U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
SCREENING-LEVEL HAZARD CHARACTERIZATION
Isocyanic Acid, /w-phenylenediiso-propylidene (CASRN: 2778-42-9)
The High Production Volume (HPV) Challenge Program1 was conceived as a voluntary
initiative aimed at developing and making publicly available screening-level health and
environmental effects information on chemicals manufactured in or imported into the United
States in quantities greater than one million pounds per year. In the Challenge Program,
producers and importers of HPV chemicals voluntarily sponsored chemicals; sponsorship
entailed the identification and initial assessment of the adequacy of existing toxicity
data/information, conducting new testing if adequate data did not exist, and making both new
and existing data and information available to the public. Each complete data submission
contains data on 18 internationally agreed to "SIDS" (Screening Information Data Set1'2)
endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the
environment.
The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is
evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored
chemicals by developing hazard characterizations (HCs). These HCs consist of an evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions.
They are not intended to be definitive statements regarding the possibility of unreasonable risk of
injury to health or the environment.
The evaluation is performed according to established EPA guidance2'3 and is based primarily on
hazard data provided by sponsors; however, in preparing the hazard characterization, EPA
considered its own comments and public comments on the original submission as well as the
sponsor's responses to comments and revisions made to the submission. In order to determine
whether any new hazard information was developed since the time of the HPV submission, a
search of the following databases was made from one year prior to the date of the HPV
Challenge submission to the present: (ChemID to locate available data sources including
Medline/PubMed, Toxline, HSDB, IRIS, NTP, AT SDR, IARC, EXTOXNET, EPA SRS, etc.),
STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS,
Merck, etc.) and Science Direct. OPPT's focus on these specific sources is based on their being
of high quality, highly relevant to hazard characterization, and publicly available.
OPPT does not develop HCs for those HPV chemicals which have already been assessed
internationally through the HPV program of the Organization for Economic Cooperation and
Development (OECD) and for which Screening Initial Data Set (SIDS) Initial Assessment
Reports (SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These documents are
presented in an international forum that involves review and endorsement by governmental
authorities around the world. OPPT is an active participant in these meetings and accepts these
documents as reliable screening-level hazard assessments.
1 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.
2 U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.
3 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
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These hazard characterizations are technical documents intended to inform subsequent decisions
and actions by OPPT. Accordingly, the documents are not written with the goal of informing the
general public. However, they do provide a vehicle for public access to a concise assessment of
the raw technical data on HPV chemicals and provide information previously not readily
available to the public.
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Chemical Abstract Service
Registry Number
(CASRN)
2778-42-9
Chemical Abstract Index
Name
Benzene, l,3-bis(l-isocyanato-l-methylethyl)-
Structural Formula
n Ti n
o
Summary
This chemical is a liquid that reacts slowly with water and has moderate vapor pressure. It is
expected to have low mobility in soil. Volatilization of this chemical is considered slow based
on its Henry's Law constant. The rate of hydrolysis is considered slow. The rate of atmospheric
photooxidation is considered moderate. This chemical is expected to have low persistence (PI)
and low bioaccumulation potential (Bl).
The acute toxicity of this chemical is low in rats and rabbits following oral and dermal exposures
respectively, but high in rats and guinea pigs exposed via inhalation. This chemical is
moderately irritating to rabbit skin and eyes and is a dermal sensitizer in guinea pigs. Repeated-
dose studies in rats exposed to this chemical via vapor and aerosol showed decreased body
weight gain, serum chemistry, hematology and urinalysis alterations, increased lung weights, and
histopathological changes in the lungs and respiratory tract. The LOAEL for systemic toxicity
was approximately 0.004 mg/L/day, and the NOAEL was not established for vapor exposure.
The LOAEL for aerosol exposure was 0.0044 mg/L/day with a NOAEL of 0.0015 mg/L/day. An
oral combined reproductive/developmental toxicity screening test in rats revealed significant
decreases in pup weight and mean litter weights during lactation days 1 and 4. The LOAEL for
developmental toxicity was 250 mg/kg-bw/day and the NOAEL was 150 mg/kg-bw/day. This
chemical did not induce gene mutations or chromosomal aberrations in vitro.
