecological hazard and
environmental risk assessment chapter by Richard C. Petrie. Here only
summary information is provided. 

Based on results from MRID 117070, glutaraldehyde is slightly toxic to
avian species on an acute oral basis.  The study fulfills guideline
requirements for a formulated product or TGAI of 50% (850.2100).  

A subacute dietary study using the TGAI may be required on a
case-by-case basis depending on the results of lower-tier ecological
studies and pertinent environmental fate characteristics in order to
establish the toxicity of a chemical to avian species.  This testing was
required for the indoor and aquatic industrial uses of glutaraldehyde. 
Results of these studies indicate that glutaraldehyde is practically
non-toxic to avian species on a subacute dietary basis.  Four of the
studies (MRIDs 117071, 125519, 117072, and 125520) qualify as fulfilling
the guideline requirement for a formulated product or TGAI of 50%
(850.2200).

Results of freshwater fish acute studies submitted for glutaraldehyde
indicate that glutaraldehyde is slightly toxic to warmwater fish and
moderately to slightly toxic to coldwater fish on an acute basis.  These
studies fulfill guideline requirements for a formulated product or TGAI
of 50% (850.1075). The acute toxicity of glutaraldehyde, complexed with
sodium bisulfite and dibasic ammonium phosphate (DAP) at varying
concentrations was also investigated.  Results of two studies indicate
that deactivation with sodium bisulfite reduces the acute toxicity of
glutaraldehyde to warmwater fish when compared to untreated
glutaraldehyde.  Not enough information was provided to assess the
efficacy of DAP.  Both studies fulfill guideline requirements for an
acute toxicity test using the fathead minnow (850.1075).

Results of three studies on toxicity of glutaraldehyde to freshwater
invertebrates showed that glutaraldehyde is highly to slightly toxic to
freshwater invertebrates.  The guideline requirement has been fulfilled
(850.1010) by these studies. The acute toxicity to Daphnia magna of
glutearaldehyde complexed with sodium bisulfite, sodium hydroxide, and
DAP at varying concentrations was also investigated. The results of
study MRID 436457-01 indicates that the acute toxicity of
glutearaldehyde to freshwater invertebrates is reduced after treatment
with DAP.  Not enough information was provided in the two supplemental
studies concerning the detoxification process of sodium bisulfite (MRID
442108-01) and sodium hydroxide (MRID 442197-01/443358-01) to determine
the adequacy of the test results.  

Acute toxicity testing with estuarine and marine organisms using the
TGAI is required in order to conduct a risk assessment for uses having
potential environmental exposure such as industrial wastewater from pulp
and paper mills, and once-through cooling towers.  Results of seven
submitted toxicity studies indicate that glutaraldehyde is slightly
toxic to estuarine/marine fish and slightly to moderately toxic to
shrimp on an acute basis.  Glutaraldehyde is highly toxic to oysters
(MRIDs 42952101, 43640301).  The studies fulfill guideline requirements
for acute toxicity to estuarine/marine animals (850.1035, 850.1055, and
850.1075).

Chronic toxicity testing (fish early life stage, 850.1400 and aquatic
invertebrate life cycle, 850.1300) is required for pesticides when
certain conditions of use and environmental fate apply.  The preferred
freshwater fish test species is fathead minnow, but other species may be
used.  The preferred freshwater invertebrate is Daphnia magna. 
Environmental fate data for glutaraldehyde indicates that it is likely
to degrade quickly in water; thus, the chronic Daphnia magna test is
held in reserve pending further analysis of glutaraldehyde fate in the
environment.....  Results of chronic toxicity tests for glutaraldehyde
in the open literature indicate that continuous exposure results in
measurable effects on coldwater fish at a concentration of 5.1 mg
a.i./L.  This study fulfills guideline requirements for a fish early
life stage chronic test (850.1400).  A second study on coldwater fish
resulted in measurable effects at 2.5 mg a.i./L.  However, this study
(MRID 46664-03) was classified as supplemental and does not fulfill
guideline requirements.  Measurable effects on freshwater invertebrates
were noted at concentrations of 8.5 mg/L product and 4.9 mg a.i./L. 
However, both studies (MRID 421125-01 and MRID 466604-03) were
classified as supplemental and do not fulfill guideline requirements for
an aquatic invertebrate life cycle test.