The acute hazard to fish, aquatic invertebrates, and aquatic plants is 0.67 mg/L, 5.2 mg/L, and
2.1 mg/L, respectively.
No data gaps were identified under the HPV Challenge Program.
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The sponsor, Cytec Industries, Inc., submitted a Test Plan and Robust Summaries to EPA for
isocyanic acid, w-phenylenediiso-propylidene [CAS No. 2778-42-9; 9th CI name: benzene, 1,3-
bis(l-isocyanato-l-methylethyl)] on September 19, 2002. EPA posted the submission on the
ChemRTK HPV Challenge website on October 10, 2002
(http://www.epa.gov/hpv/pubs/summaries/isocvani/cl3996tc.htm). EPA comments on the
original submission were posted to the website on February 6, 2003. Public comments were also
received and posted to the website. The sponsor submitted updated/re vised documents on April
9, 2003, October 3, 2003, February 8, 2004 and March 15, 2005, which were posted to the
ChemRTK website on June 6, 2003, February 8, 2005, March 8, 2005 and May 10, 2005,
respectively.
1. Chemical Identity
1.1 Identification and Purity
The HPV submission for this chemical did not include information on identification and purity in
the Test Plan (2002).
1.2 Physical-Chemical Properties
The physical-chemical properties of isocyanic acid, w-phenylenediisopropylidene are
summarized in Table 1.
Table 1. Physical-Chemical Properties of Isocyanic Acid, m-Phenylenediisopropylidene1
Property
Value
CASRN
2778-42-9
Molecular Weight
244.30
Physical State
Liquid
Melting Point
-10°C (measured)
Boiling Point
292°C (measured)
Vapor Pressure
3.2><10"3 mm Hg at 25°C (measured)
Water Solubility
5.83 mg/L at 25°C (estimated; reacts slowly with water)
Dissociation Constant (pKa)
Not applicable
Henry's Law Constant
3.22x 10"6 atm-m3/mole (estimated)
Log Kow
4.74 (estimated)
'Cytcc Industries Inc. May 10,2005. Revised Robust Summary and Test Plan for Isocyanic Acid, /w-Phenylene-
diisopropylidene. http://www.epa.gov/chemrtk/pubs/summaries/isocvani/cl3996tc.htm.
2. General Information on Exposure
2.1 Production Volume and Use Pattern
This chemical had an aggregated production and/or import volume in the United States of 1 to 10
million pounds during the calendar year 2005.
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Non-confidential information in the IUR indicated that the industrial processing and uses of the
chemical include adhesive and binding agents in the manufacturing of adhesives. Non-
confidential information in the IUR indicated that the commercial and consumer products
containing the chemical include adhesives, sealants, paints and coatings.
The HPV and eHPV submissions for this chemical state that it is primarily used in specialty
coatings, aqueous dispersions, automotive coatings, wood coatings, inks, sealants, adhesives,
thermoplastic urethanes, and lacquers. In addition, this chemical is FDA approved for use in
food-packaging under specific listings in the Code of Federal Regulations (CFR) Title 21-Food
and Drugs Chapter I-Food and Drug Administration, Department of Health and Human Services.
2.2 Environmental Exposure and Fate
No quantitative information is available on releases of this chemical to the environment.
The environmental fate properties are provided in Table 2. Isocyanic acid, m-
phenylenediisopropylidene is expected to have low mobility in soil. Isocyanic acid,
w-phenylenediisopropylidene and its hydrolysis products were not readily biodegradable using a
closed bottle (OECD 301D) test. The rate of volatilization of isocyanic acid, m-
phenylenediisopropylidene from water and moist soil is considered low based on the estimated
Henry's Law constant. The rate of hydrolysis is slow [stable for 2-3 hrs at temperatures below
40 °C] under environmental conditions. Isocyanic acid, w-phenylenediisopropylidene is
expected to have low persistence (PI) and low bioaccumulation potential (Bl).