Nontarget plant phytotoxicity tests are required for pesticides when
certain conditions of use and environmental fate apply.  Testing is
conducted with a rooted vascular plant rice (Oryza sativa), an aquatic
floating vacular macrophyte (Lemna gibba), and four species of algae: 
(1)  freshwater green alga, Selenastrum capricornutum - Pseudokershneria
subcapitatum, (2)  marine diatom, Skeletonema costatum, (3)  freshwater
diatom, Navicula pelliculosa, and (4)  bluegreen alga, Anabaena
flos-aquae.  

These tests, while reserved, are not required for uses of glutaraldehyde
classified as

indoor; however, they are required in order to conduct a nontarget plant
phytotoxicity 

risk assessment for industrial discharges or uses having environmental
exposure or if 

exposure concerns arise.  Results of available freshwater green algae
toxicity studies 

indicates that a 50% reduction in growth in green alga occurred at a
glutaraldehyde 

concentration of 0.31 mg a.i./L.  However, this study was classified as
supplemental and 

does not fulfill guideline requirements.  The light intensity used in
the study was too 

high, and the corresponding algal growth rate was too fast.

The acute toxicity of glutaraldehyde, complexed with sodium hydroxide
and sodium bisulfite, was also investigated. The results indicate that
both sodium hydroxide and sodium bisulfide can serve to reduce algal
toxicity when used in conjunction with glutaraldehyde.  Sodium bisulfite
was slightly less toxic than sodium hydroxide.  This study does not
fulfill guideline requirements.  

   Environmental fate and Transport

Data indicate that the hydrolysis of glutaraldehyde is pH and
temperature dependent.  Glutaraldehyde is hydrolytically stable under
abiotic and acidic to neutral conditions, but degrades more rapidly in
alkaline environments, forming a cyclic dimmer.  Also, the stability of
glutaraldehyde decreases as the temperature increases.  At 25(C,
glutaraldehydes degrades with half-lives of 628, 394, and 63.8 days at
pH levels of 5, 7, and 9, respectively.  At 70(C hydrolysis of
glutaraldehyde proceeds more rapidly with half-lives of 53, 6.5, and
0.23 days at pH levels of 5, 7, and 9, respectively.   Photolytically,
glutaraldehyde degrades slightly in natural sunlight at 25(C in a pH 5
buffered aqueous solution with a calculated half-life of 195 days. 
Based on its stability, glutaraldehyde may be of concern as a
contaminant in surface water runoff.

When glutaraldehyde is introduced into the environment, it is most
likely to remain in the aquatic compartment, given the small air/water
partition and soil/water partition coefficients.  Aquatic metabolism,
under aerobic and anaerobic conditions, and aerobic soil metabolism are
major routes of dissipation of glutaraldehyde. The calculated aerobic
and anaerobic pseudo first-order half-lives of glutaraldehyde in flooded
river sediment are 10.6 and 7.7 hours, respectively.  Glutaraldehyde
meets the OECD criteria for classification as readily biodegradable in
freshwater environments and as having the potential to be biodegradable
in marine environments.  Because of its biodegradation, glutaraldehyde
is not likely to contaminate surface and ground waters.

Glutaraldehyde’s tendency to bind with agricultural soils varies
according to soil type.  Glutaraldehyde is very mobile in loam, silt
loam, and clay loam soils; and is mobile in loamy sand soil. The
Freundlich  Kadsorp  and  Kdesorp values range from 0.183-6.3 and
0.278-1.55, respectively.  Based on its Kadsorp and Kdesorp values, and
the tendency for glutaraldehyde to partition into the water phase,
glutaraldehyde is not likely to contaminate soils.  There may be a
water/sediment partitioning issue and acute adverse impacts on benthic
organisms.  However, glutaraldehyde degrades fairly rapidly in
freshwater and soils, and the impacts may be short-lived. 

Environmental Exposure and Risk

Freshwater and estuarine/marine aquatic animals and plants could
potentially be exposed to glutaraldehyde discharged into the aquatic
environment.  Screening level modeling was conducted to estimate the
exposure and environment risk resulting from industrial wastewater
releases of glutaraldehyde into surface water following registered use
in once-through cooling towers.  This site was selected as having
maximum potential for environmental exposure of all labeled
glutaraldehyde sites.  An analysis of glutaraldehyde use by the
University of Michigan and the Great Lakes Research Laboratory, NOAA
indicates that most current applications of glutaraldehyde result in
relatively infrequent environmental releases over limited spatial areas
(MRID 466664-03).  

Endangered Species Consideration

 Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2),
requires all federal agencies to consult with the National Marine
Fisheries Service (NMFS) for marine and andronomus listed species, or
the United States Fish and Wildlife Services (FWS) for listed wildlife
and freshwater organisms, if they are proposing an "action" that may
affect listed species or their designated habitat.  Each federal agency
is required under the Act to insure that any action they authorize,
fund, or carry out is not likely to jeopardize the continued existence
of a listed species or result in the destruction or adverse modification
of designated critical habitat.  To jeopardize the continued existence
of a listed species means "to engage in an action that reasonably would
be expected, directly or indirectly, to reduce appreciably the
likelihood of both the survival and recovery of a listed species in the
wild by reducing the reproduction, numbers, or distribution of the
species." 50 C.F.R. ( 402.02.

To facilitate compliance with the requirements of the Endangered Species
Act subsection (a)(2) the Environmental Protection Agency, Office of
Pesticide Programs has established procedures to evaluate whether a
proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed
species in the wild by reducing the reproduction, numbers, or
distribution of any listed species (U.S. EPA 2004).  After the Agency(s
screening-level risk assessment is performed, if any of the Agency(s
Listed Species LOC Criteria are exceeded for either direct or indirect
effects, a determination is made to identify if any listed or candidate
species may co-occur in the area of the proposed pesticide use.  If
determined that listed or candidate species may be present in the
proposed use areas, further biological assessment is undertaken.  The
extent to which listed species may be at risk then determines the need
for the development of a more comprehensive consultation package as
required by the Endangered Species Act.

For certain use categories, the Agency assumes there will be minimal
environmental exposure, and, therefore, only a minimal toxicity data set
is required (Overview of the Ecological Risk Assessment Process in the
Office of Pesticide Programs U.S. Environmental Protection Agency -
Endangered and Threatened Species Effects Determinations, 1/23/04,
Appendix A, Section IIB, pg.81).  Chemicals in these categories
therefore do not undergo a full screening-level risk assessment, and are
considered to fall under a (no effect( determination.  The majority of
glutaraldehyde uses are spray applications to indoor surfaces such as
hospital, veterinary, nursing home, and food processing plant equipment
and is not expected to result in significant discharge into the
environment.  

PDM4 modeling indicates that glutaraldehyde discharges under a number of
modeled scenarios are may adversely affect endangered/threatened fish
and aquatic invertebrates (both freshwater and marine).  For
endangered/threatened species, freshwater/marine invertebrates and green
algae are at risk from all modeled scenarios.  Glutaraldehyde is
expected to be acutely toxic to endangered/threatened fish, all modeled
scenarios, except for the low maintenance dosage having medium stream
flow.  The Agency is not currently aware of any endangered or threatened
green alga species, however, the non-target plant risk assessment is
incomplete due to outstanding data for other aquatic plant species.  

Factors that serve to reduce discharge impacts on aquatic species
include the NPDES permitting process, rapid glutaraldehyde breakdown in
the environment, and relatively short term impacts on aquatic ecosystems
from currently registered uses.  The PDM4 model does not account for
degradation rates of glutaraldehyde in soil or water.  An endangered
species determination cannot be made at this time and will be deferred
until confirmatory data are made available.  