Table 2. Environmental Fate Characteristics of Isocyanic acid, m-
phenylenediisopropylidene1
Property
Value
Photodegradation Half-life
12.7 hours (estimated)
Hydrolysis Half-life
Stable to hydrolysis for hours to days
Biodegradation
13.7% after 28 days (not readily biodegradable)
Bioconcentration
BCF = 900 (estimated)3
Log Koc
5.05 (estimated)3
Fugacity
(Level III Model)
Air = 0.779%
Water = 18.1%
Soil = 62.6%
Sediment = 18.5%
Persistence4
PI (low)
Bi oaccumul ati on4
Bl (low)
'Cytcc Industries Inc. May 10,2005. Revised Robust Summary for Isocyanic Acid, /w-Phenylenediisopropyli-
dene. http://www.epa.gov/chemrtk/pubs/summaries/isocYani/cl3996tc.htm.
2http://www.cvtec.com/specialtv-chemicals/pdf/UPT-797-B-TMXDI%20Dispersions.pdf and
http://www.cytec.com/specialty-chemicals/PDFs/SpecialtyUrethanes/Novel%20PUD3_07.pdf
3U.S. EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States
Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
4Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances.
Federal Register 64, Number 213 (November 4, 1999) pp. 60194-60204.
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3. Human Health Hazard
Acute Oral Toxicity
(1) Sprague-Dawley rats (5/sex/dose) were administered isocyanic acid, w-phenylenediiso-
propylidene via oral gavage at 0, 2.8, 3.6, 4.5, 5.6 or 7.1 ml/kg-bw (approximately 0, 2968, 3816,
4770, 5936 or 7526 mg/kg-bw) and observed for 15 days. Mortality occurred at all exposure
doses (2/10 on day 3 at 2.8; 1/10 on day 3 at 3.6; 5/10 on days 2 and 4 at 4.5; and 10/10 on days
2 and 3 at 7.1 ml/kg-bw). Treated animals gained less weight compared to controls and lost
weight for 1 - 3 days post-dosing. There were no significant differences when compared to the
control. Necropsy findings did not reveal any abnormalities.
LD50 ~ 5300 mg/kg-bw
(2) Sprague-Dawley rats (5/sex) were administered undiluted isocyanic acid, w-phenylenediiso-
propylidene via oral gavage at 5000 mg/kg-bw and observed for 14 days. No signs of toxicity
were observed on the day of dosing. Two females died on day 2. At necropsy irritation of the
small intestinal mucosa was seen in three animals.
LD50 > 5000 mg/kg-bw
Acute Inhalation Toxicity
(1) Sprague-Dawley rats (5/sex/concentration) were exposed (whole body) to the aerosol of
isocyanic acid, w-phenylenediiso-propylidene at mean measured concentrations of 0, 0.0200,
0.0533, 0.0935 or 0.316 mg/L for 4 hours and observed for 14 days. Mortality occurred at all
exposure concentrations (10/10 at 0.316; 10/10 at 0.0935; 9/10 at 0.0533; and 3/10 at 0.02
mg/L). Clinical signs during exposure included respiratory abnormalities, whole body
hypothermia, red/brown discharge from the jaws and snout, immobility, emaciation, swollen
abdomen, lethargy, a dark appearance of the eyes, salivation, and wet fur around snout, matted
fur and opacity of the eyes. Necropsy examinations revealed congestion and swollen lungs, a
white frothy fluid in the trachea, a fluid-filled thoracic cavity, distension of the gastrointestinal
tract with gas.