INCIDENT REPORT ASSESSMENT	

The Following databases were consulted for poisoning incidence data on
glutaraldehyde: 

Office of Pesticides Programs (OPP) Incident Data System (IDS)

Poison Control Centers

California Department of Pesticide Regulations

National Pesticide Telecommunications Network (NTPT)

Published Scientific Literature on Incidences

9.1	OPP’s Incident Data System (IDS)		

A total of 267 human incident cases submitted to the Office of Pesticide
Programs were associated with exposure to glutaraldehyde.  The most
common symptoms reported for cases of dermal exposure were skin
irritation/burning, rash, itching, skin discoloration/redness,
blistering.  The most common symptoms reported for cases of inhalation
exposure were respiratory irritation/burning, irritation to
mouth/throat/nose, coughing/choking, shortness of breath, and sore
throat.

9.2	Poison Control Center	

There were no glutaraldehyde-specific incidents reported in the Poison
Control Center database. 

9.3	California Data- 1982-through 2003.			

A total of 403 incidents were reported in the California Pesticide
Surveillance Program Database (1982-2003) as definitely or probably
glutaraldehyde related (Mehler, 2005).  [This is a personal
communication.  Provide a formal written reference,]  Symptoms
associated with eyes were the primary localized symptoms reported  in
all of the associated incidents.  The primary systemic effects reported
were nausea, dizziness, headache, and sore throat [not a system
effect.]. The primary dermal effects reported were rash, burning
sensation, numbness, itching, and discolored (white/brownish) skin.    

    National Pesticide Telecommunications Network (NPTN) 		

There were no reported incidents  in the NPTN database related to
glutaraldehyde exposure.

Published Scientific Literature  [It should be noted that the effects
reported are associated with use for high level
disinfection/sterilization, where use rates are significantly higher
than those occurring in industrial and residential sites and where use
scenarios are significantly different.]

 Vyas et al. (2000) reported on 348 nurses from endoscopy units in
hospitals in the United Kingdom who were surveyed for symptoms possibly
related to glutaraldehyde exposure.  Forty-four percent reported work
related contact dermatitis, 13.5% reported eye irritation, 19.8%
reported nose irritation and 8.5% reported lower respiratory symptoms. 
In another survey of 167 nurses exposed to glutaraldehyde, 49%
complained of eye irritation, 41% complained of skin discoloration or
irritation, 36% complained of headache and 34% complained of a cough or
shortness of breath (Calder et al., 1992).  Yet another survey of 150
staff in two hospitals who were exposed to glutaraldehyde showed that
30.7% had runny eyes, 22.7% skin irritation, 18.7% runny nose, 16.7%
discoloration of the skin, 14.7% upper respiratory tract irritation,
14.0% cough, 11.3% unpleasant taste, 9.3% wheezy chest and 3.3% chronic
dermatitis (Waldron, 1992).  A fourth survey of 135 endoscopy nurses in
Australia found that nurses exposed to glutaraldehyde were significantly
more likely to report headache, lethargy and skin, eye and throat
symptoms compared with controls (Pisaniello et al., 1997).  When a
hospital in Nairobi switched to glutaraldehyde for instrument
decontamination, doctors reported itchy and watery eyes as well as
sneezing and nasal irritation whereas nurses reported periorbital
swellings, itching and watery eyes, headaches, nausea, skin swelling,
coughing, breathlessness and wheezing, acute rhinitis and bronchitis
(Mwaniki and Guthua, 1992). A nurse in charge of an endoscopy unit in
Great Britain was frequently exposed to glutaraldehyde and reported
irritant conjunctivitis as well as increasing breathlessness (Benson,
1984).

There is evidence that glutaraldehyde can cause occupational asthma.  In
one specific case, a 46-year-old endoscopy nurse developed symptoms of
occupational asthma after seven years of exposure to glutaraldehyde
(Stenton et al., 1994).  Another case in Australia has been documented
of a nurse who cleaned equipment with glutaraldehyde and developed
occupational asthma, including an irritating cough and frequent episodes
of upper respiratory tract symptoms (Loats, 1995).  There was
considerable improvement in her symptoms after she had been away for a
year on maternity leave, but after the maternity leave the symptoms
returned including a cough that produced yellow sputum, wheezing and a
rash on her arms (Issues in Occupational Health and Safety, 1995).  One
study reported seven cases of occupational asthma due to glutaraldehyde
in endoscopy and x-ray departments (Gannon et al., 1995).  Another
report from Britain states that here were thirty recorded cases of
occupational asthma due to glutaraldehyde in the period from 1989 to
1991.  All cases were in health care workers (Menzies, 1995).  Di
Stefano et al. (1999) report on a series of 24 health care workers with
respiratory symptoms suggestive of occupational asthma due to
glutaraldehyde exposure.  In eight of the workers, the diagnosis was
confirmed.  

Products containing glutaraldehyde can be used in dentists’ offices as
hand dips to prevent transmission of microbes between a dentist’s
hands and a patient’s mouth.  Sporicidin is one such product.  It has
been reported (Little, 1986) that while Sporicidin is effective, the
dermal irritation, sensitivity and yellowing caused by its use is
objectionable.  Ten of the eleven participants in this five-day study
who dipped their hands in Sporicidin experienced some degree of
irritation, sensitivity or yellowing of the skin.  In another case at a
dentist’s office, a 36-year-old dental nurse was seen for an intensely
itchy eczema on the hands, arms and face.  She was found to be allergic
to glutaraldehyde and benzalkonium chloride (Cusano and Luciano, 1993). 
An orthodontic patient received a chemical burn in her mouth when a
dental instrument was used that had not been thoroughly rinsed after
being sterilized in a solution containing glutaraldehyde (Moore and
Igel, 1988).  

One study documented a case where a radiologist and an x-ray technician
both exhibited chronic, fissured dermatitis of the fingers and both had
strongly positive patch test reactions to a 1% aqueous glutaraldehyde
solution.  With greater care to avoid exposure, their dermatitis healed
(Fisher, 1981).

Glutaraldehyde is also a dermal sensitizer.  In one study (Shaffer and
Belsito, 2000), 468 people were patch tested to glutaraldehyde.  A
comparison of the results was made between those employed in a
healthcare related field and those who were not.  Health care workers
were 8x as likely to be allergic to glutaraldehyde as people working in
other fields.  Two hospital workers acquired an allergic contact
dermatitis of the hands after disinfecting endoscopes with Sporicidin. 
Both showed strong positive reactions to a 1% aqueous solution of
glutaraldehyde (Fisher, 1990).  Three cleaning women used Cidex, a
glutaraldehyde containing product, for disinfecting crockery.  About six
months after starting its usage, they developed an itchy
papulo-vesicular reaction on the backs of their hands and forearms. 
Their lesions improved on holidays and weekends.  A 50-year-old woman
who worked on the cleaning and disinfection of endoscopy material
developed the same kind of vesicular dermatitis four months after
starting the work and improved after stopping the work.  A 39-year-old
female nurse also developed an eczematous reaction on her hands,
forearms, face and neck after using Cidex to sterilize hemodialysis
equipment for several months (Goncalo et al., 1984).  A 51-year-old male
who worked as a cleaner in a hospital developed eczematous dermatitis on
the hands four months after Cidex had been introduced for the
disinfection of surgical instruments.  He used rubber gloves (Di Prima
et al., 1988).  A 25-year-old surgical instruments nurse developed
chronic dermatitis of both hands with marked dryness, redness,
infiltration and fissures.  Patch testing showed a strong positive to
Cidex.  A 34-year-old nurse responsible for the disinfection of
endoscopy instruments with Cidex developed contact dermatitis 6 months
after starting with redness, dryness and hyperkeratosis of her hands and
feet.  Patch tests again were again positive for Cidex and
glutaraldehyde (Bardazzi et al., 1986).  Another product containing
glutaraldehyde, Korsolin, was blamed for the development of dermatitis
and eczema on the hands and forearms of a 50-year-old cleaning woman and
a 42-year-old assistant nurse in an intensive care section of a
hospital.  They gave positive patch tests to glutaraldehyde (Hansen,
1983).  A 22-year-old woman using a hair conditioner containing
glutaraldehyde at less than 1% was treated for acute and chronic
eczematous changes to the scalp with secondary infection and hair loss. 
This began when she began using the glutaraldehyde containing
conditioner.  She was patch tested for glutaraldehyde and tested
positive.  Once she discontinued use of the conditioner, her hair grew
back (Jaworsky et al., 1987).  Glutaraldehyde can have very serious
effects on the skin including deep ulcers that leave a scar as in the
case of a young woman who applied 25% aqueous glutaraldehyde nightly for
2 weeks as a treatment for warts (Turner, 1983).