LC50 = 0.027 mg/L
(2) English Smooth-Haired guinea pigs (5/sex/concentration) were exposed to isocyanic acid, m-
phenylenediiso-propylidene as an aerosol at concentrations of 0, 0.195, 0.233, 0.355 or 0.457
mg/L for 1 hour. Mortality occurred at all exposure concentrations (the number of deaths and
the days were not specified for the study). Clinical signs included weakness, lethargy,
gasping/rales and discharge from eyes, nose or mouth. Body weight losses occurred in all
treatment groups. Gross pathology of the animals that died showed swollen, congested,
reddened and rubbery lungs. Survivors showed swelling, reddening, collapse and foci of
discoloration in lungs during the necropsy.
LC50 = 0.240 mg/L
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Acute Dermal Toxicity
New Zealand White rabbits (5/sex) were administered isocyanic acid, w-phenylenediiso-
propylidene dermally at 2000 mg/kg-bw on to the abraded skin under occluded conditions for 24
hours. Dermal irritation and eschar formation was seen at the application site on day 4 and was
most severe 14 days after test substance application with a mean score of 3.9 out of 4. The
irritation persisted until the day of scheduled sacrifice.
LD50 > 2000 mg/kg-bw
Repeated-Dose Toxicity
(1) Sprague-Dawley rats (10/sex/concentration) were exposed (whole-body) to isocyanic acid,
w-phenylenediiso-propylidene vapor at nominal concentrations of 0, 0.4, 0.8 or 1.6 ppm for 6
hours/day, 5 days/week for 13 weeks. Mean analytical concentrations were 0, 0.31, 0.72 and
1.46 ppm (0, approximately 0.004, 0.008 and 0.015 mg/L, respectively). Three male rats at the
high-concentration died on days 15-18. Exposure-related clinical signs included respiratory
difficulties at 1.46 ppm and were present sporadically at 0.72 ppm. A significant decrease in
body weight gains were seen in males and females at the highest concentration during weeks 7
and 14. Increased mean corpuscular volume (MCV), erythrocyte count; decreased albumin
concentration, glucose concentration and urine volume were seen at 0.31 and 0.72 ppm. At
necropsy, discolored and emphysematous lungs were observed in animals that died or were
humanely killed. Increased lung weights were noted at all concentrations. Microscopic
examinations revealed significant increases in rhinitis and squamous metaplasia at all exposure;
nasal cavity mucus at the mid- and high doses; and olfactory epithelium degeneration at the
highest dose. Histopathological examinations showed inflammatory changes and lesions in the
respiratory tract, (nasal cavity, larynx and trachea) consisting of necrosis, ulceration, squamous
metaplasia, congestion and hemorrhage Bronchiolar submucosal fibrosis was noted in several
animals.
LOAEL ~ 0.004 mg/L/day (based on decreased body weight gains, changes in serum chemistry,
hematology and urinalysis, increased lung weight and histopathological changes in the
respiratory tract)
NOAEL = Not established
(2) CD-I mice (10/sex/concentration) were exposed (whole-body) to isocyanic acid, m-
phenylenediiso-propylidene vapor at nominal concentrations of 0, 0.4, 0.8 or 1.6 ppm for 6
hours/day, 5 days/week for 13 weeks. Mean analytical concentrations were 0, 0.31, 0.72 and
1.46 ppm (0, approximately 0.004, 0.008 and 0.015 mg/L, respectively). Mortalities for male
mice were 1/10 at 0.4 on day 18, 2/10 at 0.8 on days 25-66, and 7/10 at 1.6 ppm on days 6-24.
Mortalities for female mice were 2/10 at 0.8 on days 18-27, and 9/10 at 1.6 ppm on days 7-38. A
Decreased body weight gain was significantly different in mice at 1.46 ppm of weeks 7 and 8 in
both males and females. Exposure-related clinical signs included respiratory difficulties (e.g.,
gasping, audible respiration) at 1.46 ppm and were observed sporadically at 0.72 ppm.
Involuntary sporadic contraction of the eyes and alopecia were also observed at 0.72 and 1.46
ppm. At necropsy, discoloration and emphysematous lungs were observed in animals that died
or were humanely killed. For mice that died, pulmonary congestion and alopecia were observed.
Microscopic evaluations showed rhinitis and accumulated nasal mucus at all doses; acidophilic
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droplets at the low to mid-doses; Increased lungs weights were noted at all concentrations.
Histopathological examination revealed inflammatory changes and lesions in the respiratory tract
included lesions in the nasal cavity, larynx, trachea (consisting of necrosis, ulceration, squamous
metaplasia, congestion and hemorrhage). Bronchiolar submucosal fibrosis was noted in several
animals.
LOAEL ~ 0.004 mg/L/day (based on mortality, decreased body weight gains, increased lungs
weight and histopathological changes in respiratory tract)
NOAEL = Not established
(3) Sprague-Dawley rats (5/sex/concentration) were exposed (whole-body) to aerosols of
isocyanic acid, w-phenylenediiso-propylidene at nominal concentrations of 0, 0.0005, 0.0015 or
0.005 mg/L for 6 hours/day, 5 days/week for 4 weeks. The mean analytical exposure
concentrations were 0, 0.00038, 0.0015 and 0.0044 mg/L. All animals survived the duration of
the study at all concentrations tested. Body weights were significantly decreased in males and
females at the high concentration on days 5-8. Serum calcium and phosphorous levels of high-
concentration males were significantly increased and females showed a similar trend, but were
not significantly different. High-concentration females had a significant increase in relative lung
weights, but not in absolute lung weights. Gross postmortem evaluations showed evidence of
discolored lungs in one of five males exposed to the low concentration, one male and one female
exposed to the mid-dose and four of five males at the high-concentration. Microscopic findings
at high concentration included subacute/chronic inflammations of the lungs only in some animals
and the appearance of hyperplastic and metaplastic changes in the bronchi of several animals.
These changes were not seen in animals from the control or the two lower exposure levels.
LOAEL = 0.0044 mg/L/day (based on decreased body weight, serum chemistry alterations,
histopathological changes in the lungs)
NOAEL = 0.0015 mg/L/day
Reproductive/Developmental Toxicity
In a combined reproductive/developmental toxicity screening test, Sprague-Dawley rats
(10/sex/dose) were administered isocyanic acid, w-phenylenediiso-propylidene via oral gavage at
0, 15, 150 or 250 mg/kg-bw/day. Males were exposed for 19 days and females for 40-41 days.
Mortality was observed at all doses (four low-dose, five mid-dose and four high-dose animals)
but was attributed to the mal-administration of isocyanic acid, w-phenylenediiso-propylidene.
Body weight gain was decreased in females at the high dose throughout gestation and day 1-4
post-partum, but was not significantly different. There was no effect of treatment on fertility or
mating performance. Male and female fertility indices were 100% at the low- and mid-doses and
90% at the high-dose. One high-dose and one control pair failed to mate. There was no effect of
treatment on pre-coital interval or gestation or parturition length. There were no effects of
treatment on live birth or viability index, litter size, pinna unfolding, surface righting reflex or
sex ratio. There were no treatment-related gross abnormalities in offspring at termination. The
mean pup weight was significantly decreased on days 1 and 4 of lactation at the high dose that
led to a decrease in the total mean litter weight compared to controls. Offspring weights of high-
dose animals were lower than historical controls.
LOAEL = 250 mg/kg-bw/day (based on decreased pup weight and decreased litter weight
during lactation days 1 and 4)
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NOAEL = 150 mg/kg-bw/day
Genetic Toxicity — Gene Mutation
In vitro
Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 were exposed to
isocyanic acid, w-phenylenediiso-propylidene at concentrations of 0.1, 1, 10 or 100 |j,g/plate in
the presence and absence of metabolic activation. The cytotoxic concentration was 100 - 10,000
Hg/plate. Positive and vehicle controls were tested concurrently and responded appropriately.
Isocyanic acid, m-phenylenediiso-propylidene was not mutagenic in this assay.