Other symptoms that may be brought on by glutaraldehyde exposure include
heart palpitations and tachycardia (Connaughton, 1993).  

There was a case of keratopathy induced by a Hoskin lens, which had been
inadequately rinsed after soaking in buffered glutaraldehyde.  This
happened to an 88-year-old woman who underwent cataract extraction. 
When the Hoskin lens was placed, a white plaque formed that covered one
third of her cornea.  The next day the upper third of the cornea was
opaque and edemous.  The surgeon also noticed a painless white lesion on
his finger where he had held the Hoskin lens.  After three weeks the
inflammation and keratopathy was resolved (Dailey et al., 1993). 
Another eye injury was documented when leakage of glutaraldehyde
occurred from an anesthesia mask and entered the eye of a 57-year-old
woman.  The fluid was thought to be tears until its odor was recognized
as glutaraldehyde.  The mask was immediately removed and the eyes
irrigated with sterile saline.  By the sixth postoperative hour, the
patient’s eyes were tearing and the eyelids were swollen. 
Conjunctival inflammation, burning pain and photophobia were also
evident.  The inflammation was completely resolved and vision back to
normal three days later (Murray and Ruddy, 1985).  

There was also a case of severe tongue swelling reported in a
67-year-old male after he had surgery under general anesthesia.  One of
the instruments used in his tracheal intubation had been sterilized in a
2% glutaraldehyde solution.  After surgery when the tube was removed,
his tongue started swelling until it filled his entire oral cavity and
forced his mouth wide open.  His tongue returned to normal size after
four hours and it was speculated that this whole episode may have been
due to prior sensitization to glutaraldehyde (Grigsby et al., 1990).

Conclusions

Human exposure to glutaraldehyde can occur by the dermal, ocular and
inhalation routes.    Most of the incidents are associated with using
glutaraldehyde in sterilization of medical or dental equipment, a use
that is under the authority of FDA.

Dermal exposure is considered a significant  route of exposure.  [EPA
must explain how dermal exposure can be assumed a significant route of
exposure when it appears that the Agency is assuming most
volatilizes/aerosolizes.  A discussion of how EPA has partitioned
available glutaraldehyde between the inhalation and dermal routes is
necessary to assure that double counting on exposure is not occurring.] 
The most common symptoms reported for cases of dermal exposure were skin
irritation/burning, rash, itching, skin discoloration/redness.  Allergic
type reactions have also been reported. Published scientific literature
also indicates that health care workers are more than 8 times more
likely to be allergic to glutearaldehyde than non-health care working
peers

Eye pain, burning of eyes, conjunctivitis, blurring vision, and acute
inflammation are the primary symptoms associated with ocular exposure
incidents.

The most common symptoms reported for cases of inhalation exposure were
respiratory irritation/burning, irritation to mouth/throat/nose,
coughing/choking, shortness of breath, dizziness.  There is evidence as
well that glutaraldehyde can cause occupational asthma.  

Other systemic effects associated with glutaraldehyde include headache,
dizziness, nausea, stomach ache, sore throats, numbness of limbs, and
cardiac effects (heart palpitations and tachycardia).



10.0  References

Product Chemistry References

40088901  Marcia Powell, 1987, Chemistry Data .  Performing Labs:
Bio-Lab, Inc. PO

                    Box 1489, Decatur, GA: 30031

40133301 Richard Gruhl and Patrick Braden, 1987, Product Chemistry
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                  Performing Lab: Pascal Company, Inc. PO Box 1478,
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                  1478

 

41161501 Product Chemistry Data, 1989 For Glutasept. Submitted by:
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42601701 Robert Baker, 1992, Product Chemistry of Technical Grade of
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42919314 Charles Anthony, 1992. Polycide. Physical and Chemical
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43519701 Jack Scoville, 1995. Product Chemistry Data.  Performing Lab:
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USEPA. 2005. Ortho Phenylphenol, and its Sodium and Potassium Salts.
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USEPA: February 2006.  End Point Selection Memo (ADTC Memo) from Tim
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