Genetic Toxicity — Chromosomal Aberrations
In vitro
Chinese hamster ovary (CHO) cells were exposed to isocyanic acid, w-phenylenediiso-
propylidene at concentrations of 0 - 40 |j,g/mL in the absence of metabolic activation, and 0-40
or 0 - 20 |j,g/mL in the presence of metabolic activation. The cytotoxic concentration was > 20
Hg/mL. Positive and vehicle controls were tested concurrently and responded appropriately.
Isocyanic acid, m-phenylenediiso-propylidene did not induce chromosomal aberrations in
this assay.
Additional Information
Skin Irritation
Rabbits (6 males) were administered 0.5 mL of isocyanic acid, w-phenylenediiso-propylidene
dermally onto two intact and two abraded skin sites under occluded conditions for 24 hours and
were monitored for 13 days. Erythema ranged from mild to severe for intact sites and severe for
abraded sites. Mild edema was observed for both skin types.
Isocyanic acid, m-phenylenediiso-propylidene was moderately irritating to rabbit skin in
this assay.
Eye Irritation
Rabbits (9 females) were administered 0.1 mL of undiluted isocyanic acid, w-phenylenediiso-
propylidene into the conjunctival sac of the right eye of each rabbit; the left eye was untreated
and served as a control. Six rabbits received no further treatment. Three rabbits had their eyes
rinsed for 60 seconds, 30 seconds after the test substance instillation. All rabbits survived and
gained weight. Ocular exposure produced no corneal damage at any time. All treated eyes
responded to light; however, discharge, chemosis, inflammation and opacity was also observed.
Isocyanic acid, m-phenylenediiso-propylidene was mildly irritating to rabbit eyes in this
assay.
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Sensitization
(1) Guinea pigs (10) were administered 25 |j,L a single epicutaneous application of a 0.36 molar
solution of isocyanic acid, w-phenylenediiso-propylidene. Five days after the single induction
application, each animal was exposed to the same concentration and amount of test substance to
a previously untreated site. No patch was applied to the induction site or challenge sites. Nine
days after the initial challenge, the animals were subjected to a re-challenge at sites that had not
been previously exposed. Animals were observed twice per day for clinical signs. Skin
condition was evaluated at 24 and 48 hours after each application. Contact sensitization was
evident for the test substance at the initial (5 days post-induction) challenge. Evidence of
sensitization was negligible upon re-challenge (14 days post-induction).
Isocyanic acid, m-phenylenediiso-propylidene was sensitizing in this assay.
(2) Guinea pigs (12/dose) were exposed whole-body to isocyanic acid, w-phenylenediiso-
propylidene at a nominal aerosol concentration 36 |j,g/L (26.7 |j,g/L measured concentration) for
3 hours a day for 5 days. A negative control group was also tested. On challenge days 22, 23
and 26, animals were exposed nose-only to a nominal aerosol concentration of 0.015 - 0.020
mg/L for a 20-minute period. On study day 24, the animals were challenged for skin
sensitization potential by intradermal dosing with 100 |j,L of 0.0333% isocyanic acid, m-
phenylenediiso-propylidene and control substance at different sites. Lethargy and nasal and oral
discharge were observed in both groups. None of the animals showed an increase in respiratory
rate equal to or greater than the value of 36% used as a threshold value of a positive response.
There was no evidence of respiratory sensitization and there were no treatment-related effects on
lung weights. There was no evidence of skin sensitization as there was an absence of scores > 2
for erythema.
Isocyanic acid, m-phenylenediiso-propylidene was not a dermal or respiratory sensitizer in
this assay.
Conclusion: The acute toxicity of this chemical is low in rats and rabbits following oral and
dermal exposures respectively, but high in rats and guinea pigs exposed via inhalation. This
chemical is moderately irritating to rabbit skin and eyes and is a dermal sensitizer in guinea pigs.
Repeated-dose studies in rats exposed to this chemical via vapor and aerosol showed decreased
body weight gain, serum chemistry, hematology and urinalysis alterations, increased lung
weights, and histopathological changes in the lungs and respiratory tract. The LOAEL for
systemic toxicity was approximately 0.004 mg/L/day, and the NOAEL was not established for
vapor exposure. The LOAEL for aerosol exposure was 0.0044 mg/L/day and the NOAEL was
0.0015 mg/L/day. An oral combined reproductive/developmental toxicity screening test in rats
revealed significant decreases in pup weight and mean litter weights during lactation days 1 and
4. The developmental toxicity LOAEL was 250 mg/kg-bw/day with a NOAEL of 150 mg/kg-
bw/day. This chemical did not induce gene mutations or chromosomal aberrations in vitro.
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4. Hazard to the Environment
Acute Toxicity to Fish
Fathead minnows (Pimephalespromelas, 10/concentration) were exposed to isocyanic acid, m-
phenylenediiso-propylidene (in acetone) at nominal concentrations of 0, 0.10, 0.18, 0.32, 0.56 or
1.0 mg/L under static conditions for 96 hours. Measured exposure concentrations were not
provided. No effects were noted at < 0.32 mg/L. At 0.56 and 1.0 mg/L, mortality, surfacing,
loss of equilibrium and quiescence were noted.
96-h LC50 = 0.67 mg/L
Acute Toxicity to Aquatic Invertebrates
Water fleas {Daphnia magna, 10/replicate) were exposed to isocyanic acid, w-phenylenediiso-
propylidene (in acetone) at nominal concentrations of 0, 0 (solvent), 1.0, 1.8, 3.2, 5.6 and 10
mg/L under static conditions for 48 hours. Measured exposure concentrations were not
provided. Abnormal effects including mortality, quiescence, surfacing and daphnia lying on the
bottom were observed in all test concentrations.
48-h EC50 = 5.2 mg/L
Toxicity to Aquatic Plants
Green algae (Pseudokirchneriella subcapitata) were exposed to isocyanic acid, m-
phenylenediiso-propylidene (in acetone) at nominal concentrations of 0, 0 (solvent), 0.32, 1.0,
3.2, 10.0 and 32 mg/L under static conditions for 96 hours. Measured exposure concentrations
were not provided. Cell growth was insufficient at 24 and 48 hours to establish concentration-
effect relationships for all concentrations and the blank control. The median effects could not be
calculated for these time periods. The rate of cell growth was satisfactory (> 16 in 72 hours) in
controls.
96-h EC50 (growth) = 2.1 mg/L
Conclusion: The acute hazard to fish, aquatic invertebrates, and aquatic plants is 0.67 mg/L, 5.2
mg/L, and 2.1 mg/L, respectively.
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Table 2
Summary Table of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Isocyanic acid, m-phenylenediiso-propylidene
(2778-42-9)
Summary of Human Health Data
Acute Oral Toxicity
LD50 (mg/kg-bw)
>5000
Acute Inhalation Toxicity
LCso (mg/L)
0.027
Acute Dermal Toxicity
LDjo (mg/kg-bw)
>2000
Repeated-Dose Toxicity
LOAEL/NOAEL
Inhalation (mg/L/day)
Rats and Mice (vapor)
LOAEL ~ 0.004
NOAEL = Not established
Rats (aerosol)
LOAEL= 0.0044
NOAEL= 0.0015
Reproductive/Developmental Toxicity
LOAEL/NOAEL
Oral (mg/kg-bw/day)
Reproductive/Developmental Toxicity
LOAEL = 250
NOAEL = 150
Genetic Toxicity - Gene Mutation
In vitro
Negative
Genetic Toxicity - Chromosomal Aberrations
In vitro
Negative
Additional Information
Skin Irritation
Eye Irritation
Skin Sensitization
Respiratory Sensitization
Moderate
Mild
Positive
Negative
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
0.67
Aquatic Invertebrates
48-h ECS0 (mg/L)
5.2
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September, 2009
Summary Table of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Isocyanic acid, m-phenylenediiso-propylidene
(2778-42-9)
Aquatic Plants
72-h EC50 (mg/L)
(growth)
(biomass)
2.1 (96-h)
13
